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Sample records for activity involving benign

  1. [Renal involvement in benign monoclonal gammopathies: an underdiagnosed condition].

    PubMed

    Ramos, R; Poveda, R; Bernís, C; Ara, J; Sunyer, M; Arrizabalaga, P; Grinyó, J M

    2008-01-01

    Renal involvement is observed frequently in association with malignant gammopathies, mainly those related to light chain deposition, although has also been described in non-malignant monoclonal gammopathy. This study reports the clinicopathological findings and outcome in 9 patients with nephropaty secondary to monoclonal immunoglobulin deposit in absence of malignancy. They were three men and six women and they were 59.2+/-12 years old. All patients presented proteinuria and different levels of renal insufficiency (mean creatinin = 315+/-187 micromol/L) at the moment of diagnostic. Two patients required dialysis at the time of renal biopsy. The pathology studies revealed a nodular sclerosing glomerulopathy in four cases, mesangiocapilary glomerulonephritis in three cases, only tubular lesions in one and mesangial lesions in the other one. The treatment applied was: Prednisone alone (two cases), with chemotherapy associated (melfalan in two, clorambucil in one and ciclophosphamide in another one). One patient received plasmapheresis and mycophenolate and another patient undergone a bone marrow authotransplant associated to mycophenolate and prednisone. One of the two patients who required dialysis at the moment of presentation was not treated. After a follow-up of more than 4 years (4.89 +/-DE: 3.69) renal function improved or remained stable in three patients and proteinuria was disappeared in more than 50% of patients. Four patients had a worsening of renal function and they required dialysis during the time of follow-up (in 2,4 years +/- DE: 4,3). In any case malignitation was observed. Chemotherapy stabilized or improved renal function in 3 of nine patients (33%) with non-malignant monoclonal gammopathy. Non-malignant monoclonal gammopathy could go unnoticed. Appearance of abnormalities in renal routine tests deserves more in-depth diagnostic procedures, including renal biopsy. Evolution to end stage renal disease could probably be avoided or reduced in

  2. Activated carbon for aerobic oxidation: Benign approach toward 2-benzoylbenzimidazoles and 2-benzoylbenzoxazoles synthesis

    PubMed Central

    Bao, Kai; Li, Fuqing; Liu, Hanjing; Wang, Zhiwei; Shen, Qirong; Wang, Jian; Zhang, Weige

    2015-01-01

    A general strategy involving a novel and highly efficient aerobic benzylic oxidation promoted by cheap, reusable activated carbon in water is developed. Application of this method has been demonstrated in the benign synthesis of bioactive 2-benzoylbenzimidazoles and 2-benzoylbenzoxazoles derivatives. Furthermore, the activated carbon catalyst could be recovered and reused at least three times without significantly losing its activity. Preliminary research suggests that the oxidation mechanism may involve intermediate hydroperoxidation and that a portion of the final carbonyl product is obtained through a secondary benzylic alcohol intermediate. Finally, theoretical calculations reveal that the oxidation yield is closely associated with the electric density at the benzylic position of the substrate. PMID:26041483

  3. Benign mucous membrane pemphigoid with advanced periodontal involvement: diagnosis and therapy.

    PubMed

    Lilly, J P; Spivey, J D; Fotos, P G

    1995-08-01

    This paper describes a case of benign mucous membrane pemphigoid which affected the periodontal tissues and complicated ocular prosthesis placement. The clinical findings, diagnostic criteria, and therapeutic management of this disorder are reviewed. PMID:7473017

  4. MICROWAVE-ASSISTED GREENER SYNTHESIS OF PHARMACEUTICALLY ACTIVE HETEROCYCLES UNDER BENIGN CONDITIONS

    EPA Science Inventory

    Green chemistry is a rapidly developing new field that provides us a proactive avenue for the sustainable development of future science and technologies. Environmentally benign protocols have been developed for the synthesis of various pharmaceutically active heterocycles namely ...

  5. [Benign symmetrical Launois-Bensaude type II lipomatosis with market systemic involvement and psoriasis].

    PubMed

    Novak, N; Petrow, W; Bieber, T

    2000-06-01

    Benign symmetric lipomatosis of the pseudoathletic type was identified in a woman with a positive family history for the disorder and a past history of alcohol abuse. She had an exceptionally high number of additional diseases such as arthropathy with degenerative osteoporosis, hyperuricemia, hyperlipidemia, psoriasis, neuropathy, muscular atrophy, arteriosclerosis and increased cardiovascular risk factors. PMID:10907159

  6. Benign chronic neutropenia with abnormalities involving 16q22, affecting mother and daughter.

    PubMed

    Glasser, Lewis; Meloni-Ehrig, Aurelia; Joseph, Plakyil; Mendiola, Jennifer

    2006-04-01

    We report a case of familial, chronic, benign neutropenia in a 17-year-old female showing (1) the spontaneous expression of a heritable rare fragile site at 16q22 and (2) a deletion at the same region. The del(16)(q22), which most likely originated from the fragile site, was the main clonal abnormality detected in the patient's bone marrow cells, whereas a few cells with either del(16)(q22) or fra(16)(q22) were seen in the patient's peripheral blood. Interestingly, the del(16q) was also detected in the patient's uncultured cells, as demonstrated by FISH, excluding an in vitro origin of the del(16q) during culture. The bone marrow was hypocellular with decreased neutrophils and their precursors. Absolute neutrophil counts ranged from (0.62 to 1.24) x 10(9)/L with a median value of 1.02 x 10(9)/L. The patient had a more severe neutropenia than her mother, which correlated with the presence of more cells with del(16q) in the marrow. The patient's mother, who was also diagnosed with neutropenia, revealed only a few cells with the rare fra(16)(q22) in her peripheral blood cells, whereas her bone marrow showed cells with both fra(16)(q22) and del(16)(q22), although the del(16q) was present in only 2/20 cells. Some possible candidate genes contributing to the pathogenesis of the neutropenia are discussed. Chromosome abnormalities involving the 16q22 breakpoint have been observed in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). In this patient, the del(16)(q22) risk factor is unknown for subsequent development of MDS or AML. Another point to consider is the need to determine the origin of a chromosome abnormality, particularly when the clinical picture does not fit the chromosome findings. Although, the observation of a constitutional structural abnormality in a mosaic form is an extremely rare event, it is somewhat different in the case of a fragile site expression, which can, as in this case, be present in some cells and not in others. PMID:16550514

  7. Genome-wide DNA methylation profiling and its involved molecular pathways from one individual with thyroid malignant/benign tumor and hyperplasia

    PubMed Central

    Cai, Liang-Liang; Liu, Guo-Yan; Tzeng, Chi-Meng

    2016-01-01

    Abstract Background: During development, methylation permanently changes gene activity, while aberrant gene methylation is key to human tumorigenesis. Gene methylation is an epigenetic event leading to gene silencing and some tumor suppressor genes that are aberrantly methylated in both thyroid cancer and benign thyroid tumor, suggesting a role for methylation in early thyroid tumorigenesis. Specific gene methylation occurs in certain types of thyroid cancer and depends on particular signaling pathways. Most reports rely on data from varied samples that vary tremendously with respect to methylation. Results: We observed that hyperplastic/malignant (H/M) thyroid tissue and benign/manligant (B/M) tissue had the most profoundly methylated loci compared to hyperplastic/benign (H/B) tissue. These loci are mapped to 863 genes (|Δβ value| > 0.15) in B/M and 1082 genes (|Δβ value| > 0.15) in H/M. After bioinformatic analysis, these genes were found to be involved in T-cell receptor signaling pathway (B/M) and Jak–Stat signaling pathways (H/M). Conclusion: Our study offers the most comprehensive DNA methylation data for thyroid disease to date, using 1 patient with 3 tissue types and high-resolution 450K arrays. Our data may lay the foundation for future identification of novel epigenetic targets or diagnosis of thyroid cancer. PMID:27583899

  8. HMGI(Y) expression in human uterine leiomyomata. Involvement of another high-mobility group architectural factor in a benign neoplasm.

    PubMed Central

    Williams, A. J.; Powell, W. L.; Collins, T.; Morton, C. C.

    1997-01-01

    Chromosomal rearrangements involving 6p21 have been observed in uterine leiomyomata and a variety of other benign tumors. The gene for HMGI(Y), a member of the high-mobility group (HMG) family of proteins, has been localized to 6p21. To determine whether rearrangements observed in this area alter HMGI(Y) expression, we analyzed HMGI(Y) DNA-binding activity in protein extracts from uterine leiomyoma and normal myometrium tissues. This report describes a uterine leiomyoma specimen with an inv(6)(p21q15). A genomic P1 clone that contains the HMGI(Y) region of chromosome 6 is found to span the inversion breakpoint by fluorescent in situ hybridization of metaphase chromosomes. Expression of HMGI(Y) protein in this leiomyoma specimen is increased dramatically as compared with the matching normal myometrial tissue. Elevated HMGI(Y) expression was also found in 8 of 16 leiomyomas without cytogenetically detectable chromosome 6p21 aberrations but not in any of the 9 matching myometrial tissues. Analysis of the genetic events involved in the pathobiology of these benign tumors will provide a basis for understanding the process of improper cellular growth and might be important in deciphering the multistep pathway of tumorigenesis. Images Figure 1 Figure 2 Figure 3 PMID:9060829

  9. Antiinflammatory effect of androgen receptor activation in human benign prostatic hyperplasia cells.

    PubMed

    Vignozzi, Linda; Cellai, Ilaria; Santi, Raffaella; Lombardelli, Letizia; Morelli, Annamaria; Comeglio, Paolo; Filippi, Sandra; Logiodice, Federica; Carini, Marco; Nesi, Gabriella; Gacci, Mauro; Piccinni, Marie-Pierre; Adorini, Luciano; Maggi, Mario

    2012-07-01

    Progression of benign prostatic hyperplasia (BPH) involves chronic inflammation and immune dysregulation. Preclinical studies have demonstrated that prostate inflammation and tissue remodeling are exacerbated by hypogonadism and prevented by testosterone supplementation. We now investigated whether, in humans, hypogonadism was associated with more severe BPH inflammation and the in vitro effect of the selective androgen receptor agonist dihydrotestosterone (DHT) on cultures of stromal cells derived from BPH patients (hBPH). Histological analysis of inflammatory infiltrates in prostatectomy specimens from a cohort of BPH patients and correlation with serum testosterone level was performed. Even after adjusting for confounding factors, hypogonadism was associated with a fivefold increased risk of intraprostatic inflammation, which was also more severe than that observed in eugonadal BPH patients. Triggering hBPH cells by inflammatory stimuli (tumor necrosis factor α, lipopolysaccharide, or CD4(+)T cells) induced abundant secretion of inflammatory/growth factors (interleukin 6 (IL6), IL8, and basic fibroblast growth factor (bFGF)). Co-culture of CD4(+)T cells with hBPH cells induced secretion of Th1 inducer (IL12), Th1-recruiting chemokine (interferon γ inducible protein 10, IP10), and Th2 (IL9)- and Th17 (IL17)-specific cytokines. Pretreatment with DHT inhibited NF-κB activation and suppressed secretion of several inflammatory/growth factors, with the most pronounced effects on IL8, IL6, and bFGF. Reduced inflammatory cytokine production by T-cells, an increase in IL10, and a significant reduction of T cells proliferation suggested that DHT exerted a broad anti inflammatory effect on testosterone cells [corrected]. In conclusion, our data demonstrate that DHT exerts an immune regulatory role on human prostatic stromal cells, inhibiting their potential to actively induce and/or sustain autoimmune and inflammatory responses. PMID:22562653

  10. Proliferating cell nuclear antigen (PCNA) activity in hepatocellular carcinoma, benign peri-neoplastic and normal liver.

    PubMed

    Mun, Kein-Seong; Cheah, Phaik-Leng; Baharudin, Nurul Bahiyah; Looi, Lai-Meng

    2006-12-01

    Hepatocellular carcinoma (HCC) is among the ten most common cancers in Malaysian males. As cellular proliferation is an important feature of malignant transformation, we studied the proliferation pattern of normal and benign perineoplastic liver versus hepatocellular carcinoma in an attempt to further understand the tumour transformation process. 39 HCC (21 with accompanying and 18 without cirrhosis) histologically diagnosed at the Department of Pathology, University of Malaya Medical Centre between January 1992 and December 2003 were immunohistochemically studied using a monoclonal antibody to PCNA (Clone PC10: Dako). 20 livers from cases who had succumbed to traumatic injuries served as normal liver controls (NL). PCNA labeling index (PCNA-LI) was determined by counting the number of immunopositive cells in 1000 contiguous HCC, benign cirrhotic perineoplastic liver (BLC), benign perineoplastic non-cirrhotic (BLNC) and NL cells and conversion to a percentage. The PCNA-LI was also expressed as Ojanguren et al's grades. PCNA was expressed in 10% NL, 38.9% BLNC, 76.2% BLC and 71.8% HCC with BLNC, BLC and HCC showing significantly increased (p < 0.05) number of cases which expressed PCNA compared with NL. The number of BLC which expressed PCNA was also significantly increased compared with BLNC. PCNA-LI ranged from 0-2.0% (mean = 0.2%) in NL, 0-2.0% (mean = 0.3%) in BLNC, 0-3.6% (mean = 0.7%) in BLC and 0-53.8% (mean = 7.6%) in HCC with PCNA-LI significantly increased (p < 0.05) only in HCC compared with BLC, BLNC and NL. Accordingly, all NL, BLC and BLNC showed minimal (<5% cells being immunopositive) immunoreactivity on Ojanguren et al's grading system and only HCC demonstrated immunoreactivity which ranged up to grade 3 (75% of cells). From this study, there appears to be a generally increasing trend of proliferative activity from NL to BLNC to BLC and HCC. Nonetheless, BLNC and BLC, like NL, retained low PCNA-LI and only HCC had a significantly increased PCNA

  11. Activation of benign autoimmunity as both tumor and autoimmune disease immunotherapy: a comprehensive review.

    PubMed

    Cohen, Irun R

    2014-11-01

    Here, I consider how benign autoimmunity, the immunological homunculus, can be used to reinstate the healthy regulation of inflammation in both autoimmune diseases and in tumor immunotherapy. Different autoimmune diseases manifest clinically distinct phenotypes, but, in general, they all result from the transition of benign, healthy recognition of key body molecules into a damaging effector reaction. Tumors, in contrast to autoimmune diseases, grow by subverting the immune system into supporting and protecting the growing tumor from immune surveillance. Therefore our therapeutic aim in autoimmune disease is to induce the immune system to down-regulate the specific autoimmune effector reaction that causes the disease; in tumor immunotherapy, on the contrary, we aim to deprive the growing tumor of its illicit activation of immune suppression and to unleash an autoimmune disease targeted to the tumor. The recent success of anti-PD1 and anti-CTLR4 treatments exemplify the reinstatement of tumor autoimmunity subsequent to inhibition of immune suppression. With regard to the therapy of autoimmune diseases, I cite examples of immune system down-regulation of autoimmune diseases by T cell vaccination or HSP60 peptide treatment. Inducing the immune system to regulate itself is safer than global immune suppression and may be more effective in the long run. PMID:24924121

  12. Physical Activity in the Prevention of Benign Paroxysmal Positional Vertigo: Probable Association

    PubMed Central

    Bazoni, Jéssica Aparecida; Mendes, William Siqueira; Meneses-Barriviera, Caroline Luiz; Melo, Juliana Jandre; Costa, Viviane de Souza Pinho; Teixeira, Denilson de Castro; Marchiori, Luciana Lozza de Moraes

    2014-01-01

    Introduction Physical inactivity is an important risk factor for many age-related diseases and symptoms such as dizziness and vertigo. Objective The aim of the study was to investigate the possible association between benign paroxysmal positional vertigo (BPPV) and regular physical activity in elderly subjects. Methods This cross-sectional study included 491 elderly individuals who lived independently. Physical exercise was assessed through a questionnaire and BPPV by history and the Dix-Hallpike maneuver. Results The present study indicates no significant association between BPPV with lack of physical activity in men and in the total population. We have confirmed associations between BPPV with lack of physical activity in women (p = 0.01). Women with a sedentary lifestyle who do not practice physical activity are 2.62 more likely to have BPPV than those with regular physical activity. Conclusion These results highlight the importance of identifying risk factors for BPPV that can be modified through specific interventions. Regular physical activity is a lifestyle with potential to decrease the risk of vertigo in women. PMID:25992128

  13. In vivo loss of slow potassium channel activity in individuals with benign familial neonatal epilepsy in remission.

    PubMed

    Tomlinson, Susan E; Bostock, Hugh; Grinton, Bronwyn; Hanna, Michael G; Kullmann, Dimitri M; Kiernan, Matthew C; Scheffer, Ingrid E; Berkovic, Samuel F; Burke, David

    2012-10-01

    Benign familial neonatal epilepsy is a neuronal channelopathy most commonly caused by mutations in KCNQ2, which encodes the K(v)7.2 subunit of the slow K(+) channel. K(v)7.2 is expressed in both central and peripheral nervous systems. Seizures occur in the neonatal period, often in clusters within the first few days of life, and usually remit by 12 months of age. The mechanism of involvement of K(v)7.2 mutations in the process of seizure generation has not been established in vivo. In peripheral axons, K(v)7.2 contributes to the nodal slow K(+) current. The present study aimed to determine whether axonal excitability studies could detect changes in peripheral nerve function related to dysfunction or loss of slow potassium channel activity. Nerve excitability studies were performed on eight adults with KCNQ2 mutations and a history of benign familial neonatal epilepsy, now in remission. Studies detected distinctive changes in peripheral nerve, indicating a reduction in slow K(+) current. Specifically, accommodation to long-lasting depolarizing currents was reduced in mutation carriers by 24% compared with normal controls, and the threshold undershoot after 100 ms depolarizing currents was reduced by 22%. Additional changes in excitability included a reduction in the relative refractory period, an increase in superexcitability and a tendency towards reduced sub-excitability. Modelling of the nerve excitability changes suggested that peripheral nerve hyperexcitability may have been ameliorated by upregulation of other potassium channels. We conclude that subclinical dysfunction of K(v)7.2 in peripheral axons can be reliably detected non-invasively in adulthood. Related alterations in neuronal excitability may contribute to epilepsy associated with KCNQ2 mutations. PMID:23065794

  14. Duplication at Xq28 involving IKBKG is associated with progressive macrocephaly, recurrent infections, ectodermal dysplasia, benign tumors, and neuropathy.

    PubMed

    van Asbeck, Ellyze; Ramalingam, Arivudainambi; Dvorak, Chris; Chen, Tian-Jian; Morava, Eva

    2014-07-01

    Duplications on Xq28 are common, although quite variable in size, but usually include the MECP2 gene. Here, we present a patient with a unique, small, 167-kb duplication at Xq28, not including MECP2. The most important gene in the duplicated region was IKBKG, mutations in which can cause a variety of distinct syndromes. Our patient's symptoms overlapped with different IKBKG-associated phenotypes, including hypohidrotic ectodermal dysplasia, incontinentia pigmenti, immunodeficiency, recurrent isolated invasive pneumococcal disease and anhidrotic ectodermal dysplasia with immunodeficiency, osteopetrosis, and lymphedema. In addition, she also had peripheral neuropathy, gastroparesis and various benign tumors, but no intellectual disability. Mixed syndromal presentation in several patients with IKBKG defect implies that IKBKG-related phenotypes are more like a spectrum, rather than distinct syndromes. We also suggest our patient's multisystem phenotype to be a novel contiguous gene syndrome, in which the key features include immune deficiency, macrocephaly, skin abnormalities, gastroparesis, peripheral small-fiber neuropathy, and benign tumors. PMID:24721901

  15. Intrinsic brain activity as a diagnostic biomarker in children with benign epilepsy with centrotemporal spikes.

    PubMed

    Zhu, Yihong; Yu, Yang; Shinkareva, Svetlana V; Ji, Gong-Jun; Wang, Jue; Wang, Zhong-Jin; Zang, Yu-Feng; Liao, Wei; Tang, Ye-Lei

    2015-10-01

    Benign epilepsy with centrotemporal spikes (BECTS) is often associated with neural circuit dysfunction, particularly during the transient active state characterized by interictal epileptiform discharges (IEDs). Little is known, however, about the functional neural circuit abnormalities in BECTS without IEDs, or if such abnormalities could be used to differentiate BECTS patients without IEDs from healthy controls (HCs) for early diagnosis. To this end, we conducted resting-state functional magnetic resonance imaging (RS-fMRI) and simultaneous Electroencephalogram (EEG) in children with BECTS (n = 43) and age-matched HC (n = 28). The simultaneous EEG recordings distinguished BECTS with IEDs (n = 20) from without IEDs (n = 23). Intrinsic brain activity was measured in all three groups using the amplitude of low frequency fluctuation at rest. Compared to HC, BECTS patients with IEDs exhibited an intrinsic activity abnormality in the thalamus, suggesting that thalamic dysfunction could contribute to IED emergence while patients without IEDs exhibited intrinsic activity abnormalities in middle frontal gyrus and superior parietal gyrus. Using multivariate pattern classification analysis, we were able to differentiate BECTS without IEDs from HCs with 88.23% accuracy. BECTS without epileptic transients can be distinguished from HC and BECTS with IEDs by unique regional abnormalities in resting brain activity. Both transient abnormalities as reflected by IEDs and chronic abnormalities as reflected by RS-fMRI may contribute to BECTS development and expression. Intrinsic brain activity and multivariate pattern classification techniques are promising tools to diagnose and differentiate BECTS syndromes. Hum Brain Mapp 36:3878-3889, 2015. © 2015 Wiley Periodicals, Inc. PMID:26173095

  16. Parent Involvement in School-Related Activities.

    ERIC Educational Resources Information Center

    National Center for Education Statistics (ED), Washington, DC.

    Noting that some schools have adopted practices or policies that encourage parents to become more involved in their children's school activities and events, this statistical report (based on the National Household Education Survey) details the level and character of parental involvement in school activities. Findings highlighted are: (1) parents…

  17. Physical Activity and Benign Prostatic Hyperplasia-Related Outcomes and Nocturia

    PubMed Central

    WOLIN, KATHLEEN Y.; GRUBB, ROBERT L.; PAKPAHAN, RATNA; RAGARD, LAWRENCE; MABIE, JEROME; ANDRIOLE, GERALD L.; SUTCLIFFE, SIOBHAN

    2015-01-01

    ABSTRACT Introduction Benign prostatic hyperplasia (BPH) and its associated lower urinary tract symptoms (LUTS), including nocturia, are extremely common among middle- and older-age American men. Although studies on physical activity (PA) and prevalent BPH-related outcomes suggest that PA may protect against the development of this common condition, only a few studies have examined the relation between PA and incident BPH-related outcomes and LUTS with mixed findings. In addition, although nocturia is the most commonly reported and most bothersome LUTS in men with or without evidence of BPH, few studies have examined the association of PA and nocturia independent of BPH. The purpose of this analysis was to examine the association of PA with BPH-related outcomes and nocturia in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening trial. Methods We examined this association with both prevalent (n = 28,404) and incident (n = 4710) BPH-related outcomes (measured by self-report of physician diagnosis, BPH surgery, finasteride use, and clinical indicators) and nocturia. Poisson regression with robust variance was used to calculate prevalence ratios and relative risks. Results PA was weakly positively associated with several prevalent BPH-related outcomes and was strongly inversely associated with prevalent nocturia. In incident analyses, PA was only associated with nocturia. Men who were active ≥1 h·wk−1 were 13% less likely (95% confidence interval, 2%–22%) to report nocturia and 34% less likely (95% confidence interval, 15%–49%) to report severe nocturia as compared with men who reported no PA. The associations were similar for men with and without additional BPH-related outcomes, except for prevalent nocturia, where the association was stronger for men without other BPH-related outcomes. Conclusions Combined with other management strategies, PA may provide a strategy for the management of BPH-related outcomes, particularly nocturia. PMID:25010403

  18. Local Activity and Causal Connectivity in Children with Benign Epilepsy with Centrotemporal Spikes.

    PubMed

    Wu, Yun; Ji, Gong-Jun; Zang, Yu-Feng; Liao, Wei; Jin, Zhen; Liu, Ya-Li; Li, Ke; Zeng, Ya-Wei; Fang, Fang

    2015-01-01

    The aim of the current study was to localize the epileptic focus and characterize its causal relation with other brain regions, to understand the cognitive deficits in children with benign childhood epilepsy with centrotemporal spikes (BECTS). Resting-state functional magnetic resonance imaging (fMRI) was performed in 37 children with BECTS and 25 children matched for age, sex and educational achievement. We identified the potential epileptogenic zone (EZ) by comparing the amplitude of low frequency fluctuation (ALFF) of spontaneous blood oxygenation level dependent fMRI signals between the groups. Granger causality analysis was applied to explore the causal effect between EZ and the whole brain. Compared with controls, children with BECTS had significantly increased ALFF in the right postcentral gyrus and bilateral calcarine, and decreased ALFF in the left anterior cingulate cortex, bilateral putaman/caudate, and left cerebellum. ALFF values in the putaman/caudate were positively correlated with verbal IQ scores in patients. The ALFF values in cerebellum and performance IQ scores were negatively correlated in patients. These results suggest that ALFF disturbances in the putaman/caudate and cerebellum play an important role in BECTS cognitive dysfunction. Compared with controls, the patients showed increased driving effect from the EZ to the right medial frontal cortex and posterior cingulate cortex and decreased causal effects from the EZ to left inferior frontal gyrus. The causal effect of the left inferior frontal gyrus negatively correlated with disease duration, which suggests a relation between the epileptiform activity and language impairment. All together, these findings provide additional insight into the neurophysiological mechanisms of epilepitogenisis and cognitive dysfunction associated with BECTS. PMID:26225427

  19. Local Activity and Causal Connectivity in Children with Benign Epilepsy with Centrotemporal Spikes

    PubMed Central

    Zang, Yu-Feng; Liao, Wei; Jin, Zhen; Liu, Ya-Li; Li, Ke; Zeng, Ya-Wei; Fang, Fang

    2015-01-01

    The aim of the current study was to localize the epileptic focus and characterize its causal relation with other brain regions, to understand the cognitive deficits in children with benign childhood epilepsy with centrotemporal spikes (BECTS). Resting-state functional magnetic resonance imaging (fMRI) was performed in 37 children with BECTS and 25 children matched for age, sex and educational achievement. We identified the potential epileptogenic zone (EZ) by comparing the amplitude of low frequency fluctuation (ALFF) of spontaneous blood oxygenation level dependent fMRI signals between the groups. Granger causality analysis was applied to explore the causal effect between EZ and the whole brain. Compared with controls, children with BECTS had significantly increased ALFF in the right postcentral gyrus and bilateral calcarine, and decreased ALFF in the left anterior cingulate cortex, bilateral putaman/caudate, and left cerebellum. ALFF values in the putaman/caudate were positively correlated with verbal IQ scores in patients. The ALFF values in cerebellum and performance IQ scores were negatively correlated in patients. These results suggest that ALFF disturbances in the putaman/caudate and cerebellum play an important role in BECTS cognitive dysfunction. Compared with controls, the patients showed increased driving effect from the EZ to the right medial frontal cortex and posterior cingulate cortex and decreased causal effects from the EZ to left inferior frontal gyrus. The causal effect of the left inferior frontal gyrus negatively correlated with disease duration, which suggests a relation between the epileptiform activity and language impairment. All together, these findings provide additional insight into the neurophysiological mechanisms of epilepitogenisis and cognitive dysfunction associated with BECTS. PMID:26225427

  20. Promoting Active Involvement in Today's Classrooms

    ERIC Educational Resources Information Center

    Conderman, Greg; Bresnahan, Val; Hedin, Laura

    2011-01-01

    In today's diverse classrooms and age of accountability, teachers need to use efficient, research-based instructional approaches that engage all students, promote interest and variety in learning and teaching, and provide immediate and continuous informal assessment data. This article presents a rationale for using active involvement techniques,…

  1. Sustained Akt Activity Is Required to Maintain Cell Viability in Seborrheic Keratosis, a Benign Epithelial Tumor.

    PubMed

    Neel, Victor A; Todorova, Kristina; Wang, Jun; Kwon, Eunjeong; Kang, Minjeong; Liu, Qingsong; Gray, Nathanael; Lee, Sam W; Mandinova, Anna

    2016-03-01

    Seborrheic keratoses (SKs) are common benign skin tumors that share many morphological features with their malignant counterpart, squamous cell carcinoma. SKs frequently have acquired oncogenic mutations in the receptor tyrosine kinase/phosphatidylinositol 3-kinase/Akt signaling cascade. We developed a reliable culture system to study SKs in vitro and screened these cells using a library of selective kinase inhibitors to evaluate effects on cell survival. These benign tumors are sensitive to inhibition by ATP-competitive Akt inhibitors, including A-443654 and GSK690693. RNA interference-mediated Akt suppression mimicked the effects of enzyme inhibition in cultured cells. Akt inhibition suppressed phosphorylation of downstream targets of Akt kinase that are critical for cell survival, including MDM2 and FOXO3a, and induced apoptosis. Cell death was also dependent on p53, mutations in which, although common in cutaneous squamous cell carcinoma, have not been identified in SKs. Intact explants of SKs were also sensitive to Akt inhibition. In addition to the obvious therapeutic implications of these findings, identifying the signaling characteristics that differentiate benign and malignant tumors may inform our understanding of the malignant state. PMID:26739095

  2. Activating FGFR3 mutations cause mild hyperplasia in human skin, but are insufficient to drive benign or malignant skin tumors

    PubMed Central

    Duperret, Elizabeth K; Oh, Seung Ja; McNeal, Andrew; Prouty, Stephen M; Ridky, Todd W

    2014-01-01

    Fibroblast growth factor receptor 3 (FGFR3) activating mutations are drivers of malignancy in several human tissues, including bladder, lung, cervix, and blood. However, in skin, these mutations are associated predominantly with benign, common epidermal growths called seborrheic keratoses (SKs). How epidermis resists FGFR3 mediated transformation is unclear, but previous studies have suggested that FGFR3 activation in skin keratinocytes may serve a tumor-suppressive role by driving differentiation and antagonizing Ras signaling. To define the role of FGFR3 in human normal and neoplastic epidermis, and to directly test the hypothesis that FGFR3 antagonizes Ras, we engineered human skin grafts in vivo with mutant active FGFR3 or shRNA FGFR3 knockdown. We show that FGFR3 active mutants drive mild hyperproliferation, but are insufficient to support benign or malignant tumorigenesis, either alone, or in combination with G1–S checkpoint release. This suggests that additional cell-intrinsic or stromal cues are required for formation of benign SKs with FGFR3 mutations. Further, FGFR3 activation does not alter the growth kinetics or differentiation status of engineered human epidermal SCCs driven by Ras, and FGFR3 protein itself is dispensable for Ras-driven SCC. To extend these findings to patients, we examined a uniquely informative human tumor in which SCC developed in continuity with a SK, raising the hypothesis that one of the tumors evolved from the other. However, mutational analysis from each tumor indicates that the overlapping SK and SCC evolved independently and supports our conclusion that FGFR3 activation is insufficient to drive SCC. PMID:24626198

  3. Multiple pathogenic and benign genomic rearrangements occur at a 35 kb duplication involving the NEMO and LAGE2 genes.

    PubMed

    Aradhya, S; Bardaro, T; Galgóczy, P; Yamagata, T; Esposito, T; Patlan, H; Ciccodicola, A; Munnich, A; Kenwrick, S; Platzer, M; D'Urso, M; Nelson, D L

    2001-10-15

    The X-linked dominant and male-lethal disorder incontinentia pigmenti (IP) is caused by mutations in a gene called NEMO (IKK-gamma). We recently reported the structure of NEMO and demonstrated that most IP patients carry an identical deletion that arises due to misalignment between repeats. Affected male abortuses with the IP deletion had provided clues that a second, incomplete copy of NEMO was present in the genome. We have now identified clones containing this truncated copy (Delta NEMO) and incorporated them into a previously constructed physical contig in distal Xq28. Delta NEMO maps 22 kb distal to NEMO and only contains exons 3-10, confirming our proposed model. A sequence of 26 kb 3' of the NEMO coding sequence is also present in the same position relative to the Delta NEMO locus, bringing the total length of the duplication to 35.5 kb. The LAGE2 gene is also located within this duplicated region, and a similar but unique LAGE1 gene is located just distal to the duplicated loci. Mapping and sequence information indicated that the duplicated regions are in opposite orientation. Analysis of the great apes suggested that the NEMO/LAGE2 duplication occurred after divergence of the lineage leading to present day humans, chimpanzees and gorillas, approximately 10-15 million years ago. Intriguingly, despite this substantial evolutionary history, only 22 single nucleotide differences exist between the two copies over the entire 35.5 kb, making the duplications >99% identical. This high sequence identity and the inverted orientations of the two copies, along with duplications of smaller internal sections within each copy, predispose this region to various genomic alterations. We detected four rearrangements that involved NEMO, Delta NEMO or LAGE1 and LAGE2. The high sequence similarity between the two NEMO/LAGE2 copies may be due to frequent gene conversion, as we have detected evidence of sequence transfer between them. Together, these data describe an unusual and

  4. Spontaneous activity in electromyography may differentiate certain benign lower motor neuron disease forms from amyotrophic lateral sclerosis.

    PubMed

    Jokela, Manu E; Jääskeläinen, Satu K; Sandell, Satu; Palmio, Johanna; Penttilä, Sini; Saukkonen, Annamaija; Soikkeli, Raija; Udd, Bjarne

    2015-08-15

    There is limited data on electromyography (EMG) findings in other motor neuron disorders than amyotrophic lateral sclerosis (ALS). We assessed whether the distribution of active denervation detected by EMG, i.e. fibrillations and fasciculations, differs between ALS and slowly progressive motor neuron disorders. We compared the initial EMG findings of 43 clinically confirmed, consecutive ALS patients with those of 41 genetically confirmed Late-onset Spinal Motor Neuronopathy and 14 Spinal and Bulbar Muscular Atrophy patients. Spontaneous activity was more frequently detected in the first dorsal interosseus and deltoid muscles of ALS patients than in patients with the slowly progressive motor neuron diseases. The most important observation was that absent fibrillations in the first dorsal interosseus muscle identified the benign forms with sensitivities of 66%-77% and a specificity of 93%. The distribution of active denervation may help to separate ALS from mimicking disorders at an early stage. PMID:26059445

  5. Benign bone tumors.

    PubMed

    Gilday, D L; Ash, J M

    1976-01-01

    There is little information in the literature concerning the role of bone scanning in benign bone neoplasms except for sporadic reports. Since the advent of 99mTc-polyphosphate, bone imaging has proven feasible and useful in locating the cause of bone pain, such as in osteoid osteomas, which are not always radiologically apparent, and in evaluating whether or not a radiologic lesion is indeed benign and solitary. Blood-pool images are particularly important in neoplastic disease, since the absence of hyperemia in the immediate postinjection period favors the diagnosis of a benign neoplasm, as does low-grade uptake on the delayed study. The scan, including pinhole magnification images, is especially valuable in diagnosing lesions in the spine and pelvis, which are poorly seen radiologically. We have studied various types of benign bone tumors, including simple and aneurysmal bone cysts, fibrous cortical defects, and nonossifying fibromas, all of which had minimal or no increased uptake of the radiopharmaceutical, unless traumatized. Although osteochondromas and enchondromas showed varied accumulation of activity, the scan was useful in differentiating these from sarcomatous lesions. All osteoid osteomas demonstrated marked activity, and could be accurately located preoperatively, as could the extent of fibrous dysplasia. The bone scan in the reticuloses also showed abnormal accumulation of activity, and aided in arriving at the prognosis and treatment of histiocytic bone lesions. PMID:1082170

  6. Inhibitory Activities of Phenolic Compounds Isolated from Adina rubella Leaves Against 5α-Reductase Associated with Benign Prostatic Hypertrophy.

    PubMed

    Yin, Jun; Heo, Jun Hyeok; Hwang, Yoon Jeong; Le, Thi Tam; Lee, Min Won

    2016-01-01

    Adina rubella Hance (AR), a plant native to Korea, has been used as traditional medicine for dysentery, eczema, intoxication, and external hemorrhages. Previous phytochemical studies of AR have reported several components, including terpenoids, phenolics, and alkaloids. The current study evaluated the anti-oxidative and anti-inflammatory activities and 5α-reductase inhibition of isolated compounds of AR leaves to find a potential therapeutic agent for benign prostatic hypertrophy (BPH). Repeated chromatographic isolation of an 80% acetone extract of AR leaves yielded seven phenolic compounds: caffeic acid (1), chlorogenic acid (2), methyl chlorogenate (3), quercetin-3-rutinoside (4), kaempferol-3-O-α-l-rhamnopyranosyl-(1→6)-β-d-glucopyranoside (5), hyperoside (6), and grandifloroside (7). Compound 7 is a novel compound in AR. Caffeoyl derivatives 1-3 and 7 showed good anti-oxidative activities. In particular, caffeic acid (1) and grandifloroside (7) showed potent anti-inflammatory activities, and 7 also exhibited potent inhibitory activity against TNF-α and 5α-reductase. Our results show that the extract and grandifloroside (7) from leaves of AR might be developed as a source of potent anti-oxidative and anti-inflammatory agents and therapeutic agent for BPH. PMID:27399661

  7. Benign familial hyperphosphatasemia

    SciTech Connect

    Siraganian, P.A.; Mulvihill, J.J.; Mulivor, R.A.; Miller, R.W. )

    1989-03-03

    Elevated alkaline phosphatase activity in serum suggests bone or liver disease or a neoplasm but can also indicate pregnancy or another benign condition. A family with benign hyperphosphatasemia was studied to elucidate the genetics and enzyme defect. Serum total alkaline phosphatase activity was greater than the population mean in all six family members, and more than 7 SDs above the mean in two of four offspring. Monoclonal antibodies to three alkaline phosphatase isoenzymes, intestinal, placental, and tissue nonspecific demonstrated markedly increased intestinal alkaline phosphatase levels in all family members and significantly elevated liver/bone/kidney activity in the two offspring. Guanidine hydrochloride denaturation of the liver/bone/kidney component showed high alkaline phosphatase activity from liver in both siblings and from bone in one. The mode of inheritance in this family is obscure, but a complex regulation of the products of two different alkaline phosphatase genes seems likely. Steps toward diagnosis are suggested. Early recognition of this benign biochemical abnormality should help to avoid unnecessary diagnostic tests.

  8. Adolescent physical activity and inactivity: a prospective study of risk of benign breast disease in young women.

    PubMed

    Berkey, Catherine S; Tamimi, Rulla M; Willett, Walter C; Rosner, Bernard; Lindsay Frazier, A; Colditz, Graham A

    2014-08-01

    In previous investigations of adolescent activity recalled in adulthood, modest reductions in risk of benign breast disease (BBD) and premenopausal breast cancer were seen with moderate-strenuous activity during high school. We therefore investigated physical activity, walking, and recreational inactivity (watching TV-videos, playing computer-videogames) reported by adolescent girls in relation to their subsequent risk for BBD as young women. The Growing Up Today Study includes 9,039 females, 9-15 years at study initiation (1996), who completed questionnaires annually through 2001, then in 2003, 2005, 2007, 2010 and 2013. Annual surveys (1996-2001) obtained data on physical and sedentary activities during the past year. Beginning in 2005, women (≥18 years) reported whether they had ever been diagnosed with BBD confirmed by breast biopsy (n = 133 cases, to 11/01/2013). Logistic regression (adjusted for baseline adiposity and age; additional factors in multivariable-adjusted models) estimated associations between adolescent activities (moderate-vigorous, walking, METS, inactivity) and biopsy-confirmed BBD in young women. Girls who walked the most had significantly lower risk of BBD (multivariable-adjusted OR = 0.61, ≥30 vs ≤15 min/day; p = .049). We observed no evidence that inactivity (≥3 vs <2 h/day OR = 1.02, p = .92) or METS (top vs bottom tertile OR = 1.19, p = .42) were associated with BBD. Accounting for factors including family history, childhood adiposity, and other activities and inactivities, adolescent girls who walked the most were at lower risk for BBD. We found no evidence that high moderate-vigorous activity might reduce risk, nor did we observe any association with inactivity. Continued follow-up will re-evaluate these findings as more BBD cases, and ultimately breast cancer, are diagnosed. PMID:25034340

  9. Adolescent Physical Activity and Inactivity: A Prospective Study of Risk of Benign Breast Disease in Young Women

    PubMed Central

    Berkey, Catherine S.; Tamimi, Rulla M.; Willett, Walter C.; Rosner, Bernard; Frazier, A. Lindsay; Colditz, Graham A.

    2016-01-01

    Purpose In previous investigations of adolescent activity recalled in adulthood, modest reductions in risk of benign breast disease (BBD) and premenopausal breast cancer were seen with moderate-strenuous activity during high school. We therefore investigated physical activity, walking, and recreational inactivity (watching TV-videos, playing computer-videogames) reported by adolescent girls in relation to their subsequent risk for BBD as young women. Methods The Growing Up Today Study (GUTS) includes 9039 females, 9–15yrs at study initiation (1996), who completed questionnaires annually through 2001, then 2003, 2005, 2007, 2010 and 2013. Annual surveys (1996–2001) obtained data on physical and sedentary activities during the past year. Beginning in 2005, women (≥18yr) reported whether they had been diagnosed with BBD confirmed by breast biopsy (n=133 cases, to 11/01/2013). Logistic regression (adjusted for baseline adiposity and age; additional factors in multivariable-adjusted models) estimated associations between adolescent activities (moderate-vigorous, walking, METS, inactivity) and biopsy-confirmed BBD in young women. Results Girls who walked the most had significantly lower risk of BBD (multivariable-adjusted OR=0.61,p=.049, ≥30min/day vs ≤15min/day). We observed no evidence that inactivity (≥3 hrs/day vs <2hr/day OR=1.02,p=.92) or METS (top vs bottom tertile OR=1.19,p=.42) were associated with BBD. Conclusion Accounting for factors including family history, childhood adiposity, other activities and inactivities, adolescent girls who walked the most were at lower risk for BBD. We found no evidence that high moderate-vigorous activity might reduce risk, nor did we observe any association with inactivity. Continued follow-up will re-evaluate these findings as more BBD cases, and ultimately breast cancer, are diagnosed. PMID:25034340

  10. Parent's Interests, Current Involvement and Level of Parental Involvement in School Activities.

    ERIC Educational Resources Information Center

    Gbadamosi, Tara; Lin, Huey-Ling

    This study examined what school activities parents were involved in and the relationship between parents' interests and level of participation. Parents completed self-report questionnaires examining activities they were currently involved in and activities they would like to do in their children's classrooms. Out of 208 surveys distributed, 114…

  11. Environmentally benign heterogeneous nano-particle catalysts: synthesis, characterization and catalytic activity of 4-nitrophenol.

    PubMed

    Murugan, Eagambaram; Jebaranjitham, J Nimita

    2011-02-01

    Pollution free catalyst is an attractive area of current interest. The p-Aminophenol is one of the most significant catalyst, because it involves the manufacture of various pharmaceuticals. Crosslinked poly(styrene)-co-poly(4-vinylimidazole) (PSPVIM) was prepared by varying the crosslinked monomer ratio as 2% and 10% respectively. The 2 (w%) of DVB, 25 (w%) of N-VIm as functional monomer and 73 (w%) of styrene as support monomer as organic phase and gelatin, boric acid and polyvinyl alcohol as aqueous phase was used to prepare cross-linked poly(styrene)-co-poly(N-vinyl imidazole) (PVIM) beads (Type-I). Similarly, Type II beads were also prepared by fixing the 10% as a cross linking ratio (DVB). The immobilization of Ag NPs onto the PS-VIm polymer matrix was performed using AgNO3 as a metal precursor solution. The k(obs) determined from UV-Vis results, reveals that the degree of reduction of 4-nitrophenol using Type-I catalysts is more effective than Type-II catalyst due to lower immobilization of AgNPs at higher cross-linked bead matrix. It was found that on increasing the amount of catalyst i.e., type-I PS-PVIm-AgNPs, the rate constant also increases. Therefore, PS-PVIm-AgNPs (Type-I) heterogeneous catalyst is superior for the reduction of 4-NP. PMID:21485850

  12. DESIGN CONSIDERATION INVOLVING ACTIVE SEDIMENT CAPS (PRESENTATION)

    EPA Science Inventory

    When contaminated sediments pose unacceptable risks to human health and the environment, management activities such as removal, treatment, or isolation of contaminated sediments may be required. Various capping designs are being considered for isolating contaminated sediment are...

  13. DESIGN CONSIDERATION INVOLVING ACTIVE SEDIMENT CAPS

    EPA Science Inventory

    When contaminated sediments pose unacceptable risks to human health and the environment, management activities such as removal, treatment, or isolation of contaminated sediments may be required. Various capping designs are being considered for isolating contaminated sediment are...

  14. The Director of Physical Activity and Staff Involvement

    ERIC Educational Resources Information Center

    Heidorn, Brent; Centeio, Erin

    2012-01-01

    Faculty and staff involvement in the Comprehensive School Physical Activity Program (CSPAP) begins with the Director of Physical Activity (DPA) motivating them to "buy in" to the need for a CSPAP. The DPA will need to train staff to develop and integrate physical activity throughout the school day, encourage them to be involved in the before- and…

  15. Endothelin involvement in respiratory centre activity.

    PubMed

    Albertini, M; Lafortuna, C L; Ciminaghi, B; Mazzola, S; Clement, M G

    2001-09-01

    To evaluate the role of endothelin (ET) in respiratory homeostasis we studied the effects of the ET(A) and ET(B) receptor blocking agent bosentan on respiratory mechanics and control in seven anaesthetised spontaneously breathing pigs, for 180 min after single bolus administration (20 mg/kg i.v.). The results show that the block of ET receptors induced a significant increase in compliance and decrease in resistance of the respiratory system, entailing a significant reduction of diaphragmatic electromyographic activity, without affecting the centroid frequency of the power spectrum. Bosentan administration induced a significant increase in tidal volume (V(T)), accompanied by a significant decrease in respiratory frequency, without any significant change in pulmonary ventilation, CO(2) arterial blood gas pressure or pH. Since the relationship between V(T) and inspiratory time remained substantially constant after bosentan administration, the changes in respiratory pattern appear to be the result of an upward shift in inspiratory off-switch threshold. Both inspiratory and expiratory times during occluded breathing were increased by block of ET receptors, suggesting also a central respiratory neuromodulator effect of ET. In conclusion the present results suggest that the block of ET receptors in spontaneously breathing pigs exerts a role on mechanical properties of the respiratory system as well as on peripheral and central mechanisms of breathing control. PMID:11728166

  16. Bond activation with an apparently benign ethynyl dithiocarbamate Ar-C≡C-S-C(S)NR2.

    PubMed

    Ung, Gaël; Frey, Guido D; Schoeller, Wolfgang W; Bertrand, Guy

    2011-10-10

    The hedgehog molecule: A simple ethynyl dithiocarbamate [Ar-C≡C-S-C(S)NR(2)] is able to cleave a broad range of enthalpically strong σ bonds and to activate carbon dioxide and elemental sulfur. Depending on the substrate, the bond activation process involves either the existence of an equilibrium with the nonobservable mesoionic carbene isomer or the cooperation of the nucleophilic carbon-carbon triple bond and the electrophilic CS carbon atom. PMID:23210141

  17. Mesothelioma - benign-fibrous

    MedlinePlus

    Mesothelioma - benign; Mesothelioma - fibrous; Pleural fibroma; Solitary fibrous tumor of the pleura ... other reasons. Other tests that may show benign mesothelioma include: CT scan of the chest Open lung ...

  18. Middle Level Activities To Involve the Invisible Student.

    ERIC Educational Resources Information Center

    Rimmer, Sue; Arico, Jim

    Involvement in student activities has many advantages for the middle level student. Such activities promote achievement, citizenship, and service to the community while developing self-esteem, self-confidence, and social cooperation. This book is intended as a tool for middle level schools to motivate, develop, guide, involve, and provide middle…

  19. Exploring Extension Involvement in Farm to School Program Activities

    ERIC Educational Resources Information Center

    Benson, Matthew C.

    2014-01-01

    The study reported here examined Extension professionals' involvement in farm-to-school program activities. Results of an online survey distributed to eight state Extension systems indicate that on average, Extension professionals are involved with one farm to school program activity, with most supporting school or community garden programs.…

  20. Silylations of Arenes with Hydrosilanes: From Transition-Metal-Catalyzed C¢X Bond Cleavage to Environmentally Benign Transition-Metal-Free C¢H Bond Activation.

    PubMed

    Xu, Zheng; Xu, Li-Wen

    2015-07-01

    The construction of carbon-silicon bonds is highlighted as an exciting achievement in the field of organosilicon chemistry and green chemistry. Recent developments in this area will enable the sustainable chemical conversion of silicon resources into synthetically useful compounds. Especially, the catalytic silylation through C¢H bond activation without directing groups and hydrogen acceptors is one of the most challenging topics in organic chemistry and green chemistry. These remarkable findings on catalytic silylation can pave the way to a more environmentally benign utilization of earth-abundant silicon-based resources in synthetic chemistry. PMID:26073645

  1. Empirical Evidence or Intuition? An Activity Involving the Scientific Method

    ERIC Educational Resources Information Center

    Overway, Ken

    2007-01-01

    Students need to have basic understanding of scientific method during their introductory science classes and for this purpose an activity was devised which involved a game based on famous Monty Hall game problem. This particular activity allowed students to banish or confirm their intuition based on empirical evidence.

  2. Studies on antibacterial, anti-inflammatory and antioxidant activity of herbal remedies used in the treatment of benign prostatic hyperplasia and prostatitis.

    PubMed

    Steenkamp, V; Gouws, M C; Gulumian, M; Elgorashi, E E; van Staden, J

    2006-01-01

    Crude water and ethanolic extracts of five herbal remedies reported in the literature for traditional treatment of benign prostatic hyperplasia (BPH) and/or prostatitis were investigated for their effect on hydroxyl scavenging activity, antibacterial activity and their ability to inhibit cyclooxygenase-1 and -2 (COX-1 and COX-2) catalysed prostaglandin biosynthesis. Both the water and ethanol extracts of Hypoxis hemerocallidea and Epilobium parviflorum inhibited the growth of Escherichia coli. All 10 extracts scavenged the hydroxyl radical but with various potencies (32-93%). Ethanolic extracts were the most active in inhibiting COX-1 catalysed prostaglandin biosynthesis. The ethanolic extract of Epilobium parviflorum showed inhibitory effects on both the COX-1 and -2 catalysed prostaglandin biosynthesis, inhibited growth of Escherichia coli and exerted antioxidant activity. Although these results support the traditional use of Epilobium parviflorum for treatment of prostatitis and BPH, further investigation is required, for this promising plant. PMID:16122891

  3. Palladium-Catalyzed Environmentally Benign Acylation.

    PubMed

    Suchand, Basuli; Satyanarayana, Gedu

    2016-08-01

    Recent trends in research have gained an orientation toward developing efficient strategies using innocuous reagents. The earlier reported transition-metal-catalyzed carbonylations involved either toxic carbon monoxide (CO) gas as carbonylating agent or functional-group-assisted ortho sp(2) C-H activation (i.e., ortho acylation) or carbonylation by activation of the carbonyl group (i.e., via the formation of enamines). Contradicting these methods, here we describe an environmentally benign process, [Pd]-catalyzed direct carbonylation starting from simple and commercially available iodo arenes and aldehydes, for the synthesis of a wide variety of ketones. Moreover, this method comprises direct coupling of iodoarenes with aldehydes without activation of the carbonyl and also without directing group assistance. Significantly, the strategy was successfully applied to the synthesis n-butylphthalide and pitofenone. PMID:27377566

  4. Adolescent Involvement in Extracurricular Activities: Influences on Leadership Skills

    ERIC Educational Resources Information Center

    Hancock, Donna; Dyk, Patricia Hyjer; Jones, Kenneth

    2012-01-01

    Study examined adolescents' participation in sports, school, and community extracurricular activities to assess the influence of different involvement roles and adult support on leadership skills. The study found that males and females who perceived their adult support more positively had more positive perceptions of their leadership skills.…

  5. Bringing Person-Centeredness and Active Involvement into Reality

    ERIC Educational Resources Information Center

    Torenholt, Rikke; Engelund, Gitte; Willaing, Ingrid

    2015-01-01

    Purpose: The purpose of this paper is to examine the use and applicability of cultural probes--an explorative participatory method to gain insights into a person's life and thoughts--to achieve person-centeredness and active involvement in self-management education for people with chronic illness. Design/methodology/approach: An education toolkit…

  6. Moon Watch: A Parental-Involvement Homework Activity.

    ERIC Educational Resources Information Center

    Rillero, Peter; Gonzalez-Jensen, Margarita; Moy, Tracy

    2000-01-01

    Presents the goals, philosophy, and methods of the SPLASH (Student-Parent Laboratories Achieving Science at Home) program. Describes an at-home, parental-involvement activity called Moon Watch in which students and their parents observe how the phases of the moon and the moon's position in the sky change over a two-week period. (WRM)

  7. Exophytic benign prostatic hyperplasia.

    PubMed

    Blaschko, Sarah D; Eisenberg, Michael L

    2011-08-01

    A 60-year-old man had incidental finding of a multilobular 8 × 7 × 7-cm mass identified posterior to the urinary bladder in continuity with the prostate. The man's prostate-specific antigen was 1.87, and he denied any lower urinary tract symptoms. A transrectal ultrasound-guided biopsy demonstrated benign prostatic tissue. A computed tomography-guided needle aspiration demonstrated a benign epithelium-lined cyst, likely prostatic in origin. Benign prostatic hyperplasia is a proliferation of prostatic epithelial and stromal cells. Although prostatic hyperplasia is usually restricted to the prostate gland, hyperplastic nodules occasionally protrude outside the prostate and rarely form exophytic pelvic masses. PMID:20869104

  8. Benign prostate hyperplasia (BPH) - resources

    MedlinePlus

    Resources - benign prostatic hyperplasia (BPH); Prostate enlargement resources; BPH resources ... organizations provide information on benign prostatic hyperplasia ( prostate enlargement ): National Kidney and Urologic Diseases Information Clearinghouse -- www. ...

  9. The Benign Hamburger.

    ERIC Educational Resources Information Center

    Peaslee, Graham; Lantz, Juliette M.; Walczak, Mary M.

    1998-01-01

    Uses a case study of food poisoning from hamburgers at the fictitious Jill-at-the-Grill to teach the nuclear science behind food irradiation. Includes case teaching notes on the benign hamburger. (ASK)

  10. Benign positional vertigo

    MedlinePlus

    ... Clinical practice guideline: Benign paroxysmal positional vertigo. Otolaryngol Head Neck Surg . 2008;139(5 Suppl 4):S47-S81. ... BH, Lund V, et al, eds. Cummings Otolaryngology: Head & Neck Surgery . 6th ed. Philadelphia, PA: Elsevier Mosby; 2015: ...

  11. Benign idiopathic partial epilepsy and brain lesion.

    PubMed

    Stephani, U; Doose, H

    1999-03-01

    A 14-year-old girl had severe head trauma from a dog bite at the age of 9 days. This resulted in extensive brain damage, tetraplegia, mental retardation, and epilepsy. The seizures were of rolandic type, and the EEG showed multifocal sharp waves. The course was benign. The initial diagnosis of a pure symptomatic epilepsy was revised after demonstrating typical benign focal sharp waves in the EEG of the healthy sister. Thus a phenocopy of a benign partial epilepsy by the brain lesion could be excluded with sufficient certainty. This observation allows the conclusion that the genetic disposition underlying the sharp-wave trait characteristic of benign partial epilepsies can be involved also in the pathogenesis of seemingly pure symptomatic epilepsies. EEG studies on siblings of such patients are needed to exclude possible phenocopies. PMID:10080522

  12. Engaging in activities involving information technology: dimensions, modes, and flow.

    PubMed

    Montgomery, Henry; Sharafi, Parvaneh; Hedman, Leif R

    2004-01-01

    An engagement mode involves a subject (e.g., a user of information technology, or IT) who is engaged in an activity with an object in a certain manner (the mode). The purpose of this study is to develop a general model of engagement modes that may be used for understanding how IT-related activities are shaped by properties of the user and the IT object. A questionnaire involving items on IT engagement and the experience of flow was administered to 300 participants. The results supported an engagement mode (EM) model involving 5 different engagement modes (enjoying/acceptance, ambition/curiosity, avoidance/hesitation, frustration/ anxiety, and efficiency/productivity) characterized on 3 dimensions (evaluation of object, locus of control between subject and object, and intrinsic or extrinsic focus of motivation). The flow experience follows from a balance between enjoying/ acceptance and efficiency/productivity propelled by ambition/curiosity. The EM model could provide a platform for considering how IT users, IT applications, and IT environments should work together to yield both enjoyment and efficiency. Actual or potential applications of this research include designing IT training programs on different levels of specificity. PMID:15359681

  13. Descriptive Study of Activities Identified by Principals as Parental Involvement Activities through Survey Research

    ERIC Educational Resources Information Center

    Anderson, Melinda

    2009-01-01

    This study was designed to identify parental involvement activities used by successful schools. Participating schools were identified as successful by an Academic Excellence Indicator System (AEIS) rating of recognized or exemplary. Using survey methods, data was collected from the principals of the schools about parental involvement activities on…

  14. Benign Essential Blepharospasm

    MedlinePlus

    ... Clinical Trials Organizations Column1 Column2 Benign Essential Blepharospasm Research Foundation 637 North 7th Street Suite 102 P.O. ... 832-0788 Fax: 409-832-0890 Dystonia Medical Research Foundation 1 East Wacker Drive Suite 2810 Chicago, IL ...

  15. Pontine respiratory activity involved in inspiratory/expiratory phase transition

    PubMed Central

    Mörschel, Michael; Dutschmann, Mathias

    2009-01-01

    Control of the timing of the inspiratory/expiratory (IE) phase transition is a hallmark of respiratory pattern formation. In principle, sensory feedback from pulmonary stretch receptors (Breuer–Hering reflex, BHR) is seen as the major controller for the IE phase transition, while pontine-based control of IE phase transition by both the pontine Kölliker–Fuse nucleus (KF) and parabrachial complex is seen as a secondary or backup mechanism. However, previous studies have shown that the BHR can habituate in vivo. Thus, habituation reduces sensory feedback, so the role of the pons, and specifically the KF, for IE phase transition may increase dramatically. Pontine-mediated control of the IE phase transition is not completely understood. In the present review, we discuss existing models for ponto-medullary interaction that may be involved in the control of inspiratory duration and IE transition. We also present intracellular recordings of pontine respiratory units derived from an in situ intra-arterially perfused brainstem preparation of rats. With the absence of lung inflation, this preparation generates a normal respiratory pattern and many of the recorded pontine units demonstrated phasic respiratory-related activity. The analysis of changes in membrane potentials of pontine respiratory neurons has allowed us to propose a number of pontine-medullary interactions not considered before. The involvement of these putative interactions in pontine-mediated control of IE phase transitions is discussed. PMID:19651653

  16. Involving Community Stakeholders to Increase Park Use and Physical Activity

    PubMed Central

    Marsh, Terry; Mariscal, Mark; Pina-Cortez, Sophia; Cohen, Deborah A.

    2014-01-01

    Objective To describe implementation of a randomized controlled trial of community-based participatory research (CBPR) approaches to increase park use and physical activity across 33 diverse neighborhoods in Los Angeles. Methods Fifty parks were randomly assigned based on park size, facilities and programs, and neighborhood socio-demographic characteristics to: park director (PD, 17 parks); PD and park advisory board of interested community members (PD+PAB, 16 parks); and no-intervention control (17 parks) arms. Between 2007 and 2012, PDs and PABs from the 33 intervention parks participated in community engagement, baseline assessment, marketing training, intervention design and implementation, and follow-up assessment. Results Intervention parks (PD and PD+PAB) invested in new and diversified signage, promotional items, outreach or support for group activities like fitness classes and walking clubs, and various marketing strategies. Scaling up CBPR methods across parks in 33 diverse neighborhoods was challenging. Working with departmental management and established structures for community input (PABs) and park policy (PDs) facilitated implementation and sustainability. Conclusion Scaling up CBPR methods across diverse communities involved tradeoffs. CBPR is useful for tailoring research and enhancing community impact and sustainability, but more work is needed to understand how to conduct multi-site trials across diverse settings using CBPR. PMID:24674853

  17. Study of erodable paint properties involved in antifouling activity.

    PubMed

    Thouvenin, M; Langlois, V; Briandet, R; Langlois, J Y; Guerin, P H; Peron, J J; Haras, D; Vallee-Rehel, K

    2003-06-01

    To produce ecological marine paints, it is necessary to understand the phenomena involved in antifouling activity. Due to the multivariable components which have to be taken into account and due to their analytical intricacy, only studies based on selected properties are conceivable. In this study, four properties have been chosen, viz. erosion, biocide release, roughness and the physicochemical characteristics of the film surface. A principal-component analysis (PCA) of the experimental data has shown that, among the selected properties, only erosion affected antifouling efficiency. A more detailed investigation of erosion by quantifying global hydration and hydrolysis of immersed paints revealed the difficulty in linking the chemical structure of binders to the final erosion properties. Biocide release from paints, quantified by chromatographic methods coupled with UV detection, was inferior to the doses stated by the paint producers. These observations allowed the conceiving of formulations with reduced amounts of active molecules. The development of erodable, biodegradable binders associated with non toxic compounds is a promising way to obtain efficient antifouling paints compatible with existing, preventive systems. PMID:14619286

  18. Malignancy and the benign lymphoepithelial lesion.

    PubMed

    Batsakis, J G; Bernacki, E G; Rice, D H; Stebler, M E

    1975-02-01

    The benign lymphoepithelial lesion of salivary glands is now considered the histological hallmark of a variety of clinical and pathological disorders affecting salivary tissues. Malignancy arising in the lesion is uncommon, but may take origin in either the epithelial or lymphoreticular components. Lymphomas and pseudolymphomas associated with salivary gland lymphoepithelial lesions have been predominately extra-salivary and strongly correlated with Sjögren's syndrome. Epithelial malignancy has not been associated with autoimmunity and with few exceptions has been of the anaplastic type. This report presents two patients with intra-salivary lymphomas arising in a benign lymphoepithelial lesion of salivary glands and a patient with anaplastic carcinoma arising in the epithelial islands of the lesion. The fourth patient manifested pseudolymphomatous lymphoreticular hyperplasia in lung and submandibular gland and illustrates the possible multiple organ involvement that may occur in patients with benign lymphoepithelial lesion, even without clinical evidence of concommitant autoimmune disorders. PMID:1172885

  19. Benign Metastasizing Leiomyoma.

    PubMed

    Pacheco-Rodriguez, Gustavo; Taveira-DaSilva, Angelo M; Moss, Joel

    2016-09-01

    Benign metastasizing leiomyoma (BML) is a rare and poorly characterized disease affecting primarily premenopausal women. Asymptomatic patients are often diagnosed incidentally by radiographs or other lung-imaging procedures performed for other indications, and the diagnosis is eventually confirmed by biopsy. Patients with BML are usually treated pharmacologically with antiestrogen therapies or surgically with oophorectomy or hysterectomy. Antiestrogen therapy is typically efficacious and, in general, most patients have a favorable prognosis. Asymptomatic patients with a confirmed diagnosis of BML, may be followed conservatively without treatment. PMID:27514603

  20. Benign metastasizing leiomyoma of the lung

    PubMed Central

    2013-01-01

    Benign leiomyomas of the uterus are uncommonly found in association with benign smooth muscle tumors beyond the confines of the uterus. Benign metastasizing leiomyoma (BML) is a rare disease in which the lung is described to be the most afflicted extrauterine organ. We present a brief review of the literature, along with case reports for four patients who were followed up after resection of a pulmonary lesion or after pathological confirmation by biopsy. The clinical course of BML varies from chronic asymptomatic appearance to rapid progression, leading to respiratory failure and death. Our BML patients did not complain of pulmonary symptoms, such as cough, dyspnea, or chest tightness. Pathology revealed benign leiomyomas with no atypia and mitotic activity <5 per 10 high-power field. Immunohistochemical staining was positive for actin and desmin. A standard treatment for BML has not yet been established. Because of the hormone-sensitive characteristics of BML, treatments are based on hormonal manipulation along with either surgical or medical oophorectomy. Benign metastasizing leiomyoma can be observed in postmenopausal women. We observed four patients who did not receive adjuvant hormonal therapy because they were postmenopausal or perimenopausal. All patients are still healthy and show no evidence of recurrence or progression of the disease. PMID:24134076

  1. Benign follicular tumors*

    PubMed Central

    Tellechea, Oscar; Cardoso, José Carlos; Reis, José Pedro; Ramos, Leonor; Gameiro, Ana Rita; Coutinho, Inês; Baptista, António Poiares

    2015-01-01

    Benign follicular tumors comprise a large and heterogeneous group of neoplasms that share a common histogenesis and display morphological features resembling one or several portions of the normal hair follicle, or recapitulate part of its embryological development. Most cases present it as clinically nondescript single lesions and essentially of dermatological relevance. Occasionally, however, these lesions be multiple and represent a cutaneous marker of complex syndromes associated with an increased risk of visceral neoplasms. In this article, the authors present the microscopic structure of the normal hair follicle as a basis to understand the type and level of differentiation of the various follicular tumors. The main clinicopathological features and differential diagnosis of benign follicular tumors are then discussed, including dilated pore of Winer, pilar sheath acanthoma, trichoadenoma, trichilemmoma, infundibuloma, proliferating trichilemmal cyst/tumor, trichoblastoma and its variants, pilomatricoma, trichodiscoma/fibrofolliculoma, neurofollicular hamartoma and trichofolliculoma. In addition, the main syndromes presenting with multiple follicular tumors are also discussed, namely Cowden, Birt-Hogg-Dubé, Rombo and Bazex-Dupré-Christol syndromes, as well as multiple tumors of follicular infundibulum (infundibulomatosis) and multiple trichoepitheliomas. Although the diagnosis of follicular tumors relies on histological examination, we highlight the importance of their knowledge for the clinician, especially when in presence of patients with multiple lesions that may be the cutaneous marker of a cancer-prone syndrome. The dermatologist is therefore in a privileged position to recognize these lesions, which is extremely important to provide further propedeutic, appropriate referral and genetic counseling for these patients. PMID:26734858

  2. Organized Activity Involvement among Rural Youth: Gender Differences in Associations between Activity Type and Developmental Outcomes

    ERIC Educational Resources Information Center

    Ferris, Kaitlyn A.; Oosterhoff, Benjamin; Metzger, Aaron

    2013-01-01

    The current study examined associations between organized activity involvement, academic achievement, and problem behavior in a sample of youth from a non-agricultural based rural community (M[subscript age] = 15.26, Age range = 11-19 years, N = 456). Analyses examined whether associations varied as a function of adolescent gender and age.…

  3. Dropping sand bags from helicopters: A low cost and environmentally benign approach to determine subsurface velocity and attenuation structure of active volcanic systems

    NASA Astrophysics Data System (ADS)

    Jolly, A. D.; Chardot, L.; Sherburn, S.; Cole-Baker, J.; Scott, B. J.; Fournier, N.; Neuberg, J. N.

    2012-04-01

    Obtaining estimates of the seismic velocity and attenuation structure of volcanic systems is considered valuable from a monitoring perspective but can be extremely costly and time consuming due to the potential environmental impacts, safety issues and the permitting process. Here, we present an easy, low cost and environmentally benign alternative whereby the shallow velocity and attenuation structure can be obtained via high impact sandbag drops from helicopter. We conducted such a sandbag drop experiment at White Island volcano on 23 September 2011, during the final stage of a 6 month deployment of 14 broadband seismometers. Three drops were attempted, two at either end of a 5 station linear array within the crater floor, and the third within the volcano's shallow active acid crater lake. The bags were dropped from ~400 m height and contained ~700 kg of fine beach sand held within nylon sacks having a volume capacity of ~2.0 m3. The impact velocity was estimated at ~70 m/s yielding a kinetic energy of about 106 to 107 Nm. The source position was established by GPS on the resulting impact crater and was accurate to within ~5 m. The lake drop position was estimated from video footage relative to known ground features and was accurate to ~30 m. Impact timing was achieved by drop placement close to, but not on, the nearby seismometer recording systems. For the crater floor drops the timing was constrained to within ~0.05 s based on distance from the closest stations. The low kinetic energy and strong attenuation of the crater floor meant that strong first-P arrival times were limited to an area within ~1 km of the impact position. We obtained a rough velocity estimate of about 1.0-1.5 km/s for the unconsolidated crater floor and a velocity of ~1.5-2.0 km/s for rays traversing mostly through the consolidated rocks comprising the crater walls. Attenuation was found to be generally very strong (Q < 10) for both consolidated and unconsolidated parts of the volcano

  4. 5 CFR 1215.24 - Claims involving criminal activity or misconduct.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 3 2013-01-01 2013-01-01 false Claims involving criminal activity or... PROCEDURES DEBT MANAGEMENT Claims Collection § 1215.24 Claims involving criminal activity or misconduct. (a) A debtor whose indebtedness involves criminal activity such as fraud, embezzlement, theft, or...

  5. 5 CFR 1215.24 - Claims involving criminal activity or misconduct.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Claims involving criminal activity or... PROCEDURES DEBT MANAGEMENT Claims Collection § 1215.24 Claims involving criminal activity or misconduct. (a) A debtor whose indebtedness involves criminal activity such as fraud, embezzlement, theft, or...

  6. 5 CFR 1215.24 - Claims involving criminal activity or misconduct.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Claims involving criminal activity or... PROCEDURES DEBT MANAGEMENT Claims Collection § 1215.24 Claims involving criminal activity or misconduct. (a) A debtor whose indebtedness involves criminal activity such as fraud, embezzlement, theft, or...

  7. 5 CFR 1215.24 - Claims involving criminal activity or misconduct.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 3 2014-01-01 2014-01-01 false Claims involving criminal activity or... PROCEDURES DEBT MANAGEMENT Claims Collection § 1215.24 Claims involving criminal activity or misconduct. (a) A debtor whose indebtedness involves criminal activity such as fraud, embezzlement, theft, or...

  8. Extracurricular Activity Involvement and Adolescent Self-Esteem

    ERIC Educational Resources Information Center

    Kort-Butler, Lisa A.

    2012-01-01

    Structured extracurricular activity participation has been linked to self-esteem and other indicators of positive youth development. This article describes the theoretical basis for this relationship, centering on extracurricular activities as a location for identity development. A summary of the empirical evidence points to the importance of…

  9. Radiation protection in radiologic technology: Apathy versus active involvement

    SciTech Connect

    Franz, K.H.

    1982-11-01

    The lack of active participation in radiation protection is a serious problem in Radiologic Technology today. Underlying the problem is professional apathy. An overview of the historical changes, as well as various recent developments in radiology, accentuate the importance of necessary changes in technologists' attitudes and activities. 22 references.

  10. Involvement of mTOR and Regulation by AMPK in Early Iodine Deficiency-Induced Thyroid Microvascular Activation.

    PubMed

    Craps, J; Joris, V; De Jongh, B; Sonveaux, P; Horman, S; Lengelé, B; Bertrand, L; Many, M-C; Colin, I M; Gérard, A-C

    2016-06-01

    Iodine deficiency (ID) induces TSH-independent microvascular activation in the thyroid via the reactive oxygen species/nitric oxide-hypoxia-inducible factor-1α/vascular endothelial growth factor (VEGF) pathway. We hypothesized the additional involvement of mammalian target of rapamycin (mTOR) as a positive regulator of this pathway and AMP-activated protein kinase (AMPK) as a negative feedback regulator to explain the transient nature of ID-induced microvascular changes under nonmalignant conditions. mTOR and AMPK involvement was investigated using an in vitro model (human thyrocytes in primary cultures) and 2 murine models of goitrogenesis (normal NMRI and RET-PTC mice [a papillary thyroid cancer model]). In NMRI mice, ID had no effect on the phosphorylation of ribosomal S6 kinase (p70S6K), a downstream target of mTOR. However, rapamycin inhibited ID-induced thyroid blood flow and VEGF protein expression. In the RET-PTC model, ID strongly increased the phosphorylation of p70S6K, whereas rapamycin completely inhibited the ID-induced increase in p70S6K phosphorylation, thyroid blood flow, and VEGF-A expression. In vitro, although ID increased p70S6K phosphorylation, the ID-stimulated hypoxia-inducible factor/VEGF pathway was inhibited by rapamycin. Activation of AMPK by metformin inhibited ID effects both in vivo and in vitro. In AMPK-α1 knockout mice, the ID-induced increase in thyroid blood flow and VEGF-A protein expression persisted throughout the treatment, whereas both parameters returned to control values in wild-type mice after 4 days of ID. In conclusion, mTOR is required for early ID-induced thyroid microvascular activation. AMPK negatively regulates this pathway, which may account for the transient nature of ID-induced TSH-independent vascular effects under benign conditions. PMID:27035650

  11. Involvement of Antilipoarabinomannan Antibodies in Classical Complement Activation in Tuberculosis

    PubMed Central

    Hetland, Geir; Wiker, Harald G.; Høgåsen, Kolbjørn; Hamasur, Beston; Svenson, Stefan B.; Harboe, Morten

    1998-01-01

    We examined alternative and classical complement activation induced by whole bacilli of Mycobacterium bovis BCG and Mycobacterium tuberculosis products. After exposure to BCG, there were higher levels of the terminal complement complex in sera from Indian tuberculosis patients than in sera from healthy controls. The addition of BCG with or without EGTA to these sera indicated that approximately 70 to 85% of the total levels of the terminal complement complex was formed by classical activation. Sera from Indian tuberculosis patients contained more antibody to lipoarabinomannan (LAM) than sera from healthy Indians. Levels of anti-LAM immunoglobulin G2 (IgG2), but not anti-LAM IgM, correlated positively with classical activation induced by BCG in the sera. By flow cytometry, deposition of C3 and terminal complement complex on bacilli incubated with normal human serum was demonstrated. The anticomplement staining was significantly reduced in the presence of EGTA and EDTA. Flow cytometry also revealed the binding of complement to BCG incubated with rabbit anti-LAM and then with factor B-depleted serum. This indicates that classical activation plays a major role in complement activation induced by mycobacteria and that anti-LAM IgG on the bacilli can mediate this response. Classical complement activation may be important for the extent of phagocytosis of M. tuberculosis by mononuclear phagocytes, which may influence the course after infection. PMID:9521145

  12. Patterns of arm muscle activation involved in octopus reaching movements.

    PubMed

    Gutfreund, Y; Flash, T; Fiorito, G; Hochner, B

    1998-08-01

    The extreme flexibility of the octopus arm allows it to perform many different movements, yet octopuses reach toward a target in a stereotyped manner using a basic invariant motor structure: a bend traveling from the base of the arm toward the tip (Gutfreund et al., 1996a). To study the neuronal control of these movements, arm muscle activation [electromyogram (EMG)] was measured together with the kinematics of reaching movements. The traveling bend is associated with a propagating wave of muscle activation, with maximal muscle activation slightly preceding the traveling bend. Tonic activation was occasionally maintained afterward. Correlation of the EMG signals with the kinematic variables (velocities and accelerations) reveals that a significant part of the kinematic variability can be explained by the level of muscle activation. Furthermore, the EMG level measured during the initial stages of movement predicts the peak velocity attained toward the end of the reaching movement. These results suggest that feed-forward motor commands play an important role in the control of movement velocity and that simple adjustment of the excitation levels at the initial stages of the movement can set the velocity profile of the whole movement. A simple model of octopus arm extension is proposed in which the driving force is set initially and is then decreased in proportion to arm diameter at the bend. The model qualitatively reproduces the typical velocity profiles of octopus reaching movements, suggesting a simple control mechanism for bend propagation in the octopus arm. PMID:9671683

  13. Public involvement in environmental activities: Initiatives and lessons learned

    SciTech Connect

    Gray, R.H.

    1995-12-31

    Efforts to communicate the results of environmental studies and involve the public in environmental decisions have increased nationwide. Outreach efforts at two US Department of Energy sites (i.e., the Hanford Site in southeastern Washington State and the Pantex Plant in the Texas Panhandle) have used a broad spectrum of communications media, including technical articles (open literature and symposium publications, annual and topical reports); information brochures and fact sheets; video productions; interactive exhibits; presentations at scientific, technical, civic, and other public meetings; and proactive interactions with the news media and with local, state, federal, and other agencies. In addition, representatives of local communities now operate offsite environmental monitoring stations and Native Americans are involved in studying cultural resources, fisheries, and other issues at Hanford and a program to obtain environmental samples from neighbor`s property is underway at the Pantex Plant. All major environmental programs, such as the multi-year effort to reconstruct past radiological doses to offsite human populations at Hanford, are now conducted with open public participation.

  14. Activation and Involvement of Ral GTPases in Colorectal Cancer

    PubMed Central

    Martin, Timothy D.; Samuel, Jonathan C.; Routh, Elizabeth D.; Der, Channing J.; Yeh, Jen Jen

    2010-01-01

    Current approaches to block KRAS oncogene function focus on inhibition of K-Ras downstream effector signaling. We evaluated the anti-tumor activity of selumetinib (AZD6244, ARRY-142886), a potent and selective MEK1/2 inhibitor, on a panel of colorectal carcinoma (CRC) cells and found no inhibition of KRAS mutant CRC cell anchorage-independent growth. While AKT activity was elevated in KRAS mutant cells, and PI3K inhibition did impair the growth of MEK inhibitor-insensitive CRC cell lines, concurrent treatment with selumetinib did not provide additional anti-tumor activity. Therefore, we speculated that inhibition of the Ral guanine exchange factor (RalGEF) effector pathway may be a more effective approach for blocking CRC growth. RalGEFs are activators of the related RalA and RalB small GTPases and we found activation of both in CRC cell lines and patient tumors. Interfering RNA stable suppression of RalA expression reduced CRC tumor cell anchorage-independent growth, but surprisingly, stable suppression of RalB greatly enhanced soft agar colony size and formation frequency. Despite their opposing activities, both RalA and RalB regulation of anchorage-independent growth required interaction with RalBP1/RLIP76 and components of the exocyst complex. Interestingly, RalA interaction with the Exo84 but not Sec5 exocyst component was necessary for supporting anchorage-independent growth, whereas RalB interaction with Sec5 but not Exo84 was necessary for inhibition of anchorage-independent growth. We suggest that anti-RalA-selective therapies may provide an effective approach for KRAS mutant CRC. PMID:21199803

  15. Artificial masculinization in tilapia involves androgen receptor activation.

    PubMed

    Golan, Matan; Levavi-Sivan, Berta

    2014-10-01

    Estrogens have a pivotal role in natural female sexual differentiation of tilapia while lack of steroids results in testicular development. Despite the fact that androgens do not participate in natural sex differentiation, synthetic androgens, mainly 17-α-methyltestosterone (MT) are effective in the production of all-male fish in aquaculture. The sex inversion potency of synthetic androgens may arise from their androgenic activity or else as inhibitors of aromatase activity. The current study is an attempt to differentiate between the two alleged activities in order to evaluate their contribution to the sex inversion process and aid the search for novel sex inversion agents. In the present study, MT inhibited aromatase activity, when applied in vitro as did the non-aromatizable androgen dihydrotestosterone (DHT). In comparison, exposure to fadrozole, a specific aromatase inhibitor, was considerably more effective. Androgenic activity of MT was evaluated by exposure of Sciaenochromis fryeri fry to the substance and testing for the appearance of blue color. Flutamide, an androgen antagonist, administered concomitantly with MT, reduced the appearance of the blue color and the sex inversion potency of MT in a dose-dependent manner. In tilapia, administration of MT, fadrozole or DHT resulted in efficient sex inversion while flutamide reduced the sex inversion potency of all three compounds. In the case of MT and DHT the decrease in sex inversion efficiency caused by flutamide is most likely due to the direct blocking of the androgen binding to its cognate receptor. The negative effect of flutamide on the efficiency of the fadrozole treatment may indicate that the masculinizing activity of fadrozole may be attributed to excess, un-aromatized, androgens accumulated in the differentiating gonad. The present study shows that when androgen receptors are blocked, there is a reduction in the efficiency of sex inversion treatments. Our results suggest that in contrast to

  16. [Benign endobronchial tumors].

    PubMed

    Nikhtianov, Kh

    1980-01-01

    Endobronchial localizations of benign neoplasms are met with in 24.5 per cent of the cases. Right lung localizations are more frequent. More than half of them are broadly based (57.5 per cent). In most of the cases it is a matter of nonepithelial tumours of which a greater intensity is displayed by hamartomas /7/, vascular /4/ and neurogenic /3/ neoformations. The size of endobronchial tumours varies from 1 to 10 cm. Cases measuring 1-3 cm are the most numerous. Those of the "iceberg" type appear to be larger. The size per se has a relative importance for the clinical picture. Endobronchial tumours exhibit a clear cut clinical picture, and run a clinical course in three stages, determined by the degree of bronchial obturation and longstanding of the condition. The most common symptoms are coughing /80.7 per cent/, expectoration /50.0 per cent/, rales /57.6 per cent/, dullness /38.4 per cent/ and lacking respiration /38.4 per cent/. The nosological entity by itself is less conclusive for the clinical course. The X-ray data have orientation and by no means decisive significance for the diagnosis. The "crab pincers" sign in the bronchial lumen during bronchography has a definite importance. Bronchoscopy in conjunction with biopsy is a dependable method of preoperative diagnosing. It contributes greatly to the nosological diagnosis. Even nowadays, the diagnosis of endobronchial tumours is difficult. A rather exact diagnosis can be made intraoperatively, whereas the most accurate diagnosis is established only after histological study. The treatment of endobronchial benign neoplasms is operative. The number of medium /lobectomies/ and extensive /pulmonectomies/ pulmonary resections is considerable. In case of early diagnosis and intervention, sparing resection is the naturally indicated size of operation - mainly resection and plasty of the bronchi without lobectomy. The advantages of circular resection are substantial. Reconstructive operations of "clarinet" and

  17. Hyperosmotic stress activates Rho: differential involvement in Rho kinase-dependent MLC phosphorylation and NKCC activation.

    PubMed

    Di Ciano-Oliveira, Caterina; Sirokmány, Gábor; Szászi, Katalin; Arthur, William T; Masszi, András; Peterson, Mark; Rotstein, Ori D; Kapus, András

    2003-09-01

    Hyperosmotic stress initiates adaptive responses, including phosphorylation of myosin light chain (MLC) and concomitant activation of Na+-K+-Cl- cotransporter (NKCC). Because the small GTPase Rho is a key regulator of MLC phosphorylation, we investigated 1) whether Rho is activated by hyperosmotic stress, and if so, what the triggering factors are, and 2) whether the Rho/Rho kinase (ROK) pathway is involved in MLC phosphorylation and NKCC activation. Rho activity was measured in tubular epithelial cells by affinity pulldown assay. Hyperosmolarity induced rapid (<1 min) and sustained (>20 min) Rho activation that was proportional to the osmotic concentration and reversed within minutes upon restoration of isotonicity. Both decreased cell volume at constant ionic strength and elevated total ionic strength at constant cell volume were capable of activating Rho. Changes in [Na+] and [K+] at normal total salinity failed to activate Rho, and Cl- depletion did not affect the hyperosmotic response. Thus alterations in cellular volume and ionic strength but not individual ion concentrations seem to be the critical triggering factors. Hyperosmolarity induced mono- and diphosphorylation of MLC, which was abrogated by the Rho-family blocker Clostridium toxin B. ROK inhibitor Y-27632 suppressed MLC phosphorylation under isotonic conditions and prevented its rise over isotonic levels in hypertonically stimulated cells. ML-7 had a smaller inhibitory effect. In contrast, it abolished the hypertonic activation of NKCC, whereas Y-27632 failed to inhibit this response. Thus hyperosmolarity activates Rho, and Rho/ROK pathway contributes to basal and hyperosmotic MLC phosphorylation. However, the hypertonic activation of NKCC is ROK independent, implying that the ROK-dependent component of MLC phosphorylation can be uncoupled from NKCC activation. PMID:12748065

  18. Getting Students Involved: Classroom Activities Which Promote Communication.

    ERIC Educational Resources Information Center

    Freeman, G. Ronald; And Others

    Three essays concerning second language classroom activities that promote learning of communication skills are presented. In "From Manipulation to Communication" (Renate A. Schulz), the importance of establishing minimal communicative objectives for classroom instruction skills is discussed, specifying situations in which students have to…

  19. Involvement of Toso in activation of monocytes, macrophages, and granulocytes.

    PubMed

    Lang, Karl S; Lang, Philipp A; Meryk, Andreas; Pandyra, Aleksandra A; Boucher, Louis-Martin; Pozdeev, Vitaly I; Tusche, Michael W; Göthert, Joachim R; Haight, Jillian; Wakeham, Andrew; You-Ten, Annick J; McIlwain, David R; Merches, Katja; Khairnar, Vishal; Recher, Mike; Nolan, Garry P; Hitoshi, Yasumichi; Funkner, Pauline; Navarini, Alexander A; Verschoor, Admar; Shaabani, Namir; Honke, Nadine; Penn, Linda Z; Ohashi, Pamela S; Häussinger, Dieter; Lee, Kyeong-Hee; Mak, Tak W

    2013-02-12

    Rapid activation of immune responses is necessary for antibacterial defense, but excessive immune activation can result in life-threatening septic shock. Understanding how these processes are balanced may provide novel therapeutic potential in treating inflammatory disease. Fc receptors are crucial for innate immune activation. However, the role of the putative Fc receptor for IgM, known as Toso/Faim3, has to this point been unclear. In this study, we generated Toso-deficient mice and used them to uncover a critical regulatory function of Toso in innate immune activation. Development of innate immune cells was intact in the absence of Toso, but Toso-deficient neutrophils exhibited more reactive oxygen species production and reduced phagocytosis of pathogens compared with controls. Cytokine production was also decreased in Toso(-/-) mice compared with WT animals, rendering them resistant to septic shock induced by lipopolysaccharide. However, Toso(-/-) mice also displayed limited cytokine production after infection with the bacterium Listeria monocytogenes that was correlated with elevated presence of Listeria throughout the body. Accordingly, Toso(-/-) mice succumbed to infections of L. monocytogenes, whereas WT mice successfully eliminated the infection. Taken together, our data reveal Toso to be a unique regulator of innate immune responses during bacterial infection and septic shock. PMID:23359703

  20. Involvement of Toso in activation of monocytes, macrophages, and granulocytes

    PubMed Central

    Lang, Karl S.; Lang, Philipp A.; Meryk, Andreas; Pandyra, Aleksandra A.; Boucher, Louis-Martin; Pozdeev, Vitaly I.; Tusche, Michael W.; Göthert, Joachim R.; Haight, Jillian; Wakeham, Andrew; You-Ten, Annick J.; McIlwain, David R.; Merches, Katja; Khairnar, Vishal; Recher, Mike; Nolan, Garry P.; Hitoshi, Yasumichi; Funkner, Pauline; Navarini, Alexander A.; Verschoor, Admar; Shaabani, Namir; Honke, Nadine; Penn, Linda Z.; Ohashi, Pamela S.; Häussinger, Dieter; Lee, Kyeong-Hee; Mak, Tak W.

    2013-01-01

    Rapid activation of immune responses is necessary for antibacterial defense, but excessive immune activation can result in life-threatening septic shock. Understanding how these processes are balanced may provide novel therapeutic potential in treating inflammatory disease. Fc receptors are crucial for innate immune activation. However, the role of the putative Fc receptor for IgM, known as Toso/Faim3, has to this point been unclear. In this study, we generated Toso-deficient mice and used them to uncover a critical regulatory function of Toso in innate immune activation. Development of innate immune cells was intact in the absence of Toso, but Toso-deficient neutrophils exhibited more reactive oxygen species production and reduced phagocytosis of pathogens compared with controls. Cytokine production was also decreased in Toso−/− mice compared with WT animals, rendering them resistant to septic shock induced by lipopolysaccharide. However, Toso−/− mice also displayed limited cytokine production after infection with the bacterium Listeria monocytogenes that was correlated with elevated presence of Listeria throughout the body. Accordingly, Toso−/− mice succumbed to infections of L. monocytogenes, whereas WT mice successfully eliminated the infection. Taken together, our data reveal Toso to be a unique regulator of innate immune responses during bacterial infection and septic shock. PMID:23359703

  1. BIOLOGICAL ACTIVITY AND POTENTIAL REMEDIATION INVOLVING GEOTEXTILE LANDFILL LEACHATE FILTERS

    EPA Science Inventory

    This paper presents the results of a biological growth study in geotextile filters used in landfill leachate collection systems. fter reviewing the first year's activity, a completely new experimental approach has been taken. sing 100 mm diameter columns for the experimental incu...

  2. Treatment Challenges with Benign Bone Tumors of the Orbit

    PubMed Central

    Merritt, Helen; Yin, Vivian T.; Pfeiffer, Margaret L.; Wang, Wei-Lien; Sniegowski, Matthew C.; Esmaeli, Bita

    2015-01-01

    Benign mesenchymal tumors of the craniofacial complex present unique challenges for orbital surgeons because of their potential for orbital compartment syndrome, ocular morbidity, and facial disfigurement and because definitive surgical management may be associated with significant morbidity. While the precise classification of such lesions depends on radiologic as well as histologic evaluations and remains controversial, benign tumors involving the bony walls of the orbit share features of bony expansion, facial deformity, and the potential to cause significant orbital and ophthalmic morbidity. We herein present 2 cases of benign mesenchymal tumors with bony involvement in the orbitofacial region (1 juvenile ossifying fibroma and 1 central giant cell granuloma) and review the current management of similar benign fibro-osseous and reactive bone lesions of the orbit. These rare entities presented share common orbital and ophthalmic manifestations and remain without any effective definitive treatment options. PMID:27171013

  3. Benign small bowel tumor.

    PubMed Central

    Wilson, J M; Melvin, D B; Gray, G; Thorbjarnarson, B

    1975-01-01

    The clinical record and histologic sections of 84 cases of benign small bowel tumor are reviewed. Manifestations of systemic diseases, congenital anomalies, and lesions of either the ileocecal valve or periampullary region were excluded. In the same time span there were 96 small bowel malignancies. Clinical presentation, pathologic findings, management and result are compared to the collected published experience of about 2000 cases. There were 36 leiomyomas, 22 lipomas, 9 angiomas, 6 neurofibromas and 4 fibromas. Thirty-six men and 48 women were affected; the majority in their fifth and sixth decade. Seventy-eight were operative and 6 autopsy diagnoses. The most common symptom was obstruction (42%) followed by hemorrhage (34%) and pain (22%), relative frequency differing for the various specific tumors. There were rarely significant physical findings. A diagnosis of small bowel tumor was made radiologically in 30 patients. Because of the nonspecificity of other signs and symptoms, an acute awareness of the possibility of small bowel tumor is mandatory for preoperative anticipation of the diagnosis. Local resection was performed in all with no deaths or significant postoperative complications. PMID:1078626

  4. Benign prostatic hyperplasia.

    PubMed

    Chughtai, Bilal; Forde, James C; Thomas, Dominique Dana Marie; Laor, Leanna; Hossack, Tania; Woo, Henry H; Te, Alexis E; Kaplan, Steven A

    2016-01-01

    Benign prostatic hyperplasia (BPH), which causes lower urinary tract symptoms (LUTS), is a common diagnosis among the ageing male population with increasing prevalence. Many risks factors, both modifiable and non-modifiable, can increase the risk of development and progression of BPH and LUTS. The symptoms can be obstructive (resulting in urinary hesitancy, weak stream, straining or prolonged voiding) or irritative (resulting in increased urinary frequency and urgency, nocturia, urge incontinence and reduced voiding volumes), or can affect the patient after micturition (for example, postvoid dribble or incomplete emptying). BPH occurs when both stromal and epithelial cells of the prostate in the transitional zone proliferate by processes that are thought to be influenced by inflammation and sex hormones, causing prostate enlargement. Patients with LUTS undergo several key diagnostic investigations before being diagnosed with BPH. Treatment options for men with BPH start at watchful waiting and progress through medical to surgical interventions. For the majority of patients, the starting point on the treatment pathway will be dictated by their symptoms and degree of bother. PMID:27147135

  5. Baritosis: a benign pneumoconiosis.

    PubMed Central

    Doig, A T

    1976-01-01

    Baritosis is one of the benign pneumoconioses in which inhaled particulate matter lies in the lungs for years without producing symptoms, abnormal physical signs, incapacity for work, interference with lung function, or liability to develop pulmonary or bronchial infections or other thoracic disease. Owing to the high radio-opacity of barium, the discrete shadows in the chest radiograph are extremely dense. Even in the most well-marked cases with extreme profusion of the opacities, massive shadows do not occur. When exposure to barium dust ceases the opacities begin slowly to disappear. Nine cases of baritosis occurring in a small factory in which barytes was crushed, graded, and milled are described. Two of the cases occurred after only 18 and 21 month's exposure, and 9 of the 10 men employed for more than one and a half years had baritosis. Five of the affected men examined at intervals since their exposure to barytes ceased in 1964 showed marked clearing of their radiological abnormalities. Images PMID:1257935

  6. The insulin receptor activation process involves localized conformational changes.

    PubMed

    Baron, V; Kaliman, P; Gautier, N; Van Obberghen, E

    1992-11-15

    The molecular process by which insulin binding to the receptor alpha-subunit induces activation of the receptor beta-subunit with ensuing substrate phosphorylation remains unclear. In this study, we aimed at approaching this molecular mechanism of signal transduction and at delineating the cytoplasmic domains implied in this process. To do this, we used antipeptide antibodies to the following sequences of the receptor beta-subunit: (i) positions 962-972 in the juxtamembrane domain, (ii) positions 1247-1261 at the end of the kinase domain, and (iii) positions 1294-1317 and (iv) positions 1309-1326, both in the receptor C terminus. We have previously shown that insulin binding to its receptor induces a conformational change in the beta-subunit C terminus. Here, we demonstrate that receptor autophosphorylation induces an additional conformational change. This process appears to be distinct from the one produced by ligand binding and can be detected in at least three different beta-subunit regions: the juxtamembrane domain, the kinase domain, and the C terminus. Hence, the cytoplasmic part of the receptor beta-subunit appears to undergo an extended conformational change upon autophosphorylation. By contrast, the insulin-induced change does not affect the juxtamembrane domain 962-972 nor the kinase domain 1247-1261 and may be limited to the receptor C terminus. Further, we show that the hormone-dependent conformational change is maintained in a kinase-deficient receptor due to a mutation at lysine 1018. Therefore, during receptor activation, the ligand-induced change could precede ATP binding and receptor autophosphorylation. We propose that insulin binding leads to a transient receptor form that may allow ATP binding and, subsequently, autophosphorylation. The second conformational change could unmask substrate-binding sites and stabilize the receptor in an active conformation. PMID:1331080

  7. Benign hereditary chorea: an update.

    PubMed

    Inzelberg, Rivka; Weinberger, Moran; Gak, Eva

    2011-06-01

    Benign hereditary chorea (BHC, MIM 118700) is a rare autosomal dominant disorder manifesting with chorea in conjunction with hypothyroidism and respiratory problems, a triad also named "brain-lung-thyroid syndrome". BHC is characterized by childhood onset with minimal or no progression into adult life and normal cognitive function. The genetic basis of BHC has been partially resolved, when mutations in the TTF1 gene on chromosome 14q13 encoding the thyroid transcription factor-1 have been identified in a number of BHC patients, suggesting that aberration of TTF1 transcriptional function or haploinsufficiency is associated with this disorder. TTF1 (also known as TITF1, TEBP or NKX2-1), belonging to the NKX2 homeodomain transcription factor family, has been implicated in several important molecular pathways essential for brain, thyroid and lung morphogenesis. Clinical evaluation of TTF1 gene mutations carrier patients exposed the involvement of each of the triad's components characterized by heterogeneity between index cases and even within families. This review highlights the current updates on expanded clinical aspects of BHC, imaging and treatment experience, its genetic markers, proposed molecular mechanisms, animal models and link to cancer. PMID:21292530

  8. Laboratory activities involving transmissible spongiform encephalopathy causing agents

    PubMed Central

    Leunda, Amaya; Van Vaerenbergh, Bernadette; Baldo, Aline; Roels, Stefan; Herman, Philippe

    2013-01-01

    Since the appearance in 1986 of epidemic of bovine spongiform encephalopathy (BSE), a new form of neurological disease in cattle which also affected human beings, many diagnostic and research activities have been performed to develop detection and therapeutic tools. A lot of progress was made in better identifying, understanding and controlling the spread of the disease by appropriate monitoring and control programs in European countries. This paper reviews the recent knowledge on pathogenesis, transmission and persistence outside the host of prion, the causative agent of transmissible spongiform encephalopathies (TSE) in mammals with a particular focus on risk (re)assessment and management of biosafety measures to be implemented in diagnostic and research laboratories in Belgium. Also, in response to the need of an increasing number of European diagnostic laboratories stopping TSE diagnosis due to a decreasing number of TSE cases reported in the last years, decontamination procedures and a protocol for decommissioning TSE diagnostic laboratories is proposed. PMID:24055928

  9. Activity of capryloyl collagenic acid against bacteria involved in acne.

    PubMed

    Fourniat, J; Bourlioux, P

    1989-12-01

    Synopsis Capryloyl collagenic acid (Lipacide C8Co) has similar bacteriostatic activity in vitro to that of benzoyl peroxide towards the bacteria found in acne lesions (Staphylococcus aureus, Staphylococcus epidermidis and Propionibacterium acnes) (MIC between 1 and 4 mg ml(-1) for C8Co, and between 0.5 and 5 mg ml(-1) for benzoyl peroxide). The presence of Emulgine M8 did not affect the bacteriostatic activity of C8Co. A 4% w/v solution of C8Co (incorporating Emulgine M8) fulfilled the criteria for an antiseptic preparation as laid down by the French Pharmacopoeia (10th Edition), and had a spectrum 5 bactericidal activity according to the French Standard AFNOR NF T 72-151. The excellent cutaneous tolerance of capryloyl collagenic acid would indicate that an aqueous solution might be of value for topical treatment of the bacterial component of acne. Résumé Activité antibactérienne de l'acide capryloyl-collagénique vis à vis des bactéries impliquées dans l'etiologie de l'acné L'acide capryloyl-collagénique (Lipacide C8Co) et le peroxyde de benzoyle présentent une activité bactériostatique in-vitroéquivalente vis à vis des espèces bactériennes retrouvées au niveau des lésions acnéiques (Staphylococcus aureus, S. epidermidis et Propionibacterium acnes) (CMI comprise entre 1 et 4 mg ml(-1) pour le lipoaminoacide, et 0,5 et 5 mg ml(-1) pour le peroxyde de benzoyle). La mise en solution aqueuse de l'acide capryloyl-collagénique en présence d'Emulgine M8 ne modifie pas son activité bactériostatique. Une telle solution, à 4% m/V d'acide capryloyl-collagénique et 5% m/V d'Emulgine M8, satisfait à l'essai d'activité des préparations antiseptiques décrit à la Pharmacopée Française (Xème Ed.) (concentration minimale antiseptique: 10% v/V, pour un temps de contact de 5 min à 32 degrees C entre les germes tests et la solution diluée en eau distillée), et posséde une activité bactéricide antiseptique spectre 5 conforme à la norme AFNOR NF T

  10. Impaired enzymatic defensive activity, mitochondrial dysfunction and proteasome activation are involved in RTT cell oxidative damage.

    PubMed

    Cervellati, Carlo; Sticozzi, Claudia; Romani, Arianna; Belmonte, Giuseppe; De Rasmo, Domenico; Signorile, Anna; Cervellati, Franco; Milanese, Chiara; Mastroberardino, Pier Giorgio; Pecorelli, Alessandra; Savelli, Vinno; Forman, Henry J; Hayek, Joussef; Valacchi, Giuseppe

    2015-10-01

    A strong correlation between oxidative stress (OS) and Rett syndrome (RTT), a rare neurodevelopmental disorder affecting females in the 95% of the cases, has been well documented although the source of OS and the effect of a redox imbalance in this pathology has not been yet investigated. Using freshly isolated skin fibroblasts from RTT patients and healthy subjects, we have demonstrated in RTT cells high levels of H2O2 and HNE protein adducts. These findings correlated with the constitutive activation of NADPH-oxidase (NOX) and that was prevented by a NOX inhibitor and iron chelator pre-treatment, showing its direct involvement. In parallel, we demonstrated an increase in mitochondrial oxidant production, altered mitochondrial biogenesis and impaired proteasome activity in RTT samples. Further, we found that the key cellular defensive enzymes: glutathione peroxidase, superoxide dismutase and thioredoxin reductases activities were also significantly lower in RTT. Taken all together, our findings suggest that the systemic OS levels in RTT can be a consequence of both: increased endogenous oxidants as well as altered mitochondrial biogenesis with a decreased activity of defensive enzymes that leads to posttranslational oxidant protein modification and a proteasome activity impairment. PMID:26189585

  11. Anticancer Activity of Metal Complexes: Involvement of Redox Processes

    PubMed Central

    Jungwirth, Ute; Kowol, Christian R.; Keppler, Bernhard K.; Hartinger, Christian G.; Berger, Walter; Heffeter, Petra

    2012-01-01

    Cells require tight regulation of the intracellular redox balance and consequently of reactive oxygen species for proper redox signaling and maintenance of metal (e.g., of iron and copper) homeostasis. In several diseases, including cancer, this balance is disturbed. Therefore, anticancer drugs targeting the redox systems, for example, glutathione and thioredoxin, have entered focus of interest. Anticancer metal complexes (platinum, gold, arsenic, ruthenium, rhodium, copper, vanadium, cobalt, manganese, gadolinium, and molybdenum) have been shown to strongly interact with or even disturb cellular redox homeostasis. In this context, especially the hypothesis of “activation by reduction” as well as the “hard and soft acids and bases” theory with respect to coordination of metal ions to cellular ligands represent important concepts to understand the molecular modes of action of anticancer metal drugs. The aim of this review is to highlight specific interactions of metal-based anticancer drugs with the cellular redox homeostasis and to explain this behavior by considering chemical properties of the respective anticancer metal complexes currently either in (pre)clinical development or in daily clinical routine in oncology. PMID:21275772

  12. HIPPARCOS satellite: Aeritalia involvement and system test activities and results

    NASA Astrophysics Data System (ADS)

    Strim, B.; Cugno, W.; Morsillo, G.

    In 1989 the European Space Agency is scheduled to launch HIPPARCOS on a 2.5-year mission that will revolutionize the state of astronomy. This is the first satellite to be dedicated to astrometry, a branch of astronomy that deals with the position of celestial objects and their motion in space. With an accuracy impossible to achieve from Earth, HIPPARCOS will make position, trigonometric parallax and proper motion measurements of some 100.000 pre-selected stars. The data will be used to calculate each star's distance and motion, providing astronomers with an unprecedented map of the heavens. In the end, the HIPPARCOS mission is expected to reveal surprisingly new insight into theories of stellar evolution, as well as into the nature of our galaxy and the universe. The program has been awarded to the MESH industrial consortium for definition, development and production. The French firm MATRA (prime contractor) and the AERITALIA SPACE SYSTEMS GROUP (major co-contractor) share program responsibility. AERITALIA is in charge of the spacecraft or "service module". This is the structural platform for the telescope payload and provides all subsystem services including thermal control, data handling, telecommunications, electrical power distribution, power generation, attitude and orbit control, and apogee kick motor. AERITALIA is responsible for the procurement of all spacecraft subsystems for which it directs the activities of a multinational team of subcontractors. In addition, it is in charge of the satellite's final assembly, integration and testing, as well as for the procurement of all ground support equipment for satellite testing. HIPPARCOS stands for HIgh Precision PARallax COllecting Satellite. Its name is also intended to honor the Greek astronomer Hipparchus (190-120 BC) who compiled the first star catalog and who first used trigonometric parallax to calculate the distance to the moon. (Parallax is the apparent shift in a celestial body's position in the sky

  13. 16 CFR 1031.5 - Criteria for Commission involvement in voluntary standards activities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Criteria for Commission involvement in... COMMISSION GENERAL COMMISSION PARTICIPATION AND COMMISSION EMPLOYEE INVOLVEMENT IN VOLUNTARY STANDARDS ACTIVITIES General Policies § 1031.5 Criteria for Commission involvement in voluntary standards...

  14. 16 CFR 1031.5 - Criteria for Commission involvement in voluntary standards activities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Criteria for Commission involvement in... COMMISSION GENERAL COMMISSION PARTICIPATION AND COMMISSION EMPLOYEE INVOLVEMENT IN VOLUNTARY STANDARDS ACTIVITIES General Policies § 1031.5 Criteria for Commission involvement in voluntary standards...

  15. Capturing Unique Dimensions of Youth Organized Activity Involvement: Theoretical and Methodological Considerations

    ERIC Educational Resources Information Center

    Bohnert, Amy; Fredricks, Jennifer; Randall, Edin

    2010-01-01

    Despite increased focus on the effects of organized activities on youth development, there is currently no consensus about the best way to assess various dimensions of involvement. This article explores the complexities of assessing involvement and focuses specifically on the following organized activity dimensions: (a) breadth, (b) intensity, (c)…

  16. Involvement in Extracurricular Activities as Related to Academic Performance, Personality, and Peer Acceptance.

    ERIC Educational Resources Information Center

    Fung, Yee-wang; Wong, Ngai-ying

    1991-01-01

    Reveals findings of a survey of 294 Hong Kong secondary school students. Evaluates relationships among involvement in extracurricular activities, academic performance, personality, and peer acceptance. Concludes that activity involvement is positively related to academic performance, personality, and peer acceptance. Suggests that further research…

  17. Breadth and Intensity: Salient, Separable, and Developmentally Significant Dimensions of Structured Youth Activity Involvement

    ERIC Educational Resources Information Center

    Busseri, Michael A.; Rose-Krasnor, Linda

    2009-01-01

    In recent years, an impressive volume of evidence has accumulated demonstrating that youth involvement in structured, organized activities (e.g. school sports, community clubs) may facilitate positive youth development. We present a theory-based framework for studying structured activity involvement (SAI) as a context for positive youth…

  18. Cholesterol and benign prostate disease.

    PubMed

    Freeman, Michael R; Solomon, Keith R

    2011-01-01

    The origins of benign prostatic diseases, such as benign prostatic hyperplasia (BPH) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), are poorly understood. Patients suffering from benign prostatic symptoms report a substantially reduced quality of life, and the relationship between benign prostate conditions and prostate cancer is uncertain. Epidemiologic data for BPH and CP/CPPS are limited, however an apparent association between BPH symptoms and cardiovascular disease (CVD) has been consistently reported. The prostate synthesizes and stores large amounts of cholesterol and prostate tissues may be particularly sensitive to perturbations in cholesterol metabolism. Hypercholesterolemia, a major risk factor for CVD, is also a risk factor for BPH. Animal model and clinical trial findings suggest that agents that inhibit cholesterol absorption from the intestine, such as the class of compounds known as polyene macrolides, can reduce prostate gland size and improve lower urinary tract symptoms (LUTS). Observational studies indicate that cholesterol-lowering drugs reduce the risk of aggressive prostate cancer, while prostate cancer cell growth and survival pathways depend in part on cholesterol-sensitive biochemical mechanisms. Here we review the evidence that cholesterol metabolism plays a role in the incidence of benign prostate disease and we highlight possible therapeutic approaches based on this concept. PMID:21862201

  19. Environmentally Benign Stab Detonators

    SciTech Connect

    Gash, A E

    2006-07-07

    The coupling of energetic metallic multilayers (a.k.a. flash metal) with energetic sol-gel synthesis and processing is an entirely new approach to forming energetic devices for several DoD and DOE needs. They are also practical and commercially viable manufacturing techniques. Improved occupational safety and health, performance, reliability, reproducibility, and environmentally acceptable processing can be achieved using these methodologies and materials. The development and fielding of this technology will enhance mission readiness and reduce the costs, environmental risks and the necessity of resolving environmental concerns related to maintaining military readiness while simultaneously enhancing safety and health. Without sacrificing current performance, we will formulate new impact initiated device (IID) compositions to replace materials from the current composition that pose significant environmental, health, and safety problems associated with functions such as synthesis, material receipt, storage, handling, processing into the composition, reaction products from testing, and safe disposal. To do this, we will advance the use of nanocomposite preparation via the use of multilayer flash metal and sol-gel technologies and apply it to new small IIDs. This work will also serve to demonstrate that these technologies and resultant materials are relevant and practical to a variety of energetic needs of DoD and DOE. The goal will be to produce an IID whose composition is acceptable by OSHA, EPA, the Clean Air Act, Clean Water Act, Resource Recovery Act, etc. standards, without sacrificing current performance. The development of environmentally benign stab detonators and igniters will result in the removal of hazardous and toxic components associated with their manufacturing, handling, and use. This will lead to improved worker safety during manufacturing as well as reduced exposure of Service personnel during their storage and or use in operations. The

  20. Benign positional vertigo -- aftercare

    MedlinePlus

    ... make symptoms worse. Avoid activities such as driving, operating heavy machinery, and climbing while you are having ... member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www. ...

  1. The rare benign liver tumors.

    PubMed

    Skalicky, T; Treska, V; Liska, V; Sutnar, A; Molacek, J; Mirka, H; Ferda, J; Ohlidalova, K

    2007-01-01

    As opposed to malignant secondary tumors, metastases of the colorectal carcinoma are benign tumors of the liver that are quite rare in the Czech Republic. From the 55 patients operated on since 2000 at our department for benign liver tumors, the most frequent are haemangiomas, focal nodular hyperplasia (FNH) and hepatocelular adenoma. Only 7.3% of them form a different histological type of a tumor than this most frequently occurring trio of tumors. The authors describe three cases of rather rare liver tumors with benign behavior that have the potential of becoming malignant. It concerns mucin producing biliary tumors, which correspond to the pancreatic intraductal papillary mucin tumor, hepatic cystadenoma with ovarian stroma and a liver hamartoma in an adult patient (Ref 13). Full Text (Free, PDF) www.bmj.sk. PMID:17694811

  2. Benign skin disease with pustules in the newborn.

    PubMed

    Reginatto, Flávia Pereira; Villa, Damie De; Cestari, Tania Ferreira

    2016-04-01

    The neonatal period comprises the first four weeks of life. It is a period of adaptation where the skin often presents several changes: transient lesions, resulting from a physiological response, others as a consequence of transient diseases and some as markers of severe disorders. The presence of pustules in the skin of the newborn is always a reason for the family and for the assisting doctor to be worried, since the newborn is especially vulnerable to bacterial, viral or fungal infection. However, the majority of neonatal skin pustules is not infectious, comprising the benign neonatal pustulosis. Benign neonatal pustuloses are a group of clinical disease characterized by pustular eruptions in which a contagious agent is not responsible for its etiology. The most common ones are erythema toxicum neonatorum, the transient neonatal pustular melanosis and the benign cephalic pustulosis. These dermatoses are usually benign, asymptomatic and self-limited. It is important that the dermatologist and the neonatologist can identify benign and transient lesions, those caused by genodermatoses, and especially differentiate between neonates with systemic involvement from those with benign skin lesions, avoiding unnecessary diagnostic tests and worries. PMID:27192509

  3. Benign skin disease with pustules in the newborn*

    PubMed Central

    Reginatto, Flávia Pereira; Villa, Damie De; Cestari, Tania Ferreira

    2016-01-01

    The neonatal period comprises the first four weeks of life. It is a period of adaptation where the skin often presents several changes: transient lesions, resulting from a physiological response, others as a consequence of transient diseases and some as markers of severe disorders. The presence of pustules in the skin of the newborn is always a reason for the family and for the assisting doctor to be worried, since the newborn is especially vulnerable to bacterial, viral or fungal infection. However, the majority of neonatal skin pustules is not infectious, comprising the benign neonatal pustulosis. Benign neonatal pustuloses are a group of clinical disease characterized by pustular eruptions in which a contagious agent is not responsible for its etiology. The most common ones are erythema toxicum neonatorum, the transient neonatal pustular melanosis and the benign cephalic pustulosis. These dermatoses are usually benign, asymptomatic and self-limited. It is important that the dermatologist and the neonatologist can identify benign and transient lesions, those caused by genodermatoses, and especially differentiate between neonates with systemic involvement from those with benign skin lesions, avoiding unnecessary diagnostic tests and worries. PMID:27192509

  4. How Are Transition-to-Kindergarten Activities Associated with Parent Involvement during Kindergarten?

    ERIC Educational Resources Information Center

    Rathbun, Amy H.; Hausken, Elvira Germino

    This study identified the types of transition activities practiced by kindergarten teachers/schools around the country, the relation of various school characteristics to transition activities, and the relation between transition activities and parent involvement during kindergarten. The study sample was comprised of 2,826 public school and 417…

  5. 48 CFR 3452.224-71 - Notice about research activities involving human subjects.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 34 CFR part 97: Notice About Research Activities Involving Human Subjects (MAR 2011) (a) Applicable... more of the categories set forth in 34 CFR 97.101(b)(1)-(6). However, if the research subjects are children, the exemption at 34 CFR 97.101(b)(2) (i.e., research involving the use of educational...

  6. 48 CFR 3452.224-72 - Research activities involving human subjects.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... human subjects covered under 34 CFR part 97: Research Activities Involving Human Subjects (MAR 2011) (a... establish and maintain procedures for the protection of human subjects. The definitions in 34 CFR 97.102... approved by the IRB. (34 CFR 97.103(f).) No covered research involving human subjects shall be...

  7. 48 CFR 3452.224-72 - Research activities involving human subjects.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... human subjects covered under 34 CFR part 97: Research Activities Involving Human Subjects (MAR 2011) (a... establish and maintain procedures for the protection of human subjects. The definitions in 34 CFR 97.102... approved by the IRB. (34 CFR 97.103(f).) No covered research involving human subjects shall be...

  8. 48 CFR 3452.224-72 - Research activities involving human subjects.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... human subjects covered under 34 CFR part 97: Research Activities Involving Human Subjects (MAR 2011) (a... establish and maintain procedures for the protection of human subjects. The definitions in 34 CFR 97.102... approved by the IRB. (34 CFR 97.103(f).) No covered research involving human subjects shall be...

  9. Diagnosing Common Benign Skin Tumors.

    PubMed

    Higgins, James C; Maher, Michael H; Douglas, Mark S

    2015-10-01

    Patients will experience a wide range of skin growths and changes over their lifetime. Family physicians should be able to distinguish potentially malignant from benign skin tumors. Most lesions can be diagnosed on the basis of history and clinical examination. Lesions that are suspicious for malignancy, those with changing characteristics, symptomatic lesions, and those that cause cosmetic problems may warrant medical therapy, a simple office procedure (e.g., excision, cryosurgery, laser ablation), or referral. Acrochordons are extremely common, small, and typically pedunculated benign neoplasms. Simple scissor or shave excision, electrodesiccation, or cryosurgery can be used for treatment. Sebaceous hyperplasia presents as asymptomatic, discrete, soft, pale yellow, shiny bumps on the forehead or cheeks, or near hair follicles. Except for cosmesis, they have no clinical significance. Lipomas are soft, flesh-colored nodules that are easily moveable under the overlying skin. Keratoacanthomas are rapidly growing, squamoproliferative benign tumors that resemble squamous cell carcinomas. Early simple excision is recommended. Pyogenic granuloma is a rapidly growing nodule that bleeds easily. Treatment includes laser ablation or shave excision with electrodesiccation of the base. Dermatofibromas are an idiopathic benign proliferation of fibroblasts. No treatment is required unless there is a change in size or color, bleeding, or irritation from trauma. Epidermal inclusion cysts can be treated by simple excision with removal of the cyst and cyst wall. Seborrheic keratoses and cherry angiomas generally do not require treatment. PMID:26447443

  10. Pathogenesis of benign adrenocortical tumors.

    PubMed

    Vezzosi, Delphine; Bertherat, Jérôme; Groussin, Lionel

    2010-12-01

    Most adrenocortical tumors (ACT) are benign unilateral adrenocortical adenomas, often discovered incidentally. Exceptionally, ACT are bilateral. However bilateral ACT have been very helpful to progress in the pathophysiology of ACT. Although most ACT are of sporadic origin, they may also be part of syndromic and/or hereditary disorders. The identification of the genetics of familial diseases associated with benign ACT has been helpful to define somatic alterations in sporadic ACT: for example, identification of PRKAR1A mutations in Carney complex or alterations of the Wnt/β-catenin pathway in Familial Adenomatous Polyposis Coli. Components of the cAMP signaling pathway-for example, adrenocorticotropic-hormone receptors and other membrane receptors, Gs protein, phosphodiesterases and protein kinase A-can be altered to various degrees in benign cortisol-secreting ACT. These progress have been important for the understanding of the pathogenesis of benign ACT, but already have profound implications for clinical management, for example in unraveling the genetic origin of disease in some patients with ACT. They also have therapeutic consequences, and should help to develop new therapeutic options. PMID:21115158

  11. Elevated expression of HIF-lα in actively growing prostate tissues is associated with clinical features of benign prostatic hyperplasia

    PubMed Central

    Li, Xin; Wang, Hui; Liu, Shuai; Wu, Haihu; Bi, Dongbin; Ding, Kejia; Lu, Jiaju

    2016-01-01

    Background Benign prostatic hyperplasia (BPH) is one of the most common diseases in middle-age or older men. Increasing evidence has shown that BPH is associated with hypoxia microenvironment. Methods We retrospectively collected patient data and tissue samples from fetal prostates(FP), normal prostates(NP), intra-acinar of BPH, peri-acinar of BPH, prostate cancers and sarcomas of prostate. The expression of HIF-1α, as well as VEGF was visualized by immunohistochemistry and statistically analyzed with clinical parameters. Results Expression of HIF-lα was observed in intra-acinar of BPH (69.5%), prostate cancer (85.7%) and all FPs, while NP and peri-acinar of BPH tissues were all stained negative. HIF-lα levels in FPs and the malignant tumors were higher than BPH tissues(p < 0.05), and the expression of HIF-lα in intra-acinar of BPH was higher than NP and peri-acinar of BPH (p < 0.05). The expression of HIF-lα was correlated with the weight of intra-acinar of prostate (p < 0.05). And patients with prostate weight larger that 72.45g were prone to have HIF-lα moderate-positive expression, according to the ROC curve (AUC = 0.734, 95%CI = 0.630-0.838). Moreover, the risk of acute urine retention (AUR) for HIF-lα moderate-positive patients increased significantly (OR=5.517, 95%CI = 2.434-12.504). Conclusions HIF-lα expression is increased in highly proliferative prostate tissues and correlated with the weight of intra-acinar prostate. Moreover, HIF-lα is also an independent risk factor for AUR occurrence in BPH patients. PMID:26919249

  12. Health benefits of serious involvement in leisure activities among older Korean adults.

    PubMed

    Kim, Junhyoung; Yamada, Naoko; Heo, Jinmoo; Han, Areum

    2014-01-01

    The existing literature suggests that serious engagement in leisure activities leads to happiness, life satisfaction, and successful aging among older adults. This qualitative study was used to examine the benefits of serious involvement in leisure activities among older Korean adults who were members of a sports club. Using an analytic data analysis, we identified three main themes associated with the benefits of serious engagement in leisure activities: 1) the experience of psychological benefits, 2) the creation of social support, and 3) the enhancement of physical health. These themes indicate that, through serious involvement in certain physical activities, participants gain various health benefits, which may contribute to successful aging. PMID:25059979

  13. Health benefits of serious involvement in leisure activities among older Korean adults

    PubMed Central

    Kim, Junhyoung; Yamada, Naoko; Heo, Jinmoo; Han, Areum

    2014-01-01

    The existing literature suggests that serious engagement in leisure activities leads to happiness, life satisfaction, and successful aging among older adults. This qualitative study was used to examine the benefits of serious involvement in leisure activities among older Korean adults who were members of a sports club. Using an analytic data analysis, we identified three main themes associated with the benefits of serious engagement in leisure activities: 1) the experience of psychological benefits, 2) the creation of social support, and 3) the enhancement of physical health. These themes indicate that, through serious involvement in certain physical activities, participants gain various health benefits, which may contribute to successful aging. PMID:25059979

  14. Environmentally Benign Stab Detonators

    SciTech Connect

    Gash, A

    2005-12-21

    Many energetic systems can be activated via mechanical means. Percussion primers in small caliber ammunition and stab detonators used in medium caliber ammunition are just two examples. Current medium caliber (20-60mm) munitions are detonated through the use of impact sensitive stab detonators. Stab detonators are very sensitive and must be small, as to meet weight and size limitations. A mix of energetic powders, sensitive to mechanical stimulus, is typically used to ignite such devices. Stab detonators are mechanically activated by forcing a firing pin through the closure disc of the device and into the stab initiating mix. Rapid heating caused by mechanically driven compression and friction of the mixture results in its ignition. The rapid decomposition of these materials generates a pressure/temperature pulse that is sufficient to initiate a transfer charge, which has enough output energy to detonate the main charge. This general type of ignition mix is used in a large variety of primers, igniters, and detonators.[1] Common primer mixes, such as NOL-130, are made up of lead styphnate (basic) 40%, lead azide (dextrinated) 20%, barium nitrate 20%, antimony sulfide 15%, and tetrazene 5%.[1] These materials pose acute and chronic toxicity hazards during mixing of the composition and later in the item life cycle after the item has been field functioned. There is an established need to replace these mixes on toxicity, health, and environmental hazard grounds. This effort attempts to demonstrate that environmentally acceptable energetic solgel coated flash metal multilayer nanocomposites can be used to replace current impact initiated devices (IIDs), which have hazardous and toxic components. Successful completion of this project will result in IIDs that include innocuous compounds, have sufficient output energy for initiation, meet current military specifications, are small, cost competitive, and perform as well as or better than current devices. We expect flash

  15. Demethylation-linked Activation of uPA is Involved in Progression of Prostate Cancer

    PubMed Central

    Pulukuri, Sai MuraliKrishna; Estes, Norman; Patel, Jitendra; Rao, Jasti S.

    2006-01-01

    Increased expression of urokinase plasminogen activator (uPA) has been reported in various malignancies including prostate cancer. However, the mechanism by which uPA is abnormally expressed in prostate cancer remains elusive. Here, we show that uPA is aberrantly expressed in a high-percentage of human prostate cancer tissues, but rarely expressed either in tumor-matched, non-neoplastic adjacent tissues (NNAT) or benign prostatic hyperplasia (BPH) samples. This aberrant expression is associated with cancer-linked demethylation of the uPA promoter. Furthermore, treatment with demethylation inhibitor S-Adenosylmethionine (Ado-Met) or stable expression of uPA shRNA significantly inhibits uPA expression and tumor cell invasion in vitro and tumor growth and incidence of lung metastasis in vivo. Collectively, these findings strongly suggest that DNA demethylation is a common mechanism underlying the abnormal expression of uPA and is a critical contributing factor to the malignant progression of human prostate tumors. PMID:17283123

  16. Thallium-201 uptake in a benign thymoma

    SciTech Connect

    Campeau, R.J.; Ey, E.H.; Varma, D.G.

    1986-07-01

    A 68-year-old woman was admitted with atypical angina. A chest radiograph showed an anterior mediastinal mass that was confirmed on CT. The mass was relatively avascular and separate from the heart and great vessels. She underwent stress thallium testing that demonstrated no exercise-induced ischemia; however, an abnormal focus of thallium activity was present in the anterior mediastinum on stress and redistribution images. Cardiac catheterization demonstrated a normal left ventriculogram, coronary arteries and thoracic aorta. Subsequent surgery and pathologic examination revealed the mass to be a benign thymoma arising in the right lobe of the thymus gland.

  17. Environmentally Benign Stab Detonators

    SciTech Connect

    Gash, A; Barbee, T; Simpson, R; Satcher, J; Walton, C

    2003-12-15

    This effort attempts to demonstrate that environmentally acceptable energetic sol-gel coated flash metal multilayer nanocomposites can be used to replace current impact initiated devices (IIDs) which have hazardous and toxic components. Successful completion of this project will result in IIDs that include innocuous compounds, have sufficient output energy for initiation, meet current military specifications, are small, cost competitive, and perform as well as or better than current devices. We expect flash metal multilayer and sol-gel to be generic technologies applicable to a wide range of devices, especially in small caliber ammunition and sub-munitions. We will replace the NOL-130 mixture with a nanocomposite that consists of a mechanically robust energetic multilayer foil that has been coated with a sol-gel energetic material. The exothermic reactions are activated in this nanocomposite are the transformation of the multilayer material to its respective intermetallic alloy and the thermite reaction, which is characterized by very high temperatures, a small pressure pulse, and hot particle ejection. The proposed materials and their reaction products consist of, but are not limited to aluminum, nickel, iron, aluminum oxide, titanium, iron oxide and boron. These materials have much more desirable environmental and health characteristics than the NOL-130 composition.

  18. Getting Involved: Exploring Latino GBT Volunteerism and Activism in AIDS and LGBT Organizations

    PubMed Central

    Ramirez-Valles, Jesus; Kuhns, Lisa M.; Vázquez, Raquel; Benjamin, Gregory D.

    2014-01-01

    The purpose of this paper is to investigate the community involvement (e.g., volunteerism, activism) of Latino gay and bisexual men and transgender persons (GBT) in two areas: AIDS/GLBT and other general causes. Drawing from volunteering and identity theories, we explore: Who is likely to get involved? What factors affect variation in the levels of involvement? Where do Latino GBT participate and what do they do? Data come from a cross-sectional sample (N=643) of Latino GBT in Chicago and San Francisco. We find high levels of involvement, but primarily focused on AIDS/GLBT. Involvement appears to be driven by income, early involvement, role modeling, and childhood stigmatization of gender nonconformity. PMID:26451081

  19. Novel mechanisms for activated protein C cytoprotective activities involving noncanonical activation of protease-activated receptor 3

    PubMed Central

    Burnier, Laurent

    2013-01-01

    The direct cytoprotective activities of activated protein C (APC) on cells convey therapeutic, relevant, beneficial effects in injury and disease models in vivo and require the endothelial protein C receptor (EPCR) and protease activated receptor 1 (PAR1). Thrombin also activates PAR1, but its effects on cells contrast APC’s cytoprotective effects. To gain insights into mechanisms for these contrasting cellular effects, protease activated receptor 3 (PAR3) activation by APC and thrombin was studied. APC cleaved PAR3 on transfected and endothelial cells in the presence of EPCR. Remarkably, APC cleaved a synthetic PAR3 N-terminal peptide at Arg41, whereas thrombin cleaved at Lys38. On cells, APC failed to cleave R41Q-PAR3, whereas K38Q-PAR3 was still cleaved by APC but not by thrombin. PAR3 tethered-ligand peptides beginning at amino acid 42, but not those beginning at amino acid 39, conveyed endothelial barrier-protective effects. In vivo, the APC-derived PAR3 tethered-ligand peptide, but not the thrombin-derived PAR3 peptide, blunted vascular endothelial growth factor (VEGF)-induced vascular permeability. These data indicate that PAR3 cleavage by APC at Arg41 can initiate distinctive APC-like cytoprotective effects. These novel insights help explain the differentiation of APC’s cytoprotective versus thrombin’s proinflammatory effects on cells and suggest a unique contributory role for PAR3 in the complex mechanisms underlying APC cytoprotective effects. PMID:23788139

  20. 48 CFR 3452.224-71 - Notice about research activities involving human subjects.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 34 CFR part 97: Notice About Research Activities Involving Human Subjects (MAR 2011) (a) Applicable... to develop or contribute to generalizable knowledge.” (34 CFR 97.102(d)). If an activity follows a... the individual, or obtains identifiable private information. (34 CFR 97.102(f)). The definition of...

  1. 48 CFR 3452.224-71 - Notice about research activities involving human subjects.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 34 CFR part 97: Notice About Research Activities Involving Human Subjects (MAR 2011) (a) Applicable... to develop or contribute to generalizable knowledge.” (34 CFR 97.102(d)). If an activity follows a... the individual, or obtains identifiable private information. (34 CFR 97.102(f)). The definition of...

  2. Understanding Threshold Effects of Organized Activity Involvement in Adolescents: Sex and Family Income as Moderators

    ERIC Educational Resources Information Center

    Randall, Edin T.; Bohnert, Amy M.

    2012-01-01

    The current study examined the curvilinear links between involvement in organized activities (OA) and sport activities specifically and various indicators of psychological and social development. Participants included 150 9th and 10th graders (57% females) from an urban, selective-enrollment high school. Eligibility for admission is based on city…

  3. A Study of Lipscomb University Students' Internet Use and Involvement in Extracurricular Activities

    ERIC Educational Resources Information Center

    Smith, Samuel Aarron

    2010-01-01

    The purpose of this study was to analyze Lipscomb University students' Internet use and involvement in extracurricular activities. A survey of students at Lipscomb University was conducted. As confirmed by the data the research was able to determine that the type of extracurricular activity a student participates in most often is related to the…

  4. A Longitudinal Study of Breadth and Intensity of Activity Involvement and the Transition to University

    ERIC Educational Resources Information Center

    Busseri, Michael A.; Rose-Krasnor, Linda; Pancer, S. Mark; Pratt, Michael W.; Adams, Gerald R.; Birnie-Lefcovitch, Shelly; Polivy, Janet; Wintre, Maxine Gallander

    2011-01-01

    We examined prospective relations between activity involvement and successful transitioning to university. A sample of 656 students from 6 Canadian universities completed questionnaires before beginning university and at the end of their first year. Breadth (number of different activity domains) and intensity (mean frequency) of activity…

  5. 48 CFR 3452.224-71 - Notice about research activities involving human subjects.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 34 CFR part 97: Notice About Research Activities Involving Human Subjects (MAR 2011) (a) Applicable... to develop or contribute to generalizable knowledge.” (34 CFR 97.102(d)). If an activity follows a... the individual, or obtains identifiable private information. (34 CFR 97.102(f)). The definition of...

  6. A Benign Cardiac Growth but Not So Indolent

    PubMed Central

    Reddy, Sahadev T.; Biederman, Robert W. W.

    2016-01-01

    Cardiac lipomatous hypertrophy is a rare benign condition that usually involves the interatrial septum. Due to its benign nature it rarely requires intervention. Its presence outside the interatrial septum is reported infrequently. We present a case of lipomatous hypertrophy in the intraventricular septum that was complicated by a severe, symptomatic, and disabling dynamic left ventricular outflow tract obstruction. The symptoms significantly improved following the excision of the mass. In our case transthoracic echocardiogram was used to visualize the mass and measure the severity of the obstruction; Cardiac Magnetic Resonance Imaging was used to characterize the mass and histopathology confirmed the diagnosis. PMID:27293911

  7. Single benign metastasising leiomyoma of an inguinal lymph node.

    PubMed

    Laban, Kamil G; Tobon-Morales, Roberto E; Hodge, Janice A L; Schreuder, Henk W R

    2016-01-01

    Benign metastasising leiomyoma (BML) is a rare benign disease associated with uterine leiomyoma and history of uterine surgery. It most frequently occurs in premenopausal woman, with a pulmonary localisation, and consisting of multiple nodules. We present an uncommon case of a 69-year-old woman with a single BML of an inguinal lymph node. CT scans of thorax and abdomen excluded other metastasis localisation. The patient was cured with surgical excision of the mass. Lymph node involvement has been reported incidentally in BML literature. Lymphangitic spread can be considered a possible mechanism of BML metastasis. PMID:27511755

  8. Benign vs. malicious ghosts in higher-derivative theories

    NASA Astrophysics Data System (ADS)

    Smilga, A. V.

    2005-02-01

    Interacting theories with higher-derivatives involve ghosts. They correspond to instabilities that display themselves at the classical level. We notice that comparatively "benign" mechanical higher-derivative systems exist, where the classical vacuum is stable with respect to small perturbations and the problems appear only at the nonperturbative level. We argue the existence of benign higher-derivative field theories which are stable with respect to small fluctuations with nonzero momenta. A particular example is the 6D N=2 higher-derivative SYM theory, which is finite and unitary at the perturbative level. The instability with respect to small fluctuations of zero-momentum modes is always present, however.

  9. A rare benign ovarian tumour.

    PubMed

    Palmeiro, Marta Morna; Cunha, Teresa Margarida; Loureiro, Ana Luisa; Esteves, Gonçalo

    2016-01-01

    Sclerosing stromal tumour (SST) of the ovary is an extremely rare and benign ovarian neoplasm, accounting for 6% of the sex cord stromal ovarian tumours subtype. Usually, it is found during the second and third decades of life. Patients commonly present with pelvic pain, a palpable pelvic mass or menstrual irregularity. We report a case of a 20-year-old woman reporting of mild pelvic pain, with normal laboratory data. On imaging examinations, a large right adnexal tumour was found, with features suggesting an ovarian sex cord tumour. The patient underwent right salpingo-oophorectomy, diagnosing a SST of the ovary. This paper also reviews the literature, and emphasises the typical pathological and imaging characteristics of these rare benign ovarian lesions, and their impact, in a conservative surgery. PMID:26933186

  10. Histiocytic sarcoma that mimics benign histiocytosis.

    PubMed

    Boisseau-Garsaud, A M; Vergier, B; Beylot-Barry, M; Nastasel-Menini, F; Dubus, P; de Mascarel, A; Eghbali, H; Beylot, C

    1996-06-01

    A 28-year-old man presented with a histiocytic sarcoma of a very uncommon origin, as it had developed for several years like a benign cutaneous histiocytosis resembling generalized eruptive histiocytoma before becoming acute, with nodal and massive pulmonary involvement. Despite various chemotherapies, the patient died within 8 months. Skin biopsies showed histiocytic proliferation in the dermis and node biopsies showed histiocytic proliferation with a sinusoidal pattern. Immunohistochemical analysis, performed on paraffin-embedded sections, demonstrated strong labeling of tumoral cells for CD68 and moderate labeling for CD3 and CD4. CD30 labeling was negative. S-100 protein was positive on a Langerhans' cell reactive subpopulation. Electron microscopy confirmed the histiocytic nature of malignant cells and showed cytoplasmic inclusions such as regularly laminated bodies, dense bodies and pleomorphic inclusions. No Birbeck granules were seen. A gene rearrangement study of T-cell receptor gamma and immunoglobulin heavy chain genes showed a germline configuration. Histiocytic sarcoma is an extremely rare true histiocytic malignancy, the existence of which has been recently debated since it has often been mistaken in the past for large cell lymphomas. Such a deceptive onset as benign cutaneous histiocytosis has not been described in the literature to our knowledge. PMID:8793665

  11. Benign Pediatric Salivary Gland Lesions.

    PubMed

    Carlson, Eric R; Ord, Robert A

    2016-02-01

    Salivary gland lesions are rare in pediatric patients. In addition, the types of salivary gland tumors are different in their distribution in specific sites in the major and minor salivary glands in children compared with adults. This article reviews benign neoplastic and nonneoplastic salivary gland disorders in pediatric patients to help clinicians to develop an orderly differential diagnosis that will lead to expedient treatment of pediatric patients with salivary gland lesions. PMID:26614702

  12. Activities involving aeronautical, space science, and technology support for minority institutions

    NASA Technical Reports Server (NTRS)

    1993-01-01

    The Final Report addressed the activities with which the Interracial Council for Business Opportunity (ICBO) was involved over the past 12 months. ICBO was involved in the design and development of a CARES Student Tracking System Software (CARES). Cares is intended to provide an effective means of maintaining relevant current and historical information on NASA-funded students through a range of educational program initiatives. ICBP was extensively involved in the formation of a minority university consortium amd implementation of collaborative research activities by the consortium as part of NASA's Mission to Planet Earth/Earth Observing System. ICBO was involved in the formation of an HBCU/MI Consortium to facilitate technology transfer efforts to the small and minority business community in their respective regions.

  13. Analysis of Gene Expression Profiling in Meningioma: Deregulated Signaling Pathways Associated with Meningioma and EGFL6 Overexpression in Benign Meningioma Tissue and Serum

    PubMed Central

    Wang, Xuanchun; Gong, Ye; Wang, Daijun; Xie, Qing; Zheng, Mingzhe; Zhou, Yu; Li, Qin; Yang, Zhen; Tang, Hailiang; Li, Yiming; Hu, Renming; Chen, Xiancheng; Mao, Ying

    2012-01-01

    Molecular mechanisms underlying the pathogenesis of meningioma are not fully elucidated. In this study, we established differential gene expression profiles between meningiomas and brain arachnoidal tissue by using Affymetrix GeneChip Human U133 Plus 2.0 Array. KEGG pathway analysis demonstrated that PI3K/Akt and TGFβ signaling pathways were up-regulated in fibroblastic meningioma, and focal adhesion and ECM-receptor interaction pathways were activated in anaplastic meningioma. EGFL6 was one of the most up-regulated genes in fibroblastic meningioma by microarray analysis. Quantitative real-time PCR demonstrated that benign meningiomas had significantly higher levels of EGFL6 mRNA than brain arachnoidal tissue and atypical and anaplastic meningiomas (P<0.001). EGFL6 gene was also highly expressed in ovarian cancer, but expressed lowly in other investigated tumors. ELISA analysis showed that patients with benign meningiomas and ovarian cancers had the highest serum levels of EGFL6 (mean concentration: 672 pg/ml for benign meningiomas, and 616 pg/ml for ovarian cancers). Healthy people and patients with other tumors, however, had low levels of serum EGFL6. In conclusion, we proposed that activation of PI3K/Akt and integrin-mediated signaling pathways was involved in the pathogenesis of benign and anaplastic meningiomas, respectively. We also presented evidence that EGFL6 was overexpressed in benign meningioma tissues and serum. PMID:23285163

  14. Addressing Three Common Issues in Research on Youth Activities: An Integrative Approach for Operationalizing and Analyzing Involvement

    ERIC Educational Resources Information Center

    Busseri, Michael A.; Rose-Krasnor, Linda

    2010-01-01

    Youth activity involvement has been operationalized and analyzed using a wide range of approaches. Researchers face the challenges of distinguishing between the effects of involvement versus noninvolvement and intensity of involvement in a particular activity, accounting simultaneously for cumulative effects of involvement, and addressing multiple…

  15. ENVIROMENTALLY BENIGN MITIGATION OF MICROBIOLOGICALLY INFLUENCED CORROSION (MIC)

    SciTech Connect

    J. Robert Paterek; Gemma Husmillo; Amrutha Daram; Vesna Trbovic

    2003-10-31

    The overall program objective is to develop and evaluate environmentally benign agents or products that are effective in the prevention, inhibition, and mitigation of microbially influenced corrosion (MIC) in the internal surfaces of metallic natural gas pipelines. The goal is to develop one or more environmentally benign (a.k.a. ''green'') products that can be applied to maintain the structure and dependability of the natural gas infrastructure. The technical approach for this quarter includes the application of the method of fractionation of the extracts by high performance liquid chromatography (HPLC); determination of antimicrobial activities of the new extracts and fractions using a growth inhibition assay, and evaluation of the extracts' ability to inhibit biofilm formation. We initiated the delivery system for these new biocides in the test cell and in mixtures of foam components and biocides/anti-biofilms. A total of 51 fractions collected by HPLC from crude extracts that were obtained from three varieties of Capsicum sp. (Serrano, Habanero, Chile de Arbol) were subjected to growth inhibition tests against two SRB strains, D. vulgaris and D. desulfuricans. Five fractions showed growth inhibition against both strains while seven inhibited D. desulfuricans only. The crude extracts did not show growth inhibition on both strains but were proven to be potent in preventing the formation of biofilm. Growth inhibition tests of the same set of crude extracts against Comamonas denitrificans did not show positive results. The fractions will be subjected to biofilm inhibition and dissociation assay as well. The delivery system to be evaluated first was foam. The ''foam pig'' components of surfactants and water were tested with the biocide addition. The first chemical and physical parameters to be tested were pH and surfactants. Tests using the fractionated pepper extracts are progressing rapidly. Gas chromatographic analysis on a number of fractions is underway

  16. Physiological heart activation by adrenaline involves parallel activation of ATP usage and supply.

    PubMed

    Korzeniewski, Bernard; Deschodt-Arsac, Véronique; Calmettes, Guillaume; Franconi, Jean-Michel; Diolez, Philippe

    2008-07-15

    During low-to-high work transition in adult mammalian heart in vivo the concentrations of free ADP, ATP, PCr (phosphocreatine), P(i) and NADH are essentially constant, in striking contrast with skeletal muscle. The direct activation by calcium ions of ATP usage and feedback activation of ATP production by ADP (and P(i)) alone cannot explain this perfect homoeostasis. A comparison of the response to adrenaline (increase in rate-pressure product and [PCr]) of the intact beating perfused rat heart with the elasticities of the PCr producer and consumer to PCr concentration demonstrated that both the ATP/PCr-producing block and ATP/PCr-consuming block are directly activated to a similar extent during physiological heart activation. Our finding constitutes a direct evidence for the parallel-activation mechanism of the regulation of oxidative phosphorylation in heart postulated previously in a theoretical way. PMID:18377364

  17. Microwave-Assisted Rapid Access to Bio-active Heterocycles: Synthesis of 1,3,4-Oxadiazoles, 1,3,4-Thiadiazoles, 1,3-Dioxanes, Pyrazoles, Hydrazones and 3,4-Dihydropyrimidin-2(1H)-ones under Benign Conditions

    EPA Science Inventory

    Green chemistry is a rapidly developing new field that provides us a proactive avenue for the sustainable development of future science and technologies.1 It emphasis the use of highly efficient and environmental benign synthetic protocols to deliver bio-active heterocycles, acc...

  18. Molecular genetic analysis of activation-tagged transcription factors thought to be involved in photomorphogenesis

    SciTech Connect

    Neff, Michael M.

    2011-06-23

    This is a final report for Department of Energy Grant No. DE-FG02-08ER15927 entitled “Molecular Genetic Analysis of Activation-Tagged Transcription Factors Thought to be Involved in Photomorphogenesis”. Based on our preliminary photobiological and genetic analysis of the sob1-D mutant, we hypothesized that OBP3 is a transcription factor involved in both phytochrome and cryptochrome-mediated signal transduction. In addition, we hypothesized that OBP3 is involved in auxin signaling and root development. Based on our preliminary photobiological and genetic analysis of the sob2-D mutant, we also hypothesized that a related gene, LEP, is involved in hormone signaling and seedling development.

  19. Idle Hands and Empty Pockets?: Youth Involvement in Extracurricular Activities, Social Capital, and Economic Status

    ERIC Educational Resources Information Center

    White, Amanda M.; Gager, Constance T.

    2007-01-01

    Using data from the Survey of Adults and Youth, the authors examine the effect of economic status on youths' involvement in both school- and nonschool-related extracurricular activities. Specifically, they assess the association between four alternative measures of economic status--recipiency of food stamps, Aid to Families with Dependent…

  20. Involving Your Child or Teen with ASD in Integrated Community Activities

    ERIC Educational Resources Information Center

    McKee, Rebecca

    2011-01-01

    Participating in outside activities and community-based endeavors can be tricky for people with special needs, like Autism Spectrum Disorder (ASD). Families meet more than a few obstacles attempting to integrate their children or teens who have special needs like ASD. Most typical children are highly involved in sports, clubs and camps. If a…

  1. An Active Self-Determination Technique: Involving Students in Effective Career Planning.

    ERIC Educational Resources Information Center

    Denison, Grace L.

    This paper discusses creating story boards to help students with disabilities to develop effective career plans. It describes storyboarding as a technique for project planning which requires active involvement of both hemispheres of the brain. A group of 6-8 people, including students, teachers, counselors, and vocational rehabilitation…

  2. Beyond Participation: The Association between School Extracurricular Activities and Involvement in Violence across Generations of Immigration

    ERIC Educational Resources Information Center

    Jiang, Xin; Peterson, Ruth D.

    2012-01-01

    Participation in extracurricular activities is purported to protect the broad spectrum of youth from a host of behavioral risks. Yet, empirical research on the extent to which this assumption holds for involvement in violence by immigrant youth is limited. Thus, using data for 13,236 (51.8% female) adolescents from the National Longitudinal Study…

  3. An Emergent Language Program Framework: Actively Involving Learners in Needs Analysis.

    ERIC Educational Resources Information Center

    Savage, William; Storer, Graeme

    1992-01-01

    Relates the experience of the staff of an aquaculture outreach program in Northeast Thailand in implementing an English for special purposes program. By actively involving learners in both the needs analysis and program design, teachers were able to adapt the program content to the requirements of the students. (15 references) (JL)

  4. INVOLVEMENT OF MICRORNAS IN EMBRYONIC GENOME ACTIVATION AS SHOWN BY DICER EXPRESSION IN RAINBOW TROUT

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Most maternal transcripts including many housekeeping genes are degraded at or around embryonic genome activation as evidenced by our initial studies. This degradation appears to be global but highly regulated. MicroRNAs are naturally occurring small (19-24bp) RNAs that are shown to be involved in m...

  5. Longitudinal Modeling of Adolescents' Activity Involvement, Problem Peer Associations, and Youth Smoking

    ERIC Educational Resources Information Center

    Metzger, Aaron; Dawes, Nickki; Mermelstein, Robin; Wakschlag, Lauren

    2011-01-01

    Longitudinal associations among different types of organized activity involvement, problem peer associations, and cigarette smoking were examined in a sample of 1040 adolescents (mean age = 15.62 at baseline, 16.89 at 15-month assessment, 17.59 at 24 months) enriched for smoking experimentation (83% had tried smoking). A structural equation model…

  6. A Longitudinal Examination of Breadth and Intensity of Youth Activity Involvement and Successful Development

    ERIC Educational Resources Information Center

    Busseri, Michael A.; Rose-Krasnor, Linda; Willoughby, Teena; Chalmers, Heather

    2006-01-01

    Connections between youth activity involvement and indicators of successful development were examined in a longitudinal high school sample. Drawing on theories of expertise skill development (e.g., J. Cote, 1999); the selection, optimization, and compensation framework (P. B. Baltes, 1997); and theories of positive youth development (e.g., R. M.…

  7. 78 FR 57818 - Commission Participation and Commission Employee Involvement in Voluntary Standards Activities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-20

    ... Commission Employee Involvement in Voluntary Standards Activities. 54 FR 6646 (Feb. 14, 1989). In 2006, the Commission amended several provisions of part 1031. 71 FR 38754 (July 10, 2006). Among other things, the 2006... the development of voluntary standards (43 FR 19216 (May 4, 1978)). Acknowledging the...

  8. 48 CFR 3452.224-72 - Research activities involving human subjects.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 7 2013-10-01 2012-10-01 true Research activities involving human subjects. 3452.224-72 Section 3452.224-72 Federal Acquisition Regulations System DEPARTMENT OF EDUCATION ACQUISITION REGULATION CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses...

  9. 45 CFR 1177.4 - Claims involving criminal activity or misconduct.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 3 2012-10-01 2012-10-01 false Claims involving criminal activity or misconduct. 1177.4 Section 1177.4 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES NATIONAL ENDOWMENT FOR THE HUMANITIES CLAIMS COLLECTION §...

  10. 45 CFR 1177.4 - Claims involving criminal activity or misconduct.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 3 2011-10-01 2011-10-01 false Claims involving criminal activity or misconduct. 1177.4 Section 1177.4 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES NATIONAL ENDOWMENT FOR THE HUMANITIES CLAIMS COLLECTION §...

  11. 45 CFR 1177.4 - Claims involving criminal activity or misconduct.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 3 2013-10-01 2013-10-01 false Claims involving criminal activity or misconduct. 1177.4 Section 1177.4 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES NATIONAL ENDOWMENT FOR THE HUMANITIES CLAIMS COLLECTION §...

  12. 45 CFR 1177.4 - Claims involving criminal activity or misconduct.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Claims involving criminal activity or misconduct. 1177.4 Section 1177.4 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES NATIONAL ENDOWMENT FOR THE HUMANITIES CLAIMS COLLECTION §...

  13. 45 CFR 1177.4 - Claims involving criminal activity or misconduct.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 3 2014-10-01 2014-10-01 false Claims involving criminal activity or misconduct. 1177.4 Section 1177.4 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES NATIONAL ENDOWMENT FOR THE HUMANITIES CLAIMS COLLECTION §...

  14. Involving Parents of Young Children in Science, Math and Literacy Activities.

    ERIC Educational Resources Information Center

    Landerholm, Elizabeth; And Others

    1995-01-01

    Describes a collaborative parent-involvement project for inner-city Hispanic primary students sponsored by the Chicago Community Trust. A university professor, two graduate assistants, the principal, and the school community representative designed a summer program featuring hospitality and support activities, free books, and hands-on science and…

  15. Increasing Student Involvement in Self-Governance Activities: A Delphi Approach.

    ERIC Educational Resources Information Center

    Miles, Jennifer M.; Miller, Michael T.

    This study used a Delphi survey to examine what undergraduate student government leaders think about increasing student involvement in self-governance activities. Twenty-students from geographically diverse institutions of higher education participated in the three rounds of the Delphi study. They generated a total of 56 different strategies and…

  16. Beyond the Classroom: Involving Students with Disabilities in Extracurricular Activities at Levy Middle School.

    ERIC Educational Resources Information Center

    Walker, Pam; And Others

    Six students in a special education classroom at Levy Middle School (Syracuse, New York) became involved in a variety of after-school activities with nondisabled students. The students participated in the school computer club, cross-country skiing, volleyball, stage crew, intramural basketball, the Spanish Club, and after-school programs at two…

  17. Benign prenatal hypophosphatasia: a treatable disease not to be missed.

    PubMed

    Matsushita, Masaki; Kitoh, Hiroshi; Michigami, Toshimi; Tachikawa, Kanako; Ishiguro, Naoki

    2014-03-01

    Prenatal bowing of the long bones is often associated with severe bone dysplasias. We report a child who presented marked bowing of the long bones at birth but showed a relatively benign postnatal course with spontaneous improvement of bowing. The fetal imaging showed normal skeletal mineralization and normal chest and abdominal circumferences despite the limb bowing and shortening. Decreased serum alkaline phosphatase activity and elevated urine phosphoethanolamine was biochemically evident, and compound heterozygous mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene were identified, which confirmed the diagnosis of a benign form of prenatal hypophosphatasia. Benign prenatal hypophosphatasia should be considered in the differential diagnosis of congenital bowing of the long bones. PMID:24145968

  18. The Conundrum of Genetic "Drivers" in Benign Conditions.

    PubMed

    Kato, Shumei; Lippman, Scott M; Flaherty, Keith T; Kurzrock, Razelle

    2016-08-01

    Advances in deep genomic sequencing have identified a spectrum of cancer-specific passenger and driver aberrations. Clones with driver anomalies are believed to be positively selected during carcinogenesis. Accumulating evidence, however, shows that genomic alterations, such as those inBRAF,RAS,EGFR,HER2,FGFR3,PIK3CA,TP53,CDKN2A, andNF1/2, all of which are considered hallmark drivers of specific cancers, can also be identified in benign and premalignant conditions, occasionally at frequencies higher than in their malignant counterparts. Targeting these genomic drivers can produce dramatic responses in advanced cancer, but the effects on their benign counterparts are less clear. This benign-malignant phenomenon is well illustrated in studies ofBRAFV600E mutations, which are paradoxically more frequent in benign nevi (∼80%) than in dysplastic nevi (∼60%) or melanoma (∼40%-45%). Similarly, human epidermal growth factor receptor 2 is more commonly overexpressed in ductal carcinoma in situ (∼27%-56%) when compared with invasive breast cancer (∼11%-20%).FGFR3mutations in bladder cancer also decrease with tumor grade (low-grade tumors, ∼61%; high-grade, ∼11%). "Driver" mutations also occur in nonmalignant settings:TP53mutations in synovial tissue from rheumatoid arthritis andFGFR3mutations in seborrheic keratosis. The latter observations suggest that the oncogenicity of these alterations may be tissue context-dependent. The conversion of benign conditions to premalignant disease may involve other genetic events and/or epigenetic reprogramming. Putative driver mutations can also be germline and associated with increased cancer risk (eg, germlineRASorTP53alterations), but germlineFGFR3orNF2abnormalities do not predispose to malignancy. We discuss the enigma of genetic "drivers" in benign and premalignant conditions and the implications for prevention strategies and theories of tumorigenesis. PMID:27059373

  19. The Conundrum of Genetic “Drivers” in Benign Conditions

    PubMed Central

    Flaherty, Keith T.; Kurzrock, Razelle

    2016-01-01

    Advances in deep genomic sequencing have identified a spectrum of cancer-specific passenger and driver aberrations. Clones with driver anomalies are believed to be positively selected during carcinogenesis. Accumulating evidence, however, shows that genomic alterations, such as those in BRAF, RAS, EGFR, HER2, FGFR3, PIK3CA, TP53, CDKN2A, and NF1/2, all of which are considered hallmark drivers of specific cancers, can also be identified in benign and premalignant conditions, occasionally at frequencies higher than in their malignant counterparts. Targeting these genomic drivers can produce dramatic responses in advanced cancer, but the effects on their benign counterparts are less clear. This benign-malignant phenomenon is well illustrated in studies of BRAF V600E mutations, which are paradoxically more frequent in benign nevi (∼80%) than in dysplastic nevi (∼60%) or melanoma (∼40%-45%). Similarly, human epidermal growth factor receptor 2 is more commonly overexpressed in ductal carcinoma in situ (∼27%-56%) when compared with invasive breast cancer (∼11%-20%). FGFR3 mutations in bladder cancer also decrease with tumor grade (low-grade tumors, ∼61%; high-grade, ∼11%). “Driver” mutations also occur in nonmalignant settings: TP53 mutations in synovial tissue from rheumatoid arthritis and FGFR3 mutations in seborrheic keratosis. The latter observations suggest that the oncogenicity of these alterations may be tissue context–dependent. The conversion of benign conditions to premalignant disease may involve other genetic events and/or epigenetic reprogramming. Putative driver mutations can also be germline and associated with increased cancer risk (eg, germline RAS or TP53 alterations), but germline FGFR3 or NF2 abnormalities do not predispose to malignancy. We discuss the enigma of genetic “drivers” in benign and premalignant conditions and the implications for prevention strategies and theories of tumorigenesis. PMID:27059373

  20. Barriers to involvement in physical activities of persons with mental illness.

    PubMed

    Shor, Ron; Shalev, Anat

    2016-03-01

    Participating in physical activities could be essential for reducing the multiple risk factors for health problems that persons with severe mental illness (SMI) may suffer. However, people with SMI are significantly less active than the general population. To develop knowledge about factors related to the perceived barriers hindering this population's participation in physical activities and the benefits this participation would have, a study was conducted in Israel with 86 people with mental illness living in community mental health facilities prior to their participation in a health promotion program. A mixed method was implemented and included: a scale designed to measure participants' perceptions of the barriers to and benefits of involvement in physical activities; instruments focusing on bio-psycho-social factors that may affect the level of barriers experienced; and personal interviews. The findings revealed high ranking for accessibility barriers hindering the participation in physical activities. Bio-psycho-social factors stemming from the participants' mental health, such as level of depression, were correlated with higher ranking of accessibility barriers. Bio-psycho-social factors reflecting positive mental health and health, such as positive appraisal of body weight, were correlated with lower ranking of accessibility barriers. Other barriers may include organizational and broader systemic barriers in the mental health facilities where the participants reside. These findings illuminate the need to consider the unique challenges that persons with mental illness may face in any attempt to advance their involvement in physical activity. PMID:25204451

  1. Differential involvement of amygdala and cortical NMDA receptors activation upon encoding in odor fear memory.

    PubMed

    Hegoburu, Chloé; Parrot, Sandrine; Ferreira, Guillaume; Mouly, Anne-Marie

    2014-12-01

    Although the basolateral amygdala (BLA) plays a crucial role for the acquisition of fear memories, sensory cortices are involved in their long-term storage in rats. However, the time course of their respective involvement has received little investigation. Here we assessed the role of the glutamatergic N-methyl-d-aspartate (NMDA) receptors in the BLA and olfactory cortex at discrete moments of an odor fear conditioning session. We showed that NMDA receptors in BLA are critically involved in odor fear acquisition during the first association but not during the next ones. In the cortex, NMDA receptor activation at encoding is not necessary for recent odor fear memory while its role in remote memory storage needs further investigation. PMID:25403452

  2. Endogenous Ligand for GPR120, Docosahexaenoic Acid, Exerts Benign Metabolic Effects on the Skeletal Muscles via AMP-activated Protein Kinase Pathway*

    PubMed Central

    Kim, Nami; Lee, Jung Ok; Lee, Hye Jeong; Kim, Hyung Ip; Kim, Joong Kwan; Lee, Yong Woo; Lee, Soo Kyung; Kim, Su Jin; Park, Sun Hwa; Kim, Hyeon Soo

    2015-01-01

    Docosahexaenoic acid (DHA) is an endogenous ligand of G protein-coupled receptor 120 (GPR120). However, the mechanisms underlying DHA action are poorly understood. In this study, DHA stimulated glucose uptake in the skeletal muscles in an AMP-activated protein kinase (AMPK)-dependent manner. GPR120-mediated increase in intracellular Ca2+ was critical for DHA-mediated AMPK phosphorylation and glucose uptake. In addition, DHA stimulated GLUT4 translocation AMPK-dependently. Inhibition of AMPK and Ca2+/calmodulin-dependent protein kinase kinase blocked DHA-induced glucose uptake. DHA and GW9508, a GPR120 agonist, increased GPR120 expression. DHA-mediated glucose uptake was not observed in GPR120 knockdown conditions. DHA increased AMPK phosphorylation, glucose uptake, and intracellular Ca2+ concentration in primary cultured myoblasts. Taken together, these results indicated that the beneficial metabolic role of DHA was attributed to its ability to regulate glucose via the GPR120-mediated AMPK pathway in the skeletal muscles. PMID:26134561

  3. Staying in or moving away from structured activities: Explanations involving parents and peers.

    PubMed

    Persson, Andreas; Kerr, Margaret; Stattin, Håkan

    2007-01-01

    Adolescent participation in structured activities, meaning those with adult leaders, regular meetings, and skill-building activities, is related to good adjustment. Participation in unstructured, unsupervised, peer-oriented activities is related to poor adjustment. Structured activity participation is high in early adolescence and then declines, raising the question of why youths leave structured activities. The authors examined explanations involving parents and peers. They used longitudinal data from 861 youths (ages 13-17 years). Results showed that, compared with youths who stayed in structured activities, those who switched to hanging out on the streets were less likely to have peers in structured activities and had less positive feelings about the home context and more negative interactions with parents. In addition, delinquency predicted switching to hanging out in the streets and never joining structured activities in the first place. The results concerning parents support a theoretical explanation of how parents might unintentionally affect youths' leisure choices. Furthermore, the authors found some indications that positive feelings at home might protect youths who switch from structured activities to hanging out on the streets from increases in delinquency. PMID:17201519

  4. Involving postgraduate's students in undergraduate small group teaching promotes active learning in both

    PubMed Central

    Kalra, Ruchi; Modi, Jyoti Nath; Vyas, Rashmi

    2015-01-01

    Background: Lecture is a common traditional method for teaching, but it may not stimulate higher order thinking and students may also be hesitant to express and interact. The postgraduate (PG) students are less involved with undergraduate (UG) teaching. Team based small group active learning method can contribute to better learning experience. Aim: To-promote active learning skills among the UG students using small group teaching methods involving PG students as facilitators to impart hands-on supervised training in teaching and managerial skills. Methodology: After Institutional approval under faculty supervision 92 UGs and 8 PGs participated in 6 small group sessions utilizing the jigsaw technique. Feedback was collected from both. Observations: Undergraduate Feedback (Percentage of Students Agreed): Learning in small groups was a good experience as it helped in better understanding of the subject (72%), students explored multiple reading resources (79%), they were actively involved in self-learning (88%), students reported initial apprehension of performance (71%), identified their learning gaps (86%), team enhanced their learning process (71%), informal learning in place of lecture was a welcome change (86%), it improved their communication skills (82%), small group learning can be useful for future self-learning (75%). Postgraduate Feedback: Majority performed facilitation for first time, perceived their performance as good (75%), it was helpful in self-learning (100%), felt confident of managing students in small groups (100%), as facilitator they improved their teaching skills, found it more useful and better identified own learning gaps (87.5%). Conclusions: Learning in small groups adopting team based approach involving both UGs and PGs promoted active learning in both and enhanced the teaching skills of the PGs. PMID:26380201

  5. Physical, Cognitive, Social, and Emotional Mediators of Activity Involvement and Health in Later Life.

    PubMed

    Matz-Costa, Christina; Carr, Dawn C; McNamara, Tay K; James, Jacquelyn Boone

    2016-10-01

    The current study tests the indirect effect of activity-related physical activity, cognitive activity, social interaction, and emotional exchange on the relationship between activity involvement and health (physical and emotional) in later life. Longitudinal data from the Health and Retirement Study (N = 5,442) were used to estimate a series of linear regression models. We found significant indirect effects for social interaction and benefit to others (emotional exchange) on emotional health (depressive symptoms) and indirect effects for use of body and benefit to others (physical) on physical health (frailty). The most potent indirect effect associated with emotional and physical health was experienced by those engaged in all four domains (use of body, use of mind, social interaction, and benefit to others). While effect sizes are small and results should be interpreted with caution, findings shed light on ways in which public health interventions aimed toward increasing role engagement in later life could be improved. PMID:26429863

  6. Involvement of NADPH oxidases in suppression of cyclooxygenase-2 promoter-dependent transcriptional activities by sesamol

    PubMed Central

    Shimizu, Satomi; Ishigamori, Rikako; Fujii, Gen; Takahashi, Mami; Onuma, Wakana; Terasaki, Masaru; Yano, Tomohiro; Mutoh, Michihiro

    2015-01-01

    Cyclooxygenase-2 (COX-2) has been shown to play an important role in colon carcinogenesis. Moreover, one of the components of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, NADPH oxidase 1 (NOX1), dominantly expressed in the colon, is implicated in the pathogenesis of colon cancer. We have reported that sesamol, one of the lignans in sesame seeds, suppressed COX-2 gene transcriptional activity in human colon cancer cells, and also suppressed intestinal polyp formation in Apc-mutant mice. In the present study, we investigated the involvement of NADPH oxidase in the inhibition of COX-2 transcriptional activity by sesamol. We found that several NADPH oxidase inhibitors, such as apocynin, showed suppressive effects on COX-2 transcriptional activity. Moreover, sesamol significantly suppressed NOX1 mRNA levels in a dose-dependent manner. In addition, we demonstrated that knockdown of NOX1 successfully suppressed COX-2 transcriptional activity. These results suggest that inhibition of NADPH oxidase, especially NOX1, may be involved in the mechanism of the suppression of COX-2 transcriptional activity by sesamol. PMID:25759517

  7. Effect of an Activated Platelet Concentrate on Differentiated Cells Involved in Tissue Healing.

    PubMed

    Brini, Anna T; Ceci, Caterina; Taschieri, Silvio; Niada, Stefania; Lolato, Alessandra; Giannasi, Chiara; Mortellaro, Carmen; Del Fabbro, Massimo

    2016-05-01

    Tissue healing is a complex process involving several players such as cells and growth factors released from platelets upon activation. Today, platelet concentrates (PCs) are used in many different medical fields including oral, orthopaedic, and reconstructive surgery since they allow growth factors delivery to the injured site, aiming at enhancing tissue regeneration. The purpose of this in vitro study was to evaluate the effect of the acellular plasma of an activated platelet concentrate obtained using a manual protocol, on the proliferation, and biological activity of differentiated cells involved in tissue healing. Human osteoblasts and dermal fibroblasts were grown in serum-free medium supplemented with PC derived from several donors. Human osteoblast and human dermal fibroblast proliferation was assessed by MTT test after 7 days and cells were count up to 12-day incubation. Human osteoblast osteo-differentiation was tested after 7 and 14-day incubation by alkaline phosphatase assay. The addition of PC to the culture medium caused an increased proliferation with respect to cells grown in standard condition. The results of the present study suggest that PC supports the proliferation of terminally differentiated cells involved in wound healing and tissue regeneration, confirming its beneficial clinical application in regenerative therapies. PMID:27054419

  8. [Radiotherapy of benign intracranial tumors].

    PubMed

    Delannes, M; Latorzeff, I; Chand, M E; Huchet, A; Dupin, C; Colin, P

    2016-09-01

    Most of the benign intracranial tumors are meningiomas, vestibular schwannomas, pituitary adenomas, craniopharyngiomas, and glomus tumors. Some of them grow very slowly, and can be observed without specific treatment, especially if they are asymptomatic. Symptomatic or growing tumors are treated by surgery, which is the reference treatment. When surgery is not possible, due to the location of the lesion, or general conditions, radiotherapy can be applied, as it is if there is a postoperative growing residual tumor, or a local relapse. Indications have to be discussed in polydisciplinary meetings, with precise evaluation of the benefit and risks of the treatments. The techniques to be used are the most modern ones, as multimodal imaging and image-guided radiation therapy. Stereotactic treatments, using fractionated or single doses depending on the size or the location of the tumors, are commonly realized, to avoid as much a possible the occurrence of late side effects. PMID:27523417

  9. Management of Benign Prostatic Hyperplasia.

    PubMed

    Kim, Eric H; Larson, Jeffrey A; Andriole, Gerald L

    2016-01-01

    Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) commonly affect older men. Age-related changes associated with metabolic disturbances, changes in hormone balance, and chronic inflammation may cause BPH development. The diagnosis of BPH hinges on a thorough medical history and focused physical examination, with attention to other conditions that may be causing LUTS. Digital rectal examination and urinalysis should be performed. Other testing may be considered depending on presentation of symptoms, including prostate-specific antigen, serum creatinine, urine cytology, imaging, cystourethroscopy, post-void residual, and pressure-flow studies. Many medical and surgical treatment options exist. Surgery should be reserved for patients who either have failed medical management or have complications from BPH, such as recurrent urinary tract infections, refractory urinary retention, bladder stones, or renal insufficiency as a result of obstructive uropathy. PMID:26331999

  10. Forest soil metagenome gene cluster involved in antifungal activity expression in Escherichia coli.

    PubMed

    Chung, Eu Jin; Lim, He Kyoung; Kim, Jin-Cheol; Choi, Gyung Ja; Park, Eun Jin; Lee, Myung Hwan; Chung, Young Ryun; Lee, Seon-Woo

    2008-02-01

    Using two forest soils, we previously constructed two fosmid libraries containing 113,700 members in total. The libraries were screened to select active antifungal clones using Saccharomyces cerevisiae as a target fungus. One clone from the Yuseong pine tree rhizosphere soil library, pEAF66, showed S. cerevisiae growth inhibition. Despite an intensive effort, active chemicals were not isolated. DNA sequence analysis and transposon mutagenesis of pEAF66 revealed 39 open reading frames (ORFs) and indicated that eight ORFs, probably in one transcriptional unit, might be directly involved in the expression of antifungal activity in Escherichia coli. The deduced amino acid sequences of eight ORFs were similar to those of the core genes encoding type II family polyketide synthases, such as the acyl carrier protein (ACP), ACP synthases, aminotransferase, and ACP reductase. The gene cluster involved in antifungal activity was similar in organization to the putative antibiotic production locus of Pseudomonas putida KT2440, although we could not select a similar active clone from the KT2440 genomic DNA library in E. coli. ORFs encoding ATP binding cassette transporters and membrane proteins were located at both ends of the antifungal gene cluster. Upstream ORFs encoding an IclR family response regulator and a LysR family response regulator were involved in the positive regulation of antifungal gene expression. Our results suggested the metagenomic approach as an alternative to search for novel antifungal antibiotics from unculturable soil bacteria. This is the first report of an antifungal gene cluster obtained from a soil metagenome using S. cerevisiae as a target fungus. PMID:18065615

  11. Characterization of bimetallic Fe/Pd nanoparticles by grape leaf aqueous extract and identification of active biomolecules involved in the synthesis.

    PubMed

    Luo, Fang; Yang, Die; Chen, Zuliang; Megharaj, Mallavarapu; Naidu, Ravi

    2016-08-15

    This paper reports the detailed composition and morphology of one-step green synthesized bimetallic Fe/Pd nanoparticles (NPs) using grape leaf aqueous extract and identification of active biomolecules involved in the synthesis employing various techniques. Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM) revealed that Fe/Pd NPs were polydispersed and quasi-spherical with a diameter ranging from 2 to 20nm. X-ray Photoelectron Spectroscopy (XPS) and Energy Dispersive X-ray Spectroscopy (EDS) provided evidence for the composition of Fe and Pd and for their species existing on the surface of Fe/Pd NPs. In addition, biomolecules in the grape leaf aqueous extract were identified but their functions are still unclear. Biomolecules in the aqueous extract such as methoxy-phenyl-oxime, N-benzoyl-2-cyano-histamine, 2-ethyl-phenol, 1,2-benzenediol, β-hydroxyquebracamine, hydroquinone, 2-methoxy-4-vinylphenol, 5-methyl-2-furancarboxaldehyde, 4-(3-hydroxybutyl)-3,5,5-trimethyl-2-cyclohexen and some polyphenolic compounds were identified as reducing and capping agents, which were studied by Chromatography-Mass Spectroscopy (GC-MS), XPS and Fourier Transform Infrared Spectroscopy (FTIR). Our finding suggests a new insight into cost-effective, simple, and environmentally benign production of bimetallic Fe/Pd NPs. PMID:27110966

  12. Beyond participation: the association between school extracurricular activities and involvement in violence across generations of immigration.

    PubMed

    Jiang, Xin; Peterson, Ruth D

    2012-03-01

    Participation in extracurricular activities is purported to protect the broad spectrum of youth from a host of behavioral risks. Yet, empirical research on the extent to which this assumption holds for involvement in violence by immigrant youth is limited. Thus, using data for 13,236 (51.8% female) adolescents from the National Longitudinal Study of Adolescent Health, this study explores how the relationship between extracurricular activities and youth violence varies by type of extracurricular activity profile (sports alone, non-sports alone, and a combination of sports and non-sports) and by generations of immigration (first, second, and third-plus). The sample is composed of 9.3% (n = 1,233) first-generation youth, 15.7% (n = 2,080) second generation, and 74.9% (n = 9,923) third-plus generation. The results reveal that adolescents from the third-plus generation (i.e., non-immigrant youth) who participate in non-sports alone or sports plus non-sports have lower odds of involvement in violence than adolescents from the same generation who do not participate in extracurricular activities. However, for first- and second-generation adolescents, participation in extracurricular activities is associated with higher rather than lower odds of violence compared to their non-participating counterparts. These findings challenge the viewpoint that participation in mainstream extracurricular activities as afforded by US schools is equally beneficial for all youth. They also call for additional research that explores why immigrant youth are less likely than non-immigrant youth to gain violence-reducing benefits when they participate in extracurricular activities. PMID:22167574

  13. Involvement of Activated Oxygen in Nitrate-Induced Senescence of Pea Root Nodules.

    PubMed Central

    Escuredo, P. R.; Minchin, F. R.; Gogorcena, Y.; Iturbe-Ormaetxe, I.; Klucas, R. V.; Becana, M.

    1996-01-01

    The effect of short-term nitrate application (10 mM, 0-4 d) on nitrogenase (N2ase) activity, antioxidant defenses, and related parameters was investigated in pea (Pisum sativum L. cv Frilene) nodules. The response of nodules to nitrate comprised two stages. In the first stage (0-2 d), there were major decreases in N2ase activity and N2ase-linked respiration and concomitant increases in carbon cost of N2ase and oxygen diffusion resistance of nodules. There was no apparent oxidative damage, and the decline in N2ase activity was, to a certain extent, reversible. The second stage (>2 d) was typical of a senescent, essentially irreversible process. It was characterized by moderate increases in oxidized proteins and catalytic Fe and by major decreases in antioxidant enzymes and metabolites. The restriction in oxygen supply to bacteroids may explain the initial decline in N2ase activity. The decrease in antioxidant protection is not involved in this process and is not specifically caused by nitrate, since it also occurs with drought stress. However, comparison of nitrate- and drought-induced senescence shows an important difference: there is no lipid degradation or lipid peroxide accumulation with nitrate, indicating that lipid peroxidation is not necessarily involved in nodule senescence. PMID:12226252

  14. The spectrum of nasal involvement in systemic lupus erythematosus and its association with the disease activity.

    PubMed

    Kusyairi, K A; Gendeh, B S; Sakthiswary, R; Shaharir, S S; Haizlene, A H; Yusof, K H

    2016-04-01

    The purpose of this study was to determine the spectrum of nasal involvement in systemic lupus erythematosus (SLE) and its association with the disease activity of SLE based on the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). This was a cross-sectional and observational study involving 73 stable SLE patients. All subjects were evaluated for the SLEDAI scores and had nasal endoscopic examination. The most commonly reported symptom was nasal congestion (31.5%) followed by nasal itchiness (26.0%), runny nose (20.5%) and nasal dryness (19.2%). Almost half (42.9%) of the subjects had nasal mucosal abnormalities, which included mucositis, crusting, ulceration, bifid middle turbinate, septal spur, Jacobson's organ, deviated nasal septum, bilateral inferior turbinate hypertrophy, everted uncinate process, nasopharynx cleft and torus palatinus. The median SLEDAI score for subjects with nasal symptoms was significantly higher than subjects without nasal symptoms (p < 0.05). Similarly, subjects with moderate to high activity (SLEDAI scores of 6-19) had a significantly higher frequency of both nasal symptoms and nasal mucosal abnormalities (p < 0.05) compared to subjects with no to mild activity (SLEDAI scores of 0-5). PMID:26657735

  15. An Initial Investigation of Sexual Minority Youth Involvement in School-Based Extracurricular Activities

    PubMed Central

    Russell, Stephen T.

    2012-01-01

    Sexual minority youth are at risk for negative school-based experiences and poor academic outcomes. Yet, little is known about their experiences in positive school-based contexts. Using the National Longitudinal Study of Adolescent Health (1,214 sexual minority and 11,427 heterosexual participants), this study compared participation rates in, predictors of, and outcomes associated with three types of school-based extracurricular activities - sports, arts, and school clubs - by sexual orientation and gender. Findings revealed several significant sexual orientation and gender differences in participation rates in school-based sports, clubs, and arts activities. Further, findings suggested that the outcomes associated with extracurricular activity involvement do not differ by sexual orientation and gender; however, predictors of participation in these domains varied across groups. PMID:24187476

  16. Psychosocial factors associated with youth involvement in community activities promoting heart health.

    PubMed

    Altman, D G; Feighery, E; Robinson, T N; Haydel, K F; Strausberg, L; Lorig, K; Killen, J D

    1998-08-01

    This study examined factors that influence youth participation in heart disease prevention activities among 2,609 ninth graders in six inner-city public high schools. Constructs derived from social cognitive, empowerment, and community development theories informed the conceptual framework employed. Study participants were diverse with respect to gender, ethnicity, parent education, acculturation, and academic achievement. Perceived incentive value, self-efficacy, outcome expectancies, sense of community, and perceived policy control were all significantly associated with participation in community activities promoting heart health. In multivariate analyses, perceived incentive value, defined as the extent to which participants valued a heart-healthy environment, was most strongly associated with community participation, accounting for 11.9% of the total variance. These findings have implications for designing school curricula and after-school and community programs targeting adolescents' involvement in health advocacy activities. PMID:9690106

  17. Oclacitinib (APOQUEL®) is a novel Janus kinase inhibitor with activity against cytokines involved in allergy

    PubMed Central

    Gonzales, A J; Bowman, J W; Fici, G J; Zhang, M; Mann, D W; Mitton-Fry, M

    2014-01-01

    Janus kinase (JAK) enzymes are involved in cell signaling pathways activated by various cytokines dysregulated in allergy. The objective of this study was to determine whether the novel JAK inhibitor oclacitinib could reduce the activity of cytokines implicated in canine allergic skin disease. Using isolated enzyme systems and in vitro human or canine cell models, potency and selectivity of oclacitinib was determined against JAK family members and cytokines that trigger JAK activation in cells. Oclacitinib inhibited JAK family members by 50% at concentrations (IC50's) ranging from 10 to 99 nm and did not inhibit a panel of 38 non-JAK kinases (IC50's > 1000 nm). Oclacitinib was most potent at inhibiting JAK1 (IC50 = 10 nm). Oclacitinib also inhibited the function of JAK1-dependent cytokines involved in allergy and inflammation (IL-2, IL-4, IL-6, and IL-13) as well as pruritus (IL-31) at IC50's ranging from 36 to 249 nm. Oclacitinib had minimal effects on cytokines that did not activate the JAK1 enzyme in cells (erythropoietin, granulocyte/macrophage colony-stimulating factor, IL-12, IL-23; IC50's > 1000 nm). These results demonstrate that oclacitinib is a targeted therapy that selectively inhibits JAK1-dependent cytokines involved in allergy, inflammation, and pruritus and suggests these are the mechanisms by which oclacitinib effectively controls clinical signs associated with allergic skin disease in dogs. PMID:24495176

  18. Activated alveolar macrophage and lymphocyte alveolitis in extrathoracic sarcoidosis without radiological mediastinopulmonary involvement

    SciTech Connect

    Wallaert, B.; Ramon, P.; Fournier, E.C.; Prin, L.; Tonnel, A.B.; Voisin, C.

    1986-01-01

    Cellular characteristics of BAL were investigated in 18 patients with proved extrathoracic sarcoidosis (that is, sarcoidosis that affected the skin, eyes, parotid glands, stomach, nose, kidneys, or meninges) without clinical or radiological mediastinopulmonary involvement. Computed tomography of the thorax was performed on five patients: four patients were normal, and one had enlarged lymph nodes (these enlargements were not detectable on the patient's chest roentgenogram). The results of pulmonary function tests were normal in all patients. The total BAL cell count did not differ significantly between controls and patients. Abnormal percentages of alveolar lymphocytes (from 18 to 87%) were noted in 15 out of 18 patients. SACE levels were normal in 15 patients. No pulmonary gallium uptake was detected. The chemiluminescence of AM's, whether spontaneous or PMA induced, was increased in five out of seven patients. The percentages of T3+ lymphocytes in sarcoidosis patients did not significantly differ from those in controls. The T4+:T8+ ratio was normal in four patients and slightly increased in one. Follow-up of patients showed that alveolar lymphocytosis is as lasting as extrathoracic involvement. Our data demonstrate increased percentages of lymphocytes and activated AM's in the BAL of patients with extrathoracic sarcoidosis. This may be due to the initial involvement of the respiratory tract in extrathoracic sarcoidosis or to the diffusion of activated macrophages and lymphocytes from an extrathoracic site into the lung.

  19. Secretion of a lysophospholipase D activity by adipocytes: involvement in lysophosphatidic acid synthesis

    PubMed Central

    Gesta, Stéphane; Simon, Marie-Françoise; Rey, Astrid; Sibrac, David; Girard, Alexia; Lafontan, Max; Valet, Philippe; Saulnier-Blache, Jean Sébastien

    2002-01-01

    The aim of the present work was to depict the metabolic pathways involved in extra-cellular production of lysophosphatidic acid (LPA) by adipocytes. LPA was followed by quantifying the accumulation of LPA in the incubation medium (conditioned medium: CM) of 3T3F442A adipocytes, or human adipose tissue explants, using a radioenzymatic assay. Surprisingly, after separation from the cells, the amount of LPA present in CM could significantly be increased by further incubation at 37°C. This suggested the presence of a LPA-synthesizing activity (LPA-SA) in CM. LPA-SA appeared as a soluble activity which was inhibited by divalent ion chelators: EDTA and phenanthrolin. The effect of EDTA was preferentially reverted by CoCl2, as described for a lysophospholipase D- (lyso-PLD) activity previously identified in rat plasma. LPA concentration could also be increased by treatment with a bacterial PLD, demonstrating the presence of PLD-sensitive LPA-precursors (mainly lysophosphatidylcholine) in adipocyte CM. LPA-SA could be increased by addition of exogenous lysophosphatidylcholine, lysophosphatidylglycerol, or lyso-platelet activating factor, demonstrating that LPA-SA resulted from the action of a lyso-PLD. LPA-SA was not inhibited, but rather activated, by primary alcohol (ethanol and 1-butanol), suggesting that adipocyte lyso-PLD was not a classical PLD. Finally, LPA-SA was found to be weaker in CM of undifferentiated adipocyte (preadipocytes) as compared to CM of differentiated adipocytes. In conclusion, our results reveal the existence of a secreted lyso-PLD activity regulated during adipocyte-differentiation and involved in extra-cellular production of synthesis of LPA by adipocytes. PMID:12032165

  20. Anticancer Activities of Pterostilbene-Isothiocyanate Conjugate in Breast Cancer Cells: Involvement of PPARγ

    PubMed Central

    Nikhil, Kumar; Sharan, Shruti; Singh, Abhimanyu K.; Chakraborty, Ajanta; Roy, Partha

    2014-01-01

    Trans-3,5-dimethoxy-4′-hydroxystilbene (PTER), a natural dimethylated analog of resveratrol, preferentially induces certain cancer cells to undergo apoptosis and could thus have a role in cancer chemoprevention. Peroxisome proliferator-activated receptor γ (PPARγ), a member of the nuclear receptor superfamily, is a ligand-dependent transcription factor whose activation results in growth arrest and/or apoptosis in a variety of cancer cells. Here we investigated the potential of PTER-isothiocyanate (ITC) conjugate, a novel class of hybrid compound (PTER-ITC) synthesized by appending an ITC moiety to the PTER backbone, to induce apoptotic cell death in hormone-dependent (MCF-7) and -independent (MDA-MB-231) breast cancer cell lines and to elucidate PPARγ involvement in PTER-ITC action. Our results showed that when pre-treated with PPARγ antagonists or PPARγ siRNA, both breast cancer cell lines suppressed PTER-ITC-induced apoptosis, as determined by annexin V/propidium iodide staining and cleaved caspase-9 expression. Furthermore, PTER-ITC significantly increased PPARγ mRNA and protein levels in a dose-dependent manner and modulated expression of PPARγ-related genes in both breast cancer cell lines. This increase in PPARγ activity was prevented by a PPARγ-specific inhibitor, in support of our hypothesis that PTER-ITC can act as a PPARγ activator. PTER-ITC-mediated upregulation of PPARγ was counteracted by co-incubation with p38 MAPK or JNK inhibitors, suggesting involvement of these pathways in PTER-ITC action. Molecular docking analysis further suggested that PTER-ITC interacted with 5 polar and 8 non-polar residues within the PPARγ ligand-binding pocket, which are reported to be critical for its activity. Collectively, our observations suggest potential applications for PTER-ITC in breast cancer prevention and treatment through modulation of the PPARγ activation pathway. PMID:25119466

  1. The effects of adiponectin and metformin on prostate and colon neoplasia involve activation of AMP-activated protein kinase.

    PubMed

    Zakikhani, Mahvash; Dowling, Ryan J O; Sonenberg, Nahum; Pollak, Michael N

    2008-10-01

    Population studies provide evidence that obesity and insulin resistance are associated not only with elevated serum insulin levels and reduced serum adiponectin levels but also with increased risk of aggressive prostate and colon cancer. We show here that adiponectin activates AMP-activated protein kinase (AMPK) in colon (HT-29) and prostate (PC-3) cancer cells. These results are consistent with prior observations in myocytes, but we show that in epithelial cancer cells AMPK activation is associated with reduction in mammalian target of rapamycin activation as estimated by Ser(2448) phosphorylation, with reduction in p70S6 kinase activation as estimated by Thr(389) phosphorylation, with ribosomal protein S6 activation as estimated by Ser(235/236) phosphorylation, with reduction in protein translation as estimated by [(35)S]methionine incorporation, and with growth inhibition. Adiponectin-induced growth inhibition is significantly attenuated when AMPK level is reduced using small interfering RNA, indicating that AMPK is involved in mediating the antiproliferative action of this adipokine. Thus, adiponectin has the characteristics of a AMPK-dependent growth inhibitor that is deficient in obesity, and this may contribute to the adverse effects of obesity on neoplastic disease. Furthermore, metformin was observed to activate AMPK and to have growth inhibitory actions on prostate and colon cancer cells, suggesting that this compound may be of particular value in attenuating the adverse effects of obesity on neoplasia. PMID:19138981

  2. Maturation of suprathreshold auditory nerve activity involves cochlear CGRP-receptor complex formation.

    PubMed

    Dickerson, Ian M; Bussey-Gaborski, Rhiannon; Holt, Joseph C; Jordan, Paivi M; Luebke, Anne E

    2016-07-01

    In adult animals, the neuropeptide calcitonin gene-related peptide (CGRP) is contained in cochlear efferent fibers projecting out to the cochlea, and contributes to increased suprathreshold sound-evoked activity in the adult auditory nerve. Similarly, CGRP applied to the lateral-line organ (hair cell organ) increases afferent nerve activity in adult frogs (post-metamorphic day 30), yet this increase is developmentally delayed from post-metamorphic day 4-30. In this study, we discovered that there was also a developmental delay in increased suprathreshold sound-evoked activity auditory nerve between juvenile and adult mice similar to what had been observed previously in frog. Moreover, juvenile mice with a targeted deletion of the αCGRP gene [CGRP null (-/-)] did not show a similar developmental increase in nerve activity, suggesting CGRP signaling is involved. This developmental delay is not due to a delay in CGRP expression, but instead is due to a delay in receptor formation. We observed that the increase in sound-evoked nerve activity is correlated with increased formation of cochlear CGRP receptors, which require three complexed proteins (CLR, RAMP1, RCP) to be functional. CGRP receptor formation in the cochlea was incomplete at 1 month of age (juvenile), but complete by 3 months (adult), which corresponded to the onset of suprathreshold enhancement of sound-evoked activity in wild-type animals. Taken together, these data support a model for cochlear function that is enhanced by maturation of CGRP receptor complexes. PMID:27440744

  3. Involvement of nigral oxytocin in locomotor activity: A behavioral, immunohistochemical and lesion study in male rats.

    PubMed

    Angioni, Laura; Cocco, Cristina; Ferri, Gian-Luca; Argiolas, Antonio; Melis, Maria Rosaria; Sanna, Fabrizio

    2016-07-01

    Oxytocin is involved in the control of different behaviors, from sexual behavior and food consumption to empathy, social and affective behaviors. An imbalance of central oxytocinergic neurotransmission has been also associated with different mental pathologies, from depression, anxiety and anorexia/bulimia to schizophrenia, autism and drug dependence. This study shows that oxytocin may also play a role in the control of locomotor activity. Accordingly, intraperitoneal oxytocin (0.5-2000μg/kg) reduced locomotor activity of adult male rats. This effect was abolished by d(CH2)5Tyr(Me)(2)-Orn(8)-vasotocin, an oxytocin receptor antagonist, given into the lateral ventricles at the dose of 2μg/rat, which was ineffective on locomotor activity. Oxytocin (50-200ng/site) also reduced and d(CH2)5Tyr(Me)(2)-Orn(8)-vasotocin (2μg/site) increased locomotor activity when injected bilaterally into the substantia nigra, a key area in the control of locomotor activity. Conversely, the destruction of nigral neurons bearing oxytocin receptors by the recently characterized neurotoxin oxytocin-saporin injected into the substantia nigra, increased basal locomotor activity. Since oxytocin-saporin injected into the substantia nigra caused a marked reduction of neurons immunoreactive for tyrosine hydroxylase (e.g., nigrostriatal dopaminergic neurons) and for vesicular glutamate transporters VGluT1, VGluT2 and VGluT3 (e.g., glutamatergic neurons), but not for glutamic acid decarboxylase (e.g., GABAergic neurons), together these findings suggest that oxytocin influences locomotor activity by acting on receptors localized presynaptically in nigral glutamatergic nerve terminals (which control the activity of nigral GABAergic efferent neurons projecting to brain stem nuclei controlling locomotor activity), rather than on receptors localized in the cell bodies/dendrites of nigrostriatal dopaminergic neurons. PMID:27189764

  4. The NALP3 inflammasome is involved in neurotoxic prion peptide-induced microglial activation

    PubMed Central

    2012-01-01

    Background Prion diseases are neurodegenerative disorders characterized by the accumulation of an abnormal disease-associated prion protein, PrPSc. In prion-infected brains, activated microglia are often present in the vicinity of PrPSc aggregates, and microglial activation is thought to play a key role in the pathogenesis of prion diseases. Although interleukin (IL)-1β release by prion-induced microglia has been widely reported, the mechanism by which primed microglia become activated and secrete IL-1β in prion diseases has not yet been elucidated. In this study, we investigated the role of the NACHT, LRR and PYD domains-containing protein (NALP)3 inflammasome in IL-1β release from lipopolysaccharide (LPS)-primed microglia after exposure to a synthetic neurotoxic prion fragment (PrP106-126). Methods The inflammasome components NALP3 and apoptosis-associated speck-like protein (ASC) were knocked down by gene silencing. IL-1β production was assessed using ELISA. The mRNA expression of NALP3, ASC, and pro-inflammatory factors was measured by quantitative PCR. Western blot analysis was used to detect the protein level of NALP3, ASC, caspase-1 and nuclear factor-κB. Results We found that that PrP106-126-induced IL-1β release depends on NALP3 inflammasome activation, that inflammasome activation is required for the synthesis of pro-inflammatory and chemotactic factors by PrP106-126-activated microglia, that inhibition of NF-κB activation abrogated PrP106-126-induced NALP3 upregulation, and that potassium efflux and production of reactive oxygen species were implicated in PrP106-126-induced NALP3 inflammasome activation in microglia. Conclusions We conclude that the NALP3 inflammasome is involved in neurotoxic prion peptide-induced microglial activation. To our knowledge, this is the first time that strong evidence for the involvement of NALP3 inflammasome in prion-associated inflammation has been found. PMID:22531291

  5. Lipopolysaccharide-induced Lung Injury Involves the Nitration-mediated Activation of RhoA*

    PubMed Central

    Rafikov, Ruslan; Dimitropoulou, Christiana; Aggarwal, Saurabh; Kangath, Archana; Gross, Christine; Pardo, Daniel; Sharma, Shruti; Jezierska-Drutel, Agnieszka; Patel, Vijay; Snead, Connie; Lucas, Rudolf; Verin, Alexander; Fulton, David; Catravas, John D.; Black, Stephen M.

    2014-01-01

    Acute lung injury (ALI) is characterized by increased endothelial hyperpermeability. Protein nitration is involved in the endothelial barrier dysfunction in LPS-exposed mice. However, the nitrated proteins involved in this process have not been identified. The activation of the small GTPase RhoA is a critical event in the barrier disruption associated with LPS. Thus, in this study we evaluated the possible role of RhoA nitration in this process. Mass spectroscopy identified a single nitration site, located at Tyr34 in RhoA. Tyr34 is located within the switch I region adjacent to the nucleotide-binding site. Utilizing this structure, we developed a peptide designated NipR1 (nitration inhibitory peptide for RhoA 1) to shield Tyr34 against nitration. TAT-fused NipR1 attenuated RhoA nitration and barrier disruption in LPS-challenged human lung microvascular endothelial cells. Further, treatment of mice with NipR1 attenuated vessel leakage and inflammatory cell infiltration and preserved lung function in a mouse model of ALI. Molecular dynamics simulations suggested that the mechanism by which Tyr34 nitration stimulates RhoA activity was through a decrease in GDP binding to the protein caused by a conformational change within a region of Switch I, mimicking the conformational shift observed when RhoA is bound to a guanine nucleotide exchange factor. Stopped flow kinetic analysis was used to confirm this prediction. Thus, we have identified a new mechanism of nitration-mediated RhoA activation involved in LPS-mediated endothelial barrier dysfunction and show the potential utility of “shielding” peptides to prevent RhoA nitration in the management of ALI. PMID:24398689

  6. Lyn is involved in CD24-induced ERK1/2 activation in colorectal cancer

    PubMed Central

    2012-01-01

    Background and aim CD24 expression is associated with human colorectal cancer (CRC). Our previous data indicated that CD24 promoted the proliferation and invasion of colorectal cancer cells through the activation of ERK1/2. Since Src family kinases are frequently deregulated in CRC and closely related to the MAPK signaling pathway, we investigated the impact of Lyn, an important member of SFKs, on CD24-induced ERK1/2 activation in CRC. Methods and Results The interaction of CD24 and Lyn was identified by co-immunoprecipitation (Co-IP) and ectopic expression of CD24-induced Lyn activation. Inhibition of Lyn activation by phosphatase PP2 in SW480CD24cells abrogated CD24-induced invasion. The results of the Co-IP and immunofluorescence assay revealed that overexpression of CD24 enhanced the interaction of Lyn and ERK1/2 and induced the nuclear translocation of Lyn. However, inhibition of Lyn activity attenuated CD24-induced ERK1/2 activation, and depletion of CD24 disrupted Lyn-ERK1/2 interaction. Immunohistochemistry analysis for 202 cases of CRC showed that the expression of both CD24 and Lyn was positively correlated with tumor grade, stage, lymph node and distant metastasis. Patients with lower expression of CD24 or Lyn had a higher survival rate. The Cox multivariate analysis showed that CD24 expression, but not Lyn expression, was an independent prognostic factor of CRC. Conclusions Our results suggest that Lyn is involved in CD24-induced ERK1/2 activation in CRC. The expression of CD24 is associated with activation of Lyn and ERK1/2, which might be a novel mechanism related to CD24-mediated regulation of CRC development. PMID:22731636

  7. AMP-activated protein kinase is involved in perfluorohexanesulfonate -induced apoptosis of neuronal cells.

    PubMed

    Lee, Youn Ju; Choi, So-Young; Yang, Jae-Ho

    2016-04-01

    Perfluorohexanesulfonate (PFHxS), one of the major perfluoroalkyl compounds (PFCs), has been used in a variety of industrial and consumer applications and detected in serum in the general population. This raised a concern over its possible detrimental health effects, including neurotoxic effects. We have previously shown that PFHxS induced neuronal apoptosis via the NMDA receptor-mediated extracellular signal-regulated kinase (ERK) pathway. Recently, it has been reported that AMP-activated protein kinase (AMPK) acts as a key signal molecule in neuronal excitotoxicity as well as providing a neuroprotective function. In the present study, we have examined the involvement of AMPK in PFHxS-induced neuronal apoptosis using neuronal differentiated PC12 cells. PFHxS induced significant increases in intracellular [Ca(2+)] via the NMDA receptor and the L-type voltage-gated calcium channel (L-VGCC). The inhibition of Ca(2+) loading by the NMDA receptor antagonist, MK801 and the L-VGCC blockers, nifedipine and diltiazem significantly reduced PFHxS-induced apoptosis. PFHxS induced sustained activation of AMPK and the inhibition of AMPK activation by compound C and AMPK siRNA significantly reduced PFHxS-induced caspase-3 activity. These results indicate the pro-apoptotic role of AMPK. The activation of AMPK was attenuated by MK801, nifedipine and diltiazem. However, the activation of AMPK was not affected by the ERK inhibitor, PD98059. Likewise, ERK activation was not affected by compound C but was substantially reduced by MK801, nifedipine or diltiazem. This suggests that the activation of AMPK and ERK is regulated by intracellular Ca(2+) loading in distinct pathways. Taken together, PFHxS-induced neuronal apoptosis is mediated by AMPK and ERK pathways, which are distinctly regulated by increased intracellular Ca(2+) via the NMDA receptor and L-VGCC. PMID:26826296

  8. Involvement of microglia activation in the lead induced long-term potentiation impairment.

    PubMed

    Liu, Ming-Chao; Liu, Xin-Qin; Wang, Wen; Shen, Xue-Feng; Che, Hong-Lei; Guo, Yan-Yan; Zhao, Ming-Gao; Chen, Jing-Yuan; Luo, Wen-Jing

    2012-01-01

    Exposure of Lead (Pb), a known neurotoxicant, can impair spatial learning and memory probably via impairing the hippocampal long-term potentiation (LTP) as well as hippocampal neuronal injury. Activation of hippocampal microglia also impairs spatial learning and memory. Thus, we raised the hypothesis that activation of microglia is involved in the Pb exposure induced hippocampal LTP impairment and neuronal injury. To test this hypothesis and clarify its underlying mechanisms, we investigated the Pb-exposure on the microglia activation, cytokine release, hippocampal LTP level as well as neuronal injury in in vivo or in vitro model. The changes of these parameters were also observed after pretreatment with minocycline, a microglia activation inhibitor. Long-term low dose Pb exposure (100 ppm for 8 weeks) caused significant reduction of LTP in acute slice preparations, meanwhile, such treatment also significantly increased hippocampal microglia activation as well as neuronal injury. In vitro Pb-exposure also induced significantly increase of microglia activation, up-regulate the release of cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and inducible nitric oxide synthase (iNOS) in microglia culture alone as well as neuronal injury in the co-culture with hippocampal neurons. Inhibiting the microglia activation with minocycline significantly reversed the above-mentioned Pb-exposure induced changes. Our results showed that Pb can cause microglia activation, which can up-regulate the level of IL-1β, TNF-α and iNOS, these proinflammatory factors may cause hippocampal neuronal injury as well as LTP deficits. PMID:22952811

  9. Caveolin-1 overexpression in benign and malignant salivary gland tumors.

    PubMed

    Jaafari-Ashkavandi, Zohreh; Ashraf, Mohammad Javad; Nazhvani, Ali Dehghani; Azizi, Zahra

    2016-02-01

    Caveolin-1, a tyrosine-phosphorylated protein, is supposed to have different regulatory roles as promoter or suppressor in many human cancers. However, no published study concerned its expression in benign and malignant salivary gland tumors. The aim of this study was to evaluate and compare the expression of Cav-1 in the most common benign and malignant salivary gland tumors and evaluate its correlation with proliferation activity. In this cross-sectional retrospective study, immunohistochemical expression of caveolin-1 and Ki67 were evaluated in 49 samples, including 11 normal salivary glands, 15 cases of pleomorphic adenoma (PA), 13 adenoid cystic carcinomas (AdCC), and 10 mucoepidermoid carcinomas (MEC). The expression of Cav-1 was seen in 18 % of normal salivary glands and 85 % of tumors. The immunoreaction in the tumors was significantly higher than normal tissues (P = 0.001), but the difference between benign and malignant tumors was not significant (P = 0.07). Expression of Cav-1 was correlated with Ki67 labeling index in PAs, but not in malignant tumors. Cav-1 expression was not in association with tumor size and stage. Overexpression of Cav-1 was found in salivary gland tumors in comparison with normal tissues, but no significant difference was observed between benign and malignant tumors. Cav-1 was inversely correlated with proliferation in PA. Therefore, this marker may participate in tumorigenesis of salivary gland tumors and may be a potential biomarker for cancer treatments. PMID:26323261

  10. The benefits of in-group contact through physical activity involvement for health and well-being among Korean immigrants

    PubMed Central

    Kim, Junhyoung; Heo, Jinmoo; Kim, Jun

    2014-01-01

    This qualitative study is designed to examine the benefits of physical activity involvement with members of the same ethnic group. For this study, Korean immigrants who were members of Korean physical activity clubs such as badminton and tennis were selected as participants. Using a constructive grounded theory methodology, three themes were identified as benefits of physical activity involvement: (1) the experience of psychological well-being, (2) the creation of a unique cultural world, and (3) the facilitation of physical activity involvement. The findings of this study suggest that Korean immigrant participants gained various social, cultural, and psychological benefits by engaging in activities with other Korean immigrants. PMID:24875239

  11. The benefits of in-group contact through physical activity involvement for health and well-being among Korean immigrants.

    PubMed

    Kim, Junhyoung; Heo, Jinmoo; Kim, Jun

    2014-01-01

    This qualitative study is designed to examine the benefits of physical activity involvement with members of the same ethnic group. For this study, Korean immigrants who were members of Korean physical activity clubs such as badminton and tennis were selected as participants. Using a constructive grounded theory methodology, three themes were identified as benefits of physical activity involvement: (1) the experience of psychological well-being, (2) the creation of a unique cultural world, and (3) the facilitation of physical activity involvement. The findings of this study suggest that Korean immigrant participants gained various social, cultural, and psychological benefits by engaging in activities with other Korean immigrants. PMID:24875239

  12. Tyrosine phosphorylation and protein degradation control the transcriptional activity of WRKY involved in benzylisoquinoline alkaloid biosynthesis.

    PubMed

    Yamada, Yasuyuki; Sato, Fumihiko

    2016-01-01

    Benzylisoquinoline alkaloids (BIQ) are among the most structurally diverse and pharmaceutically valuable secondary metabolites. A plant-specific WRKY-type transcription factor, CjWRKY1, was isolated from Coptis japonica and identified as a transcriptional activator of BIQ biosynthesis. However, the expression of CjWRKY1 gene alone was not sufficient for the activation of genes encoding biosynthetic enzymes. Here, we report the importance of post-translational regulation of CjWRKY1 in BIQ biosynthesis. First, we detected the differential accumulation of CjWRKY1 protein in two cell lines with similar CjWRKY1 gene expression but different levels of accumulated alkaloids. Further investigation of the WRKY protein identified the phosphorylation of the WRKYGQK core domain at Y115. The CjWRKY(Y115E) phosphorylation-mimic mutant showed loss of nuclear localization, DNA-binding activity, and transactivation activity compared to wild-type CjWRKY1. Rapid degradation of the CjWRKY1 protein was also confirmed following treatment with inhibitors of the 26S proteasome and protease inhibitors. The existence of two independent degradation pathways as well as protein phosphorylation suggests the fine-tuning of CjWRKY1 activities is involved in the regulation of biosynthesis of BIQs. PMID:27552928

  13. Ca2+-calcineurin signaling is involved in norepinephrine-induced cardiac fibroblasts activation

    PubMed Central

    Tian, Chun-Jing; Pang, Xiao

    2015-01-01

    Cardiac fibroblasts (CFs) activation plays a vital role in cardiac fibrosis. There are some studies demonstrate that norepinephrine (NE, an α1-adrenoceptor agonist) induced CFs proliferation. But whether Ca2+-calcineurin, a signaling concerned with growth and differentiation in various cell types, is participated in NE-induced CFs activation is unclear. In present study, we determined NE-induced CFs proliferation and differentiation, synthesis of collagen, and calcineurin (CaN) activity, and the effects of phentolamine (Phen, an α1-adrenoceptor antagonist), verapamil (Ver, a calcium channel blocker) and cyclosporine A (CsA, an inhibitor of CaN) on NE-induced CFs activation. The results showed that NE induced CFs proliferation and differentiation, increased α-SMA protein expression, increased collagen I, collagen III and fibronectin production, promoted ECM expression, activated CaN and increased CaN protein expression, which were inhibited by Phen, Ver and CsA. In vivo, more collagen deposition could be observed and total collagen volume fraction (CVF) was significantly increased in NE group. Phen, Ver and CsA decreased NE-induced collagen deposition, reduced cardiac fibrosis. Thus, our results demonstrate that Ca2+/CaN is involved in NE-induced CFs proliferation and collagen synthesis. PMID:26191219

  14. Tyrosine phosphorylation and protein degradation control the transcriptional activity of WRKY involved in benzylisoquinoline alkaloid biosynthesis

    PubMed Central

    Yamada, Yasuyuki; Sato, Fumihiko

    2016-01-01

    Benzylisoquinoline alkaloids (BIQ) are among the most structurally diverse and pharmaceutically valuable secondary metabolites. A plant-specific WRKY-type transcription factor, CjWRKY1, was isolated from Coptis japonica and identified as a transcriptional activator of BIQ biosynthesis. However, the expression of CjWRKY1 gene alone was not sufficient for the activation of genes encoding biosynthetic enzymes. Here, we report the importance of post-translational regulation of CjWRKY1 in BIQ biosynthesis. First, we detected the differential accumulation of CjWRKY1 protein in two cell lines with similar CjWRKY1 gene expression but different levels of accumulated alkaloids. Further investigation of the WRKY protein identified the phosphorylation of the WRKYGQK core domain at Y115. The CjWRKYY115E phosphorylation-mimic mutant showed loss of nuclear localization, DNA-binding activity, and transactivation activity compared to wild-type CjWRKY1. Rapid degradation of the CjWRKY1 protein was also confirmed following treatment with inhibitors of the 26S proteasome and protease inhibitors. The existence of two independent degradation pathways as well as protein phosphorylation suggests the fine-tuning of CjWRKY1 activities is involved in the regulation of biosynthesis of BIQs. PMID:27552928

  15. Inhibition of Fast Axonal Transport by Pathogenic SOD1 Involves Activation of p38 MAP Kinase

    PubMed Central

    Morfini, Gerardo A.; Bosco, Daryl A.; Brown, Hannah; Gatto, Rodolfo; Kaminska, Agnieszka; Song, Yuyu; Molla, Linda; Baker, Lisa; Marangoni, M. Natalia; Berth, Sarah; Tavassoli, Ehsan; Bagnato, Carolina; Tiwari, Ashutosh; Hayward, Lawrence J.; Pigino, Gustavo F.; Watterson, D. Martin; Huang, Chun-Fang; Banker, Gary; Brown, Robert H.; Brady, Scott T.

    2013-01-01

    Dying-back degeneration of motor neuron axons represents an established feature of familial amyotrophic lateral sclerosis (FALS) associated with superoxide dismutase 1 (SOD1) mutations, but axon-autonomous effects of pathogenic SOD1 remained undefined. Characteristics of motor neurons affected in FALS include abnormal kinase activation, aberrant neurofilament phosphorylation, and fast axonal transport (FAT) deficits, but functional relationships among these pathogenic events were unclear. Experiments in isolated squid axoplasm reveal that FALS-related SOD1 mutant polypeptides inhibit FAT through a mechanism involving a p38 mitogen activated protein kinase pathway. Mutant SOD1 activated neuronal p38 in mouse spinal cord, neuroblastoma cells and squid axoplasm. Active p38 MAP kinase phosphorylated kinesin-1, and this phosphorylation event inhibited kinesin-1. Finally, vesicle motility assays revealed previously unrecognized, isoform-specific effects of p38 on FAT. Axon-autonomous activation of the p38 pathway represents a novel gain of toxic function for FALS-linked SOD1 proteins consistent with the dying-back pattern of neurodegeneration characteristic of ALS. PMID:23776455

  16. Management of Benign Biliary Strictures

    SciTech Connect

    Laasch, Hans-Ulrich; Martin, Derrick F.

    2002-12-15

    Benign biliary strictures are most commonly a consequence of injury at laparoscopic cholecystectomy or fibrosis after biliary-enteric anastomosis. These strictures are notoriously difficult to treat and traditionally are managed by resection and fashioning of acholedocho- or hepato-jejunostomy. Promising results are being achieved with newer minimally invasive techniques using endoscopic or percutaneous dilatation and/or stenting and these are likely to play an increasing role in the management. Even low-grade biliary obstruction carries the risks of stone formation, ascending cholangitis and hepatic cirrhosis and it is important to identify and treat this group of patients. There is currently no consensus on which patient should have what type of procedure, and the full range of techniques may not be available in all hospitals. Careful assessment of the risks and likely benefits have to be made on an individual basis. This article reviews the current literature and discusses the options available. The techniques of endoscopic and percutaneous dilatation and stenting are described with evaluation of the likely success and complication rates and compared to the gold standard of biliary-enteric anastomosis.

  17. NRF2 activation is involved in ozonated human serum upregulation of HO-1 in endothelial cells

    SciTech Connect

    Pecorelli, Alessandra; Bocci, Velio; Acquaviva, Alessandra; Belmonte, Giuseppe; Gardi, Concetta; Virgili, Fabio; Ciccoli, Lucia; Valacchi, Giuseppe

    2013-02-15

    During the last decade, it has been shown that the activation of NRF2 and the binding to electrophile-responsive element (EpREs), stimulates the expression of a great number of genes responsible for the synthesis of phase I and phase II proteins, including antioxidants enzymes and heme oxygenase-1 (HO-1). This critical cell response occurs in cardiovascular, degenerative and chronic infective diseases aggravated by a chronic oxidative stress. In our previous reports we have shown that ozonated plasma is able to up-regulate HO-1 expression in endothelial cells. In the present work we investigated a candidate mechanism involved in this process. After treatment with increasing doses of ozonated serum (20, 40 and 80 μg/mL O{sub 3} per mL of serum), a clear dose dependent activation of NRF2 and the subsequent induction of HO-1 and NAD(P)H quinone oxidoreductase 1(NQO1) was observed. This effect was also present when cells were treated with serum and hydrogen peroxide (H{sub 2}O{sub 2}) or serum and 4-hydroxynonenal (4HNE). Moreover, the treatment with ozonated serum was associated with a dose-dependent activation of extracellular-signal-regulated kinases (ERK1/2) and p38 MAP kinases (p38), not directly involved in NRF2 activation. These data, provide a new insight on the mechanism responsible for the induction of HO-1 expression by ozonated serum in the endothelium, and have a practical importance as an expedient approach to the treatment of patients with both effective orthodox drugs and ozonated autohemotherapy, targeted to the restoration of redox homeostasis. - Highlights: ► Endothelial HO1 is upregulated by ozonated plasma ► This activation is induced by NRF2 and it is ERK independent. ► 4HNE and H{sub 2}O{sub 2} are the main molecules involved in this process. ► Ozonated plasma induced a hormetic effect ► Combination of orthodox medicine and ozonated plasma can be a useful treatment.

  18. Cissus sicyoides: Pharmacological Mechanisms Involved in the Anti-Inflammatory and Antidiarrheal Activities

    PubMed Central

    Beserra, Fernando Pereira; de Cássia Santos, Raquel; Périco, Larissa Lucena; Rodrigues, Vinicius Peixoto; de Almeida Kiguti, Luiz Ricardo; Saldanha, Luiz Leonardo; Pupo, André Sampaio; da Rocha, Lúcia Regina Machado; Dokkedal, Anne Lígia; Vilegas, Wagner; Hiruma-Lima, Clélia Akiko

    2016-01-01

    The objective of this study was to evaluate the pharmacological mechanisms involved in anti-inflammatory and antidiarrheal actions of hydroalcoholic extract obtained from the leaves of Cissus sicyoides (HECS). The anti-inflammatory effect was evaluated by oral administration of HECS against acute model of edema induced by xylene, and the mechanisms of action were analysed by involvement of arachidonic acid (AA) and prostaglandin E2 (PGE2). The antidiarrheal effect of HECS was observed and we analyzed the motility and accumulation of intestinal fluid. We also analyzed the antidiarrheal mechanisms of action of HECS by evaluating the role of the opioid receptor, α2 adrenergic receptor, muscarinic receptor, nitric oxide (NO) and PGE2. The oral administration of HECS inhibited the edema induced by xylene and AA and was also able to significantly decrease the levels of PGE2. The extract also exhibited significant anti-diarrheal activity by reducing motility and intestinal fluid accumulation. This extract significantly reduced intestinal transit stimulated by muscarinic agonist and intestinal secretion induced by PGE2. Our data demonstrate that the mechanism of action involved in the anti-inflammatory effect of HECS is related to PGE2. The antidiarrheal effect of this extract may be mediated by inhibition of contraction by acting on the intestinal smooth muscle and/or intestinal transit. PMID:26805827

  19. A review of two recent occurrences at the Advanced Test Reactor involving subcontractor activities

    SciTech Connect

    Dahlke, H.J.; Jensen, N.C.; Vail, J.A.

    1997-11-01

    This report documents the results of a brief, unofficial investigation into two incidents at the Idaho National Engineering and Environmental Laboratory (INEEL) Advanced Test Reactor (ATR) facility, reported on October 25 and 31, 1997. The first event was an unanticipated breach of confinement. The second involved reactor operation with an inoperable seismic scram subsystem, violating the reactor`s Technical Specifications. These two incidents have been found to be unrelated. A third event that occurred on December 16, 1996, is also discussed because of its similarities to the first event listed above. Both of these incidents were unanticipated breaches of confinement, and both involved the work of construction subcontractor personnel. The cause for the subcontractor related occurrences is a work control process that fails to effectively interface with LMITCO management. ATR Construction Project managers work sufficient close with construction subcontractor personnel to understand planned day-to-day activities. They also have sufficient training and understanding of reactor operations to ensure adherence to applicable administrative requirements. However, they may not be sufficiently involved in the work authorization and control process to bridge an apparent communications gap between subcontractor employees and Facility Operations/functional support personnel for work inside the reactor facility. The cause for the inoperable seismic scram switch (resulting from a disconnected lead) is still under investigation. It does not appear to be subcontractor related.

  20. Pathways Involved in the Synergistic Activation of Macrophages by Lipoteichoic Acid and Hemoglobin

    PubMed Central

    Cox, Kathleen H.; Cox, Michelle E.; Woo-Rasberry, Virginia; Hasty, David L.

    2012-01-01

    Lipoteichoic acid (LTA) is a Gram-positive cell surface molecule that is found in both a cell-bound form and cell-free form in the host during an infection. Hemoglobin (Hb) can synergize with LTA, a TLR2 ligand, to potently activate macrophage innate immune responses in a TLR2- and TLR4-dependent way. At low levels of LTA, the presence of Hb can result in a 200-fold increase in the secretion of IL-6 following macrophage activation. Six hours after activation, the macrophage genes that are most highly up-regulated by LTA plus Hb activation compared to LTA alone are cytokines, chemokines, receptors and interferon-regulated genes. Several of these genes exhibit a unique TLR4-dependent increase in mRNA levels that continued to rise more than eight hours after stimulation. This prolonged increase in mRNA levels could be the result of an extended period of NF-κB nuclear localization and the concurrent absence of the NF-κB inhibitor, IκBα, after stimulation with LTA plus Hb. Dynasore inhibition experiments indicate that an endocytosis-dependent pathway is required for the TLR4-dependent up-regulation of IL-6 secretion following activation with LTA plus Hb. In addition, interferon-β mRNA is present after activation with LTA plus Hb, suggesting that the TRIF/TRAM-dependent pathway may be involved. Hb alone can elicit the TLR4-dependent secretion of TNF-α from macrophages, so it may be the TLR4 ligand. Hb also led to secretion of high mobility group box 1 protein (HMGB1), which synergized with LTA to increase secretion of IL-6. The activation of both the TLR2 and TLR4 pathways by LTA plus Hb leads to an enhanced innate immune response. PMID:23071790

  1. The insulin receptor C-terminus is involved in regulation of the receptor kinase activity.

    PubMed

    Kaliman, P; Baron, V; Alengrin, F; Takata, Y; Webster, N J; Olefsky, J M; Van Obberghen, E

    1993-09-21

    During the insulin receptor activation process, ligand binding and autophosphorylation induce two distinct conformational changes in the C-terminal domain of the receptor beta-subunit. To analyze the role of this domain and the involvement of the C-terminal autophosphorylation sites (Tyr1316 and Tyr1322) in receptor activation, we used (i) antipeptide antibodies against three different C-terminal sequences (1270-1281, 1294-1317, and 1309-1326) and (ii) an insulin receptor mutant (Y/F2) where Tyr1316 and Tyr1322 have been replaced by Phe. We show that the autophosphorylation-induced C-terminal conformational change is preserved in the Y/F2 receptor, indicating that this change is not induced by phosphorylation of the C-terminal sites but most likely by phosphorylation of the major sites in the kinase domain (Tyr1146, Tyr1150, and Tyr1151). Binding of antipeptide antibodies to the C-terminal domain modulated (activated or inhibited) both mutant and wild-type receptor-mediated phosphorylation of poly(Glu/Tyr). In contrast to the wild-type receptor, Y/F2 exhibited the same C-terminal configuration before and after insulin binding, evidencing that mutation of Tyr1316 and Tyr1322 introduced conformational changes in the C-terminus. Finally, the mutant receptor was 2-fold more active than the wild-type receptor for poly(Glu/Tyr) phosphorylation. In conclusion, the whole C-terminal region of the insulin receptor beta-subunit is likely to exert a regulatory influence on the receptor kinase activity. Perturbations of the C-terminal region, such as binding of antipeptides or mutation of Tyr1316 and Tyr1322, provoke alterations at the receptor kinase level, leading to activation or inhibition of the enzymic activity. PMID:7690586

  2. Identification of key residues involved in the activation and signaling properties of dopamine D3 receptor.

    PubMed

    Kota, Kokila; Kuzhikandathil, Eldo V; Afrasiabi, Milad; Lacy, Brett; Kontoyianni, Maria; Crider, A Michael; Song, Daniel

    2015-09-01

    The dopamine D3 receptor exhibits agonist-dependent tolerance and slow response termination (SRT) signaling properties that distinguish it from the closely-related D2 receptors. While amino acid residues important for D3 receptor ligand binding have been identified, the residues involved in activation of D3 receptor signaling and induction of signaling properties have not been determined. In this paper, we used cis and trans isomers of a novel D3 receptor agonist, 8-OH-PBZI, and site-directed mutagenesis to identify key residues involved in D3 receptor signaling function. Our results show that trans-8-OH-PBZI, but not cis-8-OH-PBZI, elicit the D3 receptor tolerance and SRT properties. We show that while both agonists require a subset of residues in the orthosteric binding site of D3 receptors for activation of the receptor, the ability of the two isomers to differentially induce tolerance and SRT is mediated by interactions with specific residues in the sixth transmembrane helix and third extracellular loop of the D3 receptor. We also show that unlike cis-8-OH-PBZI, which is a partial agonist at the dopamine D2S receptor and full agonist at dopamine D2L receptor, trans-8-OH-PBZI is a full agonist at both D2S and D2L receptors. The different effect of the two isomers on D3 receptor signaling properties and D2S receptor activation correlated with differential effects of the isomers on agonist-induced mouse locomotor activity. The two isomers of 8-OH-PBZI represent novel pharmacological tools for in silico D3 and D2 receptor homology modeling and for determining the role of D3 receptor tolerance and SRT properties in signaling and behavior. PMID:26116441

  3. Antidepressant-like activity of dehydrozingerone: involvement of the serotonergic and noradrenergic systems.

    PubMed

    Martinez, Débora M; Barcellos, Angelita; Casaril, Angela M; Savegnago, Lucielli; Lernardão, Eder J

    2014-12-01

    Dehydrozingerone (DHZ) is a phenolic compound isolated from ginger rhizomes (Zingiber officinale). It is known for its diverse spectrum of biological activities as an antioxidant, anti-inflammatory and antitumor compound. The present study was designed to assess the antidepressant effect of DHZ and the involvement of the monoaminergic system and to evaluate its in vitro antioxidant activity in the hippocampus, cortex and cerebellum of mice. For this study, the tail suspension test (TST), forced swim test (FST) and yohimbine lethality test were performed. DHZ administered orally 30min prior to testing reduced the immobility time in the TST (1-40mg/kg) and the FST (10-40mg/kg), with no change in locomotor activity in the open field test. The antidepressant-like effect of DHZ (1mg/kg) was prevented by ketanserin (1mg/kg, i.p.; a 5-HT2A/2C receptor antagonist), ondansetron (1mg/kg, i.p.; a 5-HT3 receptor antagonist), prazosin (1mg/kg, i.p., an α1-adrenoceptor antagonist) and yohimbine (1mg/kg, i.p., an α2-adrenoceptor antagonist) pretreatments. Furthermore, DHZ administered at doses of 10 and 20mg/kg increased the lethality of yohimbine (35mg/kg, i.p.). DHZ had antioxidant activity on in vitro lipid peroxidation induced by sodium nitroprusside in all brain regions tested. The results revealed that DHZ has a potent antidepressant effect, which seems to involve the serotonergic and noradrenergic systems. PMID:25449795

  4. Endoscopic management of benign tracheobronchial tumors

    PubMed Central

    Gao, Hui; Ding, Xin; Wei, Dong; Cheng, Peng; Su, Xiaomei; Liu, Huanyi; Zhang, Tao

    2011-01-01

    Even though benign tracheobronchial tumors are quite rare, they still can induce airway obstruction, result in suffocation, and need emergent management to remove the obstructing lesions and make the respiratory tracts unobstructed. Although the preferred therapy is surgery, it is still difficult to deal with the tumors in some cases, and the complications of surgery are common. Therefore, bronchoscopic managements, such as Nd: YAG laser, electrocautery, APC and Cryotherapy, are very important to treat benign tracheobronchial tumors and can cure most of them. The efficacy of therapeutic endoscopy for the treatment of patients with benign airways obstruction has been established. However, in order to maximally eradicate the benign tumors with minimal damage to patients, the success of bronchoscopic managements for the treatment strongly depends on the diligent identification of the various factors, including the location, size, shape of tumor, and the age, status, cardio respiratory function of patients, and full comprehension of the limits and potential of each particular technique. Because the advantages and disadvantages of above mentioned interventional methods, single method can not solve all clinical issues. Therefore, in order to remove benign tracheobronchial tumors completely, and reduce the incidence of recurrence as far as possible, many doctors combine several methods of them to treat complicated benign tracheobronchial tumors. This article reviews the core principles and techniques available to the bronchoscope managing benign tracheobronchial tumors. PMID:22263100

  5. Involvement of trigeminal subnucleus caudalis (medullary dorsal horn) in craniofacial nociceptive reflex activity.

    PubMed

    Tsai, C M; Chiang, C Y; Yu, X M; Sessle, B J

    1999-05-01

    We have previously shown that an increase in electromyographic (EMG) activity of digastric (DIG) and masseter (MASS) muscles can be reflexly evoked by injection into the rat's temporomandibular joint (TMJ) region of the small-fibre excitant and inflammatory irritant mustard oil (MO). Since the trigeminal (V) subnucleus caudalis (Vc, i.e. medullary dorsal horn) has traditionally been viewed as an essential brainstem relay site of nociceptive information from craniofacial tissues, an EMG study was carried out in 45 anaesthetized rats to determine if Vc is involved in the MO-evoked increases in jaw muscle EMG activity. The effects of histologically confirmed surgical or chemical lesions of Vc on this evoked EMG activity were tested in different groups of rats. MO injection into the left TMJ region of intact rats evoked bilateral increases in EMG activity of DIG and MASS which could be significantly reduced by surgical transection of the left caudal brainstem at the obex level; MO injection into the right TMJ region in these same rats still readily evoked increases in EMG activity. A sagittal section medial to Vc or transection at the level of the second cervical spinal segment did not produce any significant reduction in the reflexly evoked EMG activity. Neurones in Vc, as opposed to fibres of passage, appear to be important for the MO-evoked EMG activity, since injection into Vc of the neurotoxic chemical ibotenic acid significantly reduced the mustard oil-evoked EMG activity. The Vc also appears to play a role in the activation of contralateral V motoneurons, as evidenced by the activation of the contralateral DIG and MASS muscles by the injection of MO into the left TMJ region of intact rats and by the reduction of this evoked EMG activity in the contralateral DIG and MASS of rats with a surgical transection or ibotenic acid lesion of the left Vc. These findings suggest that Vc may be a critical element in the neural pathways underlying the reflex responses evoked

  6. Detecting cardiac involvement with magnetic resonance in patients with active eosinophilic granulomatosis with polyangiitis.

    PubMed

    Yune, Sehyo; Choi, Dong-Chull; Lee, Byung-Jae; Lee, Jin-Young; Jeon, Eun-Seok; Kim, Sung Mok; Choe, Yeon Hyeon

    2016-06-01

    Cardiac involvement is the most important prognostic factor in eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome). The aims of this study were to describe findings of cardiac magnetic resonance (CMR) in patients with active EGPA and to find factors associated with cardiac involvement detected by CMR that could help identify patients who would benefit from the examination. Medical records and CMR images in 16 consecutive EGPA patients (8 women and 8 men, median age of 47 years ranging from 34 to 68 years) were reviewed. Clinical features and results of laboratory tests were compared according to the presence of myocardial late gadolinium enhancement (LGE) on CMR images. The patients were followed for the development of cardiac symptoms and signs (mean follow up duration, 40.5 ± 12.8 months). Among the total of 16 patients, 8 (50 %) had myocardial LGE according to CMR, located in the subendocardial layer in 7 of them (87.5 %). The extent of LGE had a significant negative correlation with left ventricular ejection fraction (LVEF, ρ = -0.723, p = 0.043). The presence of LGE was associated with larger end-systolic left ventricle internal dimension (34 vs. 28 mm, p = 0.027) and presence of diastolic dysfunction (75 vs. 0 %, p = 0.008) on echocardiography, elevated NT-proBNP (75 vs. 12.5 %, p = 0.012), and elevated CK-MB (62.5 vs. 0 %, p = 0.010) compared to the group without LGE. Only one patient (6.3 %) had cardiac symptoms before CMR and another patient (6.3 %) developed heart failure 4 years later during remission. The other 14 patients remained free from cardiac signs and symptoms during the follow-up period. In patients with active EGPA, CMR enables detection of cardiac involvement when cardiac symptoms are not present. Echocardiographic diastolic dysfunction and elevated NT-proBNP or CK-MB may help identify active EGPA patients who can benefit from CMR to detect cardiac involvement without cardiac symptoms. PMID

  7. 22 CFR 40.25 - Certain aliens involved in serious criminal activity who have asserted immunity from prosecution...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Certain aliens involved in serious criminal activity who have asserted immunity from prosecution. 40.25 Section 40.25 Foreign Relations DEPARTMENT OF... involved in serious criminal activity who have asserted immunity from prosecution....

  8. 22 CFR 40.25 - Certain aliens involved in serious criminal activity who have asserted immunity from prosecution...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Certain aliens involved in serious criminal activity who have asserted immunity from prosecution. 40.25 Section 40.25 Foreign Relations DEPARTMENT OF... involved in serious criminal activity who have asserted immunity from prosecution....

  9. 22 CFR 40.25 - Certain aliens involved in serious criminal activity who have asserted immunity from prosecution...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Certain aliens involved in serious criminal activity who have asserted immunity from prosecution. 40.25 Section 40.25 Foreign Relations DEPARTMENT OF... involved in serious criminal activity who have asserted immunity from prosecution....

  10. 22 CFR 40.25 - Certain aliens involved in serious criminal activity who have asserted immunity from prosecution...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Certain aliens involved in serious criminal activity who have asserted immunity from prosecution. 40.25 Section 40.25 Foreign Relations DEPARTMENT OF... involved in serious criminal activity who have asserted immunity from prosecution....

  11. 22 CFR 40.25 - Certain aliens involved in serious criminal activity who have asserted immunity from prosecution...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Certain aliens involved in serious criminal activity who have asserted immunity from prosecution. 40.25 Section 40.25 Foreign Relations DEPARTMENT OF... involved in serious criminal activity who have asserted immunity from prosecution....

  12. 30 CFR 57.4660 - Work in shafts, raises, or winzes and other activities involving hazard areas.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... activities involving hazard areas. 57.4660 Section 57.4660 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS... Work in shafts, raises, or winzes and other activities involving hazard areas. During performance of...

  13. 12 CFR 408.4 - Early involvement in foreign activities for which Eximbank financing may be requested.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 5 2014-01-01 2014-01-01 false Early involvement in foreign activities for... Implementing Procedures § 408.4 Early involvement in foreign activities for which Eximbank financing may be requested. (a) Section 1501.2(d) of the NEPA Regulations requires agencies to provide for early...

  14. 12 CFR 408.4 - Early involvement in foreign activities for which Eximbank financing may be requested.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 5 2013-01-01 2013-01-01 false Early involvement in foreign activities for... Implementing Procedures § 408.4 Early involvement in foreign activities for which Eximbank financing may be requested. (a) Section 1501.2(d) of the NEPA Regulations requires agencies to provide for early...

  15. 12 CFR 408.4 - Early involvement in foreign activities for which Eximbank financing may be requested.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 5 2012-01-01 2012-01-01 false Early involvement in foreign activities for... Implementing Procedures § 408.4 Early involvement in foreign activities for which Eximbank financing may be requested. (a) Section 1501.2(d) of the NEPA Regulations requires agencies to provide for early...

  16. Multidimensional Self-Concept: Age and Gender Differences in Australian High School Students Involved in Delinquent Activities

    ERIC Educational Resources Information Center

    Carroll, Annemaree; Houghton, Stephen; Wood, Robert; Perkins, Catherine; Bower, Julie

    2007-01-01

    The present research examined the relationship between self-concept and level of involvement in delinquent activities of 1327 (612 males, 715 females) years 8-12 high school students. Through cluster analysis, participants were identified as having either high or low involvement in delinquent activities from scores on a self-report measure of…

  17. 12 CFR 408.4 - Early involvement in foreign activities for which Eximbank financing may be requested.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 4 2011-01-01 2011-01-01 false Early involvement in foreign activities for... Implementing Procedures § 408.4 Early involvement in foreign activities for which Eximbank financing may be requested. (a) Section 1501.2(d) of the NEPA Regulations requires agencies to provide for early...

  18. 12 CFR 408.4 - Early involvement in foreign activities for which Eximbank financing may be requested.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Early involvement in foreign activities for... Implementing Procedures § 408.4 Early involvement in foreign activities for which Eximbank financing may be requested. (a) Section 1501.2(d) of the NEPA Regulations requires agencies to provide for early...

  19. Who's who in the crew? Exploring participant involvement in the Active Living Coalition.

    PubMed

    Barnes, Priscilla A; Schaefer, Samantha; Middlestadt, Susan; Knoblock, Heidi

    2015-06-01

    Health coalitions serve as an important "vehicle" to strengthen horizontal and vertical ties between organizations, community groups, and individuals whose intent and purpose is to improve wellness. Having a strong and diverse group of participants is essential for highly effective coalitions to carry out their mission in an organized and participatory manner. However, the extent that individuals become involved in coalition operations and activities remains ambiguous. A grounded theory approach was used to explore expressions of participant involvement of a local health coalition known as the Active Living Coalition (ALC). Open, axial, as well as domain and taxonomic coding were used to analyze transcripts from four focus groups (n = 37 participants) in order to develop a participant continuum that captured six network aggregates within the coalition. Findings suggest that participation, for the most part, was heterogeneous and ever-changing given the expectations of the level of partnership that best individuals' personal and professional interests. Differentiating the type of participants in health coalitions can help coalition leaders more successfully "manage" new and existing relationships. Findings imply that health coalitions can maximize coalition capacity by drawing upon the full range of potential human and material resources by further understanding the types of individuals that make up their network. PMID:25812479

  20. Involvement of a phospholipase C in the hemolytic activity of a clinical strain of Pseudomonas fluorescens

    PubMed Central

    Rossignol, Gaelle; Merieau, Annabelle; Guerillon, Josette; Veron, Wilfried; Lesouhaitier, Olivier; Feuilloley, Marc GJ; Orange, Nicole

    2008-01-01

    Background Pseudomonas fluorescens is a ubiquitous Gram-negative bacterium frequently encountered in hospitals as a contaminant of injectable material and surfaces. This psychrotrophic bacterium, commonly described as unable to grow at temperatures above 32°C, is now considered non pathogenic. We studied a recently identified clinical strain of P. fluorescens biovar I, MFN1032, which is considered to cause human lung infection and can grow at 37°C in laboratory conditions. Results We found that MFN1032 secreted extracellular factors with a lytic potential at least as high as that of MF37, a psychrotrophic strain of P. fluorescens or the mesophilic opportunistic pathogen, Pseudomonas aeruginosa PAO1. We demonstrated the direct, and indirect – through increases in biosurfactant release – involvement of a phospholipase C in the hemolytic activity of this bacterium. Sequence analysis assigned this phospholipase C to a new group of phospholipases C different from those produced by P. aeruginosa. We show that changes in PlcC production have pleiotropic effects and that plcC overexpression and plcC extinction increase MFN1032 toxicity and colonization, respectively. Conclusion This study provides the first demonstration that a PLC is involved in the secreted hemolytic activity of a clinical strain of Pseudomonas fluorescens. Moreover, this phospholipase C seems to belong to a complex biological network associated with the biosurfactant production. PMID:18973676

  1. Caveolin-1 is involved in reactive oxygen species-induced SHP-2 activation in astrocytes

    PubMed Central

    Yun, Ji Hee; Park, Soo Jung; Jo, Ara; Jou, Ilo; Park, Jung Soo

    2011-01-01

    Recent evidence supports a neuroprotective role of Src homology 2-containing protein tyrosine phosphatase 2 (SHP-2) against ischemic brain injury. However, the molecular mechanisms of SHP-2 activation and those governing how SHP-2 exerts its function under oxidative stress conditions are not well understood. Recently we have reported that reactive oxygen species (ROS)-mediated oxidative stress promotes the phosphorylation of endogenous SHP-2 through lipid rafts, and that this phosphorylation strongly occurs in astrocytes, but not in microglia. To investigate the molecules involved in events leading to phosphorylation of SHP-2, raft proteins were analyzed using astrocytes and microglia. Interestingly, caveolin-1 and -2 were detected only in astrocytes but not in microglia, whereas flotillin-1 was expressed in both cell types. To examine whether the H2O2-dependent phosphorylation of SHP-2 is mediated by caveolin-1, we used specific small interfering RNA (siRNA) to downregulate caveolin-1 expression. In the presence of caveolin-1 siRNA, the level of SHP-2 phosphorylation induced by H2O2 was significantly decreased, compared with in the presence of control siRNA. Overexpression of caveolin-1 effectively increased H2O2-induced SHP-2 phosphorylation in microglia. Lastly, H2O2 induced extracellular signal-regulated kinase (ERK) activation in astrocytes through caveolin-1. Our results suggest that caveolin-1 is involved in astrocyte-specific intracellular responses linked to the SHP-2-mediated signaling cascade following ROS-induced oxidative stress. PMID:21918362

  2. Developmental changes in brain activation involved in the production of novel speech sounds in children.

    PubMed

    Hashizume, Hiroshi; Taki, Yasuyuki; Sassa, Yuko; Thyreau, Benjamin; Asano, Michiko; Asano, Kohei; Takeuchi, Hikaru; Nouchi, Rui; Kotozaki, Yuka; Jeong, Hyeonjeong; Sugiura, Motoaki; Kawashima, Ryuta

    2014-08-01

    Older children are more successful at producing unfamiliar, non-native speech sounds than younger children during the initial stages of learning. To reveal the neuronal underpinning of the age-related increase in the accuracy of non-native speech production, we examined the developmental changes in activation involved in the production of novel speech sounds using functional magnetic resonance imaging. Healthy right-handed children (aged 6-18 years) were scanned while performing an overt repetition task and a perceptual task involving aurally presented non-native and native syllables. Productions of non-native speech sounds were recorded and evaluated by native speakers. The mouth regions in the bilateral primary sensorimotor areas were activated more significantly during the repetition task relative to the perceptual task. The hemodynamic response in the left inferior frontal gyrus pars opercularis (IFG pOp) specific to non-native speech sound production (defined by prior hypothesis) increased with age. Additionally, the accuracy of non-native speech sound production increased with age. These results provide the first evidence of developmental changes in the neural processes underlying the production of novel speech sounds. Our data further suggest that the recruitment of the left IFG pOp during the production of novel speech sounds was possibly enhanced due to the maturation of the neuronal circuits needed for speech motor planning. This, in turn, would lead to improvement in the ability to immediately imitate non-native speech. PMID:24585739

  3. CIPK23 is involved in iron acquisition of Arabidopsis by affecting ferric chelate reductase activity.

    PubMed

    Tian, Qiuying; Zhang, Xinxin; Yang, An; Wang, Tianzuo; Zhang, Wen-Hao

    2016-05-01

    Iron deficiency is one of the major limiting factors affecting quality and production of crops in calcareous soils. Numerous signaling molecules and transcription factors have been demonstrated to play a regulatory role in adaptation of plants to iron deficiency. However, the mechanisms underlying the iron deficiency-induced physiological processes remain to be fully dissected. Here, we demonstrated that the protein kinase CIPK23 was involved in iron acquisition. Lesion of CIPK23 rendered Arabidopsis mutants hypersensitive to iron deficiency, as evidenced by stronger chlorosis in young leaves and lower iron concentration than wild-type plants under iron-deficient conditions by down-regulating ferric chelate reductase activity. We found that iron deficiency evoked an increase in cytosolic Ca(2+) concentration and the elevated Ca(2+) would bind to CBL1/CBL9, leading to activation of CIPK23. These novel findings highlight the involvement of calcium-dependent CBL-CIPK23 complexes in the regulation of iron acquisition. Moreover, mutation of CIPK23 led to changes in contents of mineral elements, suggesting that CBL-CIPK23 complexes could be as "nutritional sensors" to sense and regulate the mineral homeostasis in Arabisopsis. PMID:26993237

  4. An update on renal involvement in hemophagocytic syndrome (macrophage activation syndrome)

    PubMed Central

    Esmaili, Haydarali; Mostafidi, Elmira; Mehramuz, Bahareh; Ardalan, Mohammadreza; Mohajel-Shoja, Mohammadali

    2016-01-01

    Context: Hemophagocytic syndrome (HPS) is mainly characterized by massive infiltration of bone marrow by activated macrophages and often presents with pancytopenia. Thrombotic microangiopathy (TMA) is also present with thrombocytopenia and renal involvement. Both conditions could coexist with each other and complicate the condition. Evidence Acquisition: Directory of Open Access Journals (DOAJ), EMBASE, Google Scholar, PubMed, EBSCO, and Web of Science with keywords relevant to; Hemophagocytic syndrome, macrophage activation syndrome, interferon-gamma and thrombotic microangiopathy, have been searched. Results: Viral infection, rheumatologic disease and malignancies are the main underlying causes for secondary HPS. calcineurin inhibitors and viral infections are also the main underlying causes of TMA in transplant recipients. In this review, we discussed a 39-year-old male who presented with pancytopenia and renal allograft dysfunction. With the diagnosis of HPS induced TMA his renal condition and pancytopenia improved after receiving intravenous immunoglobulin (IVIG) and plasmapheresis therapy. Conclusions: HPS is an increasingly recognized disorder in the realm of different medical specialties. Renal involvement complicates the clinical picture of the disease, and this condition even is more complex in renal transplant recipients. We should consider the possibility of HPS in any renal transplant recipient with pancytopenia and allograft dysfunction. The combination of HPS with TMA future increases the complexity of the situation. PMID:27047804

  5. Benign disease of the common bile duct.

    PubMed

    Saxena, R; Pradeep, R; Chander, J; Kumar, P; Wig, J D; Yadav, R V; Kaushik, S P

    1988-08-01

    The incidence of common bile duct (CBD) pathology in a group of patients with benign biliary disease (n = 505) was found to be 23.2 per cent. The spectrum included 111 patients (90.2 per cent) with CBD stones, 37 of whom (33.3 per cent) had no symptoms or findings pre-operatively indicating CBD involvement. Five patients had papillary stenosis, three had postoperative CBD strictures, one had a choledochal cyst and one had an external biliary fistula. Of the 100 CBDs measuring more than 10 mm in diameter, 90 harboured calculi. In the remaining 23 CBDs measuring less than 10 mm, calculi were present in 21. The presence of CBD calculi was demonstrated by intra-operative cholangiography in 49 patients. In the remaining patients (n = 74), the diagnosis of CBD pathology was made either by percutaneous transhepatic cholangiography, endoscopic retrograde cholangio-pancreatography, T-tube cholangiography or peroperative palpation. The surgical procedures performed included choledochotomy and T-tube drainage (n = 74), transduodenal sphincteroplasty (n = 27) and choledochoduodenostomy (n = 18). The overall mortality and morbidity of CBD exploration was 3.3 per cent and 24.4 per cent respectively, which was significantly greater than that for cholecystectomy alone (0.3 per cent and 8.6 per cent respectively). Transduodenal sphincteroplasty carried a much higher mortality (11 per cent) and morbidity (52 per cent) when compared with other procedures. PMID:3167536

  6. Skin conditions: benign nodular skin lesions.

    PubMed

    Nguyen, Tam; Zuniga, Ramiro

    2013-04-01

    Benign subcutaneous lesions are a common reason that patients visit family physicians. Lipomas are the most common of these lesions; they most often occur on the trunk and proximal extremities. Recent data show that as many as half of the fat cells in lipomas are atypical. Ultrasound is used increasingly to confirm lipoma diagnosis, but deep lesions should be evaluated with magnetic resonance imaging study or computed tomography scan to exclude involvement of underlying structures and/or liposarcoma. Small lesions can sometimes be managed with serial injections of midpotency steroids. Larger lesions (larger than 5 cm), those compressing other structures, or those suspicious for malignancy should be excised using standard surgical excision or, when possible, the newer minimal-scar segmental extraction technique. Ganglion cysts are another common lesion, the presence of which often is confirmed with ultrasound if the diagnosis is not clinically apparent. Management includes splinting, aspiration, and/or injection of steroids, with or without hyaluronidase. Epidermal inclusion cysts, also called sebaceous cysts, typically are asymptomatic unless they become infected. Ultrasound can aid in diagnosis. The only definitive management is surgical excision with complete removal of the cyst wall or capsule, using minimal-scar segmental extraction or conventional surgical removal. PMID:23600336

  7. Shrinkage activates a nonselective conductance: involvement of a Walker-motif protein and PKC.

    PubMed

    Nelson, D J; Tien, X Y; Xie, W; Brasitus, T A; Kaetzel, M A; Dedman, J R

    1996-01-01

    The ability of all cells to maintain their volume during an osmotic challenge is dependent on the regulated movement of salt and water across the plasma membrane. We demonstrate the phosphorylation-dependent gating of a nonselective conductance in Caco-2 cells during cellular shrinkage. Intracellular application of exogenous purified rat brain protein kinase C (PKC) resulted in the activation of a current similar to that activated during shrinkage with a Na(+)-to-Cl- permeability ratio of approximately 1.7:1. To prevent possible PKC- and/or shrinkage-dependent activation of cystic fibrosis transmembrane regulator (CFTR), which is expressed at high levels in Caco-2 cells, a functional anti-peptide antibody, anti-CFTR505-511, was introduced into the cells via the patch pipette. Anti-CFTR505-511, which is directed against the Walker motif in the first nucleotide binding fold of CFTR, prevented the PKC/shrink-age current activation. The peptide CFTR505-511 also induced current inhibition, suggesting the possible involvement of a regulatory element in close proximity to the channel that shares sequence homology with the first nucleotide binding fold of CFTR and whose binding to the channel is required for channel gating. PMID:8772443

  8. Young People's Views on Accelerometer Use in Physical Activity Research: Findings from a User Involvement Investigation.

    PubMed

    Kirby, Joanna; Tibbins, Carly; Callens, Claire; Lang, Beckie; Thorogood, Margaret; Tigbe, William; Robertson, Wendy

    2012-01-01

    The use of accelerometers to objectively measure physical activity is important in understanding young people's behaviours, as physical activity plays a key part in obesity prevention and treatment. A user-involvement qualitative study with young people aged 7-18 years (n = 35) was carried out to investigate views on accelerometer use to inform an obesity treatment research study. First impressions were often negative, with issues related to size and comfort reported. Unwanted attention from wearing an accelerometer and bullying risk were also noted. Other disadvantages included feeling embarrassed and not being able to wear the device for certain activities. Positive aspects included feeling "special" and having increased attention from friends. Views on the best time to wear accelerometers were mixed. Advice was offered on how to make accelerometers more appealing, including presenting them in a positive way, using a clip rather than elastic belt to attach, personalising the device, and having feedback on activity levels. Judgements over the way in which accelerometers are used should be made at the study development stage and based on the individual population. In particular, introducing accelerometers in a clear and positive way is important. Including a trial wearing period, considering practical issues, and providing incentives may help increase compliance. PMID:24533214

  9. Effects of negative air ions on activity of neural substrates involved in autonomic regulation in rats

    NASA Astrophysics Data System (ADS)

    Suzuki, Satoko; Yanagita, Shinya; Amemiya, Seiichiro; Kato, Yumi; Kubota, Natsuko; Ryushi, Tomoo; Kita, Ichiro

    2008-07-01

    The neural mechanism by which negative air ions (NAI) mediate the regulation of autonomic nervous system activity is still unknown. We examined the effects of NAI on physiological responses, such as blood pressure (BP), heart rate (HR), and heart rate variability (HRV) as well as neuronal activity, in the paraventricular nucleus of the hypothalamus (PVN), locus coeruleus (LC), nucleus ambiguus (NA), and nucleus of the solitary tract (NTS) with c-Fos immunohistochemistry in anesthetized, spontaneously breathing rats. In addition, we performed cervical vagotomy to reveal the afferent pathway involved in mediating the effects of NAI on autonomic regulation. NAI significantly decreased BP and HR, and increased HF power of the HRV spectrum. Significant decreases in c-Fos positive nuclei in the PVN and LC, and enhancement of c-Fos expression in the NA and NTS were induced by NAI. After vagotomy, these physiological and neuronal responses to NAI were not observed. These findings suggest that NAI can modulate autonomic regulation through inhibition of neuronal activity in PVN and LC as well as activation of NA neurons, and that these effects of NAI might be mediated via the vagus nerves.

  10. Mitochondrial Dysfunction Is Involved in the Toxic Activity of Boric Acid against Saprolegnia

    PubMed Central

    Ali, Shimaa E.; Thoen, Even; Evensen, Øystein; Wiik-Nielsen, Jannicke; Gamil, Amr A. A.; Skaar, Ida

    2014-01-01

    There has been a significant increase in the incidence of Saprolegnia infections over the past decades, especially after the banning of malachite green. Very often these infections are associated with high economic losses in salmonid farms and hatcheries. The use of boric acid to control the disease has been investigated recently both under in vitro and in vivo conditions, however its possible mode of action against fish pathogenic Saprolegnia is not known. In this study, we have explored the transformation in Saprolegnia spores/hyphae after exposure to boric acid (1 g/L) over a period 4–24 h post treatment. Using transmission electron microscopy (TEM), early changes in Saprolegnia spores were detected. Mitochondrial degeneration was the most obvious sign observed following 4 h treatment in about 20% of randomly selected spores. We also investigated the effect of the treatment on nuclear division, mitochondrial activity and function using confocal laser scanning microscopy (CLSM). Fluorescence microscopy was also used to test the effect of treatment on mitochondrial membrane potential and formation of reactive oxygen species. Additionally, the viability and proliferation of treated spores that correlated to mitochondrial enzymatic activity were tested using an MTS assay. All obtained data pointed towards changes in the mitochondrial structure, membrane potential and enzymatic activity following treatment. We have found that boric acid has no effect on the integrity of membranes of Saprolegnia spores at concentrations tested. It is therefore likely that mitochondrial dysfunction is involved in the toxic activity of boric acid against Saprolegnia spp. PMID:25354209

  11. Afferent Arteriolar Dilation to 11,12-EET Analogs Involves PP2A Activity and Ca2+-Activated K+ Channels

    PubMed Central

    Imig, John D.; Dimitropoulou, Christiana; Reddy, D. Sudarshan; White, Richard E.; Falck, John R.

    2008-01-01

    The epoxygenase metabolite, 11,12-epoxyeicosatrienoic acid (11,12-EET), has renal vascular actions. 11,12-EET analogs have been developed to determine the structure activity relationship for 11,12-EET and as a tool to investigate signaling mechanisms responsible for afferent arteriolar dilation. We hypothesized that 11,12-EET mediated afferent arteriolar dilation involves increased phosphoprotein phosphatase 2A (PP2A) and large-conductance calcium activated K+ (KCa) channels. We evaluated the chemically and/or metabolically stable 11,12-EET analogs: 11,12-EET-N-methylsulfonimide (11,12-EET-SI), 11-nonyloxy-undec-8(Z)-enoic acid (11,12-ether-EET-8-ZE), and 11,12-trans-oxidoeicosa-8(Z)-eonoic acid (11,12-tetra-EET-8-ZE). Afferent arteriolar responses were assessed. Activation of KCa channels by 11,12-EET analogs were established by single cell channel recordings in renal myocytes. Assessment of renal vascular responses revealed that 11,12-EET analogs increased afferent arteriolar diameter. Vasodilator responses to 11,12-EET analogs were abolished by K+ channel or PP2A inhibition. 11,12-EET analogs activated renal myocyte large-conductance KCa channels. 11,12-EET analogs increased cAMP by 2-fold and PP2A activity increased 3-8 fold in renal myocytes. PP2A inhibition did not significantly affect the 11,12-EET analog mediated increase in cAMP and PP2A increased renal myocyte KCa channel activity to a much greater extent than PKA. These data support the concept that 11,12-EET utilizes PP2A dependent pathways to activate large-conductance KCa channels and dilate the afferent arteriole. PMID:18260004

  12. Joint Associations of Residential Density and Neighborhood Involvement with Physical Activity among a Multiethnic Sample of Urban Adults

    ERIC Educational Resources Information Center

    Johnson-Lawrence, Vicki; Schulz, Amy J.; Zenk, Shannon N.; Israel, Barbara A.; Wineman, Jean; Marans, Robert W.; Rowe, Zachary

    2015-01-01

    Regular physical activity is associated with improvements in overall health. Although resident involvement in neighborhood social activities is positively associated with physical activity, neighborhood design features, including residential density, have varied associations with physical activity. Using data from a multiethnic sample of 696…

  13. Vimentin Is Involved in Peptidylarginine Deiminase 2-Induced Apoptosis of Activated Jurkat Cells

    PubMed Central

    Hsu, Pei-Chen; Liao, Ya-Fan; Lin, Chin-Li; Lin, Wen-Hao; Liu, Guang-Yaw; Hung, Hui-Chih

    2014-01-01

    Peptidylarginine deiminase type 2 (PADI2) deiminates (or citrullinates) arginine residues in protein to citrulline residues in a Ca2+-dependent manner, and is found in lymphocytes and macrophages. Vimentin is an intermediate filament protein and a well-known substrate of PADI2. Citrullinated vimentin is found in ionomycin-induced macrophage apoptosis. Citrullinated vimentin is the target of anti-Sa antibodies, which are specific to rheumatoid arthritis, and play a critical role in the pathogenesis of the disease. To investigate the role of PADI2 in apoptosis, we generated a Jurkat cell line that overexpressed the PADI2 transgene from a tetracycline-inducible promoter, and used a combination of 12-O-tetradecanoylphorbol-13-acetate and ionomycin to activate Jurkat cells. We found that PADI2 overexpression reduced the cell viability of activated Jurkat cells in a dose- and time-dependent manner. The PADI2-overexpressed and -activated Jurkat cells presented typical manifestations of apoptosis, and exhibited greater levels of citrullinated proteins, including citrullinated vimentin. Vimentin overexpression rescued a portion of the cells from apoptosis. In conclusion, PADI2 overexpression induces apoptosis in activated Jurkat cells. Vimentin is involved in PADI2-induced apoptosis. Moreover, PADI2-overexpressed Jurkat cells secreted greater levels of vimentin after activation, and expressed more vimentin on their cell surfaces when undergoing apoptosis. Through artificially highlighting PADI2 and vimentin, we demonstrated that PADI2 and vimentin participate in the apoptotic mechanisms of activated T lymphocytes. The secretion and surface expression of vimentin are possible ways of autoantigen presentation to the immune system. PMID:24850148

  14. Mutational Analysis of Cvab, an ABC Transporter Involved in the Secretion of Active Colicin V

    PubMed Central

    Tai, Phang C.

    2012-01-01

    CvaB is the central membrane transporter of the colicin V secretion system that belongs to an ATP-binding cassette superfamily. Previous data showed that the N-terminal and C-terminal domains of CvaB are essential for the function of CvaB. N-terminal domain of CvaB possesses Ca2+-dependent cysteine proteolytic activity, and two critical residues, Cys32 and His105, have been identified. In this study, we also identify Asp121 as being the third residue of the putative catalytic triad within the active site of the enzyme. The Asp121 mutants lose both their colicin V secretion activity and N-terminal proteolytic activity. The adjacent residue Pro122 also appears to play a critical role in the colicin V secretion. However, the reversal of the two residues D121P - P122D results in loss of activity. Based on molecular modeling and protein sequence alignment, several residues adjacent to the critical residues, Cys32 and His105, were also examined and characterized. Site-directed mutagenesis of Trp101, Asp102, Val108, Leu76, Gly77, and Gln26 indicate that the neighboring residues around the catalytic triad affect colicin V secretion. Several mutated CvaB proteins with defective secretion were also tested, including Asp121 and Pro122, and were found to be structurally stable. These results indicate that the residues surrounding the identified catalytic triad are functionally involved in the secretion of biologically active colicin V. PMID:22539970

  15. Aβ and NMDAR activation cause mitochondrial dysfunction involving ER calcium release.

    PubMed

    Ferreira, Ildete Luísa; Ferreiro, Elisabete; Schmidt, Jeannette; Cardoso, João M; Pereira, Cláudia M F; Carvalho, Ana Luísa; Oliveira, Catarina R; Rego, A Cristina

    2015-02-01

    Early cognitive deficits in Alzheimer's disease (AD) seem to be correlated to dysregulation of glutamate receptors evoked by amyloid-beta (Aβ) peptide. Aβ interference with the activity of N-methyl-d-aspartate receptors (NMDARs) may be a relevant factor for Aβ-induced mitochondrial toxicity and neuronal dysfunction. To evaluate the role of mitochondria in NMDARs activation mediated by Aβ, we followed in situ single-cell simultaneous measurement of cytosolic free Ca(2+)(Cai(2+)) and mitochondrial membrane potential in primary cortical neurons. Our results show that direct exposure to Aβ + NMDA largely increased Cai(2+) and induced immediate mitochondrial depolarization, compared with Aβ or NMDA alone. Mitochondrial depolarization induced by rotenone strongly inhibited the rise in Cai(2+) evoked by Aβ or NMDA, suggesting that mitochondria control Ca(2+) entry through NMDARs. However, incubation with rotenone did not preclude mitochondrial Ca(2+) (mitCa(2+)) retention in cells treated with Aβ. Aβ-induced Cai(2+) and mitCa(2+) rise were inhibited by ifenprodil, an antagonist of GluN2B-containing NMDARs. Exposure to Aβ + NMDA further evoked a higher mitCa(2+) retention, which was ameliorated in GluN2B(-/-) cortical neurons, largely implicating the involvement of this NMDAR subunit. Moreover, pharmacologic inhibition of endoplasmic reticulum (ER) inositol-1,4,5-triphosphate receptor (IP3R) and mitCa(2+) uniporter (MCU) evidenced that Aβ + NMDA-induced mitCa(2+) rise involves ER Ca(2+) release through IP3R and mitochondrial entry by the MCU. Altogether, data highlight mitCa(2+) dyshomeostasis and subsequent dysfunction as mechanisms relevant for early neuronal dysfunction in AD linked to Aβ-mediated GluN2B-composed NMDARs activation. PMID:25442114

  16. Determination of Dehydrogenase Activities Involved in D-Glucose Oxidation in Gluconobacter and Acetobacter Strains

    PubMed Central

    Sainz, Florencia; Jesús Torija, María; Matsutani, Minenosuke; Kataoka, Naoya; Yakushi, Toshiharu; Matsushita, Kazunobu; Mas, Albert

    2016-01-01

    Acetic acid bacteria (AAB) are known for rapid and incomplete oxidation of an extensively variety of alcohols and carbohydrates, resulting in the accumulation of organic acids as the final products. These oxidative fermentations in AAB are catalyzed by PQQ- or FAD- dependent membrane-bound dehydrogenases. In the present study, the enzyme activity of the membrane-bound dehydrogenases [membrane-bound PQQ-glucose dehydrogenase (mGDH), D-gluconate dehydrogenase (GADH) and membrane-bound glycerol dehydrogenase (GLDH)] involved in the oxidation of D-glucose and D-gluconic acid (GA) was determined in six strains of three different species of AAB (three natural and three type strains). Moreover, the effect of these activities on the production of related metabolites [GA, 2-keto-D-gluconic acid (2KGA) and 5-keto-D-gluconic acid (5KGA)] was analyzed. The natural strains belonging to Gluconobacter showed a high mGDH activity and low activity in GADH and GLDH, whereas the Acetobacter malorum strain presented low activity in the three enzymes. Nevertheless, no correlation was observed between the activity of these enzymes and the concentration of the corresponding metabolites. In fact, all the tested strains were able to oxidize D-glucose to GA, being maximal at the late exponential phase of the AAB growth (24 h), which coincided with D-glucose exhaustion and the maximum mGDH activity. Instead, only some of the tested strains were capable of producing 2KGA and/or 5KGA. In the case of Gluconobacter oxydans strains, no 2KGA production was detected which is related to the absence of GADH activity after 24 h, while in the remaining strains, detection of GADH activity after 24 h resulted in a high accumulation of 2KGA. Therefore, it is possible to choose the best strain depending on the desired product composition. Moreover, the sequences of these genes were used to construct phylogenetic trees. According to the sequence of gcd, gene coding for mGDH, Acetobacter and Komagataeibacter

  17. Determination of Dehydrogenase Activities Involved in D-Glucose Oxidation in Gluconobacter and Acetobacter Strains.

    PubMed

    Sainz, Florencia; Jesús Torija, María; Matsutani, Minenosuke; Kataoka, Naoya; Yakushi, Toshiharu; Matsushita, Kazunobu; Mas, Albert

    2016-01-01

    Acetic acid bacteria (AAB) are known for rapid and incomplete oxidation of an extensively variety of alcohols and carbohydrates, resulting in the accumulation of organic acids as the final products. These oxidative fermentations in AAB are catalyzed by PQQ- or FAD- dependent membrane-bound dehydrogenases. In the present study, the enzyme activity of the membrane-bound dehydrogenases [membrane-bound PQQ-glucose dehydrogenase (mGDH), D-gluconate dehydrogenase (GADH) and membrane-bound glycerol dehydrogenase (GLDH)] involved in the oxidation of D-glucose and D-gluconic acid (GA) was determined in six strains of three different species of AAB (three natural and three type strains). Moreover, the effect of these activities on the production of related metabolites [GA, 2-keto-D-gluconic acid (2KGA) and 5-keto-D-gluconic acid (5KGA)] was analyzed. The natural strains belonging to Gluconobacter showed a high mGDH activity and low activity in GADH and GLDH, whereas the Acetobacter malorum strain presented low activity in the three enzymes. Nevertheless, no correlation was observed between the activity of these enzymes and the concentration of the corresponding metabolites. In fact, all the tested strains were able to oxidize D-glucose to GA, being maximal at the late exponential phase of the AAB growth (24 h), which coincided with D-glucose exhaustion and the maximum mGDH activity. Instead, only some of the tested strains were capable of producing 2KGA and/or 5KGA. In the case of Gluconobacter oxydans strains, no 2KGA production was detected which is related to the absence of GADH activity after 24 h, while in the remaining strains, detection of GADH activity after 24 h resulted in a high accumulation of 2KGA. Therefore, it is possible to choose the best strain depending on the desired product composition. Moreover, the sequences of these genes were used to construct phylogenetic trees. According to the sequence of gcd, gene coding for mGDH, Acetobacter and Komagataeibacter

  18. Bakuchiol Is a Phenolic Isoprenoid with Novel Enantiomer-selective Anti-influenza A Virus Activity Involving Nrf2 Activation*

    PubMed Central

    Shoji, Masaki; Arakaki, Yumie; Esumi, Tomoyuki; Kohnomi, Shuntaro; Yamamoto, Chihiro; Suzuki, Yutaka; Takahashi, Etsuhisa; Konishi, Shiro; Kido, Hiroshi; Kuzuhara, Takashi

    2015-01-01

    Influenza represents a substantial threat to human health and requires novel therapeutic approaches. Bakuchiol is a phenolic isoprenoid compound present in Babchi (Psoralea corylifolia L.) seeds. We examined the anti-influenza viral activity of synthetic bakuchiol using Madin-Darby canine kidney cells. We found that the naturally occurring form, (+)-(S)-bakuchiol, and its enantiomer, (−)-(R)-bakuchiol, inhibited influenza A viral infection and growth and reduced the expression of viral mRNAs and proteins in these cells. Furthermore, these compounds markedly reduced the mRNA expression of the host cell influenza A virus-induced immune response genes, interferon-β and myxovirus-resistant protein 1. Interestingly, (+)-(S)-bakuchiol had greater efficacy than (−)-(R)-bakuchiol, indicating that chirality influenced anti-influenza virus activity. In vitro studies indicated that bakuchiol did not strongly inhibit the activities of influenza surface proteins or the M2 ion channel, expressed in Chinese hamster ovary cells. Analysis of luciferase reporter assay data unexpectedly indicated that bakuchiol may induce some host cell factor(s) that inhibited firefly and Renilla luciferases. Next generation sequencing and KeyMolnet analysis of influenza A virus-infected and non-infected cells exposed to bakuchiol revealed activation of transcriptional regulation by nuclear factor erythroid 2-related factor (Nrf), and an Nrf2 reporter assay showed that (+)-(S)-bakuchiol activated Nrf2. Additionally, (+)-(S)-bakuchiol up-regulated the mRNA levels of two Nrf2-induced genes, NAD(P)H quinone oxidoreductase 1 and glutathione S-transferase A3. These findings demonstrated that bakuchiol had enantiomer-selective anti-influenza viral activity involving a novel effect on the host cell oxidative stress response. PMID:26446794

  19. Molecular Genetic Analysis of Activation-tagged Transcription Factors Thought to be Involved in Photomorphogenesis

    SciTech Connect

    Neff, Michael

    2011-06-23

    Plants utilize light as a source of information via families of photoreceptors such as the red/far-red absorbing phytochromes (PHY) and the blue/UVA absorbing cryptochromes (CRY). The main goal of the Neff lab is to use molecular-genetic mutant screens to elucidate signaling components downstream of these photoreceptors. Activation-tagging mutagenesis led to the identification of two putative transcription factors that may be involved in both photomorphogenesis and hormone signaling pathways. sob1-D (suppressor of phyB-dominant) mutant phenotypes are caused by the over-expression of a Dof transcription factor previously named OBP3. Our previous studies indicate that OBP3 is a negative regulator of light-mediated cotyledon expansion and may be involved in modulating responsiveness to the growth-regulating hormone auxin. The sob2-D mutant uncovers a role for LEP, a putative AP2/EREBP-like transcription factor, in seed germination, hypocotyl elongation and responsiveness to the hormone abscisic acid. Based on photobiological and genetic analysis of OBP3-knockdown and LEP-null mutations, we hypothesize that these transcription factors are involved in both light-mediated seedling development and hormone signaling. To examine the role that these genes play in photomorphogenesis we will: 1) Further explore the genetic role of OBP3 in cotyledon/leaf expansion and other photomorphogenic processes as well as examine potential physical interactions between OBP3 and CRY1 or other signaling components that genetically interact with this transcription factor 2) Test the hypothesis that OBP3 is genetically involved in auxin signaling and root development as well as examine the affects of this hormone and light on OBP3 protein accumulation. 3) Test the hypothesis that LEP is involved in seed germination, seedling photomorphogenesis and hormone signaling. Together these experiments will lead to a greater understanding of the complexity of interactions between photoreceptors and DNA

  20. Improving the active involvement of stakeholders and the public in flood risk management - tools of an involvement strategy and case study results from Austria, Germany and Italy

    NASA Astrophysics Data System (ADS)

    Fleischhauer, M.; Greiving, S.; Flex, F.; Scheibel, M.; Stickler, T.; Sereinig, N.; Koboltschnig, G.; Malvati, P.; Vitale, V.; Grifoni, P.; Firus, K.

    2012-09-01

    The EU Flood Risk Management Directive 2007/60/EC aims at an active involvement of interested parties in the setting up of flood risk management plans and thus calls for more governance-related decision-making. This requirement has two perspectives. On the one hand, there is (1) the question of how decision-makers can improve the quality of their governance process. On the other hand, there is (2) the question of how the public shall be appropriately informed and involved. These questions were the centre of the ERA-Net CRUE-funded project IMRA (integrative flood risk governance approach for improvement of risk awareness) that aimed at an optimisation of the flood risk management process by increasing procedural efficiency with an explicit involvement strategy. To reach this goal, the IMRA project partners developed two new approaches that were implemented in three case study areas for the first time in flood risk management: 1. risk governance assessment tool: An indicator-based benchmarking and monitoring tool was used to evaluate the performance of a flood risk management system in regard to ideal risk governance principles; 2. social milieu approach: The concept of social milieus was used to gain a picture of the people living in the case study regions to learn more about their lifestyles, attitudes and values and to use this knowledge to plan custom-made information and participation activities for the broad public. This paper presents basic elements and the application of two innovative approaches as a part of an "involvement strategy" that aims at the active involvement of all interested parties (stakeholders) for assessing, reviewing and updating flood risk management plans, as formulated in the EU Flood Risk Management Directive 2007/60/EC.

  1. Yarrowia lipolytica AAL genes are involved in peroxisomal fatty acid activation.

    PubMed

    Dulermo, Rémi; Gamboa-Meléndez, Heber; Ledesma-Amaro, Rodrigo; Thevenieau, France; Nicaud, Jean-Marc

    2016-07-01

    In yeast, β-oxidation of fatty acids (FAs) essentially takes place in peroxisomes, and FA activation must precede FA oxidation. In Saccharomyces cerevisiae, a single fatty-acyl–CoA-synthetase, ScFaa2p, mediates peroxisomal FA activation. We have previously shown that this reaction also exists in the oleaginous yeast Yarrowia lipolytica; however, the protein involved in this process remains unknown. Here, we found that proteins, named Aal proteins (Acyl/Aryl-CoA-ligases), resembling the 4-coumarate–CoA-ligase-like enzymes found in plants are involved in peroxisomal FA activation in Y. lipolytica; Y. lipolytica has 10 AAL genes, eight of which are upregulated by oleate. All the Aal proteins contain a PTS1-type peroxisomal targeting sequence (A/SKL), suggesting a peroxisomal localization. The function of the Aal proteins was analyzed using the faa1Δant1Δ mutant strain, which demonstrates neither cytoplasmic FA activation (direct result of FAA1 deletion) nor peroxisomal FA activation (indirect result of ANT1 deletion, a gene coding an ATP transporter). This strain is thus highly sensitive to external FA levels and unable to store external FAs in lipid bodies (LBs). Whereas the overexpression of (cytoplasmic) AAL1ΔPTS1 was able to partially complement the growth defect observed in the faa1Δant1Δ mutant on short-, medium- and long-chain FA media, the presence of Aal2p to Aal10p only allowed growth on the short-chain FA medium. Additionally, partial LB formation was observed in the oleate medium for strains overexpressing Aal1ΔPTS1p, Aal4ΔPTS1p, Aal7ΔPTS1p, and Aal8ΔPTS1p. Finally, an analysis of the FA content of cells grown in the oleate medium suggested that Aal4p and Aal6p present substrate specificity for C16:1 and/or C18:0. PMID:27067366

  2. atRA-induced apoptosis of mouse embryonic palate mesenchymal cells involves activation of MAPK pathway

    SciTech Connect

    Yu Zengli . E-mail: yuzengli@263.net; Xing Ying . E-mail: xingy@zzu.edu.cn

    2006-08-15

    Our previous studies have shown that atRA treatment resulted in cell-cycle block and growth inhibition in mouse embryonic palatal mesenchymal (MEPM). In the current study, gestation day (GD) 13 MEPM cells were used to test the hypothesis that the growth inhibition by atRA is due to apoptosis. The effects of atRA on apoptosis were assessed by performing MTT assay, Cell Death Detection ELISA and flow cytometry, respectively. Data analysis confirmed that atRA treatment induced apoptosis-like cell death, as shown by decreased cell viability and increased fragmented DNA and sub-G1 fraction. atRA-induced apoptosis was associated with upregulation of bcl-2, translocation of bax protein to the mitochondria from the cytosol, activation of caspase-3 and cytochrome c release into cytosol. atRA-induced apoptosis was abrogated by z-DEVD-fmk, a caspase-3 specific inhibitor, and z-VAD-fmk, a general caspase inhibitor, suggesting that the atRA-induced cell death of MEPM cells occurs through the cytochrome c- and caspase-3-dependent pathways. In addition, atRA treatment caused a strong and sustained activation of c-Jun N-terminal kinase (JNK) and p38 kinase (p38), as well as an early but transient activation of extracellular signal-regulated kinase (ERK). Importantly, atRA-induced DNA fragmentation and capase-3 activation were prevented by pretreatment with the JNK inhibitor (SP600125) and the p38 MAPK inhibitor (SB202190), but not by pretreatment with MEK inhibitor (U0126). From these results, we suggest that mitogen-activated protein kinase-dependent pathways is involved in the atRA-induced apoptosis of MEPM cells.

  3. I. Evidence that lymphotoxin activity involves both cytotoxic and stimulating factors.

    PubMed

    Ryzewska, A G; Darbrowska, B K

    1976-11-01

    This paper describes experiments undertaken to determine more uniform conditions for the generation of cytotoxic lymphokine--'lymphotoxin' (LT) in differently stimulated rat lymphocyte cultures, and to compare the sensitivity of different test systems for detecting rat LT activity in vitro. Wistar rat lymphoid cells were activated by culture with phytohaemagglutinin (PHA) and mixed lymphocyte cultures (MLC) with semi-allogeneic (Wistar x August) F1 lymphoid cells. Lymphocyte supernatants harvested between 1 and 8 days were tested for their effect on metabolism and viability of cultured mouse fibroblasts (L-929 cells) by four methods: (i) inhibition of [14C]leucine incorporation; (ii) total and viable cell counts in test tube cultures ('macro test'); (iii) viable cell counts in microtitre plates ('microtest'); and (iv) chromium (51Cr) release from chromated L-cell monolayers. Cytotoxic effects on target cells of lymphocyte supernatants were evident after 3 days of PHA stimulation and 6 days of mixed lymphocyte culture, and the most sensitive indication of cytotoxic activity provided by inhibition of amino-acid incorporation and by loss of viable L cells from monolayers in tube cultures. In dilutions greater than 1:16-1:32 both cytotoxic supernatants exhibited a stimulating effect on target-cell proliferation. Stimulation of L cells growth was also observed when monolayers were exposed for 24 h to 'early' (24 h) PHA undiluted supernatants. At a later time of exposure to these supernatants a considerable loss of total and viable cells in the monolayers was evident. The results indicated that both cytotoxic and growth-stimulating lymphokines could be generated during activation of rat lymphocytes. A hypothesis is suggested whereby 'lymphotoxin' activity in vitro arises from the sequential effects of stimulating and cytotoxic lymphokine, and whereby the balance of these effects in vivo might determine the response of fibroblasts involved in reactions of chronic allergic

  4. Hereditary benign telangiectasia: first case in Iran.

    PubMed

    Javidi, Zari; Maleki, M; Mashayekhi, V; Nahidi, Y; Omidvar Borna, A

    2006-07-01

    A 14-year-old boy was referred to the Dermatology Clinic of the Medical University of Mashhad, Iran, with numerous cutaneous telangiectasias on the face, ears, lips, and back of the hands, with lesions in the temporal region being the first to appear (Figs 1-3). His mother stated that the lesions had been present for 10 years with an increase in the past 6 months. He had no history of bleeding from the nose, mouth, gastrointestinal tract, and other mucosal surfaces, and there was no sign of organ involvement. On inspection, no lesions were detected on the nasal mucosa, external ear, over the tympanic membrane, or mouth. The patient is one member of a family of six. His mother is healthy, but similar lesions were seen in his father, sister and one of his brothers with similar distributions. Lesions were also seen in his aunt and paternal grandmother, showing disease distribution in six members of this family from three generations. The oldest brother is 20 years of age and mentioned the onset of disease from the age of 10 years. The sister is 18 years of age and lesions started to appear 7 years ago; she claims that the lesions regress during her menstrual period. The youngest brother is 4 years of age and shows no sign of cutaneous lesions as yet. The parents are not consanguineous. Generalized telangiectasia with a predominant distribution on light-exposed skin, an autosomal dominant inheritance, and no sign of systemic or mucosal involvement and bleeding disorders indicates a diagnosis of hereditary benign telangiectasia. Our patient did not consent to biopsy. PMID:16863520

  5. Synthesis and Characterization of Environmentally Benign Nanoparticles

    EPA Science Inventory

    There has been a growing interest in replacing current non-biodegradable and toxic nanosystems with environmentally benign biopolymer based ones to minimize post-utilization hazards due to uncontrolled accumulation of nanoparticles in the environment. Lignin based nanoparticles (...

  6. ENVIRONMENTALLY-BENIGN MULTIPHASE CATALYSIS. (R826034)

    EPA Science Inventory

    Environmental concerns stemming from the use of conventional solvents and from hazardous waste generation have propelled research efforts aimed at developing benign chemical processing techniques that either eliminate or significantly mitigate pollution at the source. This pap...

  7. Influenza A Virus Panhandle Structure Is Directly Involved in RIG-I Activation and Interferon Induction

    PubMed Central

    Liu, GuanQun; Park, Hong-Su; Pyo, Hyun-Mi; Liu, Qiang

    2015-01-01

    ABSTRACT Retinoic acid-inducible gene I (RIG-I) is an important innate immune sensor that recognizes viral RNA in the cytoplasm. Its nonself recognition largely depends on the unique RNA structures imposed by viral RNA. The panhandle structure residing in the influenza A virus (IAV) genome, whose primary function is to serve as the viral promoter for transcription and replication, has been proposed to be a RIG-I agonist. However, this has never been proved experimentally. Here, we employed multiple approaches to determine if the IAV panhandle structure is directly involved in RIG-I activation and type I interferon (IFN) induction. First, in porcine alveolar macrophages, we demonstrated that the viral genomic coding region is dispensable for RIG-I-dependent IFN induction. Second, using in vitro-synthesized hairpin RNA, we showed that the IAV panhandle structure could directly bind to RIG-I and stimulate IFN production. Furthermore, we investigated the contributions of the wobble base pairs, mismatch, and unpaired nucleotides within the wild-type panhandle structure to RIG-I activation. Elimination of these destabilizing elements within the panhandle structure promoted RIG-I activation and IFN induction. Given the function of the panhandle structure as the viral promoter, we further monitored the promoter activity of these panhandle variants and found that viral replication was moderately affected, whereas viral transcription was impaired dramatically. In all, our results indicate that the IAV panhandle promoter region adopts a nucleotide composition that is optimal for balanced viral RNA synthesis and suboptimal for RIG-I activation. IMPORTANCE The IAV genomic panhandle structure has been proposed to be an RIG-I agonist due to its partial complementarity; however, this has not been experimentally confirmed. Here, we provide direct evidence that the IAV panhandle structure is competent in, and sufficient for, RIG-I activation and IFN induction. By constructing

  8. Flagellin-induced NADPH oxidase 4 activation is involved in atherosclerosis

    PubMed Central

    Kim, Jinoh; Seo, Misun; Kim, Su Kyung; Bae, Yun Soo

    2016-01-01

    It is widely accepted that bacterial infection-mediated inflammation facilitates development of atherosclerosis by activating toll-like receptor (TLR) signaling system. We reasoned that NADPH oxidases (Nox), required for TLR-mediated inflammatory response, are involved in atherogenesis. Here, we show that the activation of Nox4 through TLR5 regulates the inflammation of the endothelium and in atherogenesis. Flagellin-induced interaction between the COOH region of Nox4 and the TIR domain of TLR5 led to H2O2 generation, which in turn promoted the secretion of pro-inflammatory cytokines including IL-8, as well as the expression of ICAM-1 in human aortic endothelial cells (HAECs). Knockdown of the Nox4 in HAECs resulted in attenuated expressions of IL-8 and ICAM-1 leading to a reduction in the adhesion and trans-endothelial migration of monocytes. Challenge of recombinant FliC (rFliC) to the ApoE KO mice with high-fat diet (HFD) resulted in significantly increased atherosclerotic plaque sizes compared to the saline-injected mice. However, an injection of rFliC into the Nox4ApoE DKO mice with HFDs failed to generate atherosclerotic plaque, suggesting that Nox4 deficiency resulted in significant protections against rFliC-mediated atherogenesis. We conclude that TLR5-dependent Nox4 activation and subsequent H2O2 generation play critical roles for the development of atherosclerosis. PMID:27146088

  9. TRAIL induces necroptosis involving RIPK1/RIPK3-dependent PARP-1 activation

    PubMed Central

    Jouan-Lanhouet, S; Arshad, M I; Piquet-Pellorce, C; Martin-Chouly, C; Le Moigne-Muller, G; Van Herreweghe, F; Takahashi, N; Sergent, O; Lagadic-Gossmann, D; Vandenabeele, P; Samson, M; Dimanche-Boitrel, M-T

    2012-01-01

    Although TRAIL (tumor necrosis factor (TNF)-related apoptosis inducing ligand) is a well-known apoptosis inducer, we have previously demonstrated that acidic extracellular pH (pHe) switches TRAIL-induced apoptosis to regulated necrosis (or necroptosis) in human HT29 colon and HepG2 liver cancer cells. Here, we investigated the role of RIPK1 (receptor interacting protein kinase 1), RIPK3 and PARP-1 (poly (ADP-ribose) polymerase-1) in TRAIL-induced necroptosis in vitro and in concanavalin A (Con A)-induced murine hepatitis. Pretreatment of HT29 or HepG2 with pharmacological inhibitors of RIPK1 or PARP-1 (Nec-1 or PJ-34, respectively), or transient transfection with siRNAs against RIPK1 or RIPK3, inhibited both TRAIL-induced necroptosis and PARP-1-dependent intracellular ATP depletion demonstrating that RIPK1 and RIPK3 were involved upstream of PARP-1 activation and ATP depletion. In the mouse model of Con A-induced hepatitis, where death of mouse hepatocytes is dependent on TRAIL and NKT (Natural Killer T) cells, PARP-1 activity was positively correlated with liver injury and hepatitis was prevented both by Nec-1 or PJ-34. These data provide new insights into TRAIL-induced necroptosis with PARP-1 being active effector downstream of RIPK1/RIPK3 initiators and suggest that pharmacological inhibitors of RIPKs and PARP-1 could be new treatment options for immune-mediated hepatitis. PMID:22814620

  10. Astragaloside IV enhances diabetic wound healing involving upregulation of alternatively activated macrophages.

    PubMed

    Luo, Xiaochun; Huang, Ping; Yuan, Baohong; Liu, Tao; Lan, Fang; Lu, Xiaoyan; Dai, Liangcheng; Liu, Yunjun; Yin, Hui

    2016-06-01

    Astragaloside IV (AS-IV), one of the major active compounds extracted from Astragali Radix, has been used experimentally for its potent antiinflammatory and immunoregulatory activities. In this study, we further investigate the potential efficacy of AS-IV on impaired wound healing in streptozotocin-induced diabetic mice. A full-thickness skin wound was produced on the back of diabetic mice and treated with AS-IV or vehicle topically. Our results showed that AS-IV application promoted diabetic wound repair with wounds gaping narrower and exhibiting augmented reepithelialization. AS-IV enhanced the collagen deposition and the expression of extracellular matrix (ECM)-related genes such as fibronectin and collagen IIIa, which implies a direct effect of AS-IV on matrix synthesis. AS-IV also improved the new blood vessel formation in wound tissue with increased numbers of endothelial cells and enhanced expression of VEGF and vWF. Moreover, the beneficial effect of AS-IV was related to the development of polarized alternatively activated macrophages, which involved in resolution of inflammation and facilitation of wound repair. All together, these findings suggest that AS-IV may play a potential effect on maintenance of cutaneous homeostasis and acceleration of diabetic wound healing. PMID:27016716

  11. Flagellin-induced NADPH oxidase 4 activation is involved in atherosclerosis.

    PubMed

    Kim, Jinoh; Seo, Misun; Kim, Su Kyung; Bae, Yun Soo

    2016-01-01

    It is widely accepted that bacterial infection-mediated inflammation facilitates development of atherosclerosis by activating toll-like receptor (TLR) signaling system. We reasoned that NADPH oxidases (Nox), required for TLR-mediated inflammatory response, are involved in atherogenesis. Here, we show that the activation of Nox4 through TLR5 regulates the inflammation of the endothelium and in atherogenesis. Flagellin-induced interaction between the COOH region of Nox4 and the TIR domain of TLR5 led to H2O2 generation, which in turn promoted the secretion of pro-inflammatory cytokines including IL-8, as well as the expression of ICAM-1 in human aortic endothelial cells (HAECs). Knockdown of the Nox4 in HAECs resulted in attenuated expressions of IL-8 and ICAM-1 leading to a reduction in the adhesion and trans-endothelial migration of monocytes. Challenge of recombinant FliC (rFliC) to the ApoE KO mice with high-fat diet (HFD) resulted in significantly increased atherosclerotic plaque sizes compared to the saline-injected mice. However, an injection of rFliC into the Nox4ApoE DKO mice with HFDs failed to generate atherosclerotic plaque, suggesting that Nox4 deficiency resulted in significant protections against rFliC-mediated atherogenesis. We conclude that TLR5-dependent Nox4 activation and subsequent H2O2 generation play critical roles for the development of atherosclerosis. PMID:27146088

  12. Activation of PPAR{gamma} is not involved in butyrate-induced epithelial cell differentiation

    SciTech Connect

    Ulrich, S.; Waechtershaeuser, A.; Loitsch, S.; Knethen, A. von; Bruene, B.; Stein, J. . E-mail: j.stein@em.uni-frankfurt.de

    2005-10-15

    Histone deacetylase-inhibitors affect growth and differentiation of intestinal epithelial cells by inducing expression of several transcription factors, e.g. Peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) or vitamin D receptor (VDR). While activation of VDR by butyrate mainly seems to be responsible for cellular differentiation, the activation of PPAR{gamma} in intestinal cells remains to be elucidated. The aim of this study was to determine the role of PPAR{gamma} in butyrate-induced cell growth inhibition and differentiation induction in Caco-2 cells. Treatment with PPAR{gamma} ligands ciglitazone and BADGE (bisphenol A diglycidyl) enhanced butyrate-induced cell growth inhibition in a dose- and time-dependent manner, whereas cell differentiation was unaffected after treatment with PPAR{gamma} ligands rosiglitazone and MCC-555. Experiments were further performed in dominant-negative PPAR{gamma} mutant cells leading to an increase in cell growth whereas butyrate-induced cell differentiation was again unaffected. The present study clearly demonstrated that PPAR{gamma} is involved in butyrate-induced inhibition of cell growth, but seems not to play an essential role in butyrate-induced cell differentiation.

  13. Transmembrane myosin chitin synthase involved in mollusc shell formation produced in Dictyostelium is active

    SciTech Connect

    Schoenitzer, Veronika; Eichner, Norbert; Clausen-Schaumann, Hauke; Weiss, Ingrid M.

    2011-12-02

    Highlights: Black-Right-Pointing-Pointer Dictyostelium produces the 264 kDa myosin chitin synthase of bivalve mollusc Atrina. Black-Right-Pointing-Pointer Chitin synthase activity releases chitin, partly associated with the cell surface. Black-Right-Pointing-Pointer Membrane extracts of transgenic slime molds produce radiolabeled chitin in vitro. Black-Right-Pointing-Pointer Chitin producing Dictyostelium cells can be characterized by atomic force microscopy. Black-Right-Pointing-Pointer This model system enables us to study initial processes of chitin biomineralization. -- Abstract: Several mollusc shells contain chitin, which is formed by a transmembrane myosin motor enzyme. This protein could be involved in sensing mechanical and structural changes of the forming, mineralizing extracellular matrix. Here we report the heterologous expression of the transmembrane myosin chitin synthase Ar-CS1 of the bivalve mollusc Atrina rigida (2286 amino acid residues, M.W. 264 kDa/monomer) in Dictyostelium discoideum, a model organism for myosin motor proteins. Confocal laser scanning immunofluorescence microscopy (CLSM), chitin binding GFP detection of chitin on cells and released to the cell culture medium, and a radiochemical activity assay of membrane extracts revealed expression and enzymatic activity of the mollusc chitin synthase in transgenic slime mold cells. First high-resolution atomic force microscopy (AFM) images of Ar-CS1 transformed cellulose synthase deficient D. discoideumdcsA{sup -} cell lines are shown.

  14. Regulation of retinoid mediated cholesterol efflux involves liver X receptor activation in mouse macrophages.

    PubMed

    Manna, Pulak R; Sennoune, Souad R; Martinez-Zaguilan, Raul; Slominski, Andrzej T; Pruitt, Kevin

    2015-08-14

    Removal of cholesterol from macrophage-derived foam cells is a critical step to the prevention of atherosclerotic lesions. We have recently demonstrated the functional importance of retinoids in the regulation of the steroidogenic acute regulatory (StAR) protein that predominantly mediates the intramitochondrial transport of cholesterol in target tissues. In the present study, treatment of mouse macrophages with retinoids, particularly all-trans retinoic acid (atRA) and 9-cis RA, resulted in increases in cholesterol efflux to apolipoprotein AI (Apo-A1). Activation of the PKA pathway by a cAMP analog, (Bu)2cAMP, markedly augmented retinoid mediated cholesterol efflux. Macrophages overexpressing hormone-sensitive lipase increased the hydrolysis of cholesteryl esters and concomitantly enhanced the efficacy of retinoic acid receptor and liver X receptor (LXR) ligands on StAR and ATP-binding cassette transporter A1 (ABCA1) protein levels. RAs elevated StAR promoter activity in macrophages, and an increase in StAR levels augmented cholesterol efflux to Apo-A1, suggesting retinoid-mediated efflux of cholesterol involves enhanced oxysterol production. Further studies revealed that retinoids activate the LXR regulated genes, sterol receptor-element binding protein-1c and ABCA1. These findings provide insights into the regulatory events in which retinoid signaling effectively enhances macrophage cholesterol efflux and indicate that retinoid therapy may have important implications in limiting and/or regressing atherosclerotic cardiovascular disease. PMID:26119689

  15. (-)-Linalool inhibits in vitro NO formation: Probable involvement in the antinociceptive activity of this monoterpene compound.

    PubMed

    Peana, Alessandra T; Marzocco, Stefania; Popolo, Ada; Pinto, Aldo

    2006-01-11

    Recent studies performed in our laboratory have shown that (-)-linalool, the natural occurring enantiomer in essential oils, possesses anti-inflammatory, antihyperalgesic and antinociceptive effects in different animal models. The antinociceptive and antihyperalgesic effect of (-)-linalool has been ascribed to the stimulation of the cholinergic, opioidergic and dopaminergic systems, to its local anaesthetic activity and to the blockade of N-Methyl-d-aspartate receptors (NMDA). Since nitric oxide (NO) and prostaglandin E(2) (PGE(2)) play an important role in oedema formation and hyperalgesia and nociception development, to investigate the mechanism of these actions of the (-)-linalool, we examined the effects of this compound on lipopolysaccharide (LPS)-induced responses in macrophage cell line J774.A1. Exposure of LPS-stimulated cells to (-)-linalool significantly inhibited nitrite accumulation in the culture medium without inhibiting the LPS-stimulated increase of inducible nitric oxide synthase (iNOS) expression, suggesting that the inhibitory activity of (-)-linalool is mainly due to the iNOS enzyme activity. In contrast, exposure of LPS-stimulated cells to (-)-linalool failed, if not at the highest concentration, both in inhibiting PGE(2) release and in inhibiting increase of inducible cyclooxygenase-2 (COX(2)) expression in the culture medium. Collectively, these results indicate that the reduction of NO production/release is responsible, at least partially, for the molecular mechanisms of (-)-linalool antinociceptive effect, probably through mechanisms where cholinergic and glutamatergic systems are involved. PMID:16137709

  16. A simple methodology to assess endolysosomal protease activity involved in antigen processing in human primary cells

    PubMed Central

    2013-01-01

    Background Endolysosomes play a key role in maintaining the homeostasis of the cell. They are made of a complex set of proteins that degrade lipids, proteins and sugars. Studies involving endolysosome contribution to cellular functions such as MHC class I and II epitope production have used recombinant endolysosomal proteins, knockout mice that lack one of the enzymes or purified organelles from human tissue. Each of these approaches has some caveats in analyzing endolysosomal enzyme functions. Results In this study, we have developed a simple methodology to assess endolysosomal protease activity. By varying the pH in crude lysate from human peripheral blood mononuclear cells (PBMCs), we documented increased endolysosomal cathepsin activity in acidic conditions. Using this new method, we showed that the degradation of HIV peptides in low pH extracts analyzed by mass spectrometry followed similar kinetics and degradation patterns as those performed with purified endolysosomes. Conclusion By using crude lysate in the place of purified organelles this method will be a quick and useful tool to assess endolysosomal protease activities in primary cells of limited availability. This quick method will especially be useful to screen peptide susceptibility to degradation in endolysosomal compartments for antigen processing studies, following which detailed analysis using purified organelles may be used to study specific peptides. PMID:23937268

  17. Cell-matrix interactions modulate interstitial collagenase expression by human keratinocytes actively involved in wound healing.

    PubMed Central

    Saarialho-Kere, U K; Kovacs, S O; Pentland, A P; Olerud, J E; Welgus, H G; Parks, W C

    1993-01-01

    We reported that interstitial collagenase is produced by keratinocytes at the edge of ulcers in pyogenic granuloma, and in this report, we assessed if production of this metalloproteinase is a common feature of the epidermal response in a variety of wounds. In all samples of chronic ulcers, regardless of etiology, and in incision wounds, collagenase mRNA, localized by in situ hybridization, was prominently expressed by basal keratinocytes bordering the sites of active re-epithelialization indicating that collagenolytic activity is a characteristic response of the epidermis to wounding. No expression of mRNAs for 72- and 92-kD gelatinases or matrilysin was seen in keratinocytes, and no signal for any metalloproteinase was detected in normal epidermis. Immunostaining for type IV collagen showed that collagenase-positive keratinocytes were not in contact with an intact basement membrane and, unlike normal keratinocytes, expressed alpha 5 beta 1 receptors. These observations suggest that cell-matrix interactions influence collagenase expression by epidermal cells. Indeed, as determined by ELISA, primary cultures of human keratinocytes grown on basement membrane proteins (Matrigel; Collaborative Research Inc., Bedford, MA) did not express significant levels of collagenase, whereas cells grown on type I collagen produced markedly increased levels. These results suggest that migrating keratinocytes actively involved in re-epithelialization acquire a collagenolytic phenotype upon contact with the dermal matrix. Images PMID:8254040

  18. Inflammatory Responses in a Benign Prostatic Hyperplasia Epithelial Cell Line (BPH-1) Infected with Trichomonas vaginalis.

    PubMed

    Kim, Sang-Su; Kim, Jung-Hyun; Han, Ik-Hwan; Ahn, Myoung-Hee; Ryu, Jae-Sook

    2016-04-01

    Trichomonas vaginalis causes the most prevalent sexually transmitted infection worldwide. Trichomonads have been detected in prostatic tissues from prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer. Chronic prostatic inflammation is known as a risk factor for prostate enlargement, benign prostatic hyperplasia symptoms, and acute urinary retention. Our aim was to investigate whether T. vaginalis could induce inflammatory responses in cells of a benign prostatic hyperplasia epithelial cell line (BPH-1). When BPH-1 cells were infected with T. vaginalis, the protein and mRNA of inflammatory cytokines, such as CXCL8, CCL2, IL-1β, and IL-6, were increased. The activities of TLR4, ROS, MAPK, JAK2/STAT3, and NF-κB were also increased, whereas inhibitors of ROS, MAPK, PI3K, NF-κB, and anti-TLR4 antibody decreased the production of the 4 cytokines although the extent of inhibition differed. However, a JAK2 inhibitor inhibited only IL-6 production. Culture supernatants of the BPH-1 cells that had been incubated with live T. vaginalis (trichomonad-conditioned medium, TCM) contained the 4 cytokines and induced the migration of human monocytes (THP-1 cells) and mast cells (HMC-1 cells). TCM conditioned by BPH-1 cells pretreated with NF-κB inhibitor showed decreased levels of cytokines and induced less migration. Therefore, it is suggested that these cytokines are involved in migration of inflammatory cells. These results suggest that T. vaginalis infection of BPH patients may cause inflammation, which may induce lower urinary tract symptoms (LUTS). PMID:27180569

  19. Inflammatory Responses in a Benign Prostatic Hyperplasia Epithelial Cell Line (BPH-1) Infected with Trichomonas vaginalis

    PubMed Central

    Kim, Sang-Su; Kim, Jung-Hyun; Han, Ik-Hwan; Ahn, Myoung-Hee; Ryu, Jae-Sook

    2016-01-01

    Trichomonas vaginalis causes the most prevalent sexually transmitted infection worldwide. Trichomonads have been detected in prostatic tissues from prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer. Chronic prostatic inflammation is known as a risk factor for prostate enlargement, benign prostatic hyperplasia symptoms, and acute urinary retention. Our aim was to investigate whether T. vaginalis could induce inflammatory responses in cells of a benign prostatic hyperplasia epithelial cell line (BPH-1). When BPH-1 cells were infected with T. vaginalis, the protein and mRNA of inflammatory cytokines, such as CXCL8, CCL2, IL-1β, and IL-6, were increased. The activities of TLR4, ROS, MAPK, JAK2/STAT3, and NF-κB were also increased, whereas inhibitors of ROS, MAPK, PI3K, NF-κB, and anti-TLR4 antibody decreased the production of the 4 cytokines although the extent of inhibition differed. However, a JAK2 inhibitor inhibited only IL-6 production. Culture supernatants of the BPH-1 cells that had been incubated with live T. vaginalis (trichomonad-conditioned medium, TCM) contained the 4 cytokines and induced the migration of human monocytes (THP-1 cells) and mast cells (HMC-1 cells). TCM conditioned by BPH-1 cells pretreated with NF-κB inhibitor showed decreased levels of cytokines and induced less migration. Therefore, it is suggested that these cytokines are involved in migration of inflammatory cells. These results suggest that T. vaginalis infection of BPH patients may cause inflammation, which may induce lower urinary tract symptoms (LUTS). PMID:27180569

  20. Implicit trustworthiness ratings of self-resembling faces activate brain centers involved in reward.

    PubMed

    Platek, Steven M; Krill, Austen L; Wilson, Benjamin

    2009-01-01

    On the basis of Hamilton's (Hamilton, W. D. (1964). The genetical evolution of social behavior I, II. Journal of Theoretical Biology, 7, 17-52) theory of inclusive fitness, self-facial resemblance is hypothesized as a mechanism for self-referent phenotypic matching by which humans can detect kin. To understand the mechanisms underlying pro-sociality toward self-resembling faces, we investigated the neural correlates of implicit trustworthiness ratings for self-resembling faces. Here we show that idiosyncratic trustworthiness ratings of self-resembling faces predict brain activation in the ventral inferior, middle and medial frontal gyri, substrates involved in reward processing. These findings demonstrate that neural reward centers are implicated in evaluating implicit pro-social behaviors toward self-resembling faces. These findings suggest that humans have evolved to use neurocomputational architecture dedicated to face processing and reward evaluation for the differentiation of kin, which drives implicit idiosyncratic affectively regulated social interactions. PMID:18761362

  1. Carbohydrate binding activity in human spermatozoa: localization, specificity, and involvement in sperm-egg fusion.

    PubMed

    Gabriele, A; D'Andrea, G; Cordeschi, G; Properzi, G; Giammatteo, M; De Stefano, C; Romano, R; Francavilla, F; Francavilla, S

    1998-06-01

    Sperm carbohydrate binding activity is involved in gamete recognition. We identified a human sperm protein extracted under reducing conditions, and with a molecular mass of 65 kDa on sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), and which binds D-mannose coupled to albumin (DMA) in presence of cations and a neutral pH. Epifluorescence microscopy showed that fluorescein-DMA binds to dead or permeabilized sperm heads. The DMA-binding activity of human sperm heads was highly specific for a polysaccharide structure containing charged sugar residues. After capacitation, or induction of the acrosome reaction using solubilized zonae pellucidae, fluorescein-DMA was bound respectively to 10.3% (+/- 3.5%) and to 37.6% (+/- 2.1%) of viable sperm heads. The sequential analysis of viable spermatozoa for fluorescein-DMA binding and for rhodamine-Pisum sativum agglutinin binding, showed that DMA-binding sites are present in viable acrosome-reacted spermatozoa. Three dimensional analysis of fluorescence and ultrastructural studies showed that DMA-binding sites are mostly restricted to the sub-acrosomal space of the equatorial segment. Incubation of spermatozoa and zona-free hamster eggs in the presence of DMA was associated with a dose-dependent significant reduction in the number of spermatozoa bound to the oolemma, compared with a control, and to a dose-dependent inhibition of oocyte penetration. This effect was highly specific for DMA, suggesting that DMA-binding sites in human spermatozoa are involved in sperm-egg fusion. PMID:9665337

  2. A novel carotenoid cleavage activity involved in the biosynthesis of Citrus fruit-specific apocarotenoid pigments

    PubMed Central

    Rodrigo, María J.; Alquézar, Berta; Al-Babili, Salim

    2013-01-01

    Citrus is the first tree crop in terms of fruit production. The colour of Citrus fruit is one of the main quality attributes, caused by the accumulation of carotenoids and their derivative C30 apocarotenoids, mainly β-citraurin (3-hydroxy-β-apo-8′-carotenal), which provide an attractive orange-reddish tint to the peel of oranges and mandarins. Though carotenoid biosynthesis and its regulation have been extensively studied in Citrus fruits, little is known about the formation of C30 apocarotenoids. The aim of this study was to the identify carotenoid cleavage enzyme(s) [CCD(s)] involved in the peel-specific C30 apocarotenoids. In silico data mining revealed a new family of five CCD4-type genes in Citrus. One gene of this family, CCD4b1, was expressed in reproductive and vegetative tissues of different Citrus species in a pattern correlating with the accumulation of C30 apocarotenoids. Moreover, developmental processes and treatments which alter Citrus fruit peel pigmentation led to changes of β-citraurin content and CCD4b1 transcript levels. These results point to the involvement of CCD4b1 in β-citraurin formation and indicate that the accumulation of this compound is determined by the availability of the presumed precursors zeaxanthin and β-cryptoxanthin. Functional analysis of CCD4b1 by in vitro assays unequivocally demonstrated the asymmetric cleavage activity at the 7′,8′ double bond in zeaxanthin and β-cryptoxanthin, confirming its role in C30 apocarotenoid biosynthesis. Thus, a novel plant carotenoid cleavage activity targeting the 7′,8′ double bond of cyclic C40 carotenoids has been identified. These results suggest that the presented enzyme is responsible for the biosynthesis of C30 apocarotenoids in Citrus which are key pigments in fruit coloration. PMID:24006419

  3. Functional responses and molecular mechanisms involved in histone-mediated platelet activation.

    PubMed

    Carestia, A; Rivadeneyra, L; Romaniuk, M A; Fondevila, C; Negrotto, S; Schattner, M

    2013-11-01

    Histones are highly alkaline proteins found in cell nuclei and they can be released by either dying or inflammatory cells. The recent observations that histones are major components of neutrophil extracellular traps and promote platelet aggregation and platelet-dependent thrombin generation have shown that these proteins are potent prothrombotic molecules. Because the mechanism(s) of platelet activation by histones are not completely understood, we explored the ability of individual recombinant human histones H1, H2A, H2B, H3 and H4 to induce platelet activation as well as the possible molecular mechanisms involved. All histones were substrates for platelet adhesion and spreading and triggered fibrinogen binding, aggregation, von Willebrand factor release, P-selectin and phosphatidylserine (PS) exposure and the formation of platelet-leukocyte aggregates; however, H4 was the most potent. Histone-mediated fibrinogen binding, P-selectin and PS exposure and the formation of mixed aggregates were potentiated by thrombin. Histones induced the activation of ERK, Akt, p38 and NFκB. Accordingly, histone-induced platelet activation was significantly impaired by pretreatment of platelets with inhibitors of ERK (U 0126), PI3K/Akt (Ly 294002), p38 (SB 203580) and NFκB (BAY 11-7082 and Ro 106-9920). Preincubation of platelets with either aspirin or dexamethasone markedly decreased fibrinogen binding and the adhesion mediated by histones without affecting P-selectin exposure. Functional platelet responses induced by H3 and H4, but not H1, H2A and H2B, were partially mediated through interaction with Toll-like receptors -2 and -4. Our data identify histones as important triggers of haemostatic and proinflammatory platelet responses, and only haemostatic responses are partially inhibited by anti-inflammatory drugs. PMID:23965842

  4. Decreased activity of neutrophils in the presence of diferuloylmethane (curcumin) involves protein kinase C inhibition.

    PubMed

    Jancinová, Viera; Perecko, Tomás; Nosál, Radomír; Kostálová, Daniela; Bauerová, Katarína; Drábiková, Katarína

    2009-06-10

    Diferuloylmethane (curcumin) has been shown to act beneficially in arthritis, particularly through downregulated expression of proinflammatory cytokines and collagenase as well as through the modulated activities of T lymphocytes and macrophages. In this study its impact on activated neutrophils was investigated both in vitro and in experimental arthritis. Formation of reactive oxygen species in neutrophils was recorded on the basis of luminol- or isoluminol-enhanced chemiluminescence. Phosphorylation of neutrophil protein kinases C alpha and beta II was assessed by Western blotting, using phosphospecific antibodies. Adjuvant arthritis was induced in Lewis rats by heat-killed Mycobacterium butyricum. Diferuloylmethane or methotrexate was administered over a period of 28 days after arthritis induction. Under in vitro conditions, diferuloylmethane (1-100 microM) reduced dose-dependently oxidant formation both at extra- and intracellular level and it effectively reduced protein kinase C activation. Adjuvant arthritis was accompanied by an increased number of neutrophils in blood and by a more pronounced spontaneous as well as PMA (phorbol myristate acetate) stimulated chemiluminescence. Whereas the arthritis-related alterations in neutrophil count and in spontaneous chemiluminescence were not modified by diferuloylmethane, the increased reactivity of neutrophils to PMA was less evident in diferuloylmethane-treated animals. The effects of diferuloylmethane were comparable with those of methotrexate. Diferuloylmethane was found to be a potent inhibitor of neutrophil functions both in vitro and in experimental arthritis. As neutrophils are considered to be cells with the greatest capacity to inflict damage within diseased joints, the observed effects could represent a further mechanism involved in the antirheumatic activity of diferuloylmethane. PMID:19371737

  5. Involvement of ER stress and activation of apoptotic pathways in fisetin induced cytotoxicity in human melanoma.

    PubMed

    Syed, Deeba N; Lall, Rahul K; Chamcheu, Jean Christopher; Haidar, Omar; Mukhtar, Hasan

    2014-12-01

    The prognosis of malignant melanoma remains poor in spite of recent advances in therapeutic strategies for the deadly disease. Fisetin, a dietary flavonoid is currently being investigated for its growth inhibitory properties in various cancer models. We previously showed that fisetin inhibited melanoma growth in vitro and in vivo. Here, we evaluated the molecular basis of fisetin induced cytotoxicity in metastatic human melanoma cells. Fisetin treatment induced endoplasmic reticulum (ER) stress in highly aggressive A375 and 451Lu human melanoma cells, as revealed by up-regulation of ER stress markers including IRE1α, XBP1s, ATF4 and GRP78. Time course analysis indicated that the ER stress was associated with activation of the extrinsic and intrinsic apoptotic pathways. Fisetin treated 2-D melanoma cultures displayed autophagic response concomitant with induction of apoptosis. Prolonged treatment (16days) with fisetin in a 3-D reconstituted melanoma model resulted in inhibition of melanoma progression with significant apoptosis, as evidenced by increased staining of cleaved Caspase-3 in the treated constructs. However, no difference in the expression of autophagic marker LC-3 was noted between treated and control groups. Fisetin treatment to 2-D melanoma cultures resulted in phosphorylation and activation of the multifunctional AMP-activated protein kinase (AMPK) involved in the regulation of diverse cellular processes, including autophagy and apoptosis. Silencing of AMPK failed to prevent cell death indicating that fisetin induced cytotoxicity is mediated through both AMPK-dependent and -independent mechanisms. Taken together, our studies confirm apoptosis as the primary mechanism through which fisetin inhibits melanoma cell growth and that activation of both extrinsic and intrinsic pathways contributes to fisetin induced cytotoxicity. PMID:25016296

  6. Involvement of ER stress and activation of apoptotic pathways in fisetin induced cytotoxicity in human melanoma

    PubMed Central

    Chamcheu, Jean Christopher; Haidar, Omar; Mukhtar, Hasan

    2014-01-01

    The prognosis of malignant melanoma remains poor in spite of recent advances in therapeutic strategies for the deadly disease. Fisetin, a dietary flavonoid is currently being investigated for its growth inhibitory properties in various cancer models. We previously showed that fisetin inhibited melanoma growth in vitro and in vivo. Here, we evaluated the molecular basis of fisetin induced cytoxicity in metastatic human melanoma cells. Fisetin treatment induced endoplasmic reticulum (ER) stress in highly aggressive A375 and 451Lu human melanoma cells, as revealed by up- regulation of ER stress markers including IRE1α, XBP1s, ATF4 and GRP78. Time course analysis indicated that the ER stress was associated with activation of the extrinsic and intrinsic apoptotic pathways. Fisetin treated 2-D melanoma cultures displayed autophagic response concomitant with induction of apoptosis. Prolonged treatment (16 days) with fisetin in a 3-D reconstituted melanoma model resulted in inhibition of melanoma progression with significant apoptosis, as evidenced by increased staining of cleaved Caspase-3 in the treated constructs. However, no difference in the expression of autophagic marker LC-3 was noted between treated and control groups. Fisetin treatment to 2-D melanoma cultures resulted in phosphorylation and activation of the multifunctional AMPK-activated protein kinase (AMPK) involved in the regulation of diverse cellular processes, including autophagy and apoptosis. Silencing of AMPK failed to prevent cell death indicating that fisetin induced cytotoxicity is mediated through both AMPK-dependent and -independent mechanisms. Taken together, our studies confirm apoptosis as the primary mechanism through which fisetin inhibits melanoma cell growth and that activation of both extrinsic and intrinsic pathways contributes to fisetin induced cytotoxicity. PMID:25016296

  7. Aldrin-induced locomotor activity: possible involvement of the central GABAergic-cholinergic-dopaminergic interaction.

    PubMed

    Jamaluddin, S; Poddar, M K

    2001-01-01

    Aldrin (5 mg/kg/day, p.o.) under nontolerant condition, administered either for a single day or for 12 consecutive days, enhanced locomotor activity (LA) of rats. The increase in LA was greater in rats treated with aldrin for 12 consecutive days than that observed with a single dose. The aim of the present study is to evaluate the involvement of possible interactions of central GABAergic, cholinergic and dopaminergic systems using their agonist(s) and antagonist(s) in the regulation of LA in aldrin nontolerant rats. Administration of either L-DOPA along with carbidopa or bicuculline potentiated aldrin-induced increase in LA under nontolerant condition as well as LA of the control rats. Treatment with muscimol, haloperidol, atropine or physostigmine all decreased the LA of both aldrin nontolerant and control rats. Further, the application of (a) haloperidol along with bicuculline, atropine or physostigmine and (b) physostigmine along with bicuculline or L-DOPA + carbidopa significantly reduced LA but L-DOPA + carbidopa along with atropine or bicuculline increased LA of the control rats. These agonist(s)/antagonist(s)-induced decrease or increase in LA of the control rats were attenuated or potentiated, respectively, when those agonist(s)/antagonist(s) under abovementioned condition were administered to aldrin nontolerant rats. The attenuating or potentiating effects of aldrin on agonist(s)/antagonist(s) (either individually or in different combinations)-induced change in LA were greater in rats treated with aldrin for 12 consecutive days than that observed with a single-dose aldrin treatment. These results suggest that aldrin, under nontolerant condition, reduces central GABAergic activity and increases LA by activating dopaminergic system via inhibition of cholinergic activity. The treatment with aldrin for 12 consecutive days produces greater effect than that caused by a single-day treatment. PMID:11785907

  8. Intracranial benign fibrous histiocytoma mimicking parasagittal meningioma: report of two cases and review of literature

    PubMed Central

    Chen, Baoshi; Wang, Zheng; Liu, Yanwei; You, Gan; Wang, Jiangfei; Wang, Junmei; Jiang, Zhongli; Zhang, Wei

    2015-01-01

    Primary benign fibrous histiocytoma involving the central nervous system is an exceedingly rare tumor with most cases originating from the dura or parenchymal tissue. Diagnosis of primary benign fibrous histiocytoma is difficult due to its confusing histopathological characteristics. Two cases of primary intracranial benign fibrous histiocytoma mimicking parasagittal meningioma are presented in this report. Both tumors were gross totally resected and the patients showed no evidence of recurrence at follow-up of 12 months. The clinical features and prognosis of this rare tumor that were reported previously in the literature were also reviewed. Histopathological examination coupled with immunohistochemical staining is proved to be the convincing diagnostic method for the primary benign fibrous histiocytoma. Surgical resection is the recommendation for the therapy of the tumor. PMID:26617915

  9. Overexpression of SIRT5 confirms its involvement in deacetylation and activation of carbamoyl phosphate synthetase 1.

    PubMed

    Ogura, Masahito; Nakamura, Yasuhiko; Tanaka, Daisuke; Zhuang, Xiaotong; Fujita, Yoshihito; Obara, Akio; Hamasaki, Akihiro; Hosokawa, Masaya; Inagaki, Nobuya

    2010-02-26

    SIR2 protein, an NAD-dependent deacetylase, is localized to nucleus and is involved in life span extension by calorie restriction in yeast. In mammals, among the seven SIR2 homologues (SIRT1-7), SIRT3, 4, and 5 are localized to mitochondria. As SIRT5 mRNA levels in liver are increased by fasting, the physiological role of SIRT5 was investigated in liver of SIRT5-overexpressing transgenic (SIRT5 Tg) mice. We identified carbamoyl phosphate synthetase 1 (CPS1), a key enzyme of the urea cycle that catalyzes condensation of ammonia with bicarbonate to form carbamoyl phosphate, as a target of SIRT5 by two-dimensional electrophoresis comparing mitochondrial proteins in livers of SIRT5 Tg and wild-type mice. CPS1 protein was more deacetylated and activated in liver of SIRT5 Tg mice than in wild-type. In addition, urea production was upregulated in hepatocytes of SIRT5 Tg mice. These results agree with those of a previous study using SIRT5 knockout (KO) mice. Because ammonia generated during fasting is toxic, SIRT5 protein might play a protective role by converting ammonia to non-toxic urea through deacetylation and activation of CPS1. PMID:20097174

  10. Involvement of JNK and Caspase Activation in Hoiamide A-Induced Neurotoxicity in Neocortical Neurons

    PubMed Central

    Cao, Zhengyu; Li, Xichun; Zou, Xiaohan; Greenwood, Michael; Gerwick, William H.; Murray, Thomas F.

    2015-01-01

    The frequent occurrence of Moorea producens (formerly Lyngbya majuscula) blooms has been associated with adverse effects on human health. Hoiamide A is a structurally unique cyclic depsipeptide isolated from an assemblage of the marine cyanobacteria M. producens and Phormidium gracile. We examined the influence of hoiamide A on neurite outgrowth in neocortical neurons and found that it suppressed neurite outgrowth with an IC50 value of 4.89 nM. Further study demonstrated that hoiamide A stimulated lactic acid dehydrogenase (LDH) efflux, nuclear condensation and caspase-3 activity with EC50 values of 3.66, 2.55 and 4.33 nM, respectively. These data indicated that hoiamide A triggered a unique neuronal death profile that involves both necrotic and apoptotic mechanisms. The similar potencies and similar time-response relationships between LDH efflux and caspase-3 activation/nuclear condensation suggested that both necrosis and apoptosis may derive from interaction with a common molecular target. The broad-spectrum caspase inhibitor, Z-VAD-FMK completely inhibited hoiamide A-induced neurotoxicity. Additionally, hoiamide A stimulated JNK phosphorylation, and a JNK inhibitor attenuated hoiamide A-induced neurotoxicity. Collectively, these data demonstrate that hoiamide A-induced neuronal death requires both JNK and caspase signaling pathways. The potent neurotoxicity and unique neuronal cell death profile of hoiamide A represents a novel neurotoxic chemotype from marine cyanobacteria. PMID:25675001

  11. Involvement of both PKS and NRPS in antibacterial activity in Lysobacter enzymogenes OH11

    PubMed Central

    Zhang, Juan; Du, Liangcheng; Liu, Fengquan; Xu, Feifei; Hu, Baishi; Venturi, Vittorio; Qian, Guoliang

    2014-01-01

    Polyketides and nonribosomal peptides represent two large families of natural products (NPs) with diverse structures and important functions. They are synthesized by polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS), respectively. Lysobacter enzymogenes is emerging as a novel biocontrol agent against pathogens of crop plants and a new source of bioactive NPs, such as antibacterial antibiotic WAP-8294A2 and antifungal antibiotic HSAF. Genome survey of strain OH11, a Chinese L. enzymogenes isolate, detected four novel PKS, NRPS or hybrid gene clusters, designed as cluster A to D. We further individually mutated five genes (PKS or NRPS) located in these four gene clusters, and showed that a PKS gene in cluster A and an NRPS gene in cluster D were involved in the antibacterial activity via a WAP-8294A2 dependent way. The data also showed that none of the five genes was associated with antifungal activity and the regulation of HSAF biosynthesis. Our results reveal the unusual regulatory role of these PKS and NRPS genes that were discovered from genome mining in L. enzymogenes. PMID:24801439

  12. Mechanisms involved in Escherichia coli and Serratia marcescens removal during activated sludge wastewater treatment

    PubMed Central

    Orruño, Maite; Garaizabal, Idoia; Bravo, Zaloa; Parada, Claudia; Barcina, Isabel; Arana, Inés

    2014-01-01

    Wastewater treatment reduces environmental contamination by removing gross solids and mitigating the effects of pollution. Treatment also reduces the number of indicator organisms and pathogens. In this work, the fates of two coliform bacteria, Escherichia coli and Serratia marcescens, were analyzed in an activated sludge process to determine the main mechanisms involved in the reduction of pathogenic microorganisms during wastewater treatment. These bacteria, modified to express green fluorescent protein, were inoculated in an activated sludge unit and in batch systems containing wastewater. The results suggested that, among the different biological factors implied in bacterial removal, bacterivorous protozoa play a key role. Moreover, a representative number of bacteria persisted in the system as free-living or embedded cells, but their distribution into liquid or solid fractions varied depending on the bacterium tested, questioning the real value of bacterial indicators for the control of wastewater treatment process. Additionally, viable but nonculturable cells constituted an important part of the bacterial population adhered to solid fractions, what can be derived from the competition relationships with native bacteria, present in high densities in this environment. These facts, taken together, emphasize the need for reliable quantitative and qualitative analysis tools for the evaluation of pathogenic microbial composition in sludge, which could represent an undefined risk to public health and ecosystem functions when considering its recycling. PMID:25044599

  13. HSP27 Alleviates Cardiac Aging in Mice via a Mechanism Involving Antioxidation and Mitophagy Activation

    PubMed Central

    Lin, Shenglan; Wang, Yana; Zhang, Xiaojin; Kong, Qiuyue; Li, Chuanfu; Li, Yuehua; Ding, Zhengnian

    2016-01-01

    Aging-induced cardiac dysfunction is a prominent feature of cardiac aging. Heat shock protein 27 (HSP27) protects cardiac function against ischemia or chemical challenge. We hypothesized that HSP27 attenuates cardiac aging. Transgenic (Tg) mice with cardiac-specific expression of the HSP27 gene and wild-type (WT) littermates were employed in the experiments. Echocardiography revealed a significant decline in the cardiac function of old WT mice compared with young WT mice. In striking contrast, the aging-induced impairment of cardiac function was attenuated in old Tg mice compared with old WT mice. Levels of cardiac aging markers were lower in old Tg mouse hearts than in old WT mouse hearts. Less interstitial fibrosis and lower contents of reactive oxygen species and ubiquitin-conjugated proteins were detected in old Tg hearts than in old WT hearts. Furthermore, old Tg hearts demonstrated lower accumulation of LC3-II and p62 than old WT hearts. Levels of Atg13, Vps34, and Rab7 were also higher in old Tg hearts than in old WT hearts. Additionally, old Tg hearts had higher levels of PINK1 and Parkin than old WT hearts, suggesting that mitophagy was activated in old Tg hearts. Taken together, HSP27 alleviated cardiac aging and this action involved antioxidation and mitophagy activation. PMID:27110324

  14. Mechanisms involved in Escherichia coli and Serratia marcescens removal during activated sludge wastewater treatment.

    PubMed

    Orruño, Maite; Garaizabal, Idoia; Bravo, Zaloa; Parada, Claudia; Barcina, Isabel; Arana, Inés

    2014-10-01

    Wastewater treatment reduces environmental contamination by removing gross solids and mitigating the effects of pollution. Treatment also reduces the number of indicator organisms and pathogens. In this work, the fates of two coliform bacteria, Escherichia coli and Serratia marcescens, were analyzed in an activated sludge process to determine the main mechanisms involved in the reduction of pathogenic microorganisms during wastewater treatment. These bacteria, modified to express green fluorescent protein, were inoculated in an activated sludge unit and in batch systems containing wastewater. The results suggested that, among the different biological factors implied in bacterial removal, bacterivorous protozoa play a key role. Moreover, a representative number of bacteria persisted in the system as free-living or embedded cells, but their distribution into liquid or solid fractions varied depending on the bacterium tested, questioning the real value of bacterial indicators for the control of wastewater treatment process. Additionally, viable but nonculturable cells constituted an important part of the bacterial population adhered to solid fractions, what can be derived from the competition relationships with native bacteria, present in high densities in this environment. These facts, taken together, emphasize the need for reliable quantitative and qualitative analysis tools for the evaluation of pathogenic microbial composition in sludge, which could represent an undefined risk to public health and ecosystem functions when considering its recycling. PMID:25044599

  15. Neuroinformatics analyses reveal GABAt and SSADH as major proteins involved in anticonvulsant activity of valproic acid.

    PubMed

    Piplani, Sakshi; Verma, Prabhakar Kumar; Kumar, Ajit

    2016-07-01

    The unequivocal hypotheses about anticonvulsant activity of valproic acid (VPA) have always been a basic hurdle in designing next generation neurotherapeutics, particularly the anti-epileptic drugs. The present study reports about a comprehensive in-silico investigation into qualitative and quantitative binding of VPA and corresponding natural ligands of four major enzymes involved in neurotransmissions, namely-GABA transaminase (GABAt), α-keto glutarate dehydrogenase (α-KGDH), Succinate Semialdehyde dehydrogenase (SSADH) and Glutamate Decarboxylase (GAD), respectively. The molecular docking analyses revealed that VPA inhibits GABAt and α-KGDH through allosteric while SSADH through competitive mode of binding. There is an observed elevation in binding of glutamate over GAD in the presence of VPA. The docking inhibition constant (Ki) of VPA to all the studied enzymatic receptors were observed to be well below the therapeutic concentration of VPA in blood, except for α-KGDH, thus favouring GABAergic over glutamatergic mode of anticonvulsant activity of VPA. The report is probably the first comprehensive in-silico molecular study about VPA action. PMID:27261619

  16. Involvement of IL-1 in the Maintenance of Masseter Muscle Activity and Glucose Homeostasis

    PubMed Central

    Chiba, Ko; Tsuchiya, Masahiro; Koide, Masashi; Hagiwara, Yoshihiro; Sasaki, Keiichi; Hattori, Yoshinori; Watanabe, Makoto; Sugawara, Shunji; Kanzaki, Makoto; Endo, Yasuo

    2015-01-01

    Physical exercise reportedly stimulates IL-1 production within working skeletal muscles, but its physiological significance remains unknown due to the existence of two distinct IL-1 isoforms, IL-1α and IL-1β. The regulatory complexities of these two isoforms, in terms of which cells in muscles produce them and their distinct/redundant biological actions, have yet to be elucidated. Taking advantage of our masticatory behavior (Restrained/Gnawing) model, we herein show that IL-1α/1β-double-knockout (IL-1-KO) mice exhibit compromised masseter muscle (MM) activity which is at least partially attributable to abnormalities of glucose handling (rapid glycogen depletion along with impaired glucose uptake) and dysfunction of IL-6 upregulation in working MMs. In wild-type mice, masticatory behavior clearly increased IL-1β mRNA expression but no incremental protein abundance was detectable in whole MM homogenates, whereas immunohistochemical staining analysis revealed that both IL-1α- and IL-1β-immunopositive cells were recruited around blood vessels in the perimysium of MMs after masticatory behavior. In addition to the aforementioned phenotype of IL-1-KO mice, we found the IL-6 mRNA and protein levels in MMs after masticatory behavior to be significantly lower in IL-1-KO than in WT. Thus, our findings confirm that the locally-increased IL-1 elicited by masticatory behavior, although present small in amounts, contributes to supporting MM activity by maintaining normal glucose homeostasis in these muscles. Our data also underscore the importance of IL-1-mediated local interplay between autocrine myokines including IL-6 and paracrine cytokines in active skeletal muscles. This interplay is directly involved in MM performance and fatigability, perhaps mediated through maintaining muscular glucose homeostasis. PMID:26599867

  17. Pathogenesis of aortic dilatation in mucopolysaccharidosis VII mice may involve complement activation

    PubMed Central

    Baldo, Guilherme; Wu, Susan; Howe, Ruth A.; Ramamoothy, Meera; Knutsen, Russell H.; Fang, Jiali; Mecham, Robert P.; Liu, Yuli; Wu, Xiaobo; Atkinson, John P.; Ponder, Katherine P.

    2012-01-01

    Mucopolysaccharidosis VII (MPS VII) is due to mutations within the gene encoding the lysosomal enzyme β-glucuronidase, and results in the accumulation of glycosaminoglycans. MPS VII causes aortic dilatation and elastin fragmentation, which is associated with upregulation of the elastases cathepsin S (CtsS) and matrix metalloproteinase 12 (MMP12). To test the role of these enzymes, MPS VII mice were crossed with mice deficient in CtsS or MMP12, and the effect upon aortic dilatation was determined. CtsS deficiency did not protect against aortic dilatation in MPS VII mice, but also failed to prevent an upregulation of cathepsin enzyme activity. Further analysis with substrates and inhibitors specific for particular cathepsins suggests that this enzyme activity was due to CtsB, which could contribute to elastin fragmentation. Similarly, MMP12 deficiency and deficiency of both MMP12 and CtsS could not prevent aortic dilatation in MPS VII mice. Microarray and reverse-transcriptase real-time PCR were performed to look for upregulation of other elastases. This demonstrated that mRNA for complement component D was elevated in MPS VII mice, while immunostaining demonstrated high levels of complement component C3 on surfaces within the aortic media. Finally, we demonstrate that neonatal intravenous injection of a retroviral vector encoding β-glucuronidase reduced aortic dilatation. We conclude that neither CtsS nor MMP12 are necessary for elastin fragmentation in MPS VII mouse aorta, and propose that CtsB and/or complement component D may be involved. Complement may be activated by the GAGs that accumulate, and may play a role in signal transduction pathways that upregulate elastases. PMID:21944884

  18. Nelfinavir and other protease inhibitors in cancer: mechanisms involved in anticancer activity

    PubMed Central

    Koltai, Tomas

    2015-01-01

    Objective: To review the mechanisms of anti-cancer activity of nelfinavir and other protease inhibitors (PIs) based on evidences reported in the published literature. Methods: We extensively reviewed the literature concerning nelfinavir (NFV) as an off target anti-cancer drug and other PIs. A classification of PIs based on anti-cancer mode of action was proposed. Controversies regarding nelfinavir mode of action were also addressed. Conclusions: The two main mechanisms involved in anti-cancer activity are endoplasmic reticulum stress-unfolded protein response pathway and Akt inhibition. However there are many other effects, partially dependent and independent of those mentioned, that may be useful in cancer treatment, including MMP-9 and MMP-2 inhibition, down-regulation of CDK-2, VEGF, bFGF, NF-kB, STAT-3, HIF-1 alfa, IGF, EGFR, survivin, BCRP, androgen receptor, proteasome, fatty acid synthase (FAS), decrease in cellular ATP concentration and upregulation of TRAIL receptor DR5, Bax, increased radiosensitivity, and autophagy. The end result of all these effects is slower growth, decreased angiogenesis, decreased invasion and increased apoptosis, which means reduced proliferation and increased cancer cells death. PIs may be classified according to their anticancer activity at clinically achievable doses, in AKT inhibitors, ER stressors and Akt inhibitors/ER stressors. Beyond the phase I trials that have been recently completed, adequately powered and well-designed clinical trials are needed in the various cancer type settings, and specific trials where NFV is tested in association with other known anti-cancer pharmaceuticals should be sought, in order to find an appropriate place for NFV in cancer treatment. The analysis of controversies on the molecular mechanisms of NFV hints to the possibility that NFV works in a different way in tumor cells and in hepatocytes and adipocytes. PMID:26097685

  19. Involvement of the histamine H1 receptor in the regulation of sympathetic nerve activity.

    PubMed

    Murakami, Manabu; Yoshikawa, Takeo; Nakamura, Tadaho; Ohba, Takayoshi; Matsuzaki, Yasushi; Sawamura, Daisuke; Kuwasako, Kenji; Yanagisawa, Teruyuki; Ono, Kyouichi; Nakaji, Shigeyuki; Yanai, Kazuhiko

    2015-03-13

    The histamine system is involved in the regulation of the autonomic nervous system. We used gene-targeted mice to investigate the role of histamine receptors in the regulation of the sympathetic nervous system. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed histamine H1, H2, and H3 receptor expression in the superior cervical ganglion, which contains sympathetic nerve cell bodies. We measured the heart rate variability (HRV), the changes in the beat-to-beat heart rate, which is widely used to assess autonomic activity in the heart. H1 blockade attenuated the baroreflex-mediated changes in heart rate in wild-type (WT) mice, whereas the heart rate response to H2- and H3-specific blockers was unaffected. l-Histidine decarboxylase (HDC) expression in the superior cervical ganglion of H1R-null mice was higher than that in WT controls, whereas the enzyme levels in H2R- and H3R-null mice were not significantly different from those in the WT. All mutant mice (H1R-, H2R-, and H3R-null mice) showed normal electrocardiogram (ECG) patterns with little modification in ECG parameters and the expected response to the β-adrenergic blocker propranolol. Similar to our findings in WT mice, H1 blockade attenuated the baroreflex-mediated heart rate change in H1R-null mice, whereas the heart rate response was unaffected in H2R- and H3R-null mice. The HRV analysis revealed relatively unstable RR intervals, an increased standard deviation of the interbeat interval (SDNN), and low-frequency (LF) component in H1R-null mice compared with the other groups, suggesting that sympathetic nerve activity was altered in H1R-null mice. Taken together, our findings indicate that H1 receptors play a major role in the regulation of sympathetic nerve activity. PMID:25680462

  20. Mothers' and Fathers' Involvement in Home Activities with Their Children: Psychosocial Factors and the Role of Parental Self-Efficacy

    ERIC Educational Resources Information Center

    Giallo, Rebecca; Treyvaud, Karli; Cooklin, Amanda; Wade, Catherine

    2013-01-01

    Parent involvement in play, learning, and everyday home activities is important for promoting children's cognitive and language development. The aims of the study were to (a) examine differences between mothers' and fathers' self-reported involvement with their children, (b) explore the relationship between child, parent and family factors, and…

  1. Parent Involvement Activities in School Improvement Plans in the Northwest Region. Summary. Issues & Answers. REL 2008-No. 064

    ERIC Educational Resources Information Center

    Speth, Timothy; Saifer, Steffen; Forehand, Gregory

    2008-01-01

    This document presents a summary of the larger report, "Parent Involvement Activities in School Improvement Plans in the Northwest Region." Although the No Child Left Behind Act of 2001 (NCLB) spells out parent involvement requirements for schools in need of improvement, the majority of the Northwest Region school improvement plans reviewed failed…

  2. ED-12WIDESPREAD SYSTEMIC METASTASES FROM MEDULLOBLASTOMA WITHOUT EVIDENCE OF ACTIVE CNS INVOLVEMENT: A CASE SERIES

    PubMed Central

    Kumthekar, Priya; Singh, Simran; Smiley, Natasha Pillay; Lulla, Rishi

    2014-01-01

    without active CNS involvement. Follow up imaging for medulloblastoma patients should potentially include systemic surveillance in addition to routine neuroimaging.

  3. 15 CFR 712.1 - Round to zero rule that applies to activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.1 Round to...

  4. 15 CFR 712.1 - Round to zero rule that applies to activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.1 Round to...

  5. 15 CFR 712.1 - Round to zero rule that applies to activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.1 Round to...

  6. 15 CFR 712.1 - Round to zero rule that applies to activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.1 Round to...

  7. 15 CFR 712.1 - Round to zero rule that applies to activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.1 Round to...

  8. Fatty acid transport and activation and the expression patterns of genes involved in fatty acid trafficking.

    PubMed

    Sandoval, Angel; Fraisl, Peter; Arias-Barrau, Elsa; Dirusso, Concetta C; Singer, Diane; Sealls, Whitney; Black, Paul N

    2008-09-15

    These studies defined the expression patterns of genes involved in fatty acid transport, activation and trafficking using quantitative PCR (qPCR) and established the kinetic constants of fatty acid transport in an effort to define whether vectorial acylation represents a common mechanism in different cell types (3T3-L1 fibroblasts and adipocytes, Caco-2 and HepG2 cells and three endothelial cell lines (b-END3, HAEC, and HMEC)). As expected, fatty acid transport protein (FATP)1 and long-chain acyl CoA synthetase (Acsl)1 were the predominant isoforms expressed in adipocytes consistent with their roles in the transport and activation of exogenous fatty acids destined for storage in the form of triglycerides. In cells involved in fatty acid processing including Caco-2 (intestinal-like) and HepG2 (liver-like), FATP2 was the predominant isoform. The patterns of Acsl expression were distinct between these two cell types with Acsl3 and Acsl5 being predominant in Caco-2 cells and Acsl4 in HepG2 cells. In the endothelial lines, FATP1 and FATP4 were the most highly expressed isoforms; the expression patterns for the different Acsl isoforms were highly variable between the different endothelial cell lines. The transport of the fluorescent long-chain fatty acid C(1)-BODIPY-C(12) in 3T3-L1 fibroblasts and 3T3-L1 adipocytes followed typical Michaelis-Menten kinetics; the apparent efficiency (k(cat)/K(T)) of this process increases over 2-fold (2.1 x 10(6)-4.5 x 10(6)s(-1)M(-1)) upon adipocyte differentiation. The V(max) values for fatty acid transport in Caco-2 and HepG2 cells were essentially the same, yet the efficiency was 55% higher in Caco-2 cells (2.3 x 10(6)s(-1)M(-1) versus 1.5 x 10(6)s(-1)M(-1)). The kinetic parameters for fatty acid transport in three endothelial cell types demonstrated they were the least efficient cell types for this process giving V(max) values that were nearly 4-fold lower than those defined form 3T3-L1 adipocytes, Caco-2 cells and HepG2 cells. The

  9. The Effects of Adolescent Activities on Delinquency: A Differential Involvement Approach

    ERIC Educational Resources Information Center

    Wong, Siu Kwong

    2005-01-01

    T. Hirschi's (1969, "Causes of Delinquency." University of California Press, Berkeley, CA) control theory proposes that involvement, as an element of the social bond, should reduce delinquency. But, research studies have found that the effect of involvement is rather weak. This study reformulates Hirschi's involvement hypothesis by posing…

  10. Benign Mesenchymal Stromal Cells in Human Sarcomas

    PubMed Central

    Morozov, Alexei; Downey, Robert J.; Healey, John; Moreira, Andre L.; Lou, Emil; Leung, Roland; Edgar, Mark; Singer, Samuel; LaQuaglia, Michael; Maki, Robert G.; Moore, Malcolm A.S.

    2010-01-01

    Purpose Recent evidence suggests that at least some sarcomas arise through aberrant differentiation of mesenchymal stromal cells (MSCs), but MSCs have never been isolated directly from human sarcoma specimens. Experimental Design We examined human sarcoma cell lines and primary adherent cultures derived from human sarcoma surgical samples for features of MSCs. We further characterized primary cultures as either benign or malignant by the presence of tumor-defining genetic lesions and tumor formation in immunocompromised mice. Results We show that a dedifferentiated liposarcoma cell line DDLS8817 demonstrates fat, bone and cartilage trilineage differentiation potential characteristic of MSCs. Primary sarcoma cultures have the morphology, surface immunophenotype and differentiation potential characteristic of MSCs. Surprisingly, many of these cultures are benign as they do not form tumors in mice and lack sarcoma-defining genetic lesions. Consistent with the recently proposed pericyte origin of MSCs in normal human tissues, sarcoma-derived benign MSCs express markers of pericytes and cooperate with endothelial cells in tube formation assays. In human sarcoma specimens, a subset of CD146-positive microvascular pericytes express CD105, an MSC marker, while malignant cells largely do not. In an in vitro co-culture model, sarcoma-derived benign MSCs as well as normal human pericytes markedly stimulate the growth of sarcoma cell lines. Conclusions Sarcoma-derived benign MSCs/pericytes represent a previously undescribed stromal cell type in sarcoma which may contribute to tumor formation. PMID:21138865

  11. Hypervitaminosis A causing benign intracranial hypertension. A case report.

    PubMed

    Bhettay, E M; Bakst, C M

    1988-12-01

    Hypervitaminosis A is a well-recognized clinical entity, but the toxic manifestations develop so insidiously and involve so many systems that diagnosis can easily be missed or delayed. A patient with juvenile chronic arthritis developed benign intracranial hypertension and other manifestations of excessive vitamin A intake and made a complete recovery after it was withdrawn. Vitamin A is a non-prescription drug and any history of its ingestion must be obtained during evaluation of papilloedema. A plea is made for the public to be repeatedly reminded that no proposed remedy is safe or effective until it is demonstrated to be so. PMID:3194809

  12. PRESS40: a project for involving students in active seismic risk mitigation

    NASA Astrophysics Data System (ADS)

    Barnaba, Carla; Contessi, Elisa; Rosa Girardi, Maria

    2016-04-01

    To memorialize the anniversary of the 1976 Friuli earthquake, the Istituto Statale di Istruzione Superiore "Magrini Marchetti" in Gemona del Friuli (NE Italy), with the collaboration of the Istituto Nazionale di Oceanografia e di Geofisica Sperimentale (OGS), has promoted the PRESS40 Project (Prevenzione Sismica nella Scuola a 40 anni dal terremoto del Friuli, that in English sounds like "Seismic Prevention at School 40 years later the Friuli earthquake"). The project has developed in the 2015-2016 school year, starting from the 40th anniversary of the Friuli earthquake, and it aims to disseminate historical memory, seismic culture and awareness of seismic safety in the young generations, too often unconscious of past experiences, as recent seismic hazard perception tests have demonstrated. The basic idea of the PRESS40 Project is to involve the students in experimental activities to be active part of the seismic mitigation process. The Project is divided into two main parts, the first one in which students learn-receive knowledge from researchers, and the second one in which they teach-bring knowledge to younger students. In the first part of the project, 75 students of the "Magrini Marchetti" school acquired new geophysical data, covering the 23 municipalities from which they come from. These municipalities represent a wide area affected by the 1976 Friuli earthquake. In each locality a significant site was examined, represented by a school area. At least, 127 measurements of ambient noise have been acquired. Data processing and interpretation of all the results are still going on, under the supervision of OGS researchers.The second part of the project is planned for the early spring, when the students will present the results of geophysical survey to the younger ones of the monitored schools and to the citizens in occasion of events to commemorate the 40th anniversary of the Friuli earthquake.

  13. Utilization of iron-catecholamine complexes involving ferric reductase activity in Listeria monocytogenes.

    PubMed Central

    Coulanges, V; Andre, P; Ziegler, O; Buchheit, L; Vidon, D J

    1997-01-01

    Listeria monocytogenes is a ubiquitous potentially pathogenic organism requiring iron for growth and virulence. Although it does not produce siderophores, L. monocytogenes is able to obtain iron by using either exogenous siderophores produced by various microorganisms or natural catechol compounds widespread in the environment. In the presence of tropolone, an iron-chelating agent, growth of L. monocytogenes is completely inhibited. However, the growth inhibition can be relieved by the addition of dopamine or norepinephrine under their different isomeric forms, while the catecholamine derivatives 4-hydroxy-3-methoxyphenylglycol and normetanephrine did not relieve the inhibitory effect of tropolone. Preincubation of L. monocytogenes with chlorpromazine and yohimbine did not antagonize the growth-promoting effect of catecholamines in iron-complexed medium. In addition, norepinephrine stimulated the growth-promoting effect induced by human transferrin in iron-limited medium. Furthermore, dopamine and norepinephrine allowed 55Fe uptake by iron-deprived bacterial cells. The uptake of iron was energy dependent, as indicated by inhibition of 55Fe uptake at 0 degrees C as well as by preincubating the bacteria with KCN. Inhibition of 55Fe uptake by L. monocytogenes was also observed in the presence of Pt(II). Moreover, when assessed by a whole-cell ferric reductase assay, reductase activity of L. monocytogenes was inhibited by Pt(II). These data demonstrate that dopamine and norepinephrine can function as siderophore-like compounds in L. monocytogenes owing to their ortho-diphenol function and that catecholamine-mediated iron acquisition does not involve specific catecholamine receptors but acts through a cell-bound ferrireductase activity. PMID:9199450

  14. Lack of Involvement of CEP Adducts in TLR Activation and in Angiogenesis

    PubMed Central

    Gounarides, John; Cobb, Jennifer S.; Zhou, Jing; Cook, Frank; Yang, Xuemei; Yin, Hong; Meredith, Erik; Rao, Chang; Huang, Qian; Xu, YongYao; Anderson, Karen; De Erkenez, Andrea; Liao, Sha-Mei; Crowley, Maura; Buchanan, Natasha; Poor, Stephen; Qiu, Yubin; Fassbender, Elizabeth; Shen, Siyuan; Woolfenden, Amber; Jensen, Amy; Cepeda, Rosemarie; Etemad-Gilbertson, Bijan; Giza, Shelby; Mogi, Muneto; Jaffee, Bruce; Azarian, Sassan

    2014-01-01

    Proteins that are post-translationally adducted with 2-(ω-carboxyethyl)pyrrole (CEP) have been proposed to play a pathogenic role in age-related macular degeneration, by inducing angiogenesis in a Toll Like Receptor 2 (TLR2)-dependent manner. We have investigated the involvement of CEP adducts in angiogenesis and TLR activation, to assess the therapeutic potential of inhibiting CEP adducts and TLR2 for ocular angiogenesis. As tool reagents, several CEP-adducted proteins and peptides were synthetically generated by published methodology and adduction was confirmed by NMR and LC-MS/MS analyses. Structural studies showed significant changes in secondary structure in CEP-adducted proteins but not the untreated proteins. Similar structural changes were also observed in the treated unadducted proteins, which were treated by the same adduction method except for one critical step required to form the CEP group. Thus some structural changes were unrelated to CEP groups and were artificially induced by the synthesis method. In biological studies, the CEP-adducted proteins and peptides failed to activate TLR2 in cell-based assays and in an in vivo TLR2-mediated retinal leukocyte infiltration model. Neither CEP adducts nor TLR agonists were able to induce angiogenesis in a tube formation assay. In vivo, treatment of animals with CEP-adducted protein had no effect on laser-induced choroidal neovascularization. Furthermore, in vivo inactivation of TLR2 by deficiency in Myeloid Differentiation factor 88 (Myd88) had no effect on abrasion-induced corneal neovascularization. Thus the CEP-TLR2 axis, which is implicated in other wound angiogenesis models, does not appear to play a pathological role in a corneal wound angiogenesis model. Collectively, our data do not support the mechanism of action of CEP adducts in TLR2-mediated angiogenesis proposed by others. PMID:25343517

  15. Cocaine-mediated microglial activation involves the ER stress-autophagy axis.

    PubMed

    Guo, Ming-Lei; Liao, Ke; Periyasamy, Palsamy; Yang, Lu; Cai, Yu; Callen, Shannon E; Buch, Shilpa

    2015-01-01

    Cocaine abuse leads to neuroinflammation, which, in turn, contributes to the pathogenesis of neurodegeneration associated with advanced HIV-1 infection. Autophagy plays important roles in both innate and adaptive immune responses. However, the possible functional link between cocaine and autophagy has not been explored before. Herein, we demonstrate that cocaine exposure induced autophagy in both BV-2 and primary rat microglial cells as demonstrated by a dose- and time-dependent induction of autophagy-signature proteins such as BECN1/Beclin 1, ATG5, and MAP1LC3B. These findings were validated wherein cocaine treatment of BV-2 cells resulted in increased formation of puncta in cells expressing either endogenous MAP1LC3B or overexpressing GFP-MAP1LC3B. Specificity of cocaine-induced autophagy was confirmed by treating cells with inhibitors of autophagy (3-MA and wortmannin). Intriguingly, cocaine-mediated induction of autophagy involved upstream activation of 2 ER stress pathways (EIF2AK3- and ERN1-dependent), as evidenced by the ability of the ER stress inhibitor salubrinal to ameliorate cocaine-induced autophagy. In vivo validation of these findings demonstrated increased expression of BECN1, ATG5, and MAP1LC3B-II proteins in cocaine-treated mouse brains compared to untreated animals. Increased autophagy contributes to cocaine-mediated activation of microglia since pretreatment of cells with wortmannin resulted in decreased expression and release of inflammatory factors (TNF, IL1B, IL6, and CCL2) in microglial cells. Taken together, our findings suggest that cocaine exposure results in induction of autophagy that is closely linked with neuroinflammation. Targeting autophagic proteins could thus be considered as a therapeutic strategy for the treatment of cocaine-related neuroinflammation diseases. PMID:26043790

  16. Evidence for the Involvement of p38 MAPK Activation in Barnacle Larval Settlement

    PubMed Central

    He, Li-Sheng; Xu, Ying; Matsumura, Kiyotaka; Zhang, Yu; Zhang, Gen; Qi, Shu-Hua; Qian, Pei-Yuan

    2012-01-01

    The barnacle Balanus ( = Amphibalanus) amphitrite is a major marine fouling animal. Understanding the molecular mechanism of larval settlement in this species is critical for anti-fouling research. In this study, we cloned one isoform of p38 MAPK (Bar-p38 MAPK) from this species, which shares the significant characteristic of containing a TGY motif with other species such as yeast, Drosophila and humans. The activation of p38 MAPK was detected by an antibody that recognizes the conserved dual phosphorylation sites of TGY. The results showed that phospho-p38 MAPK (pp38 MAPK) was more highly expressed at the cyprid stage, particularly in aged cyprids, in comparison to other stages, including the nauplius and juvenile stages. Immunostaining showed that Bar-p38 MAPK and pp38 MAPK were mainly located at the cyprid antennules, and especially the third and fourth segments, which are responsible for substratum exploration during settlement. The expression and localization patterns of Bar-p38 MAPK suggest its involvement in larval settlement. This postulation was also supported by the larval settlement bioassay with the p38 MAPK inhibitor SB203580. Behavioral analysis by live imaging revealed that the larvae were still capable of exploring the surface of the substratum after SB203580 treatment. This shows that the effect of p38 MAPK on larval settlement might be by regulating the secretion of permanent proteinaceous substances. Furthermore, the level of pp38 MAPK dramatically decreased after full settlement, suggesting that Bar-p38 MAPK maybe plays a role in larval settlement rather than metamorphosis. Finally, we found that Bar-p38 MAPK was highly activated when larvae confronted extracts of adult barnacle containing settlement cues, whereas larvae pre-treated with SB203580 failed to respond to the crude adult extracts. PMID:23115639

  17. Current Practice of Public Involvement Activities in Biomedical Research and Innovation: A Systematic Qualitative Review

    PubMed Central

    Lander, Jonas; Hainz, Tobias; Hirschberg, Irene; Strech, Daniel

    2014-01-01

    Background A recent report from the British Nuffield Council on Bioethics associated ‘emerging biotechnologies’ with a threefold challenge: 1) uncertainty about outcomes, 2) diverse public views on the values and implications attached to biotechnologies and 3) the possibility of creating radical changes regarding societal relations and practices. To address these challenges, leading international institutions stress the need for public involvement activities (PIAs). The objective of this study was to assess the state of PIA reports in the field of biomedical research. Methods PIA reports were identified via a systematic literature search. Thematic text analysis was employed for data extraction. Results After filtering, 35 public consultation and 11 public participation studies were included in this review. Analysis and synthesis of all 46 PIA studies resulted in 6 distinguishable PIA objectives and 37 corresponding PIA methods. Reports of outcome translation and PIA evaluation were found in 9 and 10 studies respectively (20% and 22%). The paper presents qualitative details. Discussion The state of PIAs on biomedical research and innovation is characterized by a broad range of methods and awkward variation in the wording of objectives. Better comparability of PIAs might improve the translation of PIA findings into further policy development. PIA-specific reporting guidelines would help in this regard. The modest level of translation efforts is another pointer to the “deliberation to policy gap”. The results of this review could inform the design of new PIAs and future efforts to improve PIA comparability and outcome translation. PMID:25469705

  18. Nanometer Scale Titanium Surface Texturing Are Detected by Signaling Pathways Involving Transient FAK and Src Activations

    PubMed Central

    Zambuzzi, Willian F.; Bonfante, Estevam A.; Jimbo, Ryo; Hayashi, Mariko; Andersson, Martin; Alves, Gutemberg; Takamori, Esther R.; Beltrão, Paulo J.; Coelho, Paulo G.; Granjeiro, José M.

    2014-01-01

    Background It is known that physico/chemical alterations on biomaterial surfaces have the capability to modulate cellular behavior, affecting early tissue repair. Such surface modifications are aimed to improve early healing response and, clinically, offer the possibility to shorten the time from implant placement to functional loading. Since FAK and Src are intracellular proteins able to predict the quality of osteoblast adhesion, this study evaluated the osteoblast behavior in response to nanometer scale titanium surface texturing by monitoring FAK and Src phosphorylations. Methodology Four engineered titanium surfaces were used for the study: machined (M), dual acid-etched (DAA), resorbable media microblasted and acid-etched (MBAA), and acid-etch microblasted (AAMB). Surfaces were characterized by scanning electron microscopy, interferometry, atomic force microscopy, x-ray photoelectron spectroscopy and energy dispersive X-ray spectroscopy. Thereafter, those 4 samples were used to evaluate their cytotoxicity and interference on FAK and Src phosphorylations. Both Src and FAK were investigated by using specific antibody against specific phosphorylation sites. Principal Findings The results showed that both FAK and Src activations were differently modulated as a function of titanium surfaces physico/chemical configuration and protein adsorption. Conclusions It can be suggested that signaling pathways involving both FAK and Src could provide biomarkers to predict osteoblast adhesion onto different surfaces. PMID:24999733

  19. Water-soluble chlorophyll protein is involved in herbivore resistance activation during greening of Arabidopsis thaliana

    PubMed Central

    Boex-Fontvieille, Edouard; Rustgi, Sachin; von Wettstein, Diter; Reinbothe, Steffen; Reinbothe, Christiane

    2015-01-01

    Water-soluble chlorophyll proteins (WSCPs) constitute a small family of unusual chlorophyll (Chl)-binding proteins that possess a Kunitz-type protease inhibitor domain. In Arabidopsis thaliana, a WSCP has been identified, named AtWSCP, that forms complexes with Chl and the Chl precursor chlorophyllide (Chlide) in vitro. AtWSCP exhibits a quite unexpected expression pattern for a Chl binding protein and accumulated to high levels in the apical hook of etiolated plants. AtWSCP expression was negatively light-regulated. Transgenic expression of AtWSCP fused to green fluorescent protein (GFP) revealed that AtWSCP is localized to cell walls/apoplastic spaces. Biochemical assays identified AtWSCP as interacting with RD21 (RESPONSIVE TO DESICCATION 21), a granulin domain-containing cysteine protease implicated in stress responses and defense. Reconstitution experiments showed tight interactions between RD21 and WSCP that were relieved upon Chlide binding. Laboratory feeding experiments with two herbivorous isopod crustaceans, Porcellio scaber (woodlouse) and Armadillidium vulgare (pillbug), identified the apical hook as Achilles’ heel of etiolated plants and that this was protected by RD21 during greening. Because Chlide is formed in the apical hook during seedling emergence from the soil, our data suggest an unprecedented mechanism of herbivore resistance activation that is triggered by light and involves AtWSCP. PMID:26016527

  20. Water-soluble chlorophyll protein is involved in herbivore resistance activation during greening of Arabidopsis thaliana.

    PubMed

    Boex-Fontvieille, Edouard; Rustgi, Sachin; von Wettstein, Diter; Reinbothe, Steffen; Reinbothe, Christiane

    2015-06-01

    Water-soluble chlorophyll proteins (WSCPs) constitute a small family of unusual chlorophyll (Chl)-binding proteins that possess a Kunitz-type protease inhibitor domain. In Arabidopsis thaliana, a WSCP has been identified, named AtWSCP, that forms complexes with Chl and the Chl precursor chlorophyllide (Chlide) in vitro. AtWSCP exhibits a quite unexpected expression pattern for a Chl binding protein and accumulated to high levels in the apical hook of etiolated plants. AtWSCP expression was negatively light-regulated. Transgenic expression of AtWSCP fused to green fluorescent protein (GFP) revealed that AtWSCP is localized to cell walls/apoplastic spaces. Biochemical assays identified AtWSCP as interacting with RD21 (responsive to desiccation 21), a granulin domain-containing cysteine protease implicated in stress responses and defense. Reconstitution experiments showed tight interactions between RD21 and WSCP that were relieved upon Chlide binding. Laboratory feeding experiments with two herbivorous isopod crustaceans, Porcellio scaber (woodlouse) and Armadillidium vulgare (pillbug), identified the apical hook as Achilles' heel of etiolated plants and that this was protected by RD21 during greening. Because Chlide is formed in the apical hook during seedling emergence from the soil, our data suggest an unprecedented mechanism of herbivore resistance activation that is triggered by light and involves AtWSCP. PMID:26016527

  1. Assembly of spaced chromatin involvement of ATP and DNA topoisomerase activity.

    PubMed Central

    Almouzni, G; Méchali, M

    1988-01-01

    Undiluted extracts from eggs or oocytes of Xenopus laevis support the assembly of chromatin with physiologically spaced nucleosomes. Micrococcal nuclease and DNase I digestion experiments show that nucleosome formation as well as supercoiling of circular DNA concomitant to assembly do not require ATP or Mg2+. However these factors are essential for the stability and the physiological spacing of the assembled chromatin. gamma-S-ATP can substitute for ATP in this process. With topoisomers of defined linking number topological interconversions proceed by steps of unity, both in vitro as well as in vivo, indicating that topoisomerase I is dominantly acting in this process. Novobiocin sensitivity occurred only with diluted extracts and was unrelated to an inhibition of topoisomerase II. Finally, nucleosome assembly occurs efficiently on linear DNA although the assembled DNA is less stable than with circular DNA. From these results we propose that mature chromatin is formed in a two-step reaction. In the first step, nucleosome deposition occurs independently of ATP and Mg2+. Thus, nucleosome formation can be uncoupled from their spacing. In this step, topoisomerase activity is involved in the relaxation of the topological constraints generated by chromatin assembly rather than in the process of assembly itself. The second step, requiring ATP and Mg2+, generates properly spaced chromatin. Images PMID:2854062

  2. Protease-Activated Receptor 2 Is Involved in Th2 Responses against Trichinella spiralis Infection

    PubMed Central

    Park, Mi Kyung; Cho, Min Kyoung; Kang, Shin Ae; Park, Hye-Kyung; Kim, Yun Seong; Kim, Ki Uk; Ahn, Soon Cheol; Kim, Dong-Hee

    2011-01-01

    In order to get a better understanding of the role of protease-activated receptor 2 (PAR2) in type 2 helper T (Th2) cell responses against Trichinella spiralis infection, we analyzed Th2 responses in T. spiralis-infected PAR2 knockout (KO) mice. The levels of the Th2 cell-secreted cytokines, IL-4, IL-5, and IL-13 were markedly reduced in the PAR2 KO mice as compared to the wild type mice following infection with T. spiralis. The serum levels of parasite-specific IgE increased significantly in the wild type mice as the result of T. spiralis infection, but this level was not significantly increased in PAR2 KO mice. The expression level of thymic stromal lymphopoietin, IL-25, and eotaxin gene (the genes were recently known as Th2 response initiators) of mouse intestinal epithelial cells were increased as the result of treatment with T. spiralis excretory-secretory proteins. However, the expression of these chemokine genes was inhibited by protease inhibitor treatments. In conclusion, PAR2 might involve in Th2 responses against T. spiralis infection. PMID:22072823

  3. Energy Shortage: A Benign Crisis?

    ERIC Educational Resources Information Center

    Armstrong, Ellis L.

    1974-01-01

    The energy shortage will have a favorable effect on city revitalizing activities as innovative thinking is applied to city and transportation planning, building design, service and recreational facilities, and sewage treatment. (Author/MF)

  4. Linking pre-diabetes with benign prostate hyperplasia. IGFBP-3: a conductor of benign prostate hyperplasia development orchestra?

    PubMed

    Protopsaltis, Ioannis; Ploumidis, Achilles; Sergentanis, Theodoros N; Constantoulakis, Padelis; Tzirogiannis, Kostantinos; Kyprianidou, Chrysoula; Papazafiropoulou, Athanasia K; Melidonis, Andreas; Delakas, Dimitrios

    2013-01-01

    Benign prostatic hyperplasia (BPH) represents a pattern of non-malignant growth of prostatic fibromuscular stroma. Metabolic disturbances such us pre-diabetes and metabolic syndrome may have a role in BPH pathophysiology. A potential explanation for the above relationship involves the insulin-like growth factor (IGF) axis as well as IGF binding proteins, (IGFBPs) of which the most abundant form is IGFBP-3. Therefore, the aim of the present study was to investigate the association between intra-prostatic levels of IGF-1, IGF-2 as well as to evaluate the role of locally expressed IGFBP-3 in BPH development in pre-diabetes. A total of 49 patients admitted to the Urology department of a tertiary urban Greek hospital, for transurethral prostate resection, or prostatectomy and with pre-diabetes [impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) or both] were finally included. The majority of the sample consisted of subjects with IGT (51.0%), followed by IFG and IGT (32.7%) and isolated IFG (16.3%). For all participants a clinical examination was performed and blood samples were collected. In addition, total prostate (TP) volume or transitional zone (TZ) volume were estimated by transrectal ultrasonography. The results of the multivariate analysis regarding TP volume showed that higher PSA (p<0.001), larger waist circumference (p=0.007) and higher IGFBP-3 expression levels (p<0.001) independently predicted higher TP volume. The results regarding the volume of the TZ showed that higher PSA (p<0.001), larger waist circumference (p<0.001) and higher IGFBP-3 expression levels (p=0.024) were independently associated with higher TZ volume. Our findings show that intra-prostatic levels of IGFBP-3, PSA and waist circumference, but not overall obesity, are positively associated with prostate volume. IGFBP-3 seems to be a multifunctional protein, which can potentiate or inhibit IGF activity. PMID:24367483

  5. Peroxisome proliferator-activated receptor alpha is involved in the regulation of lipid metabolism by ginseng.

    PubMed

    Yoon, Michung; Lee, Hyunghee; Jeong, Sunhyo; Kim, Jung-Jae; Nicol, Christopher J; Nam, Kung Woo; Kim, Moonza; Cho, Byung Goo; Oh, Goo Taeg

    2003-04-01

    1. Peroxisome proliferator-activated receptor alpha (PPARalpha) regulates the expression of the key genes involved in lipid metabolism following activation of this receptor by various ligands. Ginseng, a highly valuable medicine in oriental societies, is also reported to modulate lipid metabolism, although the mechanism of its action remains unknown. In order to test our hypothesis that ginseng exerts its effects by altering PPARalpha-mediated pathways, the effects of Korean red ginseng on PPARalpha function and serum lipid profiles were investigated using in vivo and in vitro approaches. 2. In vivo administration of ginseng extract (GE) and ginsenosides (GS) not only inhibited mRNA levels of acyl-CoA oxidase, a rate-limiting enzyme for PPARalpha-mediated peroxisomal fatty acid beta-oxidation, induced by the potent PPARalpha ligand Wy14,643 in a dose- and time-dependent manner, but also inhibited the induction of PPARalpha target genes expected following treatment with Wy14,643. 3. Consistent with the in vivo data, both GE and GS caused dose-dependent decreases in the endogenous expression of a luciferase reporter gene containing the PPAR responsive element (PPRE), while GS significantly decreased the magnitude of reporter gene activation in the presence of Wy14,643. 4. Serological studies demonstrated that, compared with vehicle-treated mice, treatment with GS significantly increased serum concentrations of total cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol. Compared to groups treated with Wy14,643 alone, which significantly decreased serum triglyceride and HDL cholesterol levels versus controls, coadministration of either GE or GS with Wy14,643 modestly increased serum triglycerides and HDL cholesterol. 5. These results indicate that the effects of ginseng on serum lipid profiles may be mediated by changes in the expression of PPARalpha target genes, providing the first evidence that in vivo and in vitro treatments of ginseng

  6. Study of the possible mechanisms involved in the mucosal immune system activation by lactic acid bacteria.

    PubMed

    Perdigón, G; Vintiñi, E; Alvarez, S; Medina, M; Medici, M

    1999-06-01

    The induction of a mucosal immune response is not easy due to the development of oral tolerance, but under some conditions, bacteria can activate this immune system. Antigens administered orally can interact with M cells of Peyer's patches or bind to the epithelial cells. We have demonstrated that certain lactic acid bacteria are able to induce specific secretory immunity, and others will enhance the gut inflammatory immune response. The aim of this work was to establish the reason for these different behaviors and to define possible mechanisms involved in the interaction of lactic acid bacteria at the intestinal level. We studied IgA+ and IgM+ B cells comparatively in bronchus and intestine and CD4+ T cells and IgA anti-lactic acid bacteria antibodies in the intestinal fluid, induced by oral administration of Lactobacillus casei, Lb. delbrueckii ssp. bulgaricus, Lb. acidophilus, Lb. plantarum, Lb. rhamnosus, Lactococcus lactis, and Streptococcus salivarius ssp. thermophilus. The increase in the IgA+ B cells in the bronchus means that these lactic acid bacteria were able to induce the IgA cycle by interaction with M cells from Peyer's patches or intestinal epithelial cells. The IgM+ cells increased when the stimulus did not induce the switch from IgM+ to IgA+. The increase in the CD4+ cells suggests interaction of Peyer's patches and enhancement of the B- and T-cell migration. The anti-lactic acid bacteria antibody is related to the processing and presentation of the microorganisms to the immune cells. We demonstrated that Lb. casei and Lb. plantarum were able to interact with Peyer's patch cells and showed an increase in IgA-, CD4+ cells, and antibodies specific for the stimulating strain. Lactobacillus acidophilus induced gut mucosal activation by interaction with the epithelial cells without increase in the immune cells associated with the bronchus. Although Lb. rhamnosus and Strep. salivarius ssp. thermophilus interact with epithelial cells, they also induced

  7. Benign Lymphoid Hyperplasia Presenting as Bilateral Scleral Nodules

    PubMed Central

    Cumba, Ricardo J.; Vazquez-Botet, Rene

    2015-01-01

    Purpose. To report a case of transient lymphoid hyperplasia presenting as bilateral nodular scleral mass in a young male patient. Design. Observational case report. Methods. Chart review. Causes of scleritis were considered and excluded based on detailed history, physical examination, and laboratory investigations. Results. Excisional biopsy of scleral lesions indicated lymphoid tissue. Immunohistochemical studies revealed a polyclonal population of T and B cells consistent with a benign reactive process. Conclusions. Chronic exposure of the ocular adnexa to many allergens and irritants may lead to activation of the inflammatory cascade. In severely allergic patients activation may be exponential and elicit an immune-mediated response resulting in a transient lymphoid reactive process. PMID:26421203

  8. Rural Schooling in Georgia: The Experiences of a Minority Community Service Organization Involved in Local School Decision-Making Activities

    ERIC Educational Resources Information Center

    Lowe, Cynthia Louise Altman

    2010-01-01

    This dissertation study was a descriptive case study of a minority community service organization whose members were actively involved in local school decision-making and activities in a rural Northeast Georgia community. Rural schools face unique challenges in light of current educational trends. To address the challenges, rural schools must…

  9. Understanding the Meaning African-American Men Give to Their Student Leadership Involvement and Engagement Activities in College

    ERIC Educational Resources Information Center

    Brooks, Karl A.

    2012-01-01

    The purpose of this qualitative, phenomenological study was to explore and gain a deeper understanding of the lived experiences and perceptions of African-American (A-A) men who are persisting in college and who demonstrate participation in co-curricular activities defined as student leadership involvement and engagement activities (SLIEA). The…

  10. The Unusual but Benign in Pediatric Surgery

    PubMed Central

    Shandling, Barry

    1985-01-01

    The problem of what is normal and what is not is closely related to whether or not, if something is indeed abnormal, it matters. Anticipating the outcome will affect the management in infants and children of such relatively benign conditions as hydroceles, umbilical hernias, diseases of the male and female breasts, lymphadenopathy and the intact prepuce. Unnecessary investigations such as barium studies which do not affect management are inadvisable. Congenital torticollis and undescended testis, seemingly benign, must be appropriately treated, however, in order to avoid lifelong sequelae. PMID:21274156

  11. Osteoid osteoma and benign osteoblastoma in childhood.

    PubMed Central

    Black, J A; Levick, R K; Sharrard, W J

    1979-01-01

    Three cases of osteoid osteoma and one of benign osteoblastoma in children are described. The main complaint was severe pain which was worse at night; it was relieved by aspirin or other analgesics. The diagnosis was made on clinical and radiological grounds and was confirmed on histological examination of the central nidus removed at operation. The pain was relieved in the patients with osteoid osteoma, and it was very much less after operative removal of the benign osteoblastoma. Both conditions are probably variations of the same disease process, depending on the anatomical site and the type of bone affected. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:475430

  12. Radiofrequency ablation for benign thyroid nodules.

    PubMed

    Bernardi, S; Stacul, F; Zecchin, M; Dobrinja, C; Zanconati, F; Fabris, B

    2016-09-01

    Benign thyroid nodules are an extremely common occurrence. Radiofrequency ablation (RFA) is gaining ground as an effective technique for their treatment, in case they become symptomatic. Here we review what are the current indications to RFA, its outcomes in terms of efficacy, tolerability, and cost, and also how it compares to the other conventional and experimental treatment modalities for benign thyroid nodules. Moreover, we will also address the issue of treating with this technique patients with cardiac pacemakers (PM) or implantable cardioverter-defibrillators (ICD), as it is a rather frequent occurrence that has never been addressed in detail in the literature. PMID:27098804

  13. Benign Cystic Mesothelioma Misdiagnosed as Peritoneal Carcinomatosis

    PubMed Central

    Shin, Hyun Deok; Kim, Suk Bae

    2016-01-01

    Benign cystic mesothelioma (BCM) is a rare benign disease that forms multicystic masses in the abdomen, pelvis, and retroperitoneum. It occurs predominantly in young to middle-aged women. The majority of cases were associated with a history of abdominal or pelvic operation, a history of endometriosis, and pelvic inflammatory disease. We present a unique case of BCM which is different to the previous cases. The patient was a 52-year-old man showing features of peritoneal carcinomatosis accompanied by ascites on abdominal computed tomography scans. We herein report a case of BCM misdiagnosed with peritoneal carcinomatosis.

  14. [Interstitial laser coagulation of benign prostatic hyperplasia].

    PubMed

    Muschter, R; Hessel, S; Hofstetter, A; Keiditsch, E; Rothenberger, K H; Schneede, P; Frank, F

    1993-07-01

    We report on the new method of interstitial laser coagulation for the treatment of benign prostatic hyperplasia (BPH). The procedure is based on the interstitial application of Nd:YAG laser irradiation, delivered through a new light guide system. Such light applicators coagulate constant tissue volumes in a homogeneous manner, as proven by in vitro studies in different tissues, including surgically removed prostate adenoma. The extent of the coagulation is determined by laser power and irradiation time. At 5 W, for example, and during a 10-min period, this zone reached a diameter of up to 20 mm. Temperatures generated in the process were over 100 degrees C, as measured by time/space resolution. These results were confirmed by in vivo studies in canine prostates. In the course of 7 weeks, the coagulated areas formed scars with degeneration and fibrosis, accompanied by marked shrinking. Neighbouring organs were not affected. The method was successfully transferred to clinical practice. The application of the light guides to the lateral lobes was performed percutaneously from the perineum under transrectal ultrasound guidance. The median lobe was punctured transurethrally under direct vision. Twenty-seven patients with an average age of 67.7 years were treated between July 1991 and March 1992. At the time of evaluation 15 patients had a follow-up of more than 2 months. They experienced a mean increase of peak flow rate from 6.6 to 15.2 ml/s and a mean decrease of residual volume from 206 to 38 ml. This was accompanied by a marked lessening of symptoms. The average prostate weight decreased from 63 to 44 g. Sexually active patients did not experience retrograde ejaculation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7690498

  15. Active involvement of people with intellectual disabilities in health research - A structured literature review.

    PubMed

    Frankena, Tessa Kim; Naaldenberg, Jenneken; Cardol, Mieke; Linehan, Christine; van Schrojenstein Lantman-de Valk, Henny

    2015-01-01

    Actively involving people with intellectual disabilities (ID) in health research, also known as inclusive health research, is increasingly popular. Currently, insight into experiences of this type of research is scarce. To gain insight into this topic, a structured literature review was conducted focussing on (1) existing theories, (2) inclusive methods, (3) added value and (4) barriers and facilitators. Literature published between January 2000 and January 2014 was included covering keywords related to ID and inclusive health research. Searches were performed in Pubmed, CINAHL, PsycINFO, EMBASE and MEDLINE databases, resulting in 26 included papers. Papers were quality assessed and analysed using qualitative data analysis software. Four theories were often simultaneously addressed: participatory research, emancipatory research, inclusive research and Arnstein's ladder. Barriers and facilitators could be divided into preparing, undertaking and finalising phases of research. Authors indicated that their motivation to conduct inclusive health research was based on demands by policy and funding bodies or was based on ethical considerations (i.e., ethical notions and giving people with ID a voice). Upon completion, authors perceived increased quality and validity of their research and several benefits for stakeholders (i.e., people with ID, researchers and healthcare professionals). Overall, there was consistency in their perception of the most important aspects of inclusive health research. Based on the analysis of included papers, four recommendations of inclusive health research with people with ID were found. Inclusive health research should be: (1) tailoring to the specific study; (2) anticipating all stakeholders; (3) considering its added value; and (4) providing insight into its process. PMID:26280692

  16. Identification of Tyrosine Residues in Constitutively Activated Fibroblast Growth Factor Receptor 3 Involved in Mitogenesis, Stat Activation, and Phosphatidylinositol 3-Kinase Activation

    PubMed Central

    Hart, Kristen C.; Robertson, Scott C.; Donoghue, Daniel J.

    2001-01-01

    Fibroblast growth factor receptor 3 (FGFR3) mutations are frequently involved in human developmental disorders and cancer. Activation of FGFR3, through mutation or ligand stimulation, results in autophosphorylation of multiple tyrosine residues within the intracellular domain. To assess the importance of the six conserved tyrosine residues within the intracellular domain of FGFR3 for signaling, derivatives were constructed containing an N-terminal myristylation signal for plasma membrane localization and a point mutation (K650E) that confers constitutive kinase activation. A derivative containing all conserved tyrosine residues stimulates cellular transformation and activation of several FGFR3 signaling pathways. Substitution of all nonactivation loop tyrosine residues with phenylalanine rendered this FGFR3 construct inactive, despite the presence of the activating K650E mutation. Addition of a single tyrosine residue, Y724, restored its ability to stimulate cellular transformation, phosphatidylinositol 3-kinase activation, and phosphorylation of Shp2, MAPK, Stat1, and Stat3. These results demonstrate a critical role for Y724 in the activation of multiple signaling pathways by constitutively activated mutants of FGFR3. PMID:11294897

  17. Family involvement in music impacts participation of children with cochlear implants in music education and music activities

    PubMed Central

    Driscoll, Virginia; Gfeller, Kate; Tan, Xueli; See, Rachel L.; Cheng, Hsin-Yi; Kanemitsu, Mikiko

    2014-01-01

    Objective Children with cochlear implants (CIs) participate in musical activities in school and daily lives. Considerable variability exists regarding the amount of music involvement and enjoyment. Using the Music Engagement Questionnaire-Preschool/Elementary (MEQ-P/E), we wanted to determine patterns of musical participation and the impact of familial factors on engagement. Methods Parents of 32 children with CIs (16 preschool, 16 elementary) completed a questionnaire regarding the musical involvement of their child with an implant and a normal-hearing (NH) sibling (if one existed). We compared CI children's involvement to that of their NH siblings as well as across groups of children with and without CIs. Correlations between parent ratings of music importance, demographic factors, and involvement of CI and NH children were conducted within and across groups. Results No significant differences were found between children with CIs and NH siblings, meaning children from the same family showed similar levels of musical involvement. When compared at the same developmental stage, no significant differences were found between preschool children with and without CIs. Parents who rated the importance of music as “low” or “middle” had children (NH and CI) who were less involved in music activities. Children whose parents rated music importance as “high” were involved in monthly to weekly music activities with 81.25% reporting daily music listening. Conclusion Despite a less-than-ideal auditory signal for music, preschool and school-aged CI children enjoy and are involved in musical experiences. Families who enjoy and spend a greater amount of time involved in music tend to have children who also engage more actively in music. PMID:25431978

  18. Family involvement in music impacts participation of children with cochlear implants in music education and music activities.

    PubMed

    Driscoll, Virginia; Gfeller, Kate; Tan, Xueli; See, Rachel L; Cheng, Hsin-Yi; Kanemitsu, Mikiko

    2015-05-01

    Objective Children with cochlear implants (CIs) participate in musical activities in school and daily lives. Considerable variability exists regarding the amount of music involvement and enjoyment. Using the Music Engagement Questionnaire-Preschool/Elementary (MEQ-P/E), we wanted to determine patterns of musical participation and the impact of familial factors on engagement. Methods Parents of 32 children with CIs (16 preschool and 16 elementary) completed a questionnaire regarding the musical involvement of their child with an implant and a normal-hearing (NH) sibling (if one existed). We compared CI children's involvement to that of their NH siblings as well as across groups of children with and without CIs. Correlations between parent ratings of music importance, demographic factors, and involvement of CI and NH children were conducted within and across groups. Results No significant differences were found between children with CIs and NH siblings, meaning children from the same family showed similar levels of musical involvement. When compared at the same developmental stage, no significant differences were found between preschool children with and without CIs. Parents who rated the importance of music as 'low' or 'middle' had children (NH and CI) who were less involved in music activities. Children whose parents rated music importance as 'high' were involved in monthly to weekly music activities with 81.25% reporting daily music listening. Conclusion Despite a less-than-ideal auditory signal for music, preschool and school-aged CI children enjoy and are involved in musical experiences. Families who enjoy and spend a greater amount of time involved in music tend to have children who also engage more actively in music. PMID:25431978

  19. Spontaneous activity in the developing gerbil auditory cortex in vivo involves GABAergic transmission

    PubMed Central

    Kotak, Vibhakar C.; Péndola, L. Martín; Rodríguez-Contreras, Adrián

    2012-01-01

    A salient feature of the developing brain is that spontaneous oscillations (SOs) and waves may influence the emergence of synaptic connections. Whilst gamma-amino butyric acid (GABA) produces depolarization and may support SOs in the neurons of developing rodents, it elicits hyperpolarization and diminishes SOs in developing gerbil auditory cortex (ACx). Therefore, we asked whether SOs exist in developing gerbil ACx in vivo and if GABAergic involvement can be manipulated. In vivo extracellular recordings in P3-5 ACx revealed SOs with longer burst durations and shorter inter-event intervals compared to ACx SOs in slices. ACx was then validated by gross anatomical features and lesions created at the in vivo recording site that corresponded with the electrophysiological coordinates of thalamorecipient ACx in slices. Further, NeuroVue Red, a lipophilic dye loaded at the in vivo recording sites, stained anatomically identifiable fiber tracks between the ACx and the auditory thalamus, medial geniculate body (MG). Separately, to chronically perturb GABAergic role in SOs, P2-5 pups were administered daily with GABAA receptor blocker, bicuculline (BIC). We then recorded from P14-17 ACx neurons in slices generated after hearing onset. ACx neurons from BIC-administered pups exhibited spontaneous action potentials in contrast to subthreshold synaptic potentials in neurons from sham-injected animals. Finally, to elucidate whether the gap junction blocker mefloquine (MFQ) previously shown to dampen ACx SOs in slices affected GABAergic transmission, MFQ was acutely applied in P3-5 slices while spontaneous inhibitory postsynaptic currents (sIPSCs) were recorded. Whereas MFQ increased the amplitude and frequency of sIPSCs in ACx neurons, the broad-spectrum gap junction blocker carbenoxolone decreased sIPSC amplitudes only. Together, we show that P2-5 gerbil ACx can endogenously generate SOs in vivo. Persistence of activity in ACx in P14-17 slices from pups administered with BIC at

  20. Differential Involvement of Amygdala and Cortical NMDA Receptors Activation upon Encoding in Odor Fear Memory

    ERIC Educational Resources Information Center

    Hegoburu, Chloé; Parrot, Sandrine; Ferreira, Guilaume; Mouly, Anne-Marie

    2014-01-01

    Although the basolateral amygdala (BLA) plays a crucial role for the acquisition of fear memories, sensory cortices are involved in their long-term storage in rats. However, the time course of their respective involvement has received little investigation. Here we assessed the role of the glutamatergic N-methyl-D-aspartate (NMDA) receptors in the…

  1. Involving Parents of Young Children in Science, Math and Literacy Activities.

    ERIC Educational Resources Information Center

    Landerholm, Elizabeth; And Others

    A summer parent involvement project was set up in a Chicago inner city public school in a Hispanic neighborhood. The eight-session program was intended to help parents: (1) become involved with the school program by becoming comfortable with the school setting; (2) enjoy reading and writing and replicate these experiences with their children; (3)…

  2. The Theory of Active Involvement: Processes Underlying Interventions that Engage Adolescents in Message Planning and/or Production

    PubMed Central

    Greene, Kathryn

    2013-01-01

    Adolescence is a time of increased risk-taking and recent intervention strategies have included adolescents planning or producing anti-risk messages for their peers. Although these projects may generate enthusiasm, we know little about message planning or production as a strategy for changing adolescent decision-making and behavior. The paper articulates the Theory of Active Involvement (TAI) to describe and explain the processes through which these active involvement interventions influence adolescents. TAI is based on social cognitive theory’s notion of self-regulation and examines multiple perspective-taking and activating the self-reflection processes. The theory specifically describes the process of cognitive changes experienced by participants in active involvement interventions. The sequence is conceptualized as starting when engagement with the intervention (arousal and involvement) produces skill and knowledge gains (immediate outcomes) that lead to reflection (perceived discrepancy) and then other cognitions (expectancies, norms, intentions), with the ultimate outcome being behavior change. Engaging the target audience in a process of self-reflection is conceptualized as the crucial ingredient for meaningful and sustainable change in cognitions and behavior. This paper provides valuable insight into how active involvement strategies function and how to best design these interventions, particularly those targeting adolescents. PMID:23980581

  3. Combining active farmer involvement with detailed farm data in Denmark: a promising method for achieving water framework directive targets?

    PubMed

    Wright, Stuart A L; Jacobsen, Brian H

    2010-01-01

    The Water Framework Directive (WFD) encourages active involvement during its implementation, although no specific participatory methods are suggested, whilst implementing the target-oriented Directive will require detailed agri-environmental data at catchment and farm level. The paper is a case study of the Danish AGWAplan project, which actively involved farmers in the selection of measures to reduce diffuse nutrient pollution at farm and catchment level, thereby providing an example of how active involvement might be operationalised. Active involvement has been identified as being of central importance to the success of the WFD. The project also entailed the accumulation of extensive agri-environmental data. The aim of the paper is to evaluate AGWAplan to establish the extent to which its expected objectives have been achieved and how, and to determine whether the project approach might facilitate WFD goals if implemented in forthcoming river basin management plans (RBMPs). AGWAplan resulted in advantageous outcomes, including win-win solutions to reduce nutrient leaching and greater acceptance of policy, although the original reduction targets where not fully reached. The paper concludes that actively involving farmers in a similar manner in RBMPs may make an important contribution to the implementation of the WFD, although caveats regarding its potential for transfer to other areas are identified. PMID:20453337

  4. Identification and Functions of Amino Acid Residues in PotB and PotC Involved in Spermidine Uptake Activity*

    PubMed Central

    Higashi, Kyohei; Sakamaki, Yoshiharu; Herai, Emiko; Demizu, Risa; Uemura, Takeshi; Saroj, Sunil D.; Zenda, Risa; Terui, Yusuke; Nishimura, Kazuhiro; Toida, Toshihiko; Kashiwagi, Keiko; Igarashi, Kazuei

    2010-01-01

    Amino acid residues on PotB and PotC involved in spermidine uptake were identified by random and site-directed mutagenesis. It was found that Trp8, Tyr43, Trp100, Leu110, and Tyr261 in PotB and Trp46, Asp108, Glu169, Ser196, Asp198, and Asp199 in PotC were strongly involved in spermidine uptake and that Tyr160, Glu172, and Leu274 in PotB and Tyr19, Tyr88, Tyr148, Glu160, Leu195, and Tyr211 in PotC were moderately involved in spermidine uptake. Among 11 amino acid residues that were strongly involved in spermidine uptake, Trp8 in PotB was important for insertion of PotB and PotC into membranes. Tyr43, Trp100, and Leu110 in PotB and Trp46, Asp108, Ser196, and Asp198 in PotC were found to be involved in the interaction with PotD. Leu110 and Tyr261 in PotB and Asp108, Asp198, and Asp199 in PotC were involved in the recognition of spermidine, and Trp100 and Tyr261 in PotB and Asp108, Glu169, and Asp198 in PotC were involved in ATPase activity of PotA. Accordingly, Trp100 in PotB was involved in both PotD recognition and ATPase activity, Leu110 in PotB was involved in both PotD and spermidine recognition, and Tyr261 in PotB was involved in both spermidine recognition and ATPase activity. Asp108 and Asp198 in PotC were involved in PotD and spermidine recognition as well as ATPase activity. These results suggest that spermidine passage from PotD to the cytoplasm is coupled to the ATPase activity of PotA through a structural change of PotA by its ATPase activity. PMID:20937813

  5. Character Development within Youth Development Programs: Exploring Multiple Dimensions of Activity Involvement.

    PubMed

    Lynch, Alicia Doyle; Ferris, Kaitlyn A; Burkhard, Brian; Wang, Jun; Hershberg, Rachel M; Lerner, Richard M

    2016-03-01

    We examined links among three dimensions of youth involvement (intensity, duration, and engagement) in Boy Scouts of America (BSA), an international out-of-school time (OST) youth development program designed to promote moral and performance character in boys. Using data from 737 youth and their parents who participated in one of 40 BSA program sites (commonly referred to as "packs"), we first considered how individual- and pack-level measures of program involvement were differentially linked with character development. Next, we examined whether pack-level involvement characteristics moderate individual-level involvement characteristics, hypothesizing that highly involved packs would serve to further enhance the positive effects of high levels of individual involvement. Results indicated engagement was the strongest, most frequent predictor of increases in both moral and performance character. Although there were no direct effects of pack-level intensity, duration, or engagement, the effects of individual-level engagement were moderated by pack-level engagement, suggesting that the largest increases in moral and performance character occurred among highly engaged youth who were enrolled in highly engaged packs. These results highlight the need to examine multiple dimensions of OST program involvement simultaneously, and suggest that strengthening youth engagement in programming may provide a means for enhancing the positive effects of high-quality youth programming. PMID:27217313

  6. Benign Prostatic Hyperplasia: from Bench to Clinic

    PubMed Central

    Cho, Hee Ju

    2012-01-01

    Benign prostatic hyperplasia (BPH) is a prevalent disease, especially in old men, and often results in lower urinary tract symptoms (LUTS). This chronic disease has important care implications and financial risks to the health care system. LUTS are caused not only by mechanical prostatic obstruction but also by the dynamic component of obstruction. The exact etiology of BPH and its consequences, benign prostatic enlargement and benign prostatic obstruction, are not identified. Various theories concerning the causes of benign prostate enlargement and LUTS, such as metabolic syndrome, inflammation, growth factors, androgen receptor, epithelial-stromal interaction, and lifestyle, are discussed. Incomplete overlap of prostatic enlargement with symptoms and obstruction encourages focus on symptoms rather than prostate enlargement and the shifting from surgery to medicine as the treatment of BPH. Several alpha antagonists, including alfuzosin, doxazosin, tamsulosin, and terazosin, have shown excellent efficacy without severe adverse effects. In addition, new alpha antagonists, silodosin and naftopidil, and phosphodiesterase 5 inhibitors are emerging as BPH treatments. In surgical treatment, laser surgery such as photoselective vaporization of the prostate and holmium laser prostatectomy have been introduced to reduce complications and are used as alternatives to transurethral resection of the prostate (TURP) and open prostatectomy. The status of TURP as the gold standard treatment of BPH is still evolving. We review several preclinical and clinical studies about the etiology of BPH and treatment options. PMID:22468207

  7. Unusual Benign Tumors of the Breast

    PubMed Central

    Adrada, Beatriz E; Krishnamurthy, Savitri; Carkaci, Selin; Posleman-Monetto, Flavia E; Ewere, Adesuwa; Whitman, Gary J

    2015-01-01

    The purpose of this article is to describe the imaging characteristics of a variety of benign breast tumors that may be encountered in daily practice, in order to formulate an appropriate differential diagnosis and to establish concordance between the imaging and the pathologic findings, and to assist the clinician with appropriate management. PMID:26085959

  8. CSF imaging in benign intracranial hypertension

    PubMed Central

    James, A. Everette; Harbert, J. C.; Hoffer, P. B.; DeLand, F. H.

    1974-01-01

    The cisternographic images in 10 patients with benign intracranial hypertension were reviewed. Nine were normal. Transfer of labelled tracer from the subarachnoid space was measured in five patients and was found to be abnormal in only two. The relation of these findings to the proposed pathophysiological alterations is discussed. Images

  9. Lee waves, benign and malignant

    NASA Technical Reports Server (NTRS)

    Wurtele, M. G.; Datta, A.

    1992-01-01

    The flow of an incompressible, stratified fluid over an obstacle will produce an oscillation in which buoyancy is the restoring force, called a gravity wave. For disturbances of this scale, the atmosphere may be treated as incompressible; and even the linear approximation will explain many of the phenomena observed in the lee of mountains. However, nonlinearities arise in two ways: (1) through the large (scaled) size of the mountain, and (2) from dynamically singular levels in the fluid field. These produce a complicated array of phenomena that present hazards to aircraft and to lee surface areas. If there is no dynamic barrier, these waves can penetrate vertically into the middle atmosphere (30-100 km attitude), where recent observations show them to be of a length scale that must involve the Coriolis force in any modeling. At these altitudes, the amplitude of the waves is very large, and the waves are studied with a view to their potential impact on the projected National Aerospace Plane. This paper presents the results of analyses and state-of-the-art numerical simulations, validated where possible by observational data.

  10. Staying in or Moving Away from Structured Activities: Explanations Involving Parents and Peers

    ERIC Educational Resources Information Center

    Persson, Andreas; Kerr, Margaret; Stattin, Hakan

    2007-01-01

    Adolescent participation in structured activities, meaning those with adult leaders, regular meetings, and skill-building activities, is related to good adjustment. Participation in unstructured, unsupervised, peer-oriented activities is related to poor adjustment. Structured activity participation is high in early adolescence and then declines,…

  11. Personal involvement is related to increased search motivation and associated with activity in left BA44-a pilot study.

    PubMed

    Schaefer, Michael; Rumpel, Franziska; Sadrieh, Abdolkarim; Reimann, Martin; Denke, Claudia

    2015-01-01

    Numerous studies explore consumer perception of brands in a more or less passive way. This may still be representative for many situations or decisions we make each day. Nevertheless, sometimes we often actively search for and use information to make informed and reasoned choices, thus implying a rational and thinking consumer. Researchers suggested describing this distinction as low relative to high involvement consumer behavior. Although the involvement concept has been widely used to explain consumer behavior, behavioral and neural correlates of this concept are poorly understood. The current study aims to describe a behavioral measure that is associated with high involvement, the length of search behavior. A second aim of this study was to explore brain activations associated with involvement by employing functional magnetic resonance imaging (fMRI). We presented participants information cues for different products and told them that they had to answer questions with respect to these products at the end of the experiment. Participants were free to stop the information search if they think they gathered enough information or to continue with collecting information. Behavioral results confirmed our hypothesis of a relationship between searching behavior and personal involvement by demonstrating that the length of search correlated significantly with the degree of personal involvement of the participants. fMRI data revealed that personal involvement was associated with activation in BA44. Since this brain region is known to be involved in semantic memory, the results of this pilot study suggest that high involvement consumer behavior may be linked to cognitive load and attention towards a product. PMID:25859200

  12. Lee waves: Benign and malignant

    NASA Technical Reports Server (NTRS)

    Wurtele, M. G.; Datta, A.; Sharman, R. D.

    1993-01-01

    The flow of an incompressible fluid over an obstacle will produce an oscillation in which buoyancy is the restoring force, called a gravity wave. For disturbances of this scale, the atmosphere may be treated as dynamically incompressible, even though there exists a mean static upward density gradient. Even in the linear approximation - i.e., for small disturbances - this model explains a great many of the flow phenomena observed in the lee of mountains. However, nonlinearities do arise importantly, in three ways: (1) through amplification due to the decrease of mean density with height; (2) through the large (scaled) size of the obstacle, such as a mountain range; and (3) from dynamically singular levels in the fluid field. These effects produce a complicated array of phenomena - large departure of the streamlines from their equilibrium levels, high winds, generation of small scales, turbulence, etc. - that present hazards to aircraft and to lee surface areas. The nonlinear disturbances also interact with the larger-scale flow in such a manner as to impact global weather forecasts and the climatological momentum balance. If there is no dynamic barrier, these waves can penetrate vertically into the middle atmosphere (30-100 km), where recent observations show them to be of a length scale that must involve the coriolis force in any modeling. At these altitudes, the amplitude of the waves is very large, and the phenomena associated with these wave dynamics are being studied with a view to their potential impact on high performance aircraft, including the projected National Aerospace Plane (NASP). The presentation shows the results of analysis and of state-of-the-art numerical simulations, validated where possible by observational data, and illustrated with photographs from nature.

  13. Video Games and Children: Effects on Leisure Activities, Schoolwork, and Peer Involvement.

    ERIC Educational Resources Information Center

    Creasey, Gary L; Myers, Barbara J

    1986-01-01

    Measures the indirect effect a home video system has on children's leisure activities, school work, and peer contacts. Concludes that owning a video game does not greatly alter a child's activities. (HOD)

  14. Involvement in Extracurricular Activities: Identifying Differences in Perceptions of School Climate

    ERIC Educational Resources Information Center

    Martinez, Andrew; Coker, Crystal; McMahon, Susan D.; Cohen, Jonathan; Thapa, Amrit

    2016-01-01

    Many youth participate in extracurricular activities, and research has linked activity participation with school engagement and academic success. Social-ecological theory suggests that the social contexts of different types of extracurricular activities may differentially affect student outcomes. Yet, there is scant research examining the relation…

  15. Parental Involvement in Active Transport to School Initiatives: A Multi-Site Case Study

    ERIC Educational Resources Information Center

    Eyler, Amy; Baldwin, Julie; Carnoske, Cheryl; Nickelson, Jan; Troped, Philip; Steinman, Lesley; Pluto, Delores; Litt, Jill; Evenson, Kelly; Terpstra, Jennifer; Brownson, Ross; Schmid, Thomas

    2008-01-01

    Background: Increasing physical activity in youth is a recommended approach to curbing the childhood obesity epidemic. One way to help increase children's daily activity is to promote active transportation to and from school (ATS). Purpose: The purpose of this case study was to explore parental perception of, and participation in, ATS initiatives.…

  16. A Case of Benign Metastasizing Leiomyoma with Multiple Metastasis to the Soft Tissue, Skeletal Muscle, Lung and Breast

    PubMed Central

    Jo, Ji Hoon; Lee, Jin Hwa; Kim, Dae Cheol; Kim, Sung Hyun; Kwon, Hyuk Chan; Kim, Jae Seok

    2006-01-01

    Benign metastasizing leiomyoma (BML) is composed of well-differentiated smooth muscle cells and dense connective tissue. BML affects middle-aged women who have had previous hysterectomies due to a histologically benign-appearing uterine leiomyoma. We report here on a case of BML from the uterine leiomyoma in a 39-year-old woman that involved the soft tissues, skeletal muscles, lungs and breasts. She underwent a hysterectomy for the uterine leiomyoma, double oophorectomy for hormonal ablation and lung wedge resection to confirm the diagnosis. The microscopic findings of the breast and lung tumor were similar to those of the benign uterine leiomyoma. Therefore, we consider that these lesions were breast and pulmonary metastases of the uterine leiomyoma. We report here on a rare case of benign metastasizing uterine leiomyoma that involved the soft tissue, skeletal muscles, lungs and breasts, and we include a review of the relevant literature. PMID:17017672

  17. Relaxin activates peroxisome proliferator-activated receptor γ (PPARγ) through a pathway involving PPARγ coactivator 1α (PGC1α).

    PubMed

    Singh, Sudhir; Simpson, Ronda L; Bennett, Robert G

    2015-01-01

    Relaxin activation of its receptor RXFP1 triggers multiple signaling pathways. Previously, we have shown that relaxin activates PPARγ transcriptional activity in a ligand-independent manner, but the mechanism for this effect was unknown. In this study, we examined the signaling pathways of downstream of RXFP1 leading to PPARγ activation. Using cells stably expressing RXFP1, we found that relaxin regulation of PPARγ activity requires accumulation of cAMP and subsequent activation of cAMP-dependent protein kinase (PKA). The activated PKA subsequently phosphorylated cAMP response element-binding protein (CREB) at Ser-133 to activate it directly, as well as indirectly through mitogen activated protein kinase p38 MAPK. Activated CREB was required for relaxin stimulation of PPARγ activity, while there was no evidence for a role of the nitric oxide or ERK MAPK pathways. Relaxin increased the mRNA and protein levels of the coactivator protein PGC1α, and this effect was dependent on PKA, and was completely abrogated by a dominant-negative form of CREB. This mechanism was confirmed in a hepatic stellate cell line stably that endogenously expresses RXFP1. Reduction of PGC1α levels using siRNA diminished the regulation of PPARγ by relaxin. These results suggest that relaxin activates the cAMP/PKA and p38 MAPK pathways to phosphorylate CREB, resulting in increased PGC1α levels. This provides a mechanism for the ligand-independent activation of PPARγ in response to relaxin. PMID:25389293

  18. Relaxin Activates Peroxisome Proliferator-activated Receptor γ (PPARγ) through a Pathway Involving PPARγ Coactivator 1α (PGC1α)*

    PubMed Central

    Singh, Sudhir; Simpson, Ronda L.; Bennett, Robert G.

    2015-01-01

    Relaxin activation of its receptor RXFP1 triggers multiple signaling pathways. Previously, we have shown that relaxin activates PPARγ transcriptional activity in a ligand-independent manner, but the mechanism for this effect was unknown. In this study, we examined the signaling pathways of downstream of RXFP1 leading to PPARγ activation. Using cells stably expressing RXFP1, we found that relaxin regulation of PPARγ activity requires accumulation of cAMP and subsequent activation of cAMP-dependent protein kinase (PKA). The activated PKA subsequently phosphorylated cAMP response element-binding protein (CREB) at Ser-133 to activate it directly, as well as indirectly through mitogen activated protein kinase p38 MAPK. Activated CREB was required for relaxin stimulation of PPARγ activity, while there was no evidence for a role of the nitric oxide or ERK MAPK pathways. Relaxin increased the mRNA and protein levels of the coactivator protein PGC1α, and this effect was dependent on PKA, and was completely abrogated by a dominant-negative form of CREB. This mechanism was confirmed in a hepatic stellate cell line stably that endogenously expresses RXFP1. Reduction of PGC1α levels using siRNA diminished the regulation of PPARγ by relaxin. These results suggest that relaxin activates the cAMP/PKA and p38 MAPK pathways to phosphorylate CREB, resulting in increased PGC1α levels. This provides a mechanism for the ligand-independent activation of PPARγ in response to relaxin. PMID:25389293

  19. [BENIGN TUMORS OF MEDIASTINUM: CLINIC, DIAGNOSIS, SURGICAL TREATMENT].

    PubMed

    Kalabukha, I A; Mayetniy, E M

    2015-12-01

    Results of surgical treatment of 18 patients in a thoracic surgery clinic for benign tumors of mediastinum are presented. The symptoms of benign tumors, efficacy of application of welding technologies in operative intervention were analyzed. PMID:27025028

  20. Isolated benign primary cutaneous plasmacytosis in a child.

    PubMed

    On, Hye Rang; Lee, Sang Eun; Kim, You Chan; Kim, Soo-Chan

    2014-01-01

    Isolated benign primary cutaneous plasmacytosis in a child is a very rare and benign disease. Herein we present a case of this condition occurring in a child who showed good response to topical corticosteroid. PMID:25424220

  1. A novel benign solution for collagen processing

    NASA Astrophysics Data System (ADS)

    Arnoult, Olivier

    Collagen is the main protein constituting the extracellular matrix (ECM) of tissues in the body (skin, cartilage, blood vessels...). It exists many types of collagen, this work studies only fibrillar collagen (e.g. collagen type I contained in the skin) that exhibits a triple helical structure composed of 3 alpha-helical collagen chains. This particular and defined hierarchical structure is essential to the biological and mechanical properties of the collagen. Processing collagen into scaffolds to mimic the ECM is crucial for successful tissue engineering. Recently collagen was processed into fibrous and porous scaffold using electrospinning process. However the solvent (HFIP) used for electrospinning is extremely toxic for the user and expensive. This work shows that HFIP can be replaced by a benign mixture composed of water, salt and alcohol. Yet only three alcohols (methanol, ethanol and iso-propanol) enable the dissolution of large quantity of collagen in the benign mixture, with a wide range of alcohol to buffer ratio, and conserve the collagen hierarchical structure at least as well as the HFIP. Collagen can be electrospun from the benign mixture into sub-micron fibers with concentrations as low as 6 wt-% for a wide range of alcohol to buffer ratio, with at least 10wt-% of salt, and any of the three alcohols. Specific conditions yield nano size fibers. After processing from HFIP or a benign mixture, collagen is water soluble and needs to be chemically crosslink for tissue engineering application. Post-crosslinking with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) results in the loss of the scaffold fibrous aspect and porosity, hence it is useless for tissue engineering. Such issue could be prevented by incorporating the crosslinker into the mixture prior to electrospinning. When EDC is used alone, collagen forms a gel in the mixture within minutes, preventing electrospinning. The addition of N-hydroxysuccinimide (NHS) in excess to EDC

  2. Unique Residues Involved in Activation of the Multitasking Protease/Chaperone HtrA from Chlamydia trachomatis

    PubMed Central

    Huston, Wilhelmina M.; Tyndall, Joel D. A.; Lott, William B.; Stansfield, Scott H.; Timms, Peter

    2011-01-01

    DegP, a member of the HtrA family of proteins, conducts critical bacterial protein quality control by both chaperone and proteolysis activities. The regulatory mechanisms controlling these two distinct activities, however, are unknown. DegP activation is known to involve a unique mechanism of allosteric binding, conformational changes and oligomer formation. We have uncovered a novel role for the residues at the PDZ1:protease interface in oligomer formation specifically for chaperone substrates of Chlamydia trachomatis HtrA (DegP homolog). We have demonstrated that CtHtrA proteolysis could be activated by allosteric binding and oligomer formation. The PDZ1 activator cleft was required for the activation and oligomer formation. However, unique to CtHtrA was the critical role for residues at the PDZ1:protease interface in oligomer formation when the activator was an in vitro chaperone substrate. Furthermore, a potential in vivo chaperone substrate, the major outer membrane protein (MOMP) from Chlamydia, was able to activate CtHtrA and induce oligomer formation. Therefore, we have revealed novel residues involved in the activation of CtHtrA which are likely to have important in vivo implications for outer membrane protein assembly. PMID:21931748

  3. Unique residues involved in activation of the multitasking protease/chaperone HtrA from Chlamydia trachomatis.

    PubMed

    Huston, Wilhelmina M; Tyndall, Joel D A; Lott, William B; Stansfield, Scott H; Timms, Peter

    2011-01-01

    DegP, a member of the HtrA family of proteins, conducts critical bacterial protein quality control by both chaperone and proteolysis activities. The regulatory mechanisms controlling these two distinct activities, however, are unknown. DegP activation is known to involve a unique mechanism of allosteric binding, conformational changes and oligomer formation. We have uncovered a novel role for the residues at the PDZ1:protease interface in oligomer formation specifically for chaperone substrates of Chlamydia trachomatis HtrA (DegP homolog). We have demonstrated that CtHtrA proteolysis could be activated by allosteric binding and oligomer formation. The PDZ1 activator cleft was required for the activation and oligomer formation. However, unique to CtHtrA was the critical role for residues at the PDZ1:protease interface in oligomer formation when the activator was an in vitro chaperone substrate. Furthermore, a potential in vivo chaperone substrate, the major outer membrane protein (MOMP) from Chlamydia, was able to activate CtHtrA and induce oligomer formation. Therefore, we have revealed novel residues involved in the activation of CtHtrA which are likely to have important in vivo implications for outer membrane protein assembly. PMID:21931748

  4. Enzymatic activation of autotaxin by divalent cations without EF-hand loop region involvement.

    PubMed

    Lee, J; Jung, I D; Nam, S W; Clair, T; Jeong, E M; Hong, S Y; Han, J W; Lee, H W; Stracke, M L; Lee, H Y

    2001-07-15

    Autotaxin (ATX) is a recently described member of the nucleotide pyrophosphatase/phosphodiesterase (NPP) family of proteins with potent tumor cell motility-stimulating activity. Like other NPPs, ATX is a glycoprotein with peptide sequences homologous to the catalytic site of bovine intestinal alkaline phosphodiesterase (PDE) and the loop region of an EF-hand motif. The PDE active site of ATX has been associated with the motility-stimulating activity of ATX. In this study, we examined the roles of the EF-hand loop region and of divalent cations on the enzymatic activities of ATX. Ca(2+) or Mg(2+) was each demonstrated to increase the PDE activity of ATX in a concentration-dependent manner, whereas incubation of ATX with chelating agents abolished this activity, indicating a requirement for divalent cations. Non-linear regression analysis of enzyme kinetic data indicated that addition of these divalent cations increases reaction velocity predominantly through an effect on V(max.) Three mutant proteins, Ala(740)-, Ala(742)-, and Ala(751)-ATX, in the EF-hand loop region of ATX had enzymatic activity comparable to that of the wild-type protein. A deletion mutation of the entire loop region resulted in slightly reduced PDE activity but normal motility-stimulating activity. However, the PDE activity of this same deletion mutant remained sensitive to augmentation by cations, strongly implying that cations exert their effect by interactions outside of the EF-hand loop region. PMID:11389881

  5. ENVIRONMENTALLY BENIGN MITIGATION OF MICROBIOLOGICALLY INFLUENCED CORROSION (MIC)

    SciTech Connect

    J. Robert Paterek; Gemma Husmillo

    2002-07-01

    The overall program objective is to develop and evaluate environmental benign agents or products that are effective in the prevention, inhibition, and mitigation of microbially influenced corrosion (MIC) in the internal surfaces of metallic natural gas pipelines. The goal is one or more environmental benign, a.k.a. ''green'' products that can be applied to maintain the structure and dependability of the natural gas infrastructure. Capsicum sp. extracts and pure compounds were screened for their antimicrobial activity against MIC causing bacteria. Studies on the ability of these compounds to dissociate biofilm from the substratum were conducted using microtiter plate assays. Tests using laboratory scale pipeline simulators continued. Preliminary results showed that the natural extracts possess strong antimicrobial activity being comparable to or even better than the pure compounds tested against strains of sulfate reducers. Their minimum inhibitory concentrations had been determined. It was also found that they possess bactericidal properties at minimal concentrations. Biofilm dissociation activity as assessed by microtiter plate assays demonstrated varying degrees of differences between the treated and untreated group with the superior performance of the extracts over pure compounds. Such is an indication of the possible benefits that could be obtained from these natural products. Confirmatory experiments are underway.

  6. Examining Parent Involvement Activities in Two Immigrant-Impacted Schools: A Comparative Case Study

    ERIC Educational Resources Information Center

    Marquez, Amalia

    2012-01-01

    K-12 schools with large immigrant populations face a myriad of challenges, including low academic achievement and high dropout rates of Latino students. Parental involvement is a practical strategy in positively influencing student outcomes along the K-12 continuum. To this end, it is essential that immigrant impacted schools work together with…

  7. Parent Advocacy: Now More Than Ever Active Involvement in Educational Decisions.

    ERIC Educational Resources Information Center

    Ammer, Jerome J.; Littleton, Barbara Rhein

    Questionnaires were completed by 217 parents of handicapped children to determine their present level of involvement and their desired participation in the education process. The sample (a rural population in central West Virginia, a suburban population in affluent school districts on Long Island, New York, and a city population from a mixed set…

  8. Undergraduate Involvement in Extracurricular Activities and Leadership Development in College of Agriculture and Life Sciences Students

    ERIC Educational Resources Information Center

    Foreman, Elizabeth A.; Retallick, Michael S.

    2012-01-01

    The purpose of this study was to identify and describe experiences of undergraduate extracurricular involvement that result in increased leadership development. Senior students in the College of Agriculture and Life Sciences at Iowa State University completed an online questionnaire about their extracurricular experiences. Leadership development…

  9. Strategies for Effective Faculty Involvement in Online Activities Aimed at Promoting Critical Thinking and Deep Learning

    ERIC Educational Resources Information Center

    Abdul Razzak, Nina

    2016-01-01

    Highly-traditional education systems that mainly offer what is known as "direct instruction" usually result in graduates with a surface approach to learning rather than a deep one. What is meant by deep-learning is learning that involves critical analysis, the linking of ideas and concepts, creative problem solving, and application…

  10. Involving Children in Health and Social Research: "Human Becomings" or "Active Beings"?

    ERIC Educational Resources Information Center

    Balen, Rachel; Blyth, Eric; Calabretto, Helen; Fraser, Claire; Horrocks, Christine; Manby, Martin

    2006-01-01

    This article draws on the authors' experiences of undertaking health and social research involving children in Australia and England and focuses on securing the informed consent of children to participate in such research. A clear trend within literature, service provision, legislation and international conventions recognizes children as "active…

  11. Do a Little Dance: The Impact on Students when Librarians Get Involved in Extracurricular Activities

    ERIC Educational Resources Information Center

    Kasperek, Sheila; Johnson, Amber; Fotta, Katie; Craig, Francis

    2007-01-01

    One hundred fifty-two undergraduate students at Mansfield University of Pennsylvania were surveyed to determine if the involvement of their liaison librarian in theater productions and orchestra had an effect on their relationship with the library. The study shows positive and statistically significant results for students who participated in…

  12. Neural networks involved in adolescent reward processing: An activation likelihood estimation meta-analysis of functional neuroimaging studies.

    PubMed

    Silverman, Merav H; Jedd, Kelly; Luciana, Monica

    2015-11-15

    Behavioral responses to, and the neural processing of, rewards change dramatically during adolescence and may contribute to observed increases in risk-taking during this developmental period. Functional MRI (fMRI) studies suggest differences between adolescents and adults in neural activation during reward processing, but findings are contradictory, and effects have been found in non-predicted directions. The current study uses an activation likelihood estimation (ALE) approach for quantitative meta-analysis of functional neuroimaging studies to: (1) confirm the network of brain regions involved in adolescents' reward processing, (2) identify regions involved in specific stages (anticipation, outcome) and valence (positive, negative) of reward processing, and (3) identify differences in activation likelihood between adolescent and adult reward-related brain activation. Results reveal a subcortical network of brain regions involved in adolescent reward processing similar to that found in adults with major hubs including the ventral and dorsal striatum, insula, and posterior cingulate cortex (PCC). Contrast analyses find that adolescents exhibit greater likelihood of activation in the insula while processing anticipation relative to outcome and greater likelihood of activation in the putamen and amygdala during outcome relative to anticipation. While processing positive compared to negative valence, adolescents show increased likelihood for activation in the posterior cingulate cortex (PCC) and ventral striatum. Contrasting adolescent reward processing with the existing ALE of adult reward processing reveals increased likelihood for activation in limbic, frontolimbic, and striatal regions in adolescents compared with adults. Unlike adolescents, adults also activate executive control regions of the frontal and parietal lobes. These findings support hypothesized elevations in motivated activity during adolescence. PMID:26254587

  13. 76 FR 11529 - Gregory Desobry, Ph.D.; Order Requiring Notification of Involvement in NRC-Licensed Activities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-02

    ... accordance with the NRC E-Filing rule (72 FR 49139, August 28, 2007). The E-Filing process requires... COMMISSION Gregory Desobry, Ph.D.; Order Requiring Notification of Involvement in NRC-Licensed Activities I... Mr. Desobry, Ph.D., requests a hearing, that person shall set forth with particularity the manner...

  14. Parental Involvement in School Activities and Reading Literacy: Findings and Implications from PIRLS 2011 Data. Policy Brief No. 3

    ERIC Educational Resources Information Center

    Mirazchiyski, Plamen; Klemencic, Eva

    2014-01-01

    This policy brief presents evidence demonstrating a positive association between parental involvement in school activities and student performance in the Progress in International Reading Literacy Study (PIRLS) 2011. This association, which was evident in most of the 54 education systems analyzed, indicates that students enrolled in schools with…

  15. 77 FR 39270 - In the Matter of Mr. Timothy Goold; Order Prohibiting Involvement in NRC-Licensed Activities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-02

    ... under 10 CFR 2.315(c), must be filed in accordance with the NRC E-Filing rule (72 FR 49139; August 28... COMMISSION In the Matter of Mr. Timothy Goold; Order Prohibiting Involvement in NRC-Licensed Activities I Mr... NRC in an attempt to resolve issues associated with this matter. Mr. Goold provided a written...

  16. 77 FR 31045 - Order Prohibiting Involvement in NRC-Licensed Activities; In the Matter of Jaime Sánchez

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-24

    ... under 10 CFR 2.315(c), must be filed in accordance with NRC E-Filing rule (72 FR 49139, August 28, 2007... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Order Prohibiting Involvement in NRC-Licensed Activities; In the Matter of Jaime S nchez I Jaime...

  17. 76 FR 11526 - In the Matter of Dr. Gary Kao; Order Prohibiting Involvement In NRC-Licensed Activities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-02

    ... entities participating under 10 CFR 2.315(c), must be filed in accordance with the NRC E-Filing rule (72 FR... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION In the Matter of Dr. Gary Kao; Order Prohibiting Involvement In NRC-Licensed Activities I Dr....

  18. 75 FR 55366 - In the Matter of Mark M. Ficek; Order Prohibiting Involvement in NRC-Licensed Activities...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-10

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION [Docket No. 030-20836, License No. 25-21479-01, NRC-2009-0120, A-10- 028] In the Matter of Mark M. Ficek; Order Prohibiting Involvement in NRC-Licensed Activities (Effective Immediately) Mr. Mark M. Ficek is the President, owner, and...

  19. 77 FR 49835 - Order Prohibiting Involvement in NRC-Licensed Activities; In the Matter of Mr. Joseph Quintanilla

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-17

    ... rule (72 FR 49139; August 28, 2007). The E-Filing process requires participants to submit and serve all... COMMISSION Order Prohibiting Involvement in NRC-Licensed Activities; In the Matter of Mr. Joseph Quintanilla.... Quintanilla indicated that he was aware the camera was outside of the dark room and did not contest...

  20. Cross-Age Tutorial Program To Increase Reading Comprehension through the Use of High Interest Activities Involving Reading.

    ERIC Educational Resources Information Center

    Leatherwood, Prudence Lee

    A practicum used a program of high interest activities involving reading to address the problem of low reading comprehension grades and test scores of eight students in the second through fourth grades, who were an average of 1 year behind the norm in reading. The program's six units included a listening unit, computer technology unit, daily…

  1. 41 CFR 51-7.2 - Early involvement in private, State, and local activities requiring Federal approval.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... involvement in private, State, and local activities requiring Federal approval. (a) 40 CFR 1501.2(d) requires... of 40 CFR 1501.2(d) with respect to these actions, the Committee staff shall consult as required with... requires an environmental assessment as set forth in 40 CFR 1501.4. (c) To facilitate compliance with...

  2. 41 CFR 51-7.2 - Early involvement in private, State, and local activities requiring Federal approval.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... involvement in private, State, and local activities requiring Federal approval. (a) 40 CFR 1501.2(d) requires... of 40 CFR 1501.2(d) with respect to these actions, the Committee staff shall consult as required with... requires an environmental assessment as set forth in 40 CFR 1501.4. (c) To facilitate compliance with...

  3. 41 CFR 51-7.2 - Early involvement in private, State, and local activities requiring Federal approval.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... involvement in private, State, and local activities requiring Federal approval. (a) 40 CFR 1501.2(d) requires... of 40 CFR 1501.2(d) with respect to these actions, the Committee staff shall consult as required with... requires an environmental assessment as set forth in 40 CFR 1501.4. (c) To facilitate compliance with...

  4. Expectations of Rock Music Consumption for Entertainment and Information Relative to the Active Involvement of the User.

    ERIC Educational Resources Information Center

    Rouner, Donna; Noyes, Amy

    Before examining potentially negative effects of rock music on adolescents, it is necessary to demonstrate links between adolescent motivations for consuming rock music and active involvement relative to that use and also to consider how much rock listeners rely on rock music as a source for information about values, beliefs, and social…

  5. 41 CFR 51-7.2 - Early involvement in private, State, and local activities requiring Federal approval.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... involvement in private, State, and local activities requiring Federal approval. (a) 40 CFR 1501.2(d) requires... of 40 CFR 1501.2(d) with respect to these actions, the Committee staff shall consult as required with... requires an environmental assessment as set forth in 40 CFR 1501.4. (c) To facilitate compliance with...

  6. 41 CFR 51-7.2 - Early involvement in private, State, and local activities requiring Federal approval.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... involvement in private, State, and local activities requiring Federal approval. (a) 40 CFR 1501.2(d) requires... of 40 CFR 1501.2(d) with respect to these actions, the Committee staff shall consult as required with... requires an environmental assessment as set forth in 40 CFR 1501.4. (c) To facilitate compliance with...

  7. Predicting Adolescents' Organized Activity Involvement: The Role of Maternal Depression History, Family Relationship Quality, and Adolescent Cognitions

    ERIC Educational Resources Information Center

    Bohnert, Amy M.; Martin, Nina C.; Garber, Judy

    2007-01-01

    Although the potential benefits of organized activity involvement during high school have been documented, little is known about what familial and individual characteristics are associated with higher levels of participation. Using structural equation modeling, this longitudinal study examined the extent to which maternal depression history (i.e.,…

  8. Children's Well-Being and Involvement in Physically Active Outdoors Play in a Norwegian Kindergarten: Playful Sharing of Physical Experiences

    ERIC Educational Resources Information Center

    Bjørgen, Kathrine

    2015-01-01

    This qualitative study explores the conditions of children's level of well-being and their involvement in physically active play during kindergarten outdoors time. Observations of three to five year olds from one kindergarten in central Norway were conducted. The researcher followed the children around the kindergarten's outdoors playground and…

  9. Melanosis in Penaeus monodon: Involvement of the Laccase-like Activity of Hemocyanin.

    PubMed

    Bris, Cédric Le; Cudennec, Benoit; Dhulster, Pascal; Drider, Djamel; Duflos, Guillaume; Grard, Thierry

    2016-01-27

    In shrimp, the development of postmortem melanosis resulting from phenoloxidase activities leads to important economic losses. Phenoloxidase enzymes include catechol oxidases, laccases, and tyrosinases, but hemocyanin is also capable of phenoloxidase activities. These activities have been explored in Penaeus monodon, using different substrates. Results highlighted that tyrosinase-specific substrates were little oxidized, whereas hydroquinone (laccase-specific substrate) was more highly oxidized than l-DOPA (nonspecific substrate) in the pereopods and pleopods. Global phenoloxidase activity, assayed with l-DOPA, did not appear thermally stable over time and probably resulted from phenoloxidase enzymes. Conversely, the laccase-like activity assayed with hydroquinone was thermally stable over time, reflecting the thermal stability of hemocyanin. Independently of the anatomical compartment, the temperature, or the substrate, the highest activities were assayed in the cuticular compartments. This study demonstrates the complexity of phenoloxidase activities in P. monodon, and the importance of considering all the activities, including laccase-like activities such as that of hemocyanin. PMID:26671070

  10. Activity-Dependent Dendritic Spine Shrinkage and Growth Involve Downregulation of Cofilin via Distinct Mechanisms

    PubMed Central

    Calabrese, Barbara; Saffin, Jean-Michel; Halpain, Shelley

    2014-01-01

    A current model posits that cofilin-dependent actin severing negatively impacts dendritic spine volume. Studies suggested that increased cofilin activity underlies activity-dependent spine shrinkage, and that reduced cofilin activity induces activity-dependent spine growth. We suggest instead that both types of structural plasticity correlate with decreased cofilin activity. However, the mechanism of inhibition determines the outcome for spine morphology. RNAi in rat hippocampal cultures demonstrates that cofilin is essential for normal spine maintenance. Cofilin-F-actin binding and filament barbed-end production decrease during the early phase of activity-dependent spine shrinkage; cofilin concentration also decreases. Inhibition of the cathepsin B/L family of proteases prevents both cofilin loss and spine shrinkage. Conversely, during activity-dependent spine growth, LIM kinase stimulates cofilin phosphorylation, which activates phospholipase D-1 to promote actin polymerization. These results implicate novel molecular mechanisms and prompt a revision of the current model for how cofilin functions in activity-dependent structural plasticity. PMID:24740405

  11. Integrated imaging of hepatic tumors in childhood. Part II. Benign lesions (congenital, reparative, and inflammatory)

    SciTech Connect

    Miller, J.H.; Greenspan, B.S.

    1985-01-01

    The authors have encountered benign liver masses as frequently as malignant lesions in children with hepatomegaly. Lesions studied included abscesses, cavernous hemangioma/hemangioendothelioma, adenoma of glycogen storage disease, choledochal cysts, focal nodular hyperplasia, cystic hepatoblastoma, and hamartoma. An intergrated imaging protocol involving ultrasound, computed tomography, and scintigraphy proved to be more helpful than any one modality in establishing the benign or malignant nature of a hepatic neoplasm and the type of tumor, which is of particular importance when surgical exploration and/or biopsy is contraindicated.

  12. The Profile of Heparanase Expression Distinguishes Differentiated Thyroid Carcinoma from Benign Neoplasms

    PubMed Central

    Matos, Leandro Luongo; Suarez, Eloah Rabello; Theodoro, Thérèse Rachell; Trufelli, Damila Cristina; Melo, Carina Mucciolo; Garcia, Larissa Ferraz; Oliveira, Olivia Capela Grimaldi; Matos, Maria Graciela Luongo; Kanda, Jossi Ledo; Nader, Helena Bonciani; Martins, João Roberto Maciel; Pinhal, Maria Aparecida Silva

    2015-01-01

    Introduction The search for a specific marker that could help to distinguish between differentiated thyroid carcinoma and benign lesions remains elusive in clinical practice. Heparanase (HPSE) is an endo-beta-glucoronidase implicated in the process of tumor invasion, and the heparanase-2 (HPSE2) modulates HPSE activity. The aim of this study was to evaluate the role of heparanases in the development and differential diagnosis of follicular pattern thyroid lesions. Methods HPSE and HPSE2 expression by qRT-PCR, immunohistochemistry evaluation, western blot analysis and HPSE enzymatic activity were evaluated. Results The expression of heparanases by qRT-PCR showed an increase of HPSE2 in thyroid carcinoma (P = 0.001). HPSE activity was found to be higher in the malignant neoplasms than in the benign tumors (P<0.0001). On Western blot analysis, HPSE2 isoforms were detected only in malignant tumors. The immunohistochemical assay allowed us to establish a distinct pattern for malignant and benign tumors. Carcinomas showed a typical combination of positive labeling for neoplastic cells and negative immunostaining in colloid, when compared to benign tumors (P<0.0001). The proposed diagnostic test presents sensitivity and negative predictive value of around 100%, showing itself to be an accurate test for distinguishing between malignant and benign lesions. Conclusions This study shows, for the first time, a distinct profile of HPSE expression in thyroid carcinoma suggesting its role in carcinogenesis. PMID:26488476

  13. INVOLVEMENT OF PEPTIDOGLYCAN RECOGNITION PROTEIN L6 IN ACTIVATION OF IMMUNE DEFICIENCY PATHWAY IN THE IMMUNE RESPONSIVE SILKWORM CELLS.

    PubMed

    Tanaka, Hiromitsu; Sagisaka, Aki

    2016-06-01

    The immune deficiency (Imd) signaling pathway is activated by Gram-negative bacteria for producing antimicrobial peptides (AMPs). In Drosophila melanogaster, the activation of this pathway is initiated by the recognition of Gram-negative bacteria by peptidoglycan (PGN) recognition proteins (PGRPs), PGRP-LC and PGRP-LE. In this study, we found that the Imd pathway is involved in enhancing the promoter activity of AMP gene in response to Gram-negative bacteria or diaminopimelic (DAP) type PGNs derived from Gram-negative bacteria in an immune responsive silkworm cell line, Bm-NIAS-aff3. Using gene knockdown experiments, we further demonstrated that silkworm PGRP L6 (BmPGRP-L6) is involved in the activation of E. coli or E. coli-PGN mediated AMP promoter activation. Domain analysis revealed that BmPGRP-L6 contained a conserved PGRP domain, transmembrane domain, and RIP homotypic interaction motif like motif but lacked signal peptide sequences. BmPGRP-L6 overexpression enhances AMP promoter activity through the Imd pathway. BmPGRP-L6 binds to DAP-type PGNs, although it also binds to lysine-type PGNs that activate another immune signal pathway, the Toll pathway in Drosophila. These results indicate that BmPGRP-L6 is a key PGRP for activating the Imd pathway in immune responsive silkworm cells. PMID:26991439

  14. A qualitative study of the activities performed by people involved in clinical decision support: recommended practices for success

    PubMed Central

    Wright, Adam; Ash, Joan S; Erickson, Jessica L; Wasserman, Joe; Bunce, Arwen; Stanescu, Ana; St Hilaire, Daniel; Panzenhagen, Morgan; Gebhardt, Eric; McMullen, Carmit; Middleton, Blackford; Sittig, Dean F

    2014-01-01

    Objective To describe the activities performed by people involved in clinical decision support (CDS) at leading sites. Materials and methods We conducted ethnographic observations at seven diverse sites with a history of excellence in CDS using the Rapid Assessment Process and analyzed the data using a series of card sorts, informed by Linstone's Multiple Perspectives Model. Results We identified 18 activities and grouped them into four areas. Area 1: Fostering relationships across the organization, with activities (a) training and support, (b) visibility/presence on the floor, (c) liaising between people, (d) administration and leadership, (e) project management, (f) cheerleading/buy-in/sponsorship, (g) preparing for CDS implementation. Area 2: Assembling the system with activities (a) providing technical support, (b) CDS content development, (c) purchasing products from vendors (d) knowledge management, (e) system integration. Area 3: Using CDS to achieve the organization's goals with activities (a) reporting, (b) requirements-gathering/specifications, (c) monitoring CDS, (d) linking CDS to goals, (e) managing data. Area 4: Participation in external policy and standards activities (this area consists of only a single activity). We also identified a set of recommendations associated with these 18 activities. Discussion All 18 activities we identified were performed at all sites, although the way they were organized into roles differed substantially. We consider these activities critical to the success of a CDS program. Conclusions A series of activities are performed by sites strong in CDS, and sites adopting CDS should ensure they incorporate these activities into their efforts. PMID:23999670

  15. Family and Community Involvement in the Comprehensive School Physical Activity Program

    ERIC Educational Resources Information Center

    Cipriani, Kristin; Richardson, Cheryl; Roberts, Georgi

    2012-01-01

    Engaging families and communities in physical activities for the benefit of children is an extension of the role of a physical education instructor. Although it is possible for a physical educator to generate ideas that encourage families and communities to move, a certified director of physical activity (C-DPA) would be better trained to…

  16. Discovering the Thermodynamics of Simultaneous Equilibria: An Entropy Analysis Activity Involving Consecutive Equilibria

    ERIC Educational Resources Information Center

    Bindel, Thomas H.

    2007-01-01

    An activity is presented in which the thermodynamics of simultaneous, consecutive equilibria are explored. The activity is appropriate for second-year high school or AP chemistry. Students discover that a reactant-favored (entropy-diminishing or endergonic) reaction can be caused to happen if it is coupled with a product-favored reaction of…

  17. Optical Topography of Evoked Brain Activity during Mental Tasks Involving Whole Number Operations

    ERIC Educational Resources Information Center

    Ortiz, Enrique

    2014-01-01

    Students start to memorize arithmetic facts from early elementary school mathematics activities. Their fluency or lack of fluency with these facts could affect their efforts as they carry out mental calculations as adults. This study investigated participants' levels of brain activation and possible reasons for these levels as they solved…

  18. Mutational analysis of the major soybean UreF paralogue involved in urease activation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In soybean, mutation at Eu2 or Eu3 eliminates the urease activities of both the embryo-specific and the tissue-ubiquitous (assimilatory) isozymes, encoded by Eu1 and Eu4, respectively. Eu3 encodes UreG, a GTP’ase necessary for proper emplacement of Ni and carbon dioxide in the urease active site. ...

  19. Involvement of Cot activity in the proliferation of ALCL lymphoma cells

    SciTech Connect

    Fernandez, Margarita; Manso, Rebeca; Bernaldez, Flavia; Lopez, Pilar; Martin-Duce, Antonio; Alemany, Susana

    2011-08-12

    Highlights: {yields} We show here that ALCL lymphoma cell lines present high levels of Cot (MAP3K8). {yields} We show that Cot mediates the constitutive Erk1/2 activation in SUDHL-1 cells. {yields} Inhibition of Cot activity reduces the number of cell divisions in SUDHL-1 cells. {yields} Cot controls the activation state of p70 S6K and JunB expression in SUDHL-1 cells. -- Abstract: Anaplastic large-cell lymphoma (ALCL) cells overexpress CD30 on their cell surface, show increased levels of activated Erk1/2 and of JunB; participating JunB in the proliferative capacity of these lymphomas. Here, we show that ALCL lymphoma cells also present high expression levels of the proto-oncogenic Cot (MAP3K8). Using pharmacological drugs as well as the RNA interference technique we show that Cot protein is responsible for the constitutive Erk1/2 activation in the ALCL lymphoma cells, SUDHL-1. Besides, inhibition of Cot activity reduces the number of cell divisions which is achieved, at least in part, by the control that Cot exercises on the activation state of p70 S6K and on the expression levels of JunB. Since Cot represents an alternative mode, independently of RAF, to activate Erk1/2, all these data strongly suggest that molecular targeting of Cot may be a potential new specific strategy for ALCL lymphomas therapy, without the fully disturbance of the Erk1/2 function.

  20. Community College Involvement in Contract Training and Other Economic Development Activities.

    ERIC Educational Resources Information Center

    Lynch, Robert; And Others

    In 1989-90, a national survey was conducted to assess the scope and nature of contract training and other economic development activities at community colleges and technical institutes. The survey was sent to a random sample of 246 community colleges, requesting information on the colleges' workforce and economic development activities in 1988-89.…

  1. Control of 5-aminolaevulinate synthetase activity in Rhodopseudomonas spheroides. The involvement of sulphur metabolism

    PubMed Central

    Neuberger, Albert; Sandy, John D.; Tait, George H.

    1973-01-01

    1. The `initial' 5-aminolaevulinate synthetase activity, that is the activity observed immediately after cell disruption, in extracts prepared from unharvested semianaerobically grown Rhodopseudomonas spheroides, was twice that observed under the same assay conditions in extracts prepared from harvested cells. 2. The effect of oxygenation of a culture on the `maximum' aminolaevulinate synthetase activity, that is the activity observed 1h after disruption of harvested cells, is markedly influenced by the contents of the growth medium. Oxygenation of organisms for 1h in the medium in which they have grown produces an 80–90% decrease in maximum activity, whereas similar treatment of organisms resuspended in fresh medium produces less than a 40% decrease. 3. This protective effect of fresh medium is absolutely dependent on the presence of sulphate. When cells are suspended in sulphate-deficient fresh medium, the maximum activity falls by 65–75% even without oxygenation. A high maximum activity is regenerated when sulphate is resupplied. 4. When organisms are oxygenated in the medium in which they have grown, the cellular contents of GSH+GSSG and cysteine+cystine fall very markedly and homolanthionine is formed. Both the fall in aminolaevulinate synthetase activity and the changes in sulphur metabolism are largely prevented by the addition of compounds which stimulate synthesis of cysteine de novo or inhibit the conversion of cysteine S into homocysteine S. 5. The maximum aminolaevulinate synthetase activity was directly proportional to the GSH+GSSG content of all cell preparations. In glutathione-depleted extracts the `low'-activity enzyme could be re-activated in vitro by the addition of GSH, GSSG, cysteine or cystine, whereas in extracts with a high glutathione content the `high'-activity enzyme was unaffected by these sulphur compounds. 6. The activation of low-activity enzyme with exogenous sulphur compounds was prevented by excluding air or by adding NADH

  2. [Surgery of benign vocal fold lesions].

    PubMed

    Olthoff, A

    2016-09-01

    Surgical treatment of benign vocal fold lesions can be indicated for clinical or functional reasons. The principles of phonosurgery have to be maintained in either case. The appropriate phonosurgical technique depends on the type of vocal fold lesion. Depending on the findings, phonosurgery aims to maintain or improve voice quality. The evaluation of clinical and functional results includes indirect laryngoscopy, videostroboscopy, and voice analysis. PMID:27552826

  3. A benign maxillary tumour with malignant features.

    PubMed

    Ricalde, Rosario R; Lim, Aimee Caroline E; Lopa, Ramon Antonio B; Carnate, Jose M

    2010-06-01

    Non-specific biopsy results such as chronic inflammation, hemorrhage, necrosis can be frustrating to the clinician. This is especially true if the patient presents with clinical features suggestive of an aggressive tumour. This is a review of the clinical features, diagnostic dilemmas and surgical management of a benign maxillary mass with malignant features - a disease called hematoma-like mass of the maxillary sinus (HLMMS). Our experience with five cases will also be cited. PMID:20502750

  4. Large Penile Mass With Unusual Benign Histopathology.

    PubMed

    Johnson, Nate; Voznesensky, Maria; VerLee, Graham

    2015-09-01

    Pseudoepitheliomatous hyperplasia is an extremely rare condition presenting as a lesion on the glans penis in older men. Physical exam without biopsy cannot differentiate malignant from nonmalignant growth. We report a case of large penile mass in an elderly male with a history of lichen sclerosis, highly suspicious for malignancy. Subsequent surgical removal and biopsy demonstrated pseudoepitheliomatous hyperplasia, an unusual benign histopathologic diagnosis with unclear prognosis. We review the literature and discuss options for treatment and surveillance. PMID:26793536

  5. Benign Diseases and Neoplasms of the Penis.

    PubMed

    Wasco, Matthew J; Shah, Rajal B

    2009-03-01

    This article provides comprehensive review of benign diseases and neoplastic conditions of the penis. It describes and provides representative images of clinical, key pathologic features and ancillary techniques to aid in differential diagnoses. It examines these diseases from the epidemiologic standpoint, looks at environmental and genetic factors, and outlines the new histologic entities for penile neoplasms with distinct outcomes and clinical behavior that have been proposed in recent years. PMID:26838101

  6. Benign prostatic hyperplasia: A clinical review.

    PubMed

    Skinder, Danielle; Zacharia, Ilana; Studin, Jillian; Covino, Jean

    2016-08-01

    Benign prostatic hyperplasia (BPH) is an increasingly common diagnosis seen in men over age 50 years. Primary care providers must be aware of patient presentation, diagnostic tests, appropriate lifestyle modifications, treatment options, and potential complications in order to properly manage and educate patients with BPH. If left untreated, BPH can significantly decrease a man's quality of life; however, many pharmacologic and surgical treatments are available to control the symptoms. PMID:27367595

  7. Baking together-the coordination of actions in activities involving people with dementia.

    PubMed

    Majlesi, Ali Reza; Ekström, Anna

    2016-08-01

    This study explores interaction and collaboration between people with dementia and their spouses in relation to the performance of household chores with the focus on instruction as an interactional context to engage the person with dementia in collaboration to accomplish joint activities. Dementia is generally associated with pathological changes in people's cognitive functions such as diminishing memory functions, communicative abilities and also diminishing abilities to take initiative as well as to plan and execute tasks. Using video recordings of everyday naturally occurring activities, we analyze the sequential organization of actions (see Schegloff, 2007) oriented toward the accomplishment of a joint multi-task activity of baking. The analysis shows the specific ways of collaboration through instructional activities in which the person with dementia exhibits his competence and skills in accomplishing the given tasks through negotiating the instructions with his partner and carrying out instructed actions. Although the driving force of the collaboration seems to be a series of directive sequences only initiated by the partner throughout the baking activity, our analyses highlight how the person with dementia can actively use the material environment-including collaborating partners-to compensate for challenges and difficulties encountered in achieving everyday tasks. The sequential organization of instructions and instructed actions are in this sense argued to provide an interactional environment wherein the person with dementia can make contributions to the joint activity in an efficient way. While a collaborator has been described as necessary for a person with dementia to be able to partake in activities, this study shows that people with dementia are not only guided by their collaborators in joint activities but they can also actively use their collaborators in intricate compensatory ways. PMID:27531451

  8. Environmentally benign silicon solar cell manufacturing

    SciTech Connect

    Tsuo, Y.S.; Gee, J.M.; Menna, P.; Strebkov, D.S.; Pinov, A.; Zadde, V.

    1998-09-01

    The manufacturing of silicon devices--from polysilicon production, crystal growth, ingot slicing, wafer cleaning, device processing, to encapsulation--requires many steps that are energy intensive and use large amounts of water and toxic chemicals. In the past two years, the silicon integrated-circuit (IC) industry has initiated several programs to promote environmentally benign manufacturing, i.e., manufacturing practices that recover, recycle, and reuse materials resources with a minimal consumption of energy. Crystalline-silicon solar photovoltaic (PV) modules, which accounted for 87% of the worldwide module shipments in 1997, are large-area devices with many manufacturing steps similar to those used in the IC industry. Obviously, there are significant opportunities for the PV industry to implement more environmentally benign manufacturing approaches. Such approaches often have the potential for significant cost reduction by reducing energy use and/or the purchase volume of new chemicals and by cutting the amount of used chemicals that must be discarded. This paper will review recent accomplishments of the IC industry initiatives and discuss new processes for environmentally benign silicon solar-cell manufacturing.

  9. Involvement of antioxidant activity of Lactobacillus plantarum on functional properties of olive phenolic compounds.

    PubMed

    Kachouri, Faten; Ksontini, Hamida; Kraiem, Manel; Setti, Khaoula; Mechmeche, Manel; Hamdi, Moktar

    2015-12-01

    Eight lactic acid bacteria strains isolated from traditional fermented foods were investigated for their antioxidant activity against DPPH free radicals, β-carotene bleaching assay and linoleic acid test. L. plantarum LAB 1 at a dose of 8.2 10(9) CFU/ml showed the highest DPPH scavenging activity, with inhibition rate of 57.07 ± 0.57 % and an antioxidant activity (TAA = 43.47 ± 0.663 % and AAC = 172.65 ± 5.57), which increase with cell concentrations. When L. plantarum LAB 1 was administered to oxidative enzymes, residual activities decreased significantly with cell concentrations. The use of L. plantarum LAB 1 on olives process, favours the increase of the antioxidant activity (24 %). HPLC results showed a significant increase of orthodiphenols (74 %). Viable cells of strain were implicated directly on minimum media growth with 500 mg/l of olive phenolic compounds. Results showed an increase in their antioxidant activity. CG-SM analysis, identify the presence of compounds with higher antioxidant activity as vinyl phenol and hydroxytyrosol. PMID:26604364

  10. [Physiology of protease-activated receptors (PARs): involvement of PARs in digestive functions].

    PubMed

    Kawabata, A; Kuroda, R; Hollenberg, M D

    1999-10-01

    The protease-activated receptor (PAR), a G protein-coupled receptor present on cell surface, mediates cellular actions of extracellular proteases. Proteases cleave the extracellular N-terminal of PAR molecules at a specific site, unmasking and exposing a novel N-terminal, a tethered ligand, that binds to the body of receptor molecules resulting in receptor activation. Amongst four distinct PARs that have been cloned, PARs 1, 3 and 4 are activated by thrombin, but PAR-2 is activated by trypsin or mast cell tryptase. Human platelets express two distinct thrombin receptors, PAR-1 and PAR-4, while murine platelets express PAR-3 and PAR-4. Apart from roles of PARs in platelet activation, PARs are distributed to a number of organs in various species, predicting their physiological importance. We have been evaluating agonists specific for each PAR, using multiple procedures including a HEK cell calcium signal receptor desensitization assay. Using specific agonists that we developed, we found the following: 1) the salivary glands express PAR-2 mRNA and secret saliva in response to PAR-2 activation; 2) pancreatic juice secretion occurs following in vivo PAR-2 activation; 3) PAR-1 and PAR-2 modulate duodenal motility. Collectively, PAR plays various physiological and/or pathophysiological roles, especially in the digestive systems, and could be a novel target for drug development. PMID:10629876

  11. Benign scalp lump as an unusual presentation of extranodal Rosai-Dorfman disease

    PubMed Central

    Chen, Min Wei; King, Nicolas K. K.; Selvarajan, Sathiyamoorthy; Low, David C. Y.

    2014-01-01

    Background: Rosai–Dorfman disease (RDD) is a rare benign histioproliferative disease. It is typically characterized by benign histiocyte proliferation with lymphadenopathy, fever, and leukocytosis and was first described in 1969 by Rosai and Dorfman. Extranodal involvement has been reported in approximately up to 43% of the cases with isolated central nervous system (CNS) manifestations being even rarer. Case Description: We report our management of a 41-year-old female with extranodalpurely CNS RDD presenting as a benign scalp lump. Her lump progressed from an asymptomatic benign lesion to one causing localized cerebral edema. Treatment was surgical excision of both the cervical and CNS lesions achieving complete removal of the lesions and resolution of her symptoms. Conclusion: RDD is a rare condition and isolated CNS RDD is even less common. Benign scalp lumps have a myriad of differential diagnoses, but RDD should be a consideration in the presence of preexisting RDD lesions at other sites given its potential to progress and result in morbidity. It is imperative to be aware that symptoms may be especially deceiving as the absence of lymphadenopathy may point away from RDD as the diagnosis. PMID:25024899

  12. ENVIRONMENTAL BENIGN MITIGATION OF MICROBIOLOGICALLY INFLUENCED CORROSION (MIC)

    SciTech Connect

    J.R. Paterek

    2002-03-01

    The overall program objective is to develop and evaluate environmental benign agents or products that are effective in the prevention, inhibition, and mitigation of microbially influenced corrosion (MIC) in the internal surfaces of metallic natural gas pipelines. The goal is one or more environmental benign, a.k.a. ''green'' products that can be applied to maintain the structure and dependability of the natural gas infrastructure. The technical approach for this quarter has been to evaluate a number of real world pipeline sources for microbial communities or consortia that form biofilms under laboratory simulations of pipelines. The microorganisms will be identified using classical and molecular microbiological tools and there activities under pipeline simulating conditions will be studied. The quarter saw the collection of the first samples from the industry for isolation of the microorganisms, as well as the design and construction of the laboratory-scale pipeline simulators. Methods development for MIC and biofilm microbial isolations and identification, and laboratory design and construction of pipeline simulators were the only activities. At this stage of the study (first quarter), only preliminary results are available.

  13. B cell activation involves nanoscale receptor reorganizations and inside-out signaling by Syk

    PubMed Central

    Kläsener, Kathrin; Maity, Palash C; Hobeika, Elias; Yang, Jianying; Reth, Michael

    2014-01-01

    Binding of antigen to the B cell antigen receptor (BCR) initiates a multitude of events resulting in B cell activation. How the BCR becomes signaling-competent upon antigen binding is still a matter of controversy. Using a high-resolution proximity ligation assay (PLA) to monitor the conformation of the BCR and its interactions with co-receptors at a 10–20 nm resolution, we provide direct evidence for the opening of BCR dimers during B cell activation. We also show that upon binding Syk opens the receptor by an inside-out signaling mechanism that amplifies BCR signaling. Furthermore, we found that on resting B cells, the coreceptor CD19 is in close proximity with the IgD-BCR and on activated B cells with the IgM-BCR, indicating nanoscale reorganization of receptor clusters during B cell activation. DOI: http://dx.doi.org/10.7554/eLife.02069.001 PMID:24963139

  14. Directory of DOE and contractor personnel involved in non-government standards activities

    SciTech Connect

    1995-08-01

    This document contains a listing of DOE employees and DOE contractors who have submitted form DOE F 1300.2, Record of Non-Government Standards Activity. Additional names were added from rosters supplied by non-Government standards bodies.

  15. Activation of eNOS in endothelial cells exposed to ionizing radiation involves components of the DNA damage response pathway

    SciTech Connect

    Nagane, Masaki; Yasui, Hironobu; Sakai, Yuri; Yamamori, Tohru; Niwa, Koichi; Hattori, Yuichi; Kondo, Takashi; Inanami, Osamu

    2015-01-02

    Highlights: • eNOS activity is increased in BAECs exposed to X-rays. • ATM is involved in this increased eNOS activity. • HSP90 modulates the radiation-induced activation of ATM and eNOS. - Abstract: In this study, the involvement of ataxia telangiectasia mutated (ATM) kinase and heat shock protein 90 (HSP90) in endothelial nitric oxide synthase (eNOS) activation was investigated in X-irradiated bovine aortic endothelial cells. The activity of nitric oxide synthase (NOS) and the phosphorylation of serine 1179 of eNOS (eNOS-Ser1179) were significantly increased in irradiated cells. The radiation-induced increases in NOS activity and eNOS-Ser1179 phosphorylation levels were significantly reduced by treatment with either an ATM inhibitor (Ku-60019) or an HSP90 inhibitor (geldanamycin). Geldanamycin was furthermore found to suppress the radiation-induced phosphorylation of ATM-Ser1181. Our results indicate that the radiation-induced eNOS activation in bovine aortic endothelial cells is regulated by ATM and HSP90.

  16. Involvement of Antibiotic Efflux Machinery in Glutathione-Mediated Decreased Ciprofloxacin Activity in Escherichia coli.

    PubMed

    Goswami, Manish; Subramanian, Mahesh; Kumar, Ranjeet; Jass, Jana; Jawali, Narendra

    2016-07-01

    We have analyzed the contribution of different efflux components to glutathione-mediated abrogation of ciprofloxacin's activity in Escherichia coli and the underlying potential mechanism(s) behind this phenomenon. The results indicated that glutathione increased the total active efflux, thereby partially contributing to glutathione-mediated neutralization of ciprofloxacin's antibacterial action in E. coli However, the role of glutathione-mediated increased efflux becomes evident in the absence of a functional TolC-AcrAB efflux pump. PMID:27139480

  17. Cdc42-Dependent Activation of NADPH Oxidase Is Involved in Ethanol-Induced Neuronal Oxidative Stress

    PubMed Central

    Wang, Xin; Ke, Zunji; Chen, Gang; Xu, Mei; Bower, Kimberly A.; Frank, Jacqueline A.; Zhang, Zhuo; Shi, Xianglin; Luo, Jia

    2012-01-01

    It has been suggested that excessive reactive oxygen species (ROS) and oxidative stress play an important role in ethanol-induced damage to both the developing and mature central nervous system (CNS). The mechanisms underlying ethanol-induced neuronal ROS, however, remain unclear. In this study, we investigated the role of NADPH oxidase (NOX) in ethanol-induced ROS generation. We demonstrated that ethanol activated NOX and inhibition of NOX reduced ethanol-promoted ROS generation. Ethanol significantly increased the expression of p47phox and p67phox, the essential subunits for NOX activation in cultured neuronal cells and the cerebral cortex of infant mice. Ethanol caused serine phosphorylation and membrane translocation of p47phox and p67phox, which were prerequisites for NOX assembly and activation. Knocking down p47phox with the small interfering RNA was sufficient to attenuate ethanol-induced ROS production and ameliorate ethanol-mediated oxidative damage, which is indicated by a decrease in protein oxidation and lipid peroxidation. Ethanol activated cell division cycle 42 (Cdc42) and overexpression of a dominant negative (DN) Cdc42 abrogate ethanol-induced NOX activation and ROS generation. These results suggest that Cdc42-dependent NOX activation mediates ethanol-induced oxidative damages to neurons. PMID:22662267

  18. Stretch-induced uterine myocyte differentiation during rat pregnancy: involvement of caspase activation.

    PubMed

    Shynlova, Oksana; Dorogin, Anna; Lye, Stephen J

    2010-06-01

    Proliferation, differentiation, and apoptosis are three major processes by which the pregnant uterus maintains homeostasis to accommodate the growing fetus. We demonstrated previously that caspase activation in the pregnant rat myometrium at midgestation coincides with the transition from uterine hyperplasia to hypertrophy. We hypothesized that this transition was induced by stasis of myometrial blood flow (and subsequent hypoxia/ischaemia insult) resulting from acute myometrial stretch induced by a growing embryo. Therefore, we measured the expression of active caspase 3 and two hypoxia markers (transcription factor HIF1A and pimonidazole hydrochloride) in pregnant rat myometrium. To investigate the effect of gravidity we used unilaterally pregnant rats. Caspase 3 was activated only in the gravid horn of the unilaterally pregnant animals on Gestational Days 12-15. This activation was associated with high levels of HIF1A and pimonidazole immunostaining, which were limited to the circular myometrial layer of the gravid horn, indicative of hypoxia within this tissue. To isolate the effect of myometrial stretch applied by the growing fetus, we inserted an expandable polymer tube (intra-uterine expandable tube [IUET]) into the empty horn of Day 13 and Day 20 unilaterally pregnant rats. Tissue was collected 2, 14, and 24 h later. In the IUET-stretched empty horn, cleaved caspase 3 was activated at midgestation (Day 14), but not at late gestation (Day 21). We speculate that hypoxia resulting from mechanical stretch may activate caspase 3 within the pregnant myometrium only in the context of a specific endocrine environment. PMID:20181619

  19. Evaluation of the results of surgery treatment in patients with benign lung tumors

    PubMed Central

    Bagheri, Reza; Haghi, Seyed Ziaollah; Dalouee, Marziyeh Nouri; Nasiri, Zakiyeh; Rajabnejad, Ata’ollah

    2015-01-01

    Background: Lung tumors are among the common tumors and can be benign or malignant. Benign lung tumors are less common compared to the malignant types. Recognition of the clinical symptoms, types of tumors, paraclinical findings, and treatment approaches can bring better therapeutic results. The present study aims to evaluate the characteristics, diagnosis methods, and therapeutic approaches of different benign lung tumors. Materials and Methods: In this retrospective study, 32 patients with a diagnosis of benign lung tumor, who had been referred to the Mashhad University of Medical Sciences between 1981 and 2009, were studied. Some of the studied variables were symptoms, the pulmonary location involved, surgery technique, pathology findings, recurrence, and surgery complications. Data were analyzed by SPSS package version 16. Results: The average age of the patients was 51.69 ± 20.5 years. Prevalence of benign lung tumors was equal in both genders. The most common symptom was cough (31.2%); right lung involvement was more common (71.9%), and the most common sampling technique was transbronchial lung biopsy (TBLB) (62.5%); 53.1% of the patients were operated on by thoracotomy and the wedge resection technique. In 78.1% of the patients, no complications occurred after surgery. There was no recurrence. Most operations were performed in one month after the start of the symptoms (68.8%). Conclusions: Benign lung tumors are commonly diagnosed by routine radiography because most of them are asymptomatic. The most common finding in radiography is the presence of mass in the lungs. Transbronchial lung biopsy is a valuable technique to be used for diagnosis. We chose thoracotomy and wedge resection for the treatment of patients. We recommend this approach as a useful method. PMID:25624593

  20. Inhibitory effect of caffeic acid on ADP-induced thrombus formation and platelet activation involves mitogen-activated protein kinases

    PubMed Central

    Lu, Yu; Li, Quan; Liu, Yu-Ying; Sun, Kai; Fan, Jing-Yu; Wang, Chuan-She; Han, Jing-Yan

    2015-01-01

    Caffeic acid (CA), one of the active constituents of Radix Salvia miltiorrhizae, exhibits antioxidant and anti-inflammatory activities. However, few studies have assessed the ability of CA to inhibit platelet mediated thrombus generation in vivo. In this study, we investigated the antithrombotic effect of CA in mouse cerebral arterioles and venules using intravital microscopy. The antiplatelet activity of CA in ADP stimulated mouse platelets in vitro was also examined in attempt to explore the underlying mechanism. Our results demonstrated that CA (1.25–5 mg/kg) significantly inhibited thrombus formation in vivo. In vitro, CA (25–100 μM) inhibited ADP-induced platelet aggregation, P-selectin expression, ATP release, Ca2+ mobilization, and integrin αIIbβ3 activation. Additionally, CA attenuated p38, ERK, and JNK activation, and enhanced cAMP levels. Taken together, these data provide evidence for the inhibition of CA on platelet-mediated thrombosis in vivo, which is, at least partly, mediated by interference in phosphorylation of ERK, p38, and JNK leading to elevation of cAMP and down-regulation of P-selectin expression and αIIbβ3 activation. These results suggest that CA may have potential for the treatment of aberrant platelet activation-related diseases. PMID:26345207

  1. Telmisartan prevention of LPS-induced microglia activation involves M2 microglia polarization via CaMKKβ-dependent AMPK activation.

    PubMed

    Xu, Yuan; Xu, Yazhou; Wang, Yurong; Wang, Yunjie; He, Ling; Jiang, Zhenzhou; Huang, Zhangjian; Liao, Hong; Li, Jia; Saavedra, Juan M; Zhang, Luyong; Pang, Tao

    2015-11-01

    Brain inflammation plays an important role in the pathophysiology of many psychiatric and neurological diseases. During brain inflammation, microglia cells are activated, producing neurotoxic molecules and neurotrophic factors depending on their pro-inflammatory M1 and anti-inflammatory M2 phenotypes. It has been demonstrated that Angiotensin II type 1 receptor blockers (ARBs) ameliorate brain inflammation and reduce M1 microglia activation. The ARB telmisartan suppresses glutamate-induced upregulation of inflammatory genes in cultured primary neurons. We wished to clarify whether telmisartan, in addition, prevents microglia activation through polarization to an anti-inflammatory M2 phenotype. We found that telmisartan promoted M2 polarization and reduced M1 polarization in LPS-stimulated BV2 and primary microglia cells, effects partially dependent on PPARγ activation. The promoting effects of telmisartan on M2 polarization, were attenuated by an AMP-activated protein kinase (AMPK) inhibitor or AMPK knockdown, indicating that AMPK activation participates on telmisartan effects. Moreover, in LPS-stimulated BV2 cells, telmisartan enhancement of M2 gene expression was prevented by the inhibitor STO-609 and siRNA of calmodulin-dependent protein kinase kinase β (CaMKKβ), an upstream kinase of AMPK. Furthermore, telmisartan enhanced brain AMPK activation and M2 gene expression in a mouse model of LPS-induced neuroinflammation. In addition, telmisartan reduced the LPS-induced sickness behavior in this in vivo model, and this effect was prevented by prior administration of an AMPK inhibitor. Our results indicate that telmisartan can be considered as a novel AMPK activator, suppressing microglia activation by promoting M2 polarization. Telmisartan may provide a novel, safe therapeutic approach to treat brain disorders associated with enhanced inflammation. PMID:26188187

  2. Possible dopaminergic stimulation of locus coeruleus alpha1-adrenoceptors involved in behavioral activation.

    PubMed

    Lin, Yan; Quartermain, David; Dunn, Adrian J; Weinshenker, David; Stone, Eric A

    2008-07-01

    alpha(1)-Adrenoceptors of the locus coeruleus (LC) have been implicated in behavioral activation in novel surroundings, but the endogenous agonist that activates these receptors has not been established. In addition to the canonical activation of alpha(1)-receptors by norepinephrine (NE), there is evidence that dopamine (DA) may also activate certain brain alpha(1)-receptors. This study examined the contribution of DA to exploratory activity in a novel cage by determining the effect of infusion of various dopaminergic and adrenergic drugs into the mouse LC. It was found that the D2/D3 agonist, quinpirole, which selectively blocks the release of CNS DA, produced a dose-dependent and virtually complete abolition of exploration and all movement in the novel cage test. The quinpirole-induced inactivity was significantly attenuated by coinfusion of DA but not by the D1 agonist, SKF38390. Furthermore, the DA attenuation of quinpirole inactivity was blocked by coinfusion of the alpha(1)-adrenergic receptor antagonist, terazosin, but not by the D1 receptor antagonist, SCH23390. LC infusions of either quinpirole or terazosin also produced profound inactivity in DA-beta-hydroxylase knockout (Dbh -/-) mice that lack NE, indicating that their behavioral effects were not due to an alteration of the release or action of LC NE. Measurement of endogenous DA, NE, and 5HT and their metabolites in the LC during exposure to the novel cage indicated an increase in the turnover of DA and NE but not 5HT. These results indicate that DA is a candidate as an endogenous agonist for behaviorally activating LC alpha(1)-receptors and may play a role in the activation of this nucleus by novel surroundings. PMID:18435418

  3. Anticonvulsant activity of Citrus aurantium blossom essential oil (neroli): involvment of the GABAergic system.

    PubMed

    Azanchi, Taravat; Shafaroodi, Hamed; Asgarpanah, Jinous

    2014-11-01

    Citrus aurantium L. blossoms are an important medicinal plant part in Iran and some other countries. It is used in traditional medicine as an antiseizure and anticonvulsant natural agent. Early in vitro research of the anticonvulsant activity of the blossom extracts were done but there has been no investigation focused on the blossom essential oil and its anticonvulsant activity. The anticonvulsant activity of the essential oil of C. aurantium blossoms (neroli) was investigated. The anticonvulsant activity of neroli was assessed in pentylenetetrazole (PTZ)-induced convulsion by i.v. and i.p. methods and maximal electroshock (MES) in mice, with diazepam as the standard drug. While mechanistic studies were conducted using flumazenil, a GABA A-benzodiazepine receptor complex site antagonist. Neroli produced protection against clonic by i.v adminiatration of PTZ at 20 and 40 mg/kg, compared with protection with benzodiazepine. The mean onset and percentage protection against convulsion in neroli-treated mice were reduced by flumazenil. Intraperitonaeal PTZ also decreased the latency of clonic seizure in the neroli (40 mg/kg) treated group. We also showed that neroli (20 and 40 mg/kg), exhibited inhibition of the tonic convulsion induced by MES and decreased the mortality rate. Neroli was analyzed by GC and GC-MS and twenty three constituents, representing 91.0 % of the chromatographical oil were identified. The major components of neroli were characterized as linalool (28.5%), linalyl acetate (19.6%), nerolidol (9.1%) E,E-farnesol (9.1%), α-terpineol (4.9%) and limonene (4.6%) which might be responsible for the anticonvulsant activity. The results suggest that neroli possesses biologically active constituent(s) that have anticonvulsant activity which supports the ethnomedicinal claims of the use of the plant in the management of seizure. PMID:25532295

  4. Premature senescence involving p53 and p16 is activated in response to constitutive MEK/MAPK mitogenic signaling

    PubMed Central

    Lin, Athena W.; Barradas, Marta; Stone, James C.; van Aelst, Linda; Serrano, Manuel; Lowe, Scott W.

    1998-01-01

    Oncogenic Ras transforms immortal rodent cells to a tumorigenic state, in part, by constitutively transmitting mitogenic signals through the mitogen-activated protein kinase (MAPK) cascade. In primary cells, Ras is initially mitogenic but eventually induces premature senescence involving the p53 and p16INK4a tumor suppressors. Constitutive activation of MEK (a component of the MAPK cascade) induces both p53 and p16, and is required for Ras-induced senescence of normal human fibroblasts. Furthermore, activated MEK permanently arrests primary murine fibroblasts but forces uncontrolled mitogenesis and transformation in cells lacking either p53 or INK4a. The precisely opposite response of normal and immortalized cells to constitutive activation of the MAPK cascade implies that premature senescence acts as a fail-safe mechanism to limit the transforming potential of excessive Ras mitogenic signaling. Consequently, constitutive MAPK signaling activates p53 and p16 as tumor suppressors. PMID:9765203

  5. Involvement of aberrant cyclin-dependent kinase 5/p25 activity in experimental traumatic brain injury.

    PubMed

    Yousuf, Mohammad A; Tan, Chunfeng; Torres-Altoro, Melissa I; Lu, Fang-Min; Plautz, Erik; Zhang, Shanrong; Takahashi, Masaya; Hernandez, Adan; Kernie, Steven G; Plattner, Florian; Bibb, James A

    2016-07-01

    Traumatic brain injury (TBI) is associated with adverse effects on brain functions, including sensation, language, emotions and/or cognition. Therapies for improving outcomes following TBI are limited. A better understanding of the pathophysiological mechanisms of TBI may suggest novel treatment strategies to facilitate recovery and improve treatment outcome. Aberrant activation of cyclin-dependent kinase 5 (Cdk5) has been implicated in neuronal injury and neurodegeneration. Cdk5 is a neuronal protein kinase activated via interaction with its cofactor p35 that regulates numerous neuronal functions, including synaptic remodeling and cognition. However, conversion of p35 to p25 via Ca(2+) -dependent activation of calpain results in an aberrantly active Cdk5/p25 complex that is associated with neuronal damage and cell death. Here, we show that mice subjected to controlled cortical impact (CCI), a well-established experimental TBI model, exhibit increased p25 levels and consistently elevated Cdk5-dependent phosphorylation of microtubule-associated protein tau and retinoblastoma (Rb) protein in hippocampal lysates. Moreover, CCI-induced neuroinflammation as indicated by increased astrocytic activation and number of reactive microglia. Brain-wide conditional Cdk5 knockout mice (Cdk5 cKO) subjected to CCI exhibited significantly reduced edema, ventricular dilation, and injury area. Finally, neurophysiological recordings revealed that CCI attenuated excitatory post-synaptic potential field responses in the hippocampal CA3-CA1 pathway 24 h after injury. This neurophysiological deficit was attenuated in Cdk5 cKO mice. Thus, TBI induces increased levels of p25 generation and aberrant Cdk5 activity, which contributes to pathophysiological processes underlying TBI progression. Hence, selectively preventing aberrant Cdk5 activity may be an effective acute strategy to improve recovery from TBI. Traumatic brain injury (TBI) increases astrogliosis and microglial activation

  6. Capsular Polysaccharide Is Involved in NLRP3 Inflammasome Activation by Klebsiella pneumoniae Serotype K1

    PubMed Central

    Yang, Feng-Ling; Chiu, Hsiao-Wen; Chou, Ju-Ching; Dong, Wei-Chih; Lin, Chien-Nan; Lin, Chai-Yi; Wang, Jin-Town; Li, Lan-Hui; Chiu, Huan-Wen; Chiu, Yi-Chich

    2015-01-01

    Klebsiella pneumoniae (strain 43816, K2 serotype) induces interleukin-1β (IL-1β) secretion, but neither the bacterial factor triggering the activation of these inflammasome-dependent responses nor whether they are mediated by NLRP3 or NLRC4 is known. In this study, we identified a capsular polysaccharide (K1-CPS) in K. pneumoniae (NTUH-K2044, K1 serotype), isolated from a primary pyogenic liver abscess (PLA K. pneumoniae), as the Klebsiella factor that induces IL-1β secretion in an NLRP3-, ASC-, and caspase-1-dependent manner in macrophages. K1-CPS induced NLRP3 inflammasome activation through reactive oxygen species (ROS) generation, mitogen-activated protein kinase phosphorylation, and NF-κB activation. Inhibition of both the mitochondrial membrane permeability transition and mitochondrial ROS generation inhibited K1-CPS-mediated NLRP3 inflammasome activation. Furthermore, IL-1β secretion in macrophages infected with PLA K. pneumoniae was shown to depend on NLRP3 but also on NLRC4 and TLR4. In macrophages infected with a K1-CPS deficiency mutant, an lipopolysaccharide (LPS) deficiency mutant, or K1-CPS and LPS double mutants, IL-1β secretion levels were lower than those in cells infected with wild-type PLA K. pneumoniae. Our findings indicate that K1-CPS is one of the Klebsiella factors of PLA K. pneumoniae that induce IL-1β secretion through the NLRP3 inflammasome. PMID:26077758

  7. Developing Science Communication in Africa: Undergraduate and Graduate Students should be Trained and Actively Involved in Outreach Activity Development and Implementation

    PubMed Central

    Karikari, Thomas K.; Yawson, Nat Ato; Quansah, Emmanuel

    2016-01-01

    Despite recent improvements in scientific research output from Africa, public understanding of science in many parts of the continent remains low. Science communication there is faced with challenges such as (i) lack of interest among some scientists, (ii) low availability of training programs for scientists, (iii) low literacy rates among the public, and (iv) multiplicity of languages. To address these challenges, new ways of training and motivating scientists to dialogue with non-scientists are essential. Developing communication skills early in researchers’ scientific career would be a good way to enhance their public engagement abilities. Therefore, a potentially effective means to develop science communication in Africa would be to actively involve trainee scientists (i.e., undergraduate and graduate students) in outreach activity development and delivery. These students are often enthusiastic about science, eager to develop their teaching and communication skills, and can be good mentors to younger students. Involving them in all aspects of outreach activity is, therefore, likely to be a productive implementation strategy. However, science communication training specifically for students and the involvement of these students in outreach activity design and delivery are lacking in Africa. Here, we argue that improving the training and involvement of budding scientists in science communication activities would be a good way to bridge the wide gap between scientists and the African public. PMID:27385932

  8. Developing Science Communication in Africa: Undergraduate and Graduate Students should be Trained and Actively Involved in Outreach Activity Development and Implementation.

    PubMed

    Karikari, Thomas K; Yawson, Nat Ato; Quansah, Emmanuel

    2016-01-01

    Despite recent improvements in scientific research output from Africa, public understanding of science in many parts of the continent remains low. Science communication there is faced with challenges such as (i) lack of interest among some scientists, (ii) low availability of training programs for scientists, (iii) low literacy rates among the public, and (iv) multiplicity of languages. To address these challenges, new ways of training and motivating scientists to dialogue with non-scientists are essential. Developing communication skills early in researchers' scientific career would be a good way to enhance their public engagement abilities. Therefore, a potentially effective means to develop science communication in Africa would be to actively involve trainee scientists (i.e., undergraduate and graduate students) in outreach activity development and delivery. These students are often enthusiastic about science, eager to develop their teaching and communication skills, and can be good mentors to younger students. Involving them in all aspects of outreach activity is, therefore, likely to be a productive implementation strategy. However, science communication training specifically for students and the involvement of these students in outreach activity design and delivery are lacking in Africa. Here, we argue that improving the training and involvement of budding scientists in science communication activities would be a good way to bridge the wide gap between scientists and the African public. PMID:27385932

  9. Teacher management behaviors and pupil task involvement during small group laboratory activities

    NASA Astrophysics Data System (ADS)

    Beasley, Warren

    A major concern of many beginning and experienced teachers is that of classroom management and control. This article describes recent research into defining classroom management procedures that are used by high school science teachers and their relationship to pupil ontaskness. The classroom is conceptualized as a manipulable behavioral system. This construct arises directly from Barker's (1968) ecological psychology, the classroom and its occupants being conceptualized as a behavior setting. The behaviors of the teacher and the pupils are an integral part of the unit (behavior setting), which in turn coerces certain behaviors from its participants. Thus settings, and, in particular, subsettings, are seen as more important determiners of social behavior than the personality of individual teacher or pupil. The methodology employed in this research has involved the extensive use of video in naturalistic science classrooms. Tapes of both teacher and pupil behaviors were continuously and independently recorded. Intensive analysis using electronic recording instruments interfaced with the computer has allowed the collection and sophisticated analysis of the observational data. Data relating to teacher management behavior in small group settings have been analyzed and the relationships to pupil task involvement have been explored.

  10. Transmembrane signal transduction in bacterial chemotaxis involves ligand-dependent activation of phosphate group transfer.

    PubMed Central

    Borkovich, K A; Kaplan, N; Hess, J F; Simon, M I

    1989-01-01

    Signal transduction in Escherichia coli involves the interaction of transmembrane receptor proteins such as the aspartate receptor, Tar, and the products of four chemotaxis genes, cheA, cheY, cheW, and cheZ. It was previously shown that the cheA gene product is an autophosphorylating protein kinase that transfers phosphate to CheY, whereas the cheZ gene product acts as a specific CheY phosphatase. Here we report that the system can be reconstituted in vitro and receptor function can be coupled to CheY phosphorylation. Coupling requires the presence of the CheW protein, the appropriate form of the receptor, and the CheA and CheY proteins. Under these conditions the accumulation of CheY-phosphate is enhanced approximately 300-fold. This rate enhancement is seen in reactions using wild-type and "tumble" mutant receptors but not "smooth" mutant receptors. The increased accumulation of phosphoprotein was inhibited by micromolar concentrations of aspartate, using wild-type, but not tumble, receptors. These results provide evidence that the signal transduction pathway in bacterial chemotaxis involves receptor-mediated alteration of the levels of phosphorylated proteins. They suggest that CheW acts as the coupling factor between receptor and phosphorylation. The results also support the suggestion that CheY-phosphate is the tumble signal. Images PMID:2645576

  11. NIK is involved in constitutive activation of the alternative NF-{kappa}B pathway and proliferation of pancreatic cancer cells

    SciTech Connect

    Nishina, Takashi; Yamaguchi, Noritaka; Gohda, Jin; Semba, Kentaro; Inoue, Jun-ichiro

    2009-10-09

    Pancreatic cancer has one of the poorest prognoses among human neoplasms. Constitutive activation of NF-{kappa}B is frequently observed in pancreatic cancer cells and is involved in their malignancy. However, little is known about the molecular mechanism of this constitutive NF-{kappa}B activation. Here, we show that the alternative pathway is constitutively activated and NF-{kappa}B-inducing kinase (NIK), a mediator of the alternative pathway, is significantly expressed in pancreatic cancer cells. siRNA-mediated silencing of NIK expression followed by subcellular fractionation revealed that NIK is constitutively involved in the processing of p100 and nuclear transport of p52 and RelB in pancreatic cancer cells. In addition, NIK silencing significantly suppressed proliferation of pancreatic cancer cells. These results clearly indicate that NIK is involved in the constitutive activation of the alternative pathway and controls cell proliferation in pancreatic cancer cells. Therefore, NIK might be a novel target for the treatment of pancreatic cancer.

  12. Tumor cell alpha-N-acetylgalactosaminidase activity and its involvement in GcMAF-related macrophage activation.

    PubMed

    Mohamad, Saharuddin B; Nagasawa, Hideko; Uto, Yoshihiro; Hori, Hitoshi

    2002-05-01

    Alpha-N-acetyl galactosaminidase (alpha-NaGalase) has been reported to accumulate in serum of cancer patients and be responsible for deglycosylation of Gc protein, which is a precursor of GcMAF-mediated macrophage activation cascade, finally leading to immunosuppression in advanced cancer patients. We studied the biochemical characterization of alpha-NaGalase from several human tumor cell lines. We also examined its effect on the potency of GcMAF to activate mouse peritoneal macrophage to produce superoxide in GcMAF-mediated macrophage activation cascade. The specific activity of alpha-NaGalases from human colon tumor cell line HCT116, human hepatoma cell line HepG2, and normal human liver cells (Chang liver cell line) were evaluated using two types of substrates; GalNAc-alpha-PNP (exo-type substrate) and Gal-beta-GalNAc-alpha-PNP (endo-type substrate). Tumor-derived alpha-NaGalase having higher activity than normal alpha-NaGalase, had higher substrate specificity to the exo-type substrate than to the endo-type substrate, and still maintained its activity at pH 7. GcMAF enhance superoxide production in mouse macrophage, and pre-treatment of GcMAF with tumor cell lysate reduce the activity. We conclude that tumor-derived alpha-NaGalase is different in biochemical characterization compared to normal alpha-NaGalase from normal Chang liver cells. In addition, tumor cell-derived alpha-NaGalase decreases the potency of GcMAF on macrophage activation. PMID:12062184

  13. The upstream activator CTF/NF1 and RNA polymerase II share a common element involved in transcriptional activation.

    PubMed Central

    Xiao, H; Lis, J T; Xiao, H; Greenblatt, J; Friesen, J D

    1994-01-01

    The carboxy-terminal domain (CTD) of the largest subunit of RNA polymerase II consists of tandem repeats of a heptapeptide with the consensus YSPTSPS. It has been shown that the heptapeptide repeat interacts directly with the general transcription factor TFIID. We report here that the CTD activates transcription when fused to the DNA-binding domain of GAL4. More importantly, we find that the proline-rich transcriptional activation domain of the CCAAT-box-binding factor CTF/NF1 contains a sequence with striking similarity to the heptapeptide repeats of the CTD. We show that this CTD-like motif is essential for the transcriptional activator function of the proline-rich domain of CTF/NF1. Deletion of and point mutations in this CTD-like motif abolish the transcriptional activator function of the proline-rich domain, while natural CTD repeats from RNA polymerase II are fully functional in place of the CTD-like motif. We further show that the proline-rich activation domain of CTF/NF1 interacts directly with the TATA-box-binding protein (TBP), and that a mutation in the CTD-like motif that abolishes transcriptional activation reduces the affinity of the proline-rich domain for TBP. These results demonstrate that a class of proline-rich activator proteins and RNA polymerase II possess a common structural and functional component which can interact with the same target in the general transcription machinery. We discuss the implications of these results for the mechanisms of transcriptional activation in eucaryotes. Images PMID:8029001

  14. Antiplasmodial activities of gold(I) complexes involving functionalized N-heterocyclic carbenes.

    PubMed

    Hemmert, Catherine; Ramadani, Arba Pramundita; Boselli, Luca; Fernández Álvarez, Álvaro; Paloque, Lucie; Augereau, Jean-Michel; Gornitzka, Heinz; Benoit-Vical, Françoise

    2016-07-01

    A series of twenty five molecules, including imidazolium salts functionalized by N-, O- or S-containing groups and their corresponding cationic, neutral or anionic gold(I) complexes were evaluated on Plasmodium falciparum in vitro and then on Vero cells to determine their selectivity. Among them, eight new compounds were synthesized and fully characterized by spectroscopic methods. The X-ray structures of three gold(I) complexes are presented. Except one complex (18), all the cationic gold(I) complexes show potent antiplasmodial activity with IC50 in the micro- and submicromolar range, correlated with their lipophilicity. Structure-activity relationships enable to evidence a lead-complex (21) displaying a good activity (IC50=210nM) close to the value obtained with chloroquine (IC50=514nM) and a weak cytotoxicity. PMID:27240469

  15. Phospholipase A{sub 2} is involved in the mechanism of activation of neutrophils by polychlorinated biphenyls

    SciTech Connect

    Tithof, P.K.; Schiamberg, E.; Ganey, P.E.; Peters-Golden, M.

    1996-01-01

    Aroclor 1242, a mixture of polychlorinated biphenyls (PCBs), activates neutrophils to produce superoxide anion (O{sub 2}{sup {minus}}) by a mechanism that involves phospholipase C-dependent hydrolysis of membrane phosphoinositides; however, subsequent signal transduction mechanisms are unknown. This study determines whether phospholipase A{sub 2}-dependent release of arachidonic acid is involved in PCB-induced O{sub 2}{sup {minus}} production. O{sub 2}{sup {minus}} production was measured in vitro in glycogen-elicited, rat neutrophils in the presence and absence of the inhibitors of phospholipase A{sub 2}: quinacrine, 4-bromophenacyl bromide (BPB), and manoalide. All three agents significantly decreased the amount of O{sub 2}{sup {minus}} detected during stimulation of neutrophils with Aroclor 1242. Similar inhibition occurred when neutrophils were activated with the classical stimuli, formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol myristate acetate. The effects of BPB and manoalide were not a result of cytotoxicity or other nonspecific effects. Significant release of {sup 3}H-arachidonic acid preceded O{sub 2}{sup {minus}} production in neutrophils stimulated with Aroclor 1242 or fMLP. Manoalide, at a concentration that abolished O{sub 2}{sup {minus}} production, also inhibited the release of {sup 3}H-arachidonate. Aspirin, zileuton, or WEB 2086 did not affect Aroclor 1242-induced O{sub 2}{sup {minus}} production, suggesting that eicosanoids and platelet-activating factor are not needed for neutrophil activation by PCBs. Activation of phos-pholipase A{sub 2} and O{sub 2}{sup {minus}} production do not appear to involve the Ah receptor. These data suggest that Aroclor 1242 stimulates neutrophils to produce O{sub 2}{sup {minus}} by a mechanism that involves phospholipase A{sub 2}-dependent release of arachiodonic acid. 49 refs., 6 figs., 2 tabs.

  16. Activation of soluble guanylyl cyclase by the nitrovasodilator 3-morpholinosydnonimine involves formation of S-nitrosoglutathione.

    PubMed

    Schrammel, A; Pfeiffer, S; Schmidt, K; Koesling, D; Mayer, B

    1998-07-01

    Soluble guanylyl cyclase (sGC) is the major physiological target of sydnonimine-based vasodilators such as molsidomine. Decomposition of sydnonimines results in the stoichiometric formation of nitric oxide (NO) and superoxide (O2-), which rapidly react to form peroxynitrite. Inasmuch as sGC is activated by NO but not by peroxynitrite, we investigated the mechanisms underlying sGC activation by 3-morpholinosydnonimine (SIN-1). Stimulation of purified bovine lung sGC by SIN-1 was found to be strongly dependent on glutathione (GSH). By contrast, GSH did not affect sGC activation by NO released from 2,2-diethyl-1-nitroso-oxyhydrazine, indicating that NO/O2- released from SIN-1 converted GSH to an activator of sGC. High performance liquid chromatography identified this product as the thionitrite S-nitrosoglutathione. Further, the reaction product decomposed to release NO upon addition of Cu(NO3)2 in the presence of GSH. Activation of sGC was antagonized by the Cu(I)-specific chelator neocuproine, whereas the Cu(II)-selective drug cuprizone was less potent. Carbon dioxide (delivered as NaHCO3) antagonized S-nitrosation by peroxynitrite but not by SIN-1. Thus, NO/O2- released from SIN-1 mediates a CO2-insensitive conversion of GSH to S-nitrosoglutathione, a thionitrite that activates sGC via trace metal-catalyzed release of NO. These results may provide novel insights into the molecular mechanism underlying the nitrovasodilator action of SIN-1. PMID:9658207

  17. Macrophages migrate in an activation-dependent manner to chemokines involved in neuroinflammation

    PubMed Central

    2014-01-01

    Background In neuroinflammatory diseases, macrophages can play a dual role in the process of tissue damage, depending on their activation status (M1 / M2). M1 macrophages are considered to exert damaging effects to neurons, whereas M2 macrophages are reported to aid regeneration and repair of neurons. Their migration within the central nervous system may be of critical importance in the final outcome of neurodegeneration in neuroinflammatory diseases e.g. multiple sclerosis (MS). To provide insight into this process, we examined the migratory capacity of human monocyte-derived M1 and M2 polarised macrophages towards chemoattractants, relevant for neuroinflammatory diseases like MS. Methods Primary cultures of human monocyte-derived macrophages were exposed to interferon gamma and lipopolysaccharide (LPS) to evoke proinflammatory (M1) activation or IL-4 to evoke anti-inflammatory (M2) activation. In a TAXIScan assay, migration of M0, M1 and M2 towards chemoattractants was measured and quantified. Furthermore the adhesion capacity and the expression levels of integrins as well as chemokine receptors of M0, M1 and M2 were assessed. Alterations in cell morphology were analysed using fluorescent labelling of the cytoskeleton. Results Significant differences were observed between M1 and M2 macrophages in the migration towards chemoattractants. We show that M2 macrophages migrated over longer distances towards CCL2, CCL5, CXCL10, CXCL12 and C1q compared to non-activated (M0) and M1 macrophages. No differences were observed in the adhesion of M0, M1 and M2 macrophages to multiple matrix components, nor in the expression of integrins and chemokine receptors. Significant changes were observed in the cytoskeleton organization upon stimulation with CCL2, M0, M1 and M2 macrophages adopt a spherical morphology and the cytoskeleton is rapidly rearranged. M0 and M2 macrophages are able to form filopodia, whereas M1 macrophages only adapt a spherical morphology. Conclusions

  18. Involvement of the neuronal phosphotyrosine signal adaptor N-Shc in kainic acid-induced epileptiform activity

    PubMed Central

    Baba, Shiro; Onga, Kazuko; Kakizawa, Sho; Ohyama, Kyoji; Yasuda, Kunihiko; Otsubo, Hiroshi; Scott, Brian W.; Burnham, W. McIntyre; Matsuo, Takayuki; Nagata, Izumi; Mori, Nozomu

    2016-01-01

    BDNF-TrkB signaling is implicated in experimental seizures and epilepsy. However, the downstream signaling involved in the epileptiform activity caused by TrkB receptor activation is still unknown. The aim of the present study was to determine whether TrkB-mediated N-Shc signal transduction was involved in kainic acid (KA)-induced epileptiform activity. We investigated KA-induced behavioral seizures, epileptiform activities and neuronal cell loss in hippocampus between N-Shc deficient and control mice. There was a significant reduction in seizure severity and the frequency of epileptiform discharges in N-Shc deficient mice, as compared with wild-type and C57BL/6 mice. KA-induced neuronal cell loss in the CA3 of hippocampus was also inhibited in N-Shc deficient mice. This study demonstrates that the activation of N-Shc signaling pathway contributes to an acute KA-induced epileptiform activity and neuronal cell loss in the hippocampus. We propose that the N-Shc-mediated signaling pathway could provide a potential target for the novel therapeutic approaches of epilepsy. PMID:27273072

  19. Involvement of the neuronal phosphotyrosine signal adaptor N-Shc in kainic acid-induced epileptiform activity.

    PubMed

    Baba, Shiro; Onga, Kazuko; Kakizawa, Sho; Ohyama, Kyoji; Yasuda, Kunihiko; Otsubo, Hiroshi; Scott, Brian W; Burnham, W McIntyre; Matsuo, Takayuki; Nagata, Izumi; Mori, Nozomu

    2016-01-01

    BDNF-TrkB signaling is implicated in experimental seizures and epilepsy. However, the downstream signaling involved in the epileptiform activity caused by TrkB receptor activation is still unknown. The aim of the present study was to determine whether TrkB-mediated N-Shc signal transduction was involved in kainic acid (KA)-induced epileptiform activity. We investigated KA-induced behavioral seizures, epileptiform activities and neuronal cell loss in hippocampus between N-Shc deficient and control mice. There was a significant reduction in seizure severity and the frequency of epileptiform discharges in N-Shc deficient mice, as compared with wild-type and C57BL/6 mice. KA-induced neuronal cell loss in the CA3 of hippocampus was also inhibited in N-Shc deficient mice. This study demonstrates that the activation of N-Shc signaling pathway contributes to an acute KA-induced epileptiform activity and neuronal cell loss in the hippocampus. We propose that the N-Shc-mediated signaling pathway could provide a potential target for the novel therapeutic approaches of epilepsy. PMID:27273072

  20. Novel Antiplatelet Activity of Minocycline Involves Inhibition of MLK3-p38 Mitogen Activated Protein Kinase Axis

    PubMed Central

    Jackson, Joseph W.; Singh, Meera V.; Singh, Vir B.; Jones, Letitia D.; Davidson, Gregory A.; Ture, Sara; Morrell, Craig N.; Schifitto, Giovanni; Maggirwar, Sanjay B.

    2016-01-01

    Platelets play an essential role in hemostasis and wound healing by facilitating thrombus formation at sites of injury. Platelets also mediate inflammation and contain several pro-inflammatory molecules including cytokines and chemokines that mediate leukocyte recruitment and activation. Not surprisingly, platelet dysfunction is known to contribute to several inflammatory disorders. Antiplatelet therapies, such as aspirin, adenosine diphosphate (ADP) antagonists, glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors, and anticoagulants such as warfarin, dampen platelet activity at the risk of unwarranted bleeding. Thus, the development of drugs that reduce platelet-mediated inflammation without interfering with thrombus formation is of importance to combat platelet-associated disorders. We have shown here for the first time that the tetracycline antibiotic, minocycline, administered to HIV-infected individuals reduces plasma levels of soluble CD40L and platelet factor 4 levels, host molecules predominately released by platelets. Minocycline reduced the activation of isolated platelets in the presence of the potent platelet activator, thrombin, as measured by ELISA and flow cytometry. Platelet degranulation was reduced upon exposure to minocycline as shown by mepacrine retention and flow cytometry. However, minocycline had no effect on spreading, aggregation, GPIIb/IIIa activation, or in vivo thrombus formation. Lastly, immunoblot analysis suggests that the antiplatelet activity of minocycline is likely mediated by inhibition of mixed lineage kinase 3 (MLK3)-p38 MAPK signaling axis and loss of p38 activity. Our findings provide a better understanding of platelet biology and a novel repurposing of an established antibiotic, minocycline, to specifically reduce platelet granule release without affecting thrombosis, which may yield insights in generating novel, specific antiplatelet therapies. PMID:27270236

  1. Basolateral K+ channel involvement in forskolin-activated chloride secretion in human colon.

    PubMed

    McNamara, B; Winter, D C; Cuffe, J E; O'Sullivan, G C; Harvey, B J

    1999-08-15

    1. In this study we investigated the role of basolateral potassium transport in maintaining cAMP-activated chloride secretion in human colonic epithelium. 2. Ion transport was quantified in isolated human colonic epithelium using the short-circuit current technique. Basolateral potassium transport was studied using nystatin permeabilization. Intracellular calcium measurements were obtained from isolated human colonic crypts using fura-2 spectrofluorescence imaging. 3. In intact isolated colonic strips, forskolin and prostaglandin E2 (PGE2) activated an inward transmembrane current (ISC) consistent with anion secretion (for forskolin DeltaISC = 63.8+/-6.2 microA cm(-2), n = 6; for PGE2 DeltaISC = 34.3+/-5.2 microA cm(-2), n = 6). This current was inhibited in chloride-free Krebs solution or by inhibiting basolateral chloride uptake with bumetanide and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid DIDS). 4. The forskolin- and PGE2-induced chloride secretion was inhibited by basolateral exposure to barium (5 mM), tetrapentylammonium (10 microM) and tetraethylammonium (10 mM). 5. The transepithelial current produced under an apical to serosal K+ gradient in nystatin-perforated colon is generated at the basolateral membrane by K+ transport. Forskolin failed to activate this current under conditions of high or low calcium and failed to increase the levels of intracellular calcium in isolated crypts 6. In conclusion, we propose that potassium recycling through basolateral K+ channels is essential for cAMP-activated chloride secretion. PMID:10432355

  2. Involvement of sensor kinase gene (skrp 1122) for biocontrol activity by Pseudomonas synxantha BG33R

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous research identified Pseudomonas synxantha BG33R as potential carrier for a nematode egg-kill factor. Further research indicated that BG33R exhibits a broad-spectrum of antagonistic activity against oomycetes, fungi, nematodes and insects. Earlier screening for negative egg-kill factor indi...

  3. The Effect of the New Copyright Law on the Interlibrary Loan Activity Involving Periodicals.

    ERIC Educational Resources Information Center

    Steuben, John

    Since 1954 when Congress authorized the Copyright Office to prepare a series of studies to serve as background for revision hearings, copyright has been one of the major issues in librarianship. Although the impact that the New Copyright Law will have on interlibrary loan activity is yet to be determined, there is a need to know whether present…

  4. How Curriculum Leaders Can Involve the Right Brain in Active Reading and Writing Development.

    ERIC Educational Resources Information Center

    Sinatra, Richard; Stahl-Gemake, Josephine

    Curriculum leaders, program specialists, and teachers can intentionally arouse the activation of one hemisphere of the brain over the other through the use of right brain strategies in language learning. While most functions of the left hemisphere are concerned with convergent production (getting the right answer), functions of the right…

  5. Inventory of Federal Programs Involving Educational Activities Concerned with Improving International Understanding and Cooperation.

    ERIC Educational Resources Information Center

    Johnson, Janice M.; Hohman, David E.

    This inventory contains the results of a survey of all Federal programs for fiscal years 1966, 1967, and 1968 that included educational activities aimed at improving international understanding and cooperation. A total of 159 such programs were reported by 31 responding Federal agencies. This inventory contains the following information for each…

  6. Fantasy Activity and the Televiewing Event: Considerations for an Information Processing Construct of Involvement.

    ERIC Educational Resources Information Center

    Lindlof, Thomas R.

    The similarities between television viewing and fantasy activity (daydreaming, reverie, mind-wandering, internal dialogue) more than warrant the building of a theoretical construct, especially in the context of recent empirical research on television viewing consequences. A construct of the television viewing process, based on cognitive theories…

  7. GBA2-Encoded β-Glucosidase Activity Is Involved in the Inflammatory Response to Pseudomonas aeruginosa

    PubMed Central

    Lampronti, Ilaria; Marchetti, Nicola; Aureli, Massimo; Bassi, Rosaria; Giri, Maria Grazia; Bezzerri, Valentino; Lovato, Valentina; Cantù, Cinzia; Munari, Silvia; Cheng, Seng H.; Cavazzini, Alberto; Gambari, Roberto; Sonnino, Sandro; Cabrini, Giulio; Dechecchi, Maria Cristina

    2014-01-01

    Current anti-inflammatory strategies for the treatment of pulmonary disease in cystic fibrosis (CF) are limited; thus, there is continued interest in identifying additional molecular targets for therapeutic intervention. Given the emerging role of sphingolipids (SLs) in various respiratory disorders, including CF, drugs that selectively target the enzymes associated with SL metabolism are under development. Miglustat, a well-characterized iminosugar-based inhibitor of β-glucosidase 2 (GBA2), has shown promise in CF treatment because it reduces the inflammatory response to infection by P. aeruginosa and restores F508del-CFTR chloride channel activity. This study aimed to probe the molecular basis for the anti-inflammatory activity of miglustat by examining specifically the role of GBA2 following the infection of CF bronchial epithelial cells by P. aeruginosa. We also report the anti-inflammatory activity of another potent inhibitor of GBA2 activity, namely N-(5-adamantane-1-yl-methoxy)pentyl)-deoxynojirimycin (Genz-529648). In CF bronchial cells, inhibition of GBA2 by miglustat or Genz-529648 significantly reduced the induction of IL-8 mRNA levels and protein release following infection by P. aeruginosa. Hence, the present data demonstrate that the anti-inflammatory effects of miglustat and Genz-529648 are likely exerted through inhibition of GBA2. PMID:25141135

  8. Cultural Variation in Young Children's Opportunities for Involvement in Adult Activities.

    ERIC Educational Resources Information Center

    Morelli, Gilda A.; And Others

    This study gathered information on the extent to which children participate in the mature routines of their community, and the extent to which elders participate in child-centered activities. Subjects were children ranging in age from 30 to 45 months from the four societies of: (1) Mayan Indians living in a rural Guatemalan town; (2) the Efe…

  9. Families and School Personnel Involved in a Literacy and Physical Activity Partnership

    ERIC Educational Resources Information Center

    Richardson, James A.; Richardson, Maurine V.; Sacks, Mary Kathleen

    2006-01-01

    A traditional part of American education has been to include the families in the educational process of their children. The needs and complexities of today's families and classrooms have never been greater. Programs and activities used with families, and school interactions 10 to 15 years ago are not effective for today's complex families and…

  10. Marketing Informal Education Institutions in Israel: The Centrality of Customers' Active Involvement in Service Development

    ERIC Educational Resources Information Center

    Oplatka, Izhar

    2004-01-01

    The current paper outlines a unique marketing perspective that prevails in some informal education institutions in Israel parallel with "traditional modes of marketing", such as promotion, public relations and the like. Based on a case study research in five community centres, a service development based on active participation of the potential…

  11. School-Based Extracurricular Activity Involvement and Adolescent Self-Esteem: A Growth-Curve Analysis

    ERIC Educational Resources Information Center

    Kort-Butler, Lisa A.; Hagewen, Kellie J.

    2011-01-01

    Research on adolescent self-esteem indicates that adolescence is a time in which individuals experience important changes in their physical, cognitive, and social identities. Prior research suggests that there is a positive relationship between an adolescent's participation in structured extracurricular activities and well-being in a variety of…

  12. From Resistance to Involvement: Examining Agency and Control in a Playworld Activity

    ERIC Educational Resources Information Center

    Rainio, Anna Pauliina

    2008-01-01

    In the recent sociocultural literature, it is possible to identify at least three ways of understanding the development of individual agency in social practices: (a) through transforming the object of activity and through self-change, (b) through responsible and intentional membership, and (c) through resistance and transformation of the dominant…

  13. Regrouping: Organized Activity Involvement and Social Adjustment across the Transition to High School

    ERIC Educational Resources Information Center

    Bohnert, Amy M.; Aikins, Julie Wargo; Arola, Nicole T.

    2013-01-01

    Although organized activities (OAs) have been established as important contexts of development, limited work has examined the role of OAs across the high school transition in buffering adolescents' social adjustment by providing opportunities for visibility and peer affiliation. The transition to high school is characterized by numerous…

  14. The Development of Spatial Skills through Interventions Involving Block Building Activities

    ERIC Educational Resources Information Center

    Casey, Beth M.; Andrews, Nicole; Schindler, Holly; Kersh, Joanne E.; Samper, Alexandra; Copley, Juanita

    2008-01-01

    This study investigated the use of block-building interventions to develop spatial-reasoning skills in kindergartners. Two intervention conditions and a control condition were included to determine, first, whether the block building activities themselves benefited children's spatial skills, and secondly, whether a story context further improved…

  15. In vitro activity of aminosterols against yeasts involved in blood stream infections.

    PubMed

    Alhanout, Kamel; Djouhri, Lamia; Vidal, Nicolas; Brunel, Jean Michel; Piarroux, Renaud; Ranque, Stéphane

    2011-02-01

    Squalamine and other aminosterols have demonstrated interesting antimicrobial activities against clinical bacterial isolates and a limited number of reference yeast strains. We aimed to test whether squalamine and a synthetic aminosterol derivative (ASD) display any in vitro activity comparable to currently available systemic antifungals, an acceptable safety index, as well as to provide insights into their mechanism of action. The minimum inhibitory concentrations (MICs) of squalamine, ASD and available antifungals were determined against 21 yeast isolates that were recovered from cases of fungemia. Remarkably, homogeneous MICs ranging from 8-16 mg/L and from 1-2 mg/L were noted for squalamine and ASD, respectively, as opposes the heterogeneous in vitro activity of available systemic antifungals. Aminosterols induced haemolysis, a surrogate for toxic effects to mammalian cells, at concentrations high above their MICs. In time-kill studies, killing was as fast with ASD as with amphotericin B. Both aminosterols induced a time-dependent disruption of yeast membrane, as evidenced by gradual increase of ATP efflux. In conclusion, our preliminary data indicate that aminosterols have the potential to be further developed as antifungals. Additional work is warranted to assess their toxicity and activity in experimental models. PMID:20662632

  16. Killing of Staphylococci by θ-Defensins Involves Membrane Impairment and Activation of Autolytic Enzymes

    PubMed Central

    Wilmes, Miriam; Stockem, Marina; Bierbaum, Gabriele; Schlag, Martin; Götz, Friedrich; Tran, Dat Q.; Schaal, Justin B.; Ouellette, André J.; Selsted, Michael E.; Sahl, Hans-Georg

    2014-01-01

    θ-Defensins are cyclic antimicrobial peptides expressed in leukocytes of Old world monkeys. To get insight into their antibacterial mode of action, we studied the activity of RTDs (rhesus macaque θ-defensins) against staphylococci. We found that in contrast to other defensins, RTDs do not interfere with peptidoglycan biosynthesis, but rather induce bacterial lysis in staphylococci by interaction with the bacterial membrane and/or release of cell wall lytic enzymes. Potassium efflux experiments and membrane potential measurements revealed that the membrane impairment by RTDs strongly depends on the energization of the membrane. In addition, RTD treatment caused the release of Atl-derived cell wall lytic enzymes probably by interaction with membrane-bound lipoteichoic acid. Thus, the premature and uncontrolled activity of these enzymes contributes strongly to the overall killing by θ-defensins. Interestingly, a similar mode of action has been described for Pep5, an antimicrobial peptide of bacterial origin. PMID:25632351

  17. Involvement of ASK1 activation in apoptosis induced by NPe6-PDT

    NASA Astrophysics Data System (ADS)

    Liu, Lei; Zhang, Zhen-zhen; Zhang, Zhigang

    2010-02-01

    Photodynamic therapy (PDT) employing photosensiter N-aspartyl chlorin e6 (NPe6) can induce lysosome disruption and initiate apoptotic pathway. Apoptosis signal-regulating kinase (ASK1) is an important regulator of apoptosis in response to various stresses, such as reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, lipopolysaccharide (LPS) and calcium influx. In this study, we investigated the molecular mechanisms of apoptosis induced by NPe6-PDT in ASTC-a-1 cells. The results showed that the activities of ASK1 increased in response to NPe6-PDT. Over-expression of wild-type or activated mutant of ASK1 could obviously decrease cell viability and increase cell death; while inhibition of ASK1 significantly decreased cell apoptosis. These results suggested that ASK1 plays an important role in apoptosis induced by NPe6-PDT.

  18. The trypanocidal activity of the alkaloid oliverine involves inhibition of DNA synthesis.

    PubMed

    Garro, H A; Juri Ayub, M; Nieto, M; Lucero Estrada, C; Pungitore, C R; Tonn, C E

    2010-01-01

    The Trypanosoma cruzi parasite is an etiologic agent of the American trypanosomiasis called Chagas disease. This pathology affects more than 24 million persons and represents one of the most important public health problems in Latin America. Taking into account this, it is necessary the search of new antitrypanosomal agents that show a major level of efficacy and minor indexes of toxicity in affected patients. Vast source of them are the natural products from plants with enormous structural diversity. A particular type of these compounds is represented by aporphinoid alkaloids. In our experiments, anonaine (2), oliverine (3) and guatterine (5) displayed antitrypanosomal activity. The compound 3 showed the most important activity with an IC50 = 12.00 ± 0.36 μM. Its mechanism of action may include inhibition of DNA synthesis. PMID:20937218

  19. 'Co-active coaching' could help HIV patients. New type of counseling involves goal-setting.

    PubMed

    Garfinkel, M; Blumenthal, E

    2001-08-01

    A counseling technique that takes an action-oriented approach to helping people make major life changes, much used by business executives and other professionals in recent years, now appears to offer some value to HIV patients. Co-active coaching could be a solution to mild depression and inertia for some HIV-infected patients who have difficulty making decisions about how to spend a life-time living with the disease. PMID:11547701

  20. Involvements of chloride ion in decolorization of Acid Orange 7 by activated peroxydisulfate or peroxymonosulfate oxidation.

    PubMed

    Wang, Ping; Yang, Shiying; Shan, Liang; Niu, Rui; Shao, Xueting

    2011-01-01

    The effects of chloride anion (Cl-) (up to 1.0 mol/L) on the decolorization of a model compound, azo dye Acid Orange 7 (AO7), by sulfate radical (SO4-*) based-peroxydisulfate (PS) or peroxymonosulfate (PMS) oxidation under various activated conditions (UV254 nm/PS, Thermal (70 degrees C/PS, UV254 nm/PMS, Co2+/PMS) were investigated. Methanol and NH4+ were used as quenching reagents to determine the contributions of active chlorine species (dichloride radical (Cl2-*) and hypochlorous acid (HClO)). The results indicated that the effects of Cl- on the reaction mechanism were different under various activated conditions. For UV/PS and Thermal/PS, the inhibition tendency became more clear as the Cl- concentration increased, probably due to the reaction between Cl- and SO4-* and the generation of Cl2-* or HCIO. For UV/PMS, Cl- did not exhibit inhibition when the concentration was below 0.1 mol/L. As Cl- concentration reached to 1.0 mol/L, the decolorization rate of AO7 was, however, accelerated, possibly because PMS directly reacts with Cl- to form HClO. For Co2+/PMS, Cl- exhibited a significant inhibiting effect even at low concentration (< or = 0.01 mol/L). When Cl- concentration exceeded 0.1 mol/L, the activation of PMS by Co2+ was almost completely inhibited. Under this condition, HClO maybe played a major role in decolorization of AO7. The results implicated that chloride ion is an important factor in SO4(-*) -based degradation of organic contamination in chloride-containing water. PMID:22432303

  1. Kindergarten Practitioners' Experience of Promoting Children's Involvement in and Enjoyment of Physically Active Play: Does the Contagion of Physical Energy Affect Physically Active Play?

    ERIC Educational Resources Information Center

    Bjørgen, Kathrine; Svendsen, Birgit

    2015-01-01

    This research is based on interviews that explore the reflections of 10 Norwegian kindergarten practitioners with regard to the importance of their involvement in children's physically active outdoor playtime. The data were analysed from a qualitative phenomenological perspective and resulted in basic themes that describe the practitioners'…

  2. Involvement of Fungal Pectin Methylesterase Activity in the Interaction Between Fusarium graminearum and Wheat.

    PubMed

    Sella, Luca; Castiglioni, Carla; Paccanaro, Maria Chiara; Janni, Michela; Schäfer, Wilhelm; D'Ovidio, Renato; Favaron, Francesco

    2016-04-01

    The genome of Fusarium graminearum, the causal agent of Fusarium head blight of wheat, contains two putative pectin methylesterase (PME)-encoding genes. However, when grown in liquid culture containing pectin, F. graminearum produces only a single PME, which was purified and identified. Its encoding gene, expressed during wheat spike infection, was disrupted by targeted homologous recombination. Two Δpme mutant strains lacked PME activity but were still able to grow on highly methyl-esterified pectin even though their polygalacturonase (PG) activity showed a reduced capacity to depolymerize this substrate. The enzymatic assays performed with purified F. graminearum PG and PME demonstrated an increase in PG activity in the presence of PME on highly methyl-esterified pectin. The virulence of the mutant strains was tested on Triticum aestivum and Triticum durum spikes, and a significant reduction in the percentage of symptomatic spikelets was observed between 7 and 12 days postinfection compared with wild type, demonstrating that the F. graminearum PME contributes to fungal virulence on wheat by promoting spike colonization in the initial and middle stages of infection. In contrast, transgenic wheat plants with increased levels of pectin methyl esterification did not show any increase in resistance to the Δpme mutant, indicating that the infectivity of the fungus relies only to a certain degree on pectin degradation. PMID:26713352

  3. Cell Wall Polymers of Bacillus sphaericus: Activities of Enzymes Involved in Peptidoglycan Precursor Synthesis During Sporulation

    PubMed Central

    Linnett, Paul E.; Tipper, Donald J.

    1974-01-01

    In synchronously sporulating cells of Bacillus sphaericus 9602, the specific activities of those enzymes specifically required for the synthesis of the UDP-N-acetyl-muramyl-pentapeptide precursor of vegetative cell wall peptidoglycan decay by 50% after the end of exponential cell division, probably as a consequence of dilution by newly synthesized protein. The meso-diaminopimelate ligase is the only new activity whose synthesis is required for synthesis of the nucleotide-pentapeptide precursor of spore cortex peptidoglycan. The addition of d-Ala-d-Ala to the nucleotide tripeptide is catalyzed by an enzyme present in both vegetative and sporulating cells, which apparently does not discriminate between lysine- and diaminopimelate-containing acceptors. The activities of the l-Ala and d-Ala-d-Ala ligases and of the d-Ala-d-Ala synthetase increases in parallel with the appearance of the diaminopimelate ligase, indicating coordinate derepression and suggesting operon-like organization of the appropriate structural genes. PMID:4417383

  4. GABAergic neural activity involved in salicylate-induced auditory cortex gain enhancement.

    PubMed

    Lu, J; Lobarinas, E; Deng, A; Goodey, R; Stolzberg, D; Salvi, R J; Sun, W

    2011-08-25

    Although high doses of sodium salicylate impair cochlear function, it paradoxically enhances sound-evoked activity in the auditory cortex (AC) and augments acoustic startle reflex responses, neural and behavioral metrics associated with hyperexcitability and hyperacusis. To explore the neural mechanisms underlying salicylate (SS)-induced hyperexcitability and "increased central gain," we examined the effects of GABA receptor agonists and antagonists on SS-induced hyperexcitability in the AC and startle reflex responses. Consistent with our previous findings, local or systemic application of SS significantly increased the amplitude of sound-evoked AC neural activity, but generally reduced spontaneous activity in the AC. Systemic injection of SS also significantly increased the acoustic startle reflex. S-baclofen or R-baclofen, GABA-B agonists, which suppressed sound-evoked AC neural firing rate and local field potentials, also suppressed the SS-induced enhancement of the AC field potential and the acoustic startle reflex. Local application of vigabatrin, which enhances GABA concentration in the brain, suppressed the SS-induced enhancement of AC firing rate. Systemic injection of vigabatrin also reduced the SS-induced enhancement of acoustic startle reflex. Collectively, these results suggest that the sound-evoked behavioral and neural hyperactivity induced by SS may arise from a SS-induced suppression of GABAergic inhibition in the AC. PMID:21664433

  5. Endogenous nitric oxide accumulation is involved in the antifungal activity of Shikonin against Candida albicans.

    PubMed

    Liao, Zebin; Yan, Yu; Dong, Huaihuai; Zhu, Zhenyu; Jiang, Yuanying; Cao, Yingying

    2016-01-01

    The aim of the present study was to investigate the role of nitric oxide (NO) in the antifungal activity of Shikonin (SK) against Candida albicans (C. albicans) and to clarify the underlying mechanism. The results showed that the NO donors S-nitrosoglutathione (GSNO) and L-arginine could enhance the antifungal activity of SK, whereas the NO production inhibitor Nω-nitro-L-arginine methyl ester (L-NAME) attenuated antifungal action. Using the fluorescent dye 3-amino,4-aminomethyl-2', 7-difluorescein, diacetate (DAF-FM DA), we found that the accumulation of NO in C. albicans was increased markedly by SK in a time- and dose-dependent manner. In addition, the results of real-time reverse transcription-PCR (RT-PCR) demonstrated that the transcription level of YHB1 in C. albicans was greatly increased upon incubation of SK. Consistently, the YHB1-null mutant (yhb1Δ/Δ) exhibited a higher susceptibility to SK than wild-type cells. In addition, although the transcription level of CTA4 in C. albicans was not significantly changed when exposed to SK, the CTA4-null mutant (cta4Δ/Δ) was more susceptible to SK. Collectively, SK is the agent found to execute its antifungal activity directly via endogenous NO accumulation, and NO-mediated damage is related to the suppression of YHB1 and the function of CTA4. PMID:27530748

  6. Gene-Specific Involvement of β-Oxidation in Wound-Activated Responses in Arabidopsis1

    PubMed Central

    Castillo, M. Cruz; Martínez, Cristina; Buchala, Antony; Métraux, Jean-Pierre; León, José

    2004-01-01

    The coordinated induced expression of β-oxidation genes is essential to provide the energy supply for germination and postgerminative development. However, very little is known about other functions of β-oxidation in nonreserve organs. We have identified a gene-specific pattern of induced β-oxidation gene expression in wounded leaves of Arabidopsis. Mechanical damage triggered the local and systemic induction of only ACX1 among acyl-coenzyme A oxidase (ACX) genes, and KAT2/PED1 among 3-ketoacyl-coenzyme A thiolase (KAT) genes in Arabidopsis. In turn, wounding induced KAT5/PKT2 only systemically. Although most of the β-oxidation genes were activated by wound-related factors such as dehydration and abscisic acid, jasmonic acid (JA) induced only ACX1 and KAT5. Reduced expression of ACX1 or KAT2 genes, in transgenic plants expressing their corresponding mRNAs in antisense orientation, correlated with defective wound-activated synthesis of JA and with reduced expression of JA-responsive genes. Induced expression of JA-responsive genes by exogenous application of JA was unaffected in those transgenic plants, suggesting that ACX1 and KAT2 play a major role in driving wound-activated responses by participating in the biosynthesis of JA in wounded Arabidopsis plants. PMID:15141068

  7. Novel DNA mismatch repair activity involving YB-1 in human mitochondria

    PubMed Central

    de Souza-Pinto, Nadja C.; Mason, Penelope A.; Hashiguchi, Kazunari; Weissman, Lior; Tian, Jingyan; Guay, David; Lebel, Michel; Stevnsner, Tinna V.; Rasmussen, Lene Juel; Bohr, Vilhelm A.

    2009-01-01

    Maintenance of the mitochondrial genome (mtDNA) is essential for proper cellular function. The accumulation of damage and mutations in the mtDNA leads to diseases, cancer, and aging. Mammalian mitochondria have proficient base excision repair, but the existence of other DNA repair pathways is still unclear. Deficiencies in DNA mismatch repair (MMR), which corrects base mismatches and small loops, are associated with DNA microsatellite instability, accumulation of mutations, and cancer. MMR proteins have been identified in yeast and coral mitochondria; however, MMR proteins and function have not yet been detected in human mitochondria. Here we show that human mitochondria have a robust mismatch-repair activity, which is distinct from nuclear MMR. Key nuclear MMR factors were not detected in mitochondria, and similar mismatch-binding activity was observed in mitochondrial extracts from cells lacking MSH2, suggesting distinctive pathways for nuclear and mitochondrial MMR. We identified the repair factor YB-1 as a key candidate for a mitochondrial mismatch-binding protein. This protein localizes to mitochondria in human cells, and contributes significantly to the mismatch-binding and mismatch-repair activity detected in HeLa mitochondrial extracts, which are significantly decreased when the intracellular levels of YB-1 are diminished. Moreover, YB-1 depletion in cells increases mitochondrial DNA mutagenesis. Our results show that human mitochondria contain a functional MMR repair pathway in which YB-1 participates, likely in the mismatch binding and recognition steps. PMID:19272840

  8. Activism and Leadership Development: Examining the Relationship between College Student Activism Involvement and Socially Responsible Leadership Capacity

    ERIC Educational Resources Information Center

    Page, Jeremy Dale

    2010-01-01

    The purpose of this study was to examine the relationship between participation in student activism and leadership development among college students. This study applied the social change model of leadership development (SCM) as the theoretical model used to measure socially responsible leadership capacity in students. The study utilized data…

  9. ENVIRONMENTALLY BENIGN MITIGATION OF MICROBIOLOGICALLY INFLUENCED CORROSION (MIC)

    SciTech Connect

    John J. Kilbane II; William Bogan

    2004-01-31

    The overall program objective is to develop and evaluate environmentally benign agents or products that are effective in the prevention, inhibition, and mitigation of microbially influenced corrosion (MIC) in the internal surfaces of metallic natural gas pipelines. The goal is to develop one or more environmentally benign (a.k.a. ''green'') products that can be applied to maintain the structure and dependability of the natural gas infrastructure. The technical approach for this quarter included the fractionation of extracts prepared from several varieties of pepper plants, and using several solvents, by high performance liquid chromatography (HPLC). A preliminary determination of antimicrobial activities of the new extracts and fractions using a growth inhibition assay, and evaluation of the extracts ability to inhibit biofilm formation was also performed. The analysis of multiple extracts of pepper plants and fractions of extracts of pepper plants obtained by HPLC illustrated that these extracts and fractions are extremely complex mixtures of chemicals. Gas chromatography-mass spectrometry was used to identify the chemical constituents of these extracts and fractions to the greatest degree possible. Analysis of the chemical composition of various extracts of pepper plants has illustrated the complexity of the chemical mixtures present, and while additional work will be performed to further characterize the extracts to identify bioactive compounds the focus of efforts should now shift to an evaluation of the ability of extracts to inhibit corrosion in mixed culture biofilms, and in pure cultures of bacterial types which are known or believed to be important in corrosion.

  10. ENVIRONMENTAL BENIGN MITIGATION OF MICROBIOLOGICALLY INFLUENCED CORROSION (MIC)

    SciTech Connect

    J.R. Paterek; G. Husmillo

    2002-11-01

    The overall program objective is to develop and evaluate environmental benign agents or products that are effective in the prevention, inhibition, and mitigation of microbially influenced corrosion (MIC) in the internal surfaces of metallic natural gas pipelines. The goal is one or more environmental benign, a.k.a. ''green'' products that can be applied to maintain the structure and dependability of the natural gas infrastructure. The technical approach for this quarter were monitoring the development of Desulfovibrio species biofilm using the continuous flow cell system, evaluation of pepper compounds by microtiter plate assay for mitigating and inhibiting biofilm formation, and testing the effective concentrations to verify the extent of corrosion on metal coupons. Biofilm formation of Desulfovibrio vulgaris and D. desulfuricans was monitored and documented over a 7-day period. The use of a continuous flow cell system proved to be efficient and non-destructive in studying biofilm growth. Live/Dead BacLight was an efficient stain to determine cell viability. The extracts showed 9-25% biofilm formation inhibition against the two organisms, and 18-19% activity in detaching the already formed biofilm. Preliminary data were obtained on the extent of corrosion of metal coupons when treated with pepper extracts as against the untreated ones. Confirmatory tests are underway. A presentation was prepared and give at the US DOE NETL meeting on gas and petroleum infrastructure. The presentation is include as an addition to this report.

  11. Sertoliform cystadenoma: a rare benign tumour of the rete testis

    PubMed Central

    2013-01-01

    Abstract Sertoliform cystadenoma of the rete testis represents an uncommon benign tumour. They appear in patients from 26 to 62 years of age. We describe a case of a 66-year-old man with a tumour in the area of the epididymal head. The tumour markers were not increased. Under the assumption of a malignant testicular tumour an inguinal orchiectomy was performed. The cut surface of this tumour was of grey/white color and showed small cysts. The tumour consisted of two compartments. The epithelial like tumour cells showed a sertoliform growth pattern and cystic dilatations. In between the tumour cells repeatedly actin expressing sclerotic areas could be recognized as the second tumour component. Proliferative activity was not increased. Immunohistochemically the tumour cells were positiv for inhibin, S-100, and CD 99. Alpha feto protein (AFP), human chorionic gonadotropin (ß-HCG) and placental alkaline phosphatase (PLAP) as well as synaptophysin, epithelial membrane antigene (EMA), and BCL-2 were not expressed. As far as we know this is the sixth reported case of this tumour. Because of the benign nature of this tumour the correct diagnosis is important for the intra- and postoperative management. Here we present a case of this rare tumour and discuss potential differential diagnosis. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1956026143857335 PMID:23406299

  12. Mammary blood flow and metabolic activity are linked by a feedback mechanism involving nitric oxide synthesis.

    PubMed

    Cieslar, S R L; Madsen, T G; Purdie, N G; Trout, D R; Osborne, V R; Cant, J P

    2014-01-01

    To test which, if any, of the major milk precursors can elicit a rapid change in the rate of mammary blood flow (MBF) and to define the time course and magnitude of such changes, 4 lactating cows were infused with glucose, amino acids, or triacylglycerol into the external iliac artery feeding one udder half while iliac plasma flow (IPF) was monitored continuously by dye dilution. Adenosine and saline were infused as positive and negative controls, respectively, and insulin was infused to characterize the response to a centrally produced anabolic hormone. To test the roles of cyclooxygenase, NO synthase and ATP-sensitive K (KATP) channels in nutrient-mediated changes in blood flow, their respective inhibitors-indomethacin, Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), and glibenclamide-were infused simultaneously with glucose. Each day, 1 infusate was given twice to each cow, over a 20-min period each time, separated by a 20-min washout period. In addition, each treatment protocol was administered on 2 separate days. A 73% increase in IPF during adenosine infusion showed that the mammary vasodilatory response was quadratic in time, with most changes occurring in the first 5min. Glucose infusion decreased IPF by 9% in a quadratic manner, most rapidly in the first 5min, indicating that a feedback mechanism of local blood flow control, likely through adenosine release, was operative in the mammary vasculature. Amino acid infusion increased IPF 9% in a linear manner, suggesting that mammary ATP utilization was stimulated more than ATP production. This could reflect a stimulation of protein synthesis. Triacylglycerol only tended to decrease IPF and insulin did not affect IPF. A lack of IPF response to glibenclamide indicates that KATP channels are not involved in MBF regulation. Indomethacin and L-NAME both depressed IPF. In the presence of indomethacin, glucose infusion caused a quadratic 9% increase in IPF. Indomethacin is an inhibitor of mitochondrial

  13. Involvement of protein kinase C and IP3-mediated Ca2+ release in activity modulation by paraoxon in snail neurons.

    PubMed

    Vatanparast, Jafar; Janahmadi, Mahyar; Asgari, Ali Reza

    2007-10-01

    We have previously reported that paraoxon, an organophosphate compound, at submicromolar concentrations effectively suppresses Ca2+ action potentials and modulates the activity of snail neurons. This effect was unrelated to acetylcholinesterase inhibition but was found to involve the direct or indirect modulation of ion channels [Vatanparast, J., Janahmadi, M., Asgari, A.R., Sepehri, H., Haeri-Rohani, A., 2006a. Paraoxon suppresses Ca2+ action potential and afterhyperpolarization in snail neurons: Relevance to the hyperexcitability induction. Brain Res. 1083 (1), 110-117]. In the present work, the interaction of paraoxon with protein kinase C (PKC) and inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ release, on the modulation of Ca2+ action potentials and neuronal activity was investigated. Phorbol 12, 13 dibutyrate (PdBu), the activator of PKC, suppressed afterhyperpolarization and increased the activity of snail neurons without any significant effect on the Ca2+ action potential duration. Pretreatment with PKC activator attenuated the suppressing effect of paraoxon on the duration of Ca2+ action potentials. Staurosporine, a selective blocker of PKC, did not block the effect of paraoxon on Ca2+ action potential suppression and hyperexcitability induction. Our findings did not support the involvement PKC in the paraoxon induced Ca2+ action potential suppression and neuronal activity modulation, although activation of this protein kinase could attenuate some effects of paraoxon. Pretreatment with 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8), an antagonist of IP3-mediated Ca2+ release, abolished the secondary silencing effect of paraoxon, which is observed after primary paraoxon-induced hyperexcitability. It was concluded that slow activation of intracellular cascades by paraoxon could induce an IP3 mediated Ca2+ release from intracellular stores and participate to its secondary silencing effect by mechanisms dependent on intracellular

  14. Belinostat-induced apoptosis and growth inhibition in pancreatic cancer cells involve activation of TAK1-AMPK signaling axis

    SciTech Connect

    Wang, Bing Wang, Xin-bao; Chen, Li-yu; Huang, Ling; Dong, Rui-zen

    2013-07-19

    Highlights: •Belinostat activates AMPK in cultured pancreatic cancer cells. •Activation of AMPK is important for belinostat-induced cytotoxic effects. •ROS and TAK1 are involved in belinostat-induced AMPK activation. •AMPK activation mediates mTOR inhibition by belinostat. -- Abstract: Pancreatic cancer accounts for more than 250,000 deaths worldwide each year. Recent studies have shown that belinostat, a novel pan histone deacetylases inhibitor (HDACi) induces apoptosis and growth inhibition in pancreatic cancer cells. However, the underlying mechanisms are not fully understood. In the current study, we found that AMP-activated protein kinase (AMPK) activation was required for belinostat-induced apoptosis and anti-proliferation in PANC-1 pancreatic cancer cells. A significant AMPK activation was induced by belinostat in PANC-1 cells. Inhibition of AMPK by RNAi knockdown or dominant negative (DN) mutation significantly inhibited belinostat-induced apoptosis in PANC-1 cells. Reversely, AMPK activator AICAR and A-769662 exerted strong cytotoxicity in PANC-1 cells. Belinostat promoted reactive oxygen species (ROS) production in PANC-1 cells, increased ROS induced transforming growth factor-β-activating kinase 1 (TAK1)/AMPK association to activate AMPK. Meanwhile, anti-oxidants N-Acetyl-Cysteine (NAC) and MnTBAP as well as TAK1 shRNA knockdown suppressed belinostat-induced AMPK activation and PANC-1 cell apoptosis. In conclusion, we propose that belinostat-induced apoptosis and growth inhibition require the activation of ROS-TAK1-AMPK signaling axis in cultured pancreatic cancer cells.

  15. Involvement of PRMT1 in hnRNPQ activation and internalization of insulin receptor

    SciTech Connect

    Iwasaki, Hiroaki

    2008-07-25

    Insulin signaling in skeletal L6 myotubes is known to be affected by arginine methylation catalyzed by protein N-arginine methyltransferase 1 (PRMT1), however, the mechanism by which this occurs has not yet been defined. This study aimed to determine the exact substrate involved in the methylation and regulating insulin signaling in cells. Insulin enhanced arginine methylation of a 66-kDa protein (p66) concomitant with translocation of PRMT1 to the membrane fraction. Peptide mass fingerprinting identified p66 as a heterogeneous nuclear ribonucleoprotein, hnRNPQ that was bound to and methylated by PRMT1. Pharmacological inhibition of methylation (MTA) and small interfering RNA against PRMT1 (PRMT1-siRNA) attenuated insulin-stimulated tyrosine phosphorylation of hnRNPQ and insulin receptor (IR), and the interaction between hnRNPQ and IR. MTA, PRMT1-siRNA, and hnRNPQ-siRNA inhibited internalization of IR in the same manner. These data suggest that the PRMT1-mediated methylation of hnRNPQ is implicated in IR trafficking and insulin signaling in skeletal L6 myotubes.

  16. Identification of novel transcriptional regulators involved in macrophage differentiation and activation in U937 cells

    PubMed Central

    Baek, Young-Sook; Haas, Stefan; Hackstein, Holger; Bein, Gregor; Hernandez-Santana, Maria; Lehrach, Hans; Sauer, Sascha; Seitz, Harald

    2009-01-01

    Background Monocytes and macrophages play essential role in innate immunity. Understanding the underlying mechanism of macrophage differentiation and the identification of regulatory mechanisms will help to find new strategies to prevent their harmful effects in chronic inflammatory diseases and sepsis. Results Maturation of blood monocytes into tissue macrophages and subsequent inflammatory response was mimicked in U937 cells of human histocytic lymphoma origin. Whole genome array analysis was employed to evaluate gene expression profile to identify underlying transcriptional networks implicated during the processes of differentiation and inflammation. In addition to already known transcription factors (i.e. MAFB, EGR, IRF, BCL6, NFkB, AP1, Nur77), gene expression analysis further revealed novel genes (i.e. MEF2, BRI, HLX, HDAC5, H2AV, TCF7L2, NFIL3) previously uncharacterized to be involved in the differentiation process. A total of 58 selected genes representing cytokines, chemokines, surface antigens, signaling molecules and transcription factors were validated by real time PCR and compared to primary monocyte-derived macrophages. Beside the verification of several new genes, the comparison reveals individual heterogeneity of blood donors. Conclusion Up regulation of MEF2 family, HDACs, and H2AV during cell differentiation and inflammation sheds new lights onto regulation events on transcriptional and epigenetic level controlling these processes. Data generated will serve as a source for further investigation of macrophages differentiation pathways and related biological responses. PMID:19341462

  17. Fast Photochromism Involving Thermally-Activated Valence Isomerization of Phenoxyl-Imidazolyl Radical Complex Derivatives.

    PubMed

    Kobayashi, Yoichi; Shima, Kentaro; Mutoh, Katsuya; Abe, Jiro

    2016-08-18

    Open-shell biradicals have received considerable attention in material science because of their high two-photon absorption cross sections and broad and high absorptive features over the visible region. However, the instability of the biradical caused by the open-shell nature was one of the drawbacks; therefore, novel radical compounds which can suppress unwanted reactions by tuning the open-shell features are desired to expand the versatility of the radical compounds. Here, we report a novel radical-dissociation-type photochromic compound whose photochromic reaction involves a valence isomerization from the open-shell biradical to closed-shell quinoidal forms by using a phenoxyl-imidazolyl radical complex framework. The valence isomerization from the biradical to quinoid forms effectively tunes the open-shell feature in time and drastically changes the spectral features, which were revealed by time-resolved Fourier transform infrared spectroscopy. This novel fast photochromic property not only is important for fundamental spin chemistry but also expands the versatility of the radical compounds for novel advanced photofunctional materials. PMID:27454008

  18. Two-step mechanism involving active-site conformational changes regulates human telomerase DNA binding.

    PubMed

    Tomlinson, Christopher G; Moye, Aaron L; Holien, Jessica K; Parker, Michael W; Cohen, Scott B; Bryan, Tracy M

    2015-01-15

    The ribonucleoprotein enzyme telomerase maintains telomeres and is essential for cellular immortality in most cancers. Insight into the telomerase mechanism can be gained from syndromes such as dyskeratosis congenita, in which mutation of telomerase components manifests in telomere dysfunction. We carried out detailed kinetic and thermodynamic analyses of wild-type telomerase and two disease-associated mutations in the reverse transcriptase domain. Differences in dissociation rates between primers with different 3' ends were independent of DNA affinities, revealing that initial binding of telomerase to telomeric DNA occurs through a previously undescribed two-step mechanism involving enzyme conformational changes. Both mutations affected DNA binding, but through different mechanisms: P704S specifically affected protein conformational changes during DNA binding, whereas R865H showed defects in binding to the 3' region of the DNA. To gain further insight at the structural level, we generated the first homology model of the human telomerase reverse transcriptase domain; the positions of P704S and R865H corroborate their observed mechanistic defects, providing validation for the structural model. Our data reveal the importance of protein interactions with the 3' end of telomeric DNA and the role of protein conformational change in telomerase DNA binding, and highlight naturally occurring disease mutations as a rich source of mechanistic insight. PMID:25365545

  19. Regulation of human CYP2C9 expression by electrophilic stress involves activator protein 1 activation and DNA looping.

    PubMed

    Makia, Ngome L; Surapureddi, Sailesh; Monostory, Katalin; Prough, Russell A; Goldstein, Joyce A

    2014-08-01

    Cytochrome P450 (CYP)2C9 and CYP2C19 are important human enzymes that metabolize therapeutic drugs, environmental chemicals, and physiologically important endogenous compounds. Initial studies using primary human hepatocytes showed induction of both the CYP2C9 and CYP2C19 genes by tert-butylhydroquinone (tBHQ). As a pro-oxidant, tBHQ regulates the expression of cytoprotective genes by activation of redox-sensing transcription factors, such as the nuclear factor E2-related factor 2 (Nrf2) and members of the activator protein 1 (AP-1) family of proteins. The promoter region of CYP2C9 contains two putative AP-1 sites (TGAGTCA) at positions -2201 and -1930, which are also highly conserved in CYP2C19. The CYP2C9 promoter is activated by ectopic expression of cFos and JunD, whereas Nrf2 had no effect. Using specific kinase inhibitors for mitogen-activated protein kinase, we showed that extracellular signal-regulated kinase and Jun N-terminal kinase are essential for tBHQ-induced expression of CYP2C9. Electrophoretic mobility shift assays demonstrate that cFos distinctly interacts with the distal AP-1 site and JunD with the proximal site. Because cFos regulates target genes as heterodimers with Jun proteins, we hypothesized that DNA looping might be required to bring the distal and proximal AP-1 sites together to activate the CYP2C9 promoter. Chromosome conformation capture analyses confirmed the formation of a DNA loop in the CYP2C9 promoter, possibly allowing interaction between cFos at the distal site and JunD at the proximal site to activate CYP2C9 transcription in response to electrophiles. These results indicate that oxidative stress generated by exposure to electrophilic xenobiotics and metabolites induces the expression of CYP2C9 and CYP2C19 in human hepatocytes. PMID:24830941

  20. Clarithromycin Culprit of Benign Intracranial Hypertension

    PubMed Central

    Khan, Habib Rehman; Mason, Colin; Mulcahy, Riona

    2015-01-01

    Benign intracranial hypertension is characterized with increase in CSF opening pressure with no specific etiology. It is predominantly found in women of child bearing age and particularly in individuals with obesity. Visual disturbances or loss and associated headaches are common and can lead to blindness if left untreated. Diagnosis can be achieved once other causes of visual loss, headaches and high opening pressures are excluded. Management consists of serial optic disc assessments although no specific treatment is available despite recent trials using carbonic anhydrase inhibitors. Diet modification and weight management can help in therapy. PMID:26713029

  1. OTC tamsulosin for benign prostatic hyperplasia.

    PubMed

    2010-10-01

    Earlier this year, tamsulosin, an alpha blocker previously only available on prescription, became available for sale by pharmacists as a treatment for functional symptoms of benign prostatic hyperplasia (BPH) in men aged 45-75 years (Flomax Relief MR - Boehringer Ingelheim). A television advert for the over-the-counter (OTC) product claims that it is a "simple and effective" treatment that can relieve symptoms within 1 week, allowing the user to "take control of your annoying pee problems".¹ Here we review the evidence on tamsulosin and assess whether its availability as an OTC product confers worthwhile advantages. PMID:20926447

  2. Models for studying benign prostatic hyperplasia.

    PubMed

    Mahapokai, W; Van Sluijs, F J; Schalken, J A

    2000-07-01

    Benign prostatic hyperplasia (BPH) is one of the most common diseases affecting aging man. Attempts have been made to clarify the etiology and pathogenesis and, to that end, experimental models have been developed. To date, in vitro and in vivo models have been used, depending on the concept of the study. Spontaneous animal models are limited to the chimpanzee and the dog. Ethical and financial factors restrict the applicability of these models. The hormonal-induced canine BPH model is a good alternative that closely resembles human BPH in many aspects. The experimental models currently used for studying BPH are reviewed. Prostate Cancer and Prostatic Diseases (2000) 3, 28-33 PMID:12497158

  3. Benign schwannoma of the maxillary antrum

    PubMed Central

    Hegde, Oshin; Desai, Dinkar; Bhandarkar, Gowri P.; Paul, Tony

    2016-01-01

    Schwannoma also known commonly as neurilemmoma and schwann cell tumor is a benign nerve sheath tumor. About 1/3rd cases of schwannoma arise from the head and neck region but rarely from the nasal and paranasal sinuses. The recurrence rate in these cases has reported to be very rare. We report a rare case of schwannoma in a 60-year-old woman arising from the maxillary sinus further eroding the orbital floor and nasal bone. We have also described the clinical presentation, radiological, histological findings, and management of the case. PMID:27095911

  4. Endoscopic management of benign biliary strictures

    PubMed Central

    Visrodia, Kavel H; Tabibian, James H; Baron, Todd H

    2015-01-01

    Endoscopic management of biliary obstruction has evolved tremendously since the introduction of flexible fiberoptic endoscopes over 50 years ago. For the last several decades, endoscopic retrograde cholangiopancreatography (ERCP) has become established as the mainstay for definitively diagnosing and relieving biliary obstruction. In addition, and more recently, endoscopic ultrasonography (EUS) has gained increasing favor as an auxiliary diagnostic and therapeutic modality in facilitating decompression of the biliary tree. Here, we provide a review of the current and continually evolving role of gastrointestinal endoscopy, including both ERCP and EUS, in the management of biliary obstruction with a focus on benign biliary strictures. PMID:26322153

  5. Functional domains of the human orphan receptor ARP-1/COUP-TFII involved in active repression and transrepression.

    PubMed

    Achatz, G; Hölzl, B; Speckmayer, R; Hauser, C; Sandhofer, F; Paulweber, B

    1997-09-01

    The orphan receptor ARP-1/COUP-TFII, a member of the chicken ovalbumin upstream promoter transcription factor (COUP-TF) subfamily of nuclear receptors, strongly represses transcriptional activity of numerous genes, including several apolipoprotein-encoding genes. Recently it has been demonstrated that the mechanism by which COUP-TFs reduce transcriptional activity involves active repression and transrepression. To map the domains of ARP-1/COUP-TFII required for repressor activity, a detailed deletion analysis of the protein was performed. Chimeric proteins in which various segments of the ARP-1/COUP-TFII carboxy terminus were fused to the GAL4 DNA binding domain were used to characterize its active repression domain. The smallest segment confering active repressor activity to a heterologous DNA binding domain was found to comprise residues 210 to 414. This domain encompasses the region of ARP-1/COUP-TFII corresponding to helices 3 to 12 in the recently published crystal structure of other members of the nuclear receptor superfamily. It includes the AF-2 AD core domain formed by helix 12 but not the hinge region, which is essential for interaction with a corepressor in the case of the thyroid hormone and retinoic acid receptor. Attachment of the nuclear localization signal from the simian virus 40 large T antigen (Flu tag) to the amino terminus of ARP-1/COUP-TFII abolished its ability to bind to DNA without affecting its repressor activity. By using a series of Flu-tagged mutants, the domains required for transrepressor activity of the protein were mapped. They include the DNA binding domain and the segment spanning residues 193 to 399. Transcriptional activity induced by liver-enriched transactivators such as hepatocyte nuclear factor 3 (HNF-3), C/EBP, or HNF-4 was repressed by ARP-1/COUP-TFII independent of the presence of its cognate binding site, while basal transcription or transcriptional activity induced by ATF or Sp1 was not perturbed by the protein. In

  6. Functional domains of the human orphan receptor ARP-1/COUP-TFII involved in active repression and transrepression.

    PubMed Central

    Achatz, G; Hölzl, B; Speckmayer, R; Hauser, C; Sandhofer, F; Paulweber, B

    1997-01-01

    The orphan receptor ARP-1/COUP-TFII, a member of the chicken ovalbumin upstream promoter transcription factor (COUP-TF) subfamily of nuclear receptors, strongly represses transcriptional activity of numerous genes, including several apolipoprotein-encoding genes. Recently it has been demonstrated that the mechanism by which COUP-TFs reduce transcriptional activity involves active repression and transrepression. To map the domains of ARP-1/COUP-TFII required for repressor activity, a detailed deletion analysis of the protein was performed. Chimeric proteins in which various segments of the ARP-1/COUP-TFII carboxy terminus were fused to the GAL4 DNA binding domain were used to characterize its active repression domain. The smallest segment confering active repressor activity to a heterologous DNA binding domain was found to comprise residues 210 to 414. This domain encompasses the region of ARP-1/COUP-TFII corresponding to helices 3 to 12 in the recently published crystal structure of other members of the nuclear receptor superfamily. It includes the AF-2 AD core domain formed by helix 12 but not the hinge region, which is essential for interaction with a corepressor in the case of the thyroid hormone and retinoic acid receptor. Attachment of the nuclear localization signal from the simian virus 40 large T antigen (Flu tag) to the amino terminus of ARP-1/COUP-TFII abolished its ability to bind to DNA without affecting its repressor activity. By using a series of Flu-tagged mutants, the domains required for transrepressor activity of the protein were mapped. They include the DNA binding domain and the segment spanning residues 193 to 399. Transcriptional activity induced by liver-enriched transactivators such as hepatocyte nuclear factor 3 (HNF-3), C/EBP, or HNF-4 was repressed by ARP-1/COUP-TFII independent of the presence of its cognate binding site, while basal transcription or transcriptional activity induced by ATF or Sp1 was not perturbed by the protein. In

  7. The gastroprotective effect of menthol: involvement of anti-apoptotic, antioxidant and anti-inflammatory activities.

    PubMed

    Rozza, Ariane Leite; Meira de Faria, Felipe; Souza Brito, Alba Regina; Pellizzon, Cláudia Helena

    2014-01-01

    The aim of this research was to investigate the anti-apoptotic, antioxidant and anti-inflammatory properties of menthol against ethanol-induced gastric ulcers in rats. Wistar rats were orally treated with vehicle, carbenoxolone (100 mg/kg) or menthol (50 mg/kg) and then treated with ethanol to induce gastric ulcers. After euthanasia, stomach samples were prepared for histological slides and biochemical analyses. Immunohistochemical analyses of the cytoprotective and anti-apoptotic heat-shock protein-70 (HSP-70) and the apoptotic Bax protein were performed. The neutrophils were manually counted. The activity of the myeloperoxidase (MPO) was measured. To determine the level of antioxidant functions, the levels of glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione reductase (GR) and superoxide dismutase (SOD) were measured using ELISA. The levels of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and the anti-inflammatory cytokine interleukin-10 (IL-10) were assessed using ELISA kits. The menthol treated group presented 92% gastroprotection compared to the vehicle-treated group. An increased immunolabeled area was observed for HSP-70, and a decreased immunolabeled area was observed for the Bax protein in the menthol treated group. Menthol treatment induced a decrease in the activity of MPO and SOD, and the protein levels of GSH, GSH-Px and GR were increased. There was also a decrease in the levels of TNF-α and IL-6 and an increase in the level of IL-10. In conclusion, oral treatment with menthol displayed a gastroprotective activity through anti-apoptotic, antixidant and anti-inflammatory mechanisms. PMID:24466200

  8. Pseudomonas aeruginosa wound infection involves activation of its iron acquisition system in response to fascial contact

    PubMed Central

    Kim, M.; Christley, S.; Khodarev, N. N.; Fleming, I.; Huang, Y.; Chang, E.; Zaborina, O.; Alverdy, J.

    2015-01-01

    Background Wound infections are traditionally thought to occur when microbial burden exceeds the innate clearance capacity of host immune system. Here we introduce the idea that the wound environment itself plays a significant contributory role to wound infection. Methods We developed a clinically relevant murine model of soft tissue infection to explore the role of activation of microbial virulence in response to tissue factors as a mechanism by which pathogenic bacteria cause wound infections. Mice underwent abdominal skin incision and light muscle injury with a crushing forceps versus skin incision alone followed by topical inoculation of P. aeruginosa. Mice were sacrificed on postoperative day 6 and abdominal tissues analyzed for clinical signs of wound infection. To determine if specific wound tissues components induce bacterial virulence, P. aeruginosa was exposed to skin, fascia, and muscle. Results Gross wound infection due to P. aeruginosa was observed to be significantly increased in injured tissues vs non-injured (80% vs 10%) tissues (n=20/group, p<0.0001). Exposure of P. aeruginosa to individual tissue components demonstrated that fascia significantly induced bacterial virulence as judged by the production of pyocyanin, a redox-active phenazine compound known to kill immune cells. Whole genome transcriptional profiling of P. aeruginosa exposed to fascia demonstrated activation of multiple genes responsible for the synthesis of the iron scavenging molecule pyochelin. Conclusion We conclude that wound elements, in particular fascia, may play a significant role in enhancing the virulence of P. aeruginosa and may contribute to the pathogenesis of clinical wound infection. PMID:25807409

  9. Pb-inhibited mitotic activity in onion roots involves DNA damage and disruption of oxidative metabolism.

    PubMed

    Kaur, Gurpreet; Singh, Harminder Pal; Batish, Daizy Rani; Kohli, Ravinder Kumar

    2014-09-01

    Plant responses to abiotic stress significantly affect the development of cells, tissues and organs. However, no studies correlating Pb-induced mitotic inhibition and DNA damage and the alterations in redox homeostasis during root division per se were found in the literature. Therefore, an experiment was conducted to evaluate the impact of Pb on mitotic activity and the associated changes in the oxidative metabolism in onion roots. The cytotoxic effect of Pb on cell division was assessed in the root meristems of Allium cepa (onion). The mitotic index (MI) was calculated and chromosomal abnormalities were sought. Pb-treatment induced a dose-dependent decrease in MI in the onion root tips and caused mitotic abnormalities such as distorted metaphase, fragments, sticky chromosomes, laggards, vagrant chromosomes and bridges. Single Cell Gel Electrophoresis was also performed to evaluate Pb induced genotoxicity. It was accompanied by altered oxidative metabolism in the onion root tips suggesting the interference of Pb with the redox homeostasis during cell division. There was a higher accumulation of malondialdehyde, conjugated dienes and hydrogen peroxide, and a significant increase in the activities of superoxide dismutases, ascorbate peroxidases, guaiacol peroxidases and glutathione reductases in Pb-treated onion roots, whereas catalases activity exhibited a decreasing pattern upon Pb exposure. The study concludes that Pb-induced cytotoxicity and genotoxicity in the onion roots is mediated through ROS and is also tightly linked to the cell cycle. The exposure to higher concentrations arrested cell cycle leading to cell death, whereas different repair responses are generated at lower concentrations, thereby allowing the cell to complete the cell cycle. PMID:25023386

  10. Enhanced spontaneous locomotor activity in bovine GH transgenic mice involves peripheral mechanisms.

    PubMed

    Bohlooly-Y, M; Olsson, B; Gritli-Linde, A; Brusehed, O; Isaksson, O G; Ohlsson, C; Söderpalm, B; Törnell, J; Ola, B

    2001-10-01

    Clinical and experimental studies indicate a role for GH in mechanisms related to anhedonia/hedonia, psychic energy, and reward. Recently we showed that transgenic mice with general overexpression of bovine GH display increased spontaneous locomotor activity. In the present study, we investigated whether this behavioral change is owing to a direct action of GH in the central nervous system or to peripheral GH actions. A transgenic construct, containing the glial fibrillary acidic protein promoter directing specific expression of bovine GH to the central nervous system, was designed. The central nervous system-specific expression of bovine GH in the glial fibrillary acidic protein-bovine GH transgenic mice was confirmed, but no effect on spontaneous locomotor activity was observed. Serum bovine GH levels were increased in glial fibrillary acidic protein-bovine GH transgenic mice but clearly lower than in transgenic mice with general overexpression of bovine GH. In contrast to the transgenic mice with general overexpression of bovine GH, glial fibrillary acidic protein-bovine GH mice did not display any difference in serum IGF-I levels. The levels of free T(3) and the conversion of the free T(4) to free T(3) were only increased in transgenic mice with general overexpression of bovine GH, but serum corticosterone levels were similarly increased in both transgenic models. These results suggest that free T(3) and/or IGF-I, affecting dopamine and serotonin systems in the central nervous system, may mediate the enhanced locomotor activity observed in transgenic mice with general overexpression of bovine GH. PMID:11564723

  11. Involvement of p38 MAPK in the Anticancer Activity of Cultivated Cordyceps militaris.

    PubMed

    Chou, Shang-Min; Lai, Wan-Jung; Hong, Tzuwen; Tsai, Sheng-Hong; Chen, Yen-Hsun; Kao, Cheng-Hsiang; Chu, Richard; Shen, Tang-Long; Li, Tsai-Kun

    2015-01-01

    Cordyceps militaris is a traditional Chinese medicine frequently used for tonic and therapeutic purposes. Reports from our laboratory and others have demonstrated that extracts of the cultivated fruiting bodies of C. militaris (CM) exhibit a potent cytotoxic effect against many cancer cell lines, especially human leukemia cells. Here, we further investigated the underlying mechanism through which CM is cytotoxic to cancer cells. The CM-mediated induction of PARP cleavage and its related DNA damage signal (γH2AX) was diminished by caspase inhibitor I. In contrast, a ROS scavenger failed to prevent CM-mediated leukemia cell death. Moreover, two signaling molecules, AKT and p38 MAPK, were activated during the course of apoptosis induction. Employing MTT analysis, we found that a p38 MAPK inhibitor but not an AKT inhibitor could rescue cells from CM-mediated cell death, as well as inhibit the cleavage of PARP, formation of apoptotic bodies and up-regulation of the γH2AX signal. These results suggest that CM-mediated leukemia cell death occurs through the activation of the p38 MAPK pathway, indicating its potential therapeutic effects against human leukemia. PMID:26205966

  12. Adolescent pathways to adulthood drinking: sport activity involvement is not necessarily risky or protective

    PubMed Central

    Peck, Stephen C.; Vida, Mina; Eccles, Jacquelynne S.

    2015-01-01

    Aims Use pattern-centered methods to examine how adolescents’ alcohol use and sports activities are related both to childhood sport and problem behavior and to heavy drinking in early adulthood. Design The data used in this study come from four waves of the Michigan Study of Adolescent Life Transitions (MSALT) that began in 1983, when participants were approximately age 12, and continued into early adulthood, when participants were approximately age 28. Participants Sixty per cent of the approximately 1000 MSALT youth living in south-eastern Michigan were females and 97% were European American. Approximately 28% of one or both parents held at least a college degree, and 45% held a high school diploma or lower. Findings Pattern-centered analyses revealed that the relation between adolescent sport activity and age 28 heavy alcohol use obtained primarily for sport participants who were also using more than the average amount of alcohol and other drugs at age 18. Similarly, children who were characterized by relatively high levels of sport participation, aggression and other problem behavior at age 12 were more likely than expected by chance to become sport participants who used more than the average amount of alcohol and other drugs at age 18. Conclusions The results indicate that childhood problem behavior and adolescent sport participation can, but do not necessarily, presage heavy drinking in adulthood and that pattern-centered analytical techniques are useful for revealing such theoretically generated predictions. PMID:18426541

  13. Photocontrol of Elicitor Activity of PIP-1 to Investigate Temporal Factors Involved in Phytoalexin Biosynthesis.

    PubMed

    Kim, Yonghyun; Miyashita, Masahiro; Miyagawa, Hisashi

    2015-07-01

    The peptide elicitor PIP-1 can induce various immune responses in tobacco cells. Previously, we showed that types of responses induced by PIP-1 are different depending on its stimulation periods; short-term stimulation induces weak responses, whereas long-term stimulation leads to strong responses including production of the phytoalexin capsidiol. However, key components that directly regulate the initiation of capsidiol biosynthesis in response to continuous stimulation with PIP-1 remain unclear. In this study, we designed a photocleavable PIP-1 analog containing 3-amino-3-(2-nitrophenyl)propionic acid as a photocleavable residue. The activity of the analog can be "switched off" using ultraviolet (UV) irradiation without undesired side effects. This analog induced a significant level of capsidiol production unless UV-irradiated, whereas no capsidiol production was observed when tobacco cells were UV-irradiated 1 h after treatment. Using this analog, we found that the elicitor-inducible 3-hydroxy-3-methylglutaryl-CoA reductase activity is regulated based on the duration of the stimulation with PIP-1, which could be associated with the initiation of capsidiol biosynthesis. PMID:26047371

  14. GM1 Ganglioside is Involved in Epigenetic Activation Loci of Neuronal Cells.

    PubMed

    Tsai, Yi-Tzang; Itokazu, Yutaka; Yu, Robert K

    2016-02-01

    Gangliosides are sialic acid-containing glycosphingolipids that are most abundant in the nerve tissues. The quantity and expression pattern of gangliosides in brain change drastically throughout development and are mainly regulated through stage-specific expression of glycosyltransferase (ganglioside synthase) genes. We previously demonstrated that acetylation of histones H3 and H4 on the N-acetylgalactosaminyltransferase I (GalNAcT, GA2/GM2/GD2/GT2-synthase) gene promoter resulted in recruitment of trans-activation factors. In addition, we reported that epigenetic activation of the GalNAcT gene was also detected as accompanied by an apparent induction of neuronal differentiation in neural stem cells responding to an exogenous supplement of ganglioside GM1. Here, we present evidence supporting the concept that nuclear GM1 is associated with gene regulation in neuronal cells. We found that nuclear GM1 binds acetylated histones on the promoters of the GalNAcT and NeuroD1 genes in differentiated neurons. Our study demonstrates for the first time that GM1 interacts with chromatin via acetylated histones at the nuclear periphery of neuronal cells. PMID:26498762

  15. Anti-inflammatory active gold(I) complexes involving 6-substituted-purine derivatives.

    PubMed

    Trávníček, Zdeněk; Starha, Pavel; Vančo, Ján; Silha, Tomáš; Hošek, Jan; Suchý, Pavel; Pražanová, Gabriela

    2012-05-24

    The gold(I) complexes of the general formula [Au(L(n))(PPh(3))]·xH(2)O (1-8; n = 1-8 and x = 0-1.5), where L(n) stands for a deprotonated form of the benzyl-substituted derivatives of 6-benzylaminopurine, were prepared, thoroughly characterized (elemental analyses, FT-IR, Raman and multinuclear NMR spectroscopy, ESI+ mass spectrometry, conductivity, DFT calculations), and studied for their in vitro cytotoxicity and in vitro and in vivo anti-inflammatory effects on LPS-activated macrophages (derived from THP-1 cell line) and using the carrageenan-induced hind paw edema model on rats. The obtained results indicate that the representative complexes (1, 3, 6) exhibit a strong ability to reduce the production of pro-inflammatory cytokines TNF-α, IL-1β and HMGB1 without influence on the secretion of anti-inflammatory cytokine IL-1RA in the LPS-activated macrophages. The complexes also significantly influence the formation of edema, caused by the intraplantar application of polysaccharide λ-carrageenan to rats in vivo. All the tested complexes showed similar or better biological effects as compared with Auranofin, but contrary to Auranofin they were found to be less cytotoxic in vitro. The obtained results clearly indicate that the gold(I) complexes behave as very effective anti-inflammatory agents and could prove to be useful for the treatment of difficult to treat inflammatory diseases such as rheumatoid arthritis. PMID:22541000

  16. Molecular Changes Involving MEK3-p38 MAPK Activation in Chronic Masticatory Myalgia.

    PubMed

    Meng, H; Gao, Y; Kang, Y F; Zhao, Y P; Yang, G J; Wang, Y; Cao, Y; Gan, Y H; Xie, Q F

    2016-09-01

    The exact mechanism underlying chronic masticatory myalgia (CMM), a conspicuous symptom in temporomandibular disorders, remains unclear. This investigation compared gene expression profiles between CMM patients and healthy subjects. Peripheral blood leukocytes were collected in 8 cases and 8 controls and subjected to whole genome microarray analyses. Data were analyzed with Gene Ontology and interactive pathways analyses. According to Gene Ontology analysis, categories such as ion transport, response to stimuli, and metabolic process were upregulated. The pathway analysis suggested overexpression of the mitogen-activated protein kinase (MAPK) pathway in CMM patients and to a higher degree in a pathway network. Overexpression of representative members of the MAPK pathway-including MAPK kinase 3 (MEK3), calcium voltage-gated channel auxiliary subunit gamma 2 (CACNG2), and growth arrest and DNA damage-inducible gamma (GADD45G)-was validated with real-time polymerase chain reaction. The upregulation of MEK3 was negatively correlated with the age of the CMM group. In the next step, the authors focused on MEK3, the gene that exhibited the greatest degree of differential expression, and its downstream target protein p38 MAPK. The results revealed upregulation of MEK3, as well as phosphorylated MEK3 and phosphorylated p38 MAPK, in CMM patients. These results provide a "fingerprint" for mechanistic studies of CMM in the future and highlight the importance of MEK3-p38 MAPK activation in CMM. PMID:27418173

  17. Using Long-Distance Scientist Involvement to Enhance NASA Volunteer Network Educational Activities

    NASA Astrophysics Data System (ADS)

    Ferrari, K.

    2012-12-01

    Since 1999, the NASA/JPL Solar System Ambassadors (SSA) and Solar System Educators (SSEP) programs have used specially-trained volunteers to expand education and public outreach beyond the immediate NASA center regions. Integrating nationwide volunteers in these highly effective programs has helped optimize agency funding set aside for education. Since these volunteers were trained by NASA scientists and engineers, they acted as "stand-ins" for the mission team members in communities across the country. Through the efforts of these enthusiastic volunteers, students gained an increased awareness of NASA's space exploration missions through Solar System Ambassador classroom visits, and teachers across the country became familiarized with NASA's STEM (Science, Technology, Engineering and Mathematics) educational materials through Solar System Educator workshops; however the scientist was still distant. In 2003, NASA started the Digital Learning Network (DLN) to bring scientists into the classroom via videoconferencing. The first equipment was expensive and only schools that could afford the expenditure were able to benefit; however, recent advancements in software allow classrooms to connect to the DLN via personal computers and an internet connection. Through collaboration with the DLN at NASA's Jet Propulsion Laboratory and the Goddard Spaceflight Center, Solar System Ambassadors and Solar System Educators in remote parts of the country are able to bring scientists into their classroom visits or workshops as guest speakers. The goals of this collaboration are to provide special elements to the volunteers' event, allow scientists opportunities for education involvement with minimal effort, acquaint teachers with DLN services and enrich student's classroom learning experience.;

  18. An ATP-activated channel is involved in mitogenic stimulation of human T lymphocytes.

    PubMed

    Baricordi, O R; Ferrari, D; Melchiorri, L; Chiozzi, P; Hanau, S; Chiari, E; Rubini, M; Di Virgilio, F

    1996-01-15

    We investigated the effect of pharmacologic modulation of the ATP receptor on intracellular ion changes and proliferative response of human peripheral blood lymphocytes (PBLs) and purified T lymphocytes. Extracellular ATP (ATPe) triggered in these cells an increase in the cytoplasmic Ca2+ concentration ([Ca2+]i) and plasma membrane depolarization. Whereas both Ca2+ release from intracellular stores and influx across the plasma membrane were detected in the whole PBL population, only Ca2+ influx was observed in T cells. In the presence of near physiologic extracellular Na+ concentrations (125 mmol/L), Ca2+ permeability through the ATPe-gated channel was very low, suggesting a higher selectivity for monovalent over divalent cations. The selective P2Z agonist benzoylbenzoic ATP (BzATP) increased [Ca2+]i in the presence but not the absence of extracellular Ca2+ and also caused plasma membrane depolarization. The covalent blocker oxidized ATP (oATP), an inhibitor of P2X and P2Z receptors, prevented Ca2+ influx and plasma membrane depolarization, but had no effect on Ca2+ release from stores. Stimulation with ATPe alone had no significant effects on PBL 3H-thymidine incorporation. On the contrary, ATPe or BzATP had a synergistic effect on DNA synthesis stimulated by selective T-cell mitogens such as phytohemagglutinin, anti-CD3 monoclonal antibody, or allogenic PBLs (mixed lymphocyte cultures). Treatment with oATP inhibited mitogenic stimulation by these receptor-directed agents but not by the combined application of the Ca2+ ionophore ionomycin and phorbol myristate acetate. Interleukin-2 partially relieved inhibition by oATP. These results suggest that human T lymphocytes express a plasma membrane channel gated by ATPe that is involved in mitogenic stimulation. PMID:8555491

  19. Characterization of streptococcal platelet-activating factor acetylhydrolase variants that are involved in innate immune evasion.

    PubMed

    Liu, Guanghui; Liu, Mengyao; Xie, Gang; Lei, Benfang

    2013-09-01

    Human pathogen group A streptococcus (GAS) has developed mechanisms to subvert innate immunity. We recently reported that the secreted esterase produced by serotype M1 GAS (SsE(M1)) reduces neutrophil recruitment by targeting platelet-activating factor (PAF). SsE(M1) and SsE produced by serotype M28 GAS (SsE(M28)) have a 37% sequence difference. This study aims at determining whether SsE(M28) is also a PAF acetylhydrolase and participates in innate immune evasion. We also examined whether SsE evolved to target PAF by characterizing the PAF acetylhydrolase (PAF-AH) activity and substrate specificity of SsE(M1), SsE(M28), SeE, the SsE homologue in Streptococcus equi, and human plasma PAF-AH (hpPAF-AH). PAF incubated with SsE(M28) or SeE was converted into lyso-PAF. SsE(M1) and SsE(M28) had kcat values of 373 s(-1) and 467 s(-1), respectively, that were ≥ 30-fold greater than that of hpPAF-AH (12 s(-1)). The comparison of SsE(M1), SsE(M28), and hpPAF-AH in kcat and Km in hydrolyzing triglycerides, acetyl esters, and PAF indicates that the SsE proteins are more potent hydrolases against PAF and have high affinity for PAF. SsE(M28) possesses much lower esterase activities against triglycerides and other esters than SsE(M1) but have similar potency with SsE(M1) in PAF hydrolysis. Deletion of sse(M28) in a covS deletion mutant of GAS increased neutrophil recruitment and reduced skin infection, whereas in trans expression of SsE(M28) in GAS reduced neutrophil infiltration and increased skin invasion in subcutaneous infection of mice. These results suggest that the SsE proteins evolved to target PAF for enhancing innate immune evasion and skin invasion. PMID:23774595

  20. Characterization of Streptococcal Platelet-Activating Factor Acetylhydrolase Variants That Are Involved in Innate Immune Evasion

    PubMed Central

    Liu, Guanghui; Liu, Mengyao; Xie, Gang

    2013-01-01

    Human pathogen group A streptococcus (GAS) has developed mechanisms to subvert innate immunity. We recently reported that the secreted esterase produced by serotype M1 GAS (SsEM1) reduces neutrophil recruitment by targeting platelet-activating factor (PAF). SsEM1 and SsE produced by serotype M28 GAS (SsEM28) have a 37% sequence difference. This study aims at determining whether SsEM28 is also a PAF acetylhydrolase and participates in innate immune evasion. We also examined whether SsE evolved to target PAF by characterizing the PAF acetylhydrolase (PAF-AH) activity and substrate specificity of SsEM1, SsEM28, SeE, the SsE homologue in Streptococcus equi, and human plasma PAF-AH (hpPAF-AH). PAF incubated with SsEM28 or SeE was converted into lyso-PAF. SsEM1 and SsEM28 had kcat values of 373 s−1 and 467 s−1, respectively, that were ≥30-fold greater than that of hpPAF-AH (12 s−1). The comparison of SsEM1, SsEM28, and hpPAF-AH in kcat and Km in hydrolyzing triglycerides, acetyl esters, and PAF indicates that the SsE proteins are more potent hydrolases against PAF and have high affinity for PAF. SsEM28 possesses much lower esterase activities against triglycerides and other esters than SsEM1 but have similar potency with SsEM1 in PAF hydrolysis. Deletion of sseM28 in a covS deletion mutant of GAS increased neutrophil recruitment and reduced skin infection, whereas in trans expression of SsEM28 in GAS reduced neutrophil infiltration and increased skin invasion in subcutaneous infection of mice. These results suggest that the SsE proteins evolved to target PAF for enhancing innate immune evasion and skin invasion. PMID:23774595

  1. Extracurricular activities in young applicants' résumés: what are the motives behind their involvement?

    PubMed

    Roulin, Nicolas; Bangerter, Adrian

    2013-01-01

    Applicants use résumés to demonstrate their knowledge, skills, abilities, and other personal characteristics (KSAOs) to recruiters, through education and job-related or non-job-related experiences. But research suggests that the situation for young applicants is especially competitive, since they increasingly enter the labour market with similar educational credentials and limited job-related experience. They may thus use non-job-related experiences, such as participation in extracurricular activities (ECAs) during their studies, to demonstrate KSAOs to recruiters, but also to add distinction and value to their credentials. ECAs may therefore become more important in the selection of young applicants. Yet few studies have undertaken a comprehensive and systematic analysis of the relationships students have with these activities. The purpose of this study was to investigate to what extent students' involvement in ECAs is due to internal (e.g., passion) or external (e.g., résumé-building) motives, and what factors influence these motives. Results from a study with 197 students suggest that students engage in ECAs mainly out of internal motives. But external motives are stronger for activities started closer to entering the labour market, for students active in associative or volunteering activities (as compared to sports or artistic activities), and for students holding leadership positions in their activities. Our results suggest that labour market pressure may be a key component of applicants' involvement in ECAs. Also, organizations and recruiters may want to consider that students tend not to engage in ECAs purely out of internal motives, but also to add value to their credentials and match employers' expectations. The authors thank Anna Ambrosetti for her help with the data collection. PMID:22823060

  2. In vitro activity of secnidazole against Atopobium vaginae, an anaerobic pathogen involved in bacterial vaginosis.

    PubMed

    De Backer, E; Dubreuil, L; Brauman, M; Acar, J; Vaneechoutte, M

    2010-05-01

    Bacterial vaginosis is a polymicrobial syndrome. The most important marker for bacterial vaginosis is the presence of Gardnerella vaginalis and Atopobium vaginae. In this study, the in vitro susceptibilities to metronidazole and secnidazole of 16 strains of A. vaginae were tested with the agar dilution method. We observed an MIC range for metronidazole of 4-64 mg/L (MIC(50), 8 mg/L; MIC(90), 32 mg/L) and an MIC range for secnidazole of 4-128 mg/L (MIC(50), 16 mg/L; MIC(90), 64 mg/L). According to these findings, we can conclude that the activity of secnidazole is similar to that of metronidazole. PMID:19548924

  3. Transferrin Binding to Peripheral Blood Lymphocytes Activated by Phytohemagglutinin Involves a Specific Receptor

    PubMed Central

    Galbraith, Robert M.; Werner, Phillip; Arnaud, Philippe; Galbraith, Gillian M. P.

    1980-01-01

    Immunohistological studies have indicated that membrane sites binding transferrin are present upon activated human peripheral blood lymphocytes. In this study, we have investigated transferrin uptake in human lymphocytes exposed to phytohemagglutinin (PHA), by quantitative radiobinding and immunofluorescence in parallel. In stimulated lymphocytes, binding was maximal after a 30-min incubation, being greatest at 37°C, and greater at 22°C than at 4°C. Although some shedding and endocytosis of transferrin occurred at 22° and 37°C, these factors, and resulting synthesis of new sites, did not affect measurement of binding which was found to be saturable, reversible, and specific for transferrin (Ka 0.5-2.5 × 108 M−1). Binding was greater after a 48-h exposure to PHA than after 24 h, and was maximal at 66 h. Sequential Scatchard analysis revealed no significant elevation in affinity of interaction. However, although the total number of receptors increased, the proportion of cells in which binding of ligand was detected immunohistologically increased in parallel, and after appropriate correction, the cellular density of receptors remained relatively constant throughout (60,000-80,000 sites/cell). Increments in binding during the culture period were thus due predominantly to expansion of a population of cells bearing receptors. Similar differences in binding were apparent upon comparison of cells cultured in different doses of PHA, and in unstimulated cells binding was negligible. Transferrin receptors appear, therefore, to be readily detectable only upon lymphocytes that have been activated. Images PMID:6253523

  4. The mammalian transferrin-independent iron transport system may involve a surface ferrireductase activity.

    PubMed Central

    Jordan, I; Kaplan, J

    1994-01-01

    Mammalian cells accumulate iron from ferric citrate or ferric nitrilotriacetate through the activity of a transferrin-independent iron transport system [Sturrock, Alexander, Lamb, Craven and Kaplan (1990) J. Biol. Chem. 265, 3139-3145]. The uptake system might recognize and transport ferric-anion complexes, or cells may reduce ferric iron at the surface and then transport ferrous iron. To distinguish between these possibilities we exposed cells to either [59Fe]ferric citrate or ferric [14C]citrate and determined whether accumulation of iron was accompanied by the obligatory accumulation of citrate. In HeLa cells and human skin fibroblasts the rate of accumulation of iron was three to five times greater than that of citrate. Incubation of fibroblasts with ferric citrate or ferric ammonium citrate resulted in an enhanced accumulation of iron and citrate; the molar ratio of accumulation approaching unity. A similar rate of citrate accumulation, however, was observed when ferric citrate-incubated cells were exposed to [14C]citrate alone. Further studies demonstrated the independence of iron and citrate accumulation: addition of unlabelled citrate to cells decreased the uptake of labelled citrate without affecting the accumulation of 59Fe; iron uptake was decreased by the addition of ferrous chelators whereas the uptake of citrate was unaffected; reduction of ferric iron by ascorbate increased the uptake of iron but had no effect on the uptake of citrate. When HeLa cells were depleted of calcium, iron uptake decreased, but there was little effect on citrate uptake. These results indicate that transport of iron does not require the obligatory transport of citrate and vice versa. The mammalian transferrin-independent iron transport system appears functionally similar to iron transport systems in both the bacterial and plant kingdoms which require the activities of both a surface reductase and a ferrous metal transporter. PMID:7945215

  5. The endocannabinoid anandamide induces apoptosis of rat decidual cells through a mechanism involving ceramide synthesis and p38 MAPK activation.

    PubMed

    Fonseca, B M; Correia-da-Silva, G; Teixeira, N A

    2013-12-01

    Anandamide (AEA) belongs to an endogenous family of lipid messengers, called endocannabinoids (ECs), which exert pharmacological effects by binding to selective membrane receptors, the CB1 and CB2 receptors. Increasing evidence suggests that AEA is involved in the regulation of a variety of cell signalling pathways both in experimental models and humans. We have previously demonstrated that ECs machinery operates in decidual cells and found that AEA, the principal EC, induced apoptosis in decidual cells through CB1. Here, we investigated in rat primary decidual cells the signal transduction pathways activated upon AEA binding to CB1. We found that AEA induces a significant increase in the level of intracellular ceramide. These effects were reversed by inhibiting CB1 receptor activation with AM251. The ceramide analogue, C6-ceramide, induced a decrease in decidual cell viability and of p38 MAPK phosphorylation. Additionally, the pharmacologic inhibition of de novo ceramide biosynthesis with L-cycloserine and fumonisin B reduced the AEA-effects on cell viability and p38 MAPK phosphorylation. Furthermore, AEA and C6-ceramide induced a drop in ΔΨm, an increase in ROS production and caspase-3/-7 activation, effects partially reverted by inhibitors of ceramide synthesis and of p38 MAPK. Taken together, we showed that AEA induces a reduction in decidual cell viability by a mechanism involving CB1 activation, which results in ceramide synthesis de novo and p38 phosphorylation, followed by mitochondrial stress and ROS production, leading to apoptosis. PMID:24048885

  6. Are deep eutectic solvents benign or toxic?

    PubMed

    Hayyan, Maan; Hashim, Mohd Ali; Hayyan, Adeeb; Al-Saadi, Mohammed A; AlNashef, Inas M; Mirghani, Mohamed E S; Saheed, Olorunnisola Kola

    2013-02-01

    In continuation of investigation for environmentally benign protocol for new solvents termed deep eutectic solvents (DESs), it is herein reported results concerning the toxicity and cytotoxicity of choline chloride (ChCl) based DESs with four hydrogen bond donors including glycerine, ethylene glycol, triethylene glycol and urea. The toxicity was investigated using two Gram positive bacteria Bacillus subtilis and Staphylococcus aureus, and two Gram negative bacteria Escherichia coli and Pseudomonas aeruginosa. The cytotoxicity effect was tested using the Artemia salina leach. It was found that there was no toxic effect for the tested DESs on all of the studied bacteria confirming their benign effects on these bacteria. Nevertheless, it was found that the cytotoxicity of DESs was much higher than their individual components (e.g. glycerine, ChCl) indicating that their toxicological behavior is different. For our best knowledge this is the first time that toxicity and cytotoxicity of DESs were studied. The toxicity and cytotoxicity of DESs varied depending on the structure of components. Careful usage of the terms non-toxicity and biodegradability must be considered. More investigation on this matter is required. PMID:23200570

  7. Breast-feeding and benign breast disease.

    PubMed

    Bernardi, S; Londero, A P; Bertozzi, S; Driul, L; Marchesoni, D; Petri, R

    2012-01-01

    Benign breast disease (BBD) is very common among women in their fertile age, but its correlation with breast reproductive function remains unclear. Our study aimed to investigate the relation between BBD and breast-feeding. We collected data on 105 women with BBD and 98 controls, focusing on their reproductive history and breast-feeding. We analysed data by R (version 2.12.1) considering p < 0.05 as significant. The results showed that fibroadenoma represented the most frequent BBD (55%), followed by fibrocystic changes (19%), intraductal papilloma (6%) and inflammatory breast disorders (5%). The mean age was 31.5 years (± 6.1), BMI 21.2 kg/m² (± 3.4) and age at menarche 13.0 years (± 1.5). Duration of breast-feeding was not significantly different between controls and BBD types (p = NS). Selecting women with fibroadenoma breast-feeding duration directly correlated with the number of benign lesions (p < 0.05), which remains significant also by multivariate analysis. It was concluded that there seemed to be no difference in breast-feeding among BBDs types, but lactation may influence the number of fibroadenomas. Moreover, prospective studies would better define the correlation between lactation and BBDs. PMID:22185539

  8. Evidence against direct involvement of phosphorylation in the activation of carnitine palmitoyltransferase by okadaic acid in rat hepatocytes.

    PubMed Central

    Guzman, M; Kolodziej, M P; Caldwell, A; Corstorphine, C G; Zammit, V A

    1994-01-01

    The mechanism of activation of mitochondrial overt carnitine palmitoyltransferase (CPT I) by treatment of hepatocytes with okadaic acid (OA) was investigated. Activation was observed when cells were permeabilized with digitonin, but not when a total membrane fraction was obtained by sonication. Both cell disruption methods preserved the activation of phosphorylase observed in OA-treated hepatocytes. Activation of CPT I was also observed in crude homogenates of OA-treated hepatocytes, but it was lost upon subsequent isolation of mitochondria from such homogenates. In all experiments, any activation observed did not depend on the presence or absence of fluoride ions in the permeabilization/homogenization media. When hepatocytes were permeabilized in the absence of fluoride and further incubated with exogenous phosphatases 1 and 2A, the OA-induced activation of CPT was not reversed, whereas the activation of glycogen phosphorylase in the same cells was rapidly reversed. Treatment of hepatocytes with OA, followed by permeabilization and incubation before assay of CPT I, demonstrated that OA had no short-term effect on the sensitivity of CPT I to malonyl-CoA, although the difference in sensitivity between cells isolated from fed and starved rats was fully preserved. Incubation of isolated mitochondria or purified mitochondrial outer membranes with cyclic AMP-dependent or AMP-activated protein kinases, under phosphorylating conditions, did not affect the activity of CPT I or its sensitivity to malonyl-CoA inhibition. Under the same conditions, the use of [32P]ATP resulted in the labelling of several outer-membrane proteins but, unlike [3H]etomoxir-labelled CPT I, none of them was specifically removed from membrane extracts by a specific polyclonal antibody to the enzyme. We conclude that the increase in overt CPT activity observed in permeabilized hepatocytes is not due to direct phosphorylation of CPT I, but may involve interactions between the mitochondrial outer

  9. Antidepressant activity of fluoxetine in the zinc deficiency model in rats involves the NMDA receptor complex.

    PubMed

    Doboszewska, Urszula; Szewczyk, Bernadeta; Sowa-Kućma, Magdalena; Młyniec, Katarzyna; Rafało, Anna; Ostachowicz, Beata; Lankosz, Marek; Nowak, Gabriel

    2015-01-01

    The zinc deficiency animal model of depression has been proposed; however, it has not been validated in a detailed manner. We have recently shown that depression-like behavior induced by dietary zinc restriction is associated with up-regulation of hippocampal N-methyl-d-aspartate receptor (NMDAR). Here we examined the effects of chronic administration of a selective serotonin reuptake inhibitor, fluoxetine (FLX), on behavioral and biochemical alterations (within NMDAR signaling pathway) induced by zinc deficiency. Male Sprague Dawley rats were fed a zinc adequate diet (ZnA, 50mg Zn/kg) or a zinc deficient diet (ZnD, 3mg Zn/kg) for 4 weeks. Then, FLX treatment (10mg/kg, i.p.) begun. Following 2 weeks of FLX administration the behavior of the rats was examined in the forced swim test (FST) and the spontaneous locomotor activity test. Twenty four hours later tissue was harvested. The proteins of NMDAR (GluN1, GluN2A and GluN2B) or AMPAR (GluA1) subunits, p-CREB and BDNF in the hippocampus (Western blot) and serum zinc level (TXRF) were examined. Depression-like behavior induced by ZnD in the FST was sensitive to chronic treatment with FLX. ZnD increased levels of GluN1, GluN2A, GluN2B and decreased pS485-GluA1, p-CREB and BDNF proteins. Administration of FLX counteracted the zinc restriction-induced changes in serum zinc level and hippocampal GluN1, GluN2A, GluN2B and p-CREB but not BDNF or pS845-GluA1 protein levels. This finding adds new evidence to the predictive validity of the proposed zinc deficiency model of depression. Antidepressant-like activity of FLX in the zinc deficiency model is associated with NMDAR complex. PMID:25845739

  10. Peroxidase Activity and Involvement in the Oxidative Stress Response of Roseobacter denitrificans Truncated Hemoglobin

    PubMed Central

    Wang, Yaya; Barbeau, Xavier; Bilimoria, Astha; Lagüe, Patrick; Couture, Manon; Tang, Joseph Kuo-Hsiang

    2015-01-01

    Roseobacter denitrificans is a member of the widespread marine Roseobacter genus. We report the first characterization of a truncated hemoglobin from R. denitrificans (Rd. trHb) that was purified in the heme-bound form from heterologous expression of the protein in Escherichia coli. Rd. trHb exhibits predominantly alpha-helical secondary structure and absorbs light at 412, 538 and 572 nm. The phylogenetic classification suggests that Rd. trHb falls into group II trHbs, whereas sequence alignments indicate that it shares certain important heme pocket residues with group I trHbs in addition to those of group II trHbs. The resonance Raman spectra indicate that the isolated Rd. trHb contains a ferric heme that is mostly 6-coordinate low-spin and that the heme of the ferrous form displays a mixture of 5- and 6-coordinate states. Two Fe-His stretching modes were detected, notably one at 248 cm-1, which has been reported in peroxidases and some flavohemoglobins that contain an Fe-His-Asp (or Glu) catalytic triad, but was never reported before in a trHb. We show that Rd. trHb exhibits a significant peroxidase activity with a (kcat/Km) value three orders of magnitude higher than that of bovine Hb and only one order lower than that of horseradish peroxidase. This enzymatic activity is pH-dependent with a pKa value ~6.8. Homology modeling suggests that residues known to be important for interactions with heme-bound ligands in group II trHbs from Mycobacterium tuberculosis and Bacillus subtilis are pointing toward to heme in Rd. trHb. Genomic organization and gene expression profiles imply possible functions for detoxification of reactive oxygen and nitrogen species in vivo. Altogether, Rd. trHb exhibits some distinctive features and appears equipped to help the bacterium to cope with reactive oxygen/nitrogen species and/or to operate redox biochemistry. PMID:25658318

  11. Phytochemicals from Ruta graveolens Activate TAS2R Bitter Taste Receptors and TRP Channels Involved in Gustation and Nociception.

    PubMed

    Mancuso, Giuseppe; Borgonovo, Gigliola; Scaglioni, Leonardo; Bassoli, Angela

    2015-01-01

    Ruta graveolens (rue) is a spontaneous plant in the Mediterranean area with a strong aroma and a very intense bitter taste, used in gastronomy and in folk medicine. From the leaves, stems and fruits of rue, we isolated rutin, rutamarin, three furanocoumarins, two quinolinic alkaloids, a dicoumarin and two long chain ketones. Bitter taste and chemesthetic properties have been evaluated by in vitro assays with twenty receptors of the TAS2R family and four TRP ion channels involved in gustation and nociception. Among the alkaloids, skimmianine was active as a specific agonist of T2R14, whereas kokusaginin did not activate any of the tested receptors. The furanocoumarins activates TAS2R10, 14, and 49 with different degrees of selectivity, as well as the TRPA1 somatosensory ion channel. Rutamarin is an agonist of TRPM5 and TRPV1 and a strong antagonist of TRPM8 ion channels. PMID:26501253

  12. A novel PRD I and TG binding activity involved in virus-induced transcription of IFN-A genes.

    PubMed Central

    Génin, P; Bragança, J; Darracq, N; Doly, J; Civas, A

    1995-01-01

    Comparative analysis of the inducible elements of the mouse interferon A4 and A11 gene promoters (IE-A4 and IE-A11) by transient transfection experiments, DNase 1 footprinting and electrophoretic mobility shift assays resulted in identification of a virus-induced binding activity suggested to be involved in NDV-induced activation of transcription of these genes. The virus-induced factor, termed VIF, is activated early by contact of virions with cells. It specifically recognizes the PRD I-like domain shared by both inducible elements, as well as the TG-like domain of IE-A4. This factor, distinct from the IRF-1, IRF-2 and the alpha F1 binding proteins and presenting a different affinity pattern from that of the TG protein, is proposed as a candidate for IFN-type I gene regulation. Images PMID:8559665

  13. DOE Technical Standards List. Directory of DOE and contractor personnel involved in non-government standards activities

    SciTech Connect

    1997-06-01

    This is a periodic report on the level of agency participation in non-Government standards activities. This technical standards list is intended to assist US Department of Energy (DOE) management and other personnel involved in the DOE technical Standards Program by identifying those participating individuals. The body of this document contains a listing of DOE employees and DOE contractors who have submitted a Record of Non-Government Standards Activity. Additional names were added from rosters supplied by non-Government standards bodies. Appendices to this document are provided to list the information by parent employment organization, by non-Government standards activity, and by the proper names of the non-Government standards organizations and committees.

  14. E-cadherin junction formation involves an active kinetic nucleation process

    SciTech Connect

    Biswas, Kabir H.; Hartman, Kevin L.; Yu, Cheng -han; Harrison, Oliver J.; Song, Hang; Smith, Adam W.; Huang, William Y. C.; Lin, Wan -Chen; Guo, Zhenhuan; Padmanabhan, Anup; Troyanovsky, Sergey M.; Dustin, Michael L.; Shapiro, Lawrence; Honig, Barry; Zaidel-Bar, Ronen; Groves, Jay T.

    2015-08-19

    Epithelial (E)-cadherin-mediated cell–cell junctions play important roles in the development and maintenance of tissue structure in multicellular organisms. E-cadherin adhesion is thus a key element of the cellular microenvironment that provides both mechanical and biochemical signaling inputs. Here, we report in vitro reconstitution of junction-like structures between native E-cadherin in living cells and the extracellular domain of E-cadherin in a supported membrane. Junction formation in this hybrid live cell-supported membrane configuration requires both active processes within the living cell and a supported membrane with low E-cad-ECD mobility. The hybrid junctions recruit α-catenin and exhibit remodeled cortical actin. Observations suggest that the initial stages of junction formation in this hybrid system depend on the trans but not the cis interactions between E-cadherin molecules, and proceed via a nucleation process in which protrusion and retraction of filopodia play a key role.

  15. E-cadherin junction formation involves an active kinetic nucleation process

    DOE PAGESBeta

    Biswas, Kabir H.; Hartman, Kevin L.; Yu, Cheng -han; Harrison, Oliver J.; Song, Hang; Smith, Adam W.; Huang, William Y. C.; Lin, Wan -Chen; Guo, Zhenhuan; Padmanabhan, Anup; et al

    2015-08-19

    Epithelial (E)-cadherin-mediated cell–cell junctions play important roles in the development and maintenance of tissue structure in multicellular organisms. E-cadherin adhesion is thus a key element of the cellular microenvironment that provides both mechanical and biochemical signaling inputs. Here, we report in vitro reconstitution of junction-like structures between native E-cadherin in living cells and the extracellular domain of E-cadherin in a supported membrane. Junction formation in this hybrid live cell-supported membrane configuration requires both active processes within the living cell and a supported membrane with low E-cad-ECD mobility. The hybrid junctions recruit α-catenin and exhibit remodeled cortical actin. Observations suggest thatmore » the initial stages of junction formation in this hybrid system depend on the trans but not the cis interactions between E-cadherin molecules, and proceed via a nucleation process in which protrusion and retraction of filopodia play a key role.« less

  16. Growth hormone activity in mitochondria depends on GH receptor Box 1 and involves caveolar pathway targeting

    SciTech Connect

    Perret-Vivancos, Cecile; Abbate, Aude; Ardail, Dominique; Raccurt, Mireille; Usson, Yves; Lobie, Peter E.; Morel, Gerard . E-mail: gerard.morel@univ-lyon1.fr

    2006-02-01

    Growth hormone (GH) binding to its receptor (GHR) initiates GH-dependent signal transduction and internalization pathways to generate the biological effects. The precise role and way of action of GH on mitochondrial function are not yet fully understood. We show here that GH can stimulate cellular oxygen consumption in CHO cells transfected with cDNA coding for the full-length GHR. By using different GHR cDNA constructs, we succeeded in determining the different parts of the GHR implicated in the mitochondrial response to GH. Polarography and two-photon excitation fluorescence microscopy analysis showed that the Box 1 of the GHR intracellular domain was required for an activation of the mitochondrial respiration in response to a GH exposure. However, confocal laser scanning microscopy demonstrated that cells lacking the GHR Box 1 could efficiently internalize the hormone. We demonstrated that internalization mediated either by clathrin-coated pits or by caveolae was able to regulate GH mitochondrial effect: these two pathways are both essential to obtain the GH stimulatory action on mitochondrial function. Moreover, electron microscopic and biochemical approaches allowed us to identify the caveolar pathway as essential for targeting GH and GHR to mitochondria.

  17. E-cadherin junction formation involves an active kinetic nucleation process

    PubMed Central

    Biswas, Kabir H.; Hartman, Kevin L.; Yu, Cheng-han; Harrison, Oliver J.; Song, Hang; Smith, Adam W.; Huang, William Y. C.; Lin, Wan-Chen; Guo, Zhenhuan; Padmanabhan, Anup; Troyanovsky, Sergey M.; Dustin, Michael L.; Shapiro, Lawrence; Honig, Barry; Zaidel-Bar, Ronen; Groves, Jay T.

    2015-01-01

    Epithelial (E)-cadherin-mediated cell−cell junctions play important roles in the development and maintenance of tissue structure in multicellular organisms. E-cadherin adhesion is thus a key element of the cellular microenvironment that provides both mechanical and biochemical signaling inputs. Here, we report in vitro reconstitution of junction-like structures between native E-cadherin in living cells and the extracellular domain of E-cadherin (E-cad-ECD) in a supported membrane. Junction formation in this hybrid live cell-supported membrane configuration requires both active processes within the living cell and a supported membrane with low E-cad-ECD mobility. The hybrid junctions recruit α-catenin and exhibit remodeled cortical actin. Observations suggest that the initial stages of junction formation in this hybrid system depend on the trans but not the cis interactions between E-cadherin molecules, and proceed via a nucleation process in which protrusion and retraction of filopodia play a key role. PMID:26290581

  18. Human high intelligence is involved in spectral redshift of biophotonic activities in the brain.

    PubMed

    Wang, Zhuo; Wang, Niting; Li, Zehua; Xiao, Fangyan; Dai, Jiapei

    2016-08-01

    Human beings hold higher intelligence than other animals on Earth; however, it is still unclear which brain properties might explain the underlying mechanisms. The brain is a major energy-consuming organ compared with other organs. Neural signal communications and information processing in neural circuits play an important role in the realization of various neural functions, whereas improvement in cognitive function is driven by the need for more effective communication that requires less energy. Combining the ultraweak biophoton imaging system (UBIS) with the biophoton spectral analysis device (BSAD), we found that glutamate-induced biophotonic activities and transmission in the brain, which has recently been demonstrated as a novel neural signal communication mechanism, present a spectral redshift from animals (in order of bullfrog, mouse, chicken, pig, and monkey) to humans, even up to a near-infrared wavelength (∼865 nm) in the human brain. This brain property may be a key biophysical basis for explaining high intelligence in humans because biophoton spectral redshift could be a more economical and effective measure of biophotonic signal communications and information processing in the human brain. PMID:27432962

  19. Biodegradation of ivory (natural apatite): possible involvement of fungal activity in biodeterioration of the Lewis Chessmen.

    PubMed

    Pinzari, Flavia; Tate, James; Bicchieri, Marina; Rhee, Young Joon; Gadd, Geoffrey Michael

    2013-04-01

    Fungal biodeterioration of ivory was investigated with in vitro inoculation of samples obtained from boar and walrus tusks with the fungi Aspergillus niger and Serpula himantioides, species of known geoactive abilities. A combination of light and scanning electron microscopy together with associated analytical techniques was used to characterize fungal interactions with the ivory, including changes in ivory composition, dissolution and tunnelling, and the formation of new biominerals. The research was aimed at providing further understanding of the potential roles of fungi in the colonization and deterioration of ivory in terrestrial environments, but also contributes to our knowledge regarding the possible origins of the surface damage observed on early medieval sculptures made largely from walrus tusks, referred to as 'the Lewis hoard of gaming pieces', that were presumably produced for playing chess. The experiments have shown that the possibility of damage to ivory being caused by fungi is realistic. Scanning electron microscopy revealed penetration of fungal hyphae within cracks in the walrus tusk that showed also widespread tunnelling by fungal hyphae as well as 'fungal footprints' where the surface was etched as a consequence of mycelial colonization. Similar phenomena were observed with boar tusk ivory, while production of metabolites could lead to complete dissolution of the sample. Colonization of ivory and/or exposure to fungal activity lead to extensive secondary biomineral formation, and this was identified as calcium oxalate, mainly as the monohydrate, whewellite. PMID:23157656

  20. Anti-Candida activity of geraniol involves disruption of cell membrane integrity and function.

    PubMed

    Sharma, Y; Khan, L A; Manzoor, N

    2016-09-01

    Candidiasis is a major problem in immunocompromised patients. Candida, an opportunistic fungal pathogen, is a major health concern today as conventional drugs are highly toxic with undesirable side effects. Their fungistatic nature is responsible for drug resistance in continuously evolving strains. Geraniol, an acyclic monoterpene alcohol, is a component of several plant essential oils. In the present study, an attempt has been made to understand the antifungal activity of geraniol at the cell membrane level in three Candida species. With an MIC of 30-130μg/mL, this natural compound was fungicidal at concentrations 2×MIC. There was complete suppression of fungal growth at MIC values (growth curves) and encouragingly geraniol is non-toxic even at the concentrations approaching 5×MIC (hemolysis assay). Exposed cells showed altered morphology, wherein the cells appeared either broken or shrivelled up (SEM studies). Significant reduction was seen in ergosterol levels at sub-MIC and glucose-induced H(+) efflux at concentrations>MIC values. Our results suggest that geraniol disrupts cell membrane integrity by interfering with ergosterol biosynthesis and inhibiting the very crucial PM-ATPase. It may hence be used in the management and treatment of both superficial and invasive candidiasis but further studies are required to elaborate its mode of action. PMID:27554866