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1

Promoting Active Involvement in Classrooms  

ERIC Educational Resources Information Center

This article presents a rationale for using active involvement techniques, describes large- and small-group methods based on their documented effectiveness and applicability to K-12 classrooms, and illustrates their use. These approaches include ways of engaging students in large groups (e.g., unison responses, response cards, dry-erase boards,…

Conderman, Greg; Bresnahan, Val; Hedin, Laura

2012-01-01

2

Proteomic analysis of SP600125-controlled TrkA-dependent targets in SK-N-MC neuroblastoma cells: inhibition of TrkA activity by SP600125.  

PubMed

The c-Jun N-terminal kinase (JNK) is well known to play an important role in cell death signaling of the p75 neurotrophin receptor. However, little has been studied about a role of JNK in the signaling pathways of the tropomyosin-related kinase A (TrkA) neurotrophin receptor. In this study, we investigated JNK inhibitor SP600125-controlled TrkA-dependent targets by proteomic analysis to better understand an involvement of JNK in TrkA-mediated signaling pathways. PDQuest image analysis and protein identification results showed that hnRNP C1/C2, ?-tubulin, ?-tubulin homolog, actin homolog, and eIF-5A-1 protein spots were upregulated by ectopic expression of TrkA, whereas ?-enolase, peroxiredoxin-6, PROS-27, HSP70, PP1-gamma, and PDH E1-alpha were downregulated by TrkA, and these TrkA-dependent upregulation and downregulation were significantly suppressed by SP600125. Notably, TrkA largely affected certain PTM(s) but not total protein amounts of the SP600125-controlled TrkA-dependent targets. Moreover, SP600125 strongly suppressed TrkA-mediated tyrosine phosphorylation signaling pathways as well as JNK signaling, indicating that SP600125 could function as a TrkA inhibitor. Taken together, our results suggest that TrkA could play an important role in the cytoskeleton, cell death, cellular processing, and glucose metabolism through activation or inactivation of the SP600125-controlled TrkA-dependent targets. PMID:24375967

Jung, Eun Joo; Park, Hyung Chul; Chung, Ky Hyun; Kim, Choong Won

2014-02-01

3

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...

4

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...

5

Immigrant Youth Involvement in School-Based Extracurricular Activities  

ERIC Educational Resources Information Center

Extracurricular activity involvement is generally beneficial toward student progress and success. Little is known, however, about immigrant youth involvement in school-based extracurricular activities. The author examined the patterns of Latino and Asian American youth extracurricular involvement by focusing on the pertinent role of immigrant…

Peguero, Anthony A.

2011-01-01

6

Immigrant Youth Involvement in School-Based Extracurricular Activities  

Microsoft Academic Search

Extracurricular activity involvement is generally beneficial toward student progress and success. Little is known, however, about immigrant youth involvement in school-based extracurricular activities. The author examined the patterns of Latino and Asian American youth extracurricular involvement by focusing on the pertinent role of immigrant generational status. Analyses, which draw from the Educational Longitudinal Study of 2002 and logistic regression analyses,

Anthony A. Peguero

2011-01-01

7

The Director of Physical Activity and Staff Involvement  

ERIC Educational Resources Information Center

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…

Heidorn, Brent; Centeio, Erin

2012-01-01

8

Middle Level Activities To Involve the Invisible Student.  

ERIC Educational Resources Information Center

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…

Rimmer, Sue; Arico, Jim

9

Exploring Extension Involvement in Farm to School Program Activities  

ERIC Educational Resources Information Center

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.…

Benson, Matthew C.

2014-01-01

10

Empirical Evidence or Intuition? An Activity Involving the Scientific Method  

ERIC Educational Resources Information Center

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.

Overway, Ken

2007-01-01

11

Adolescent Involvement in Extracurricular Activities: Influences on Leadership Skills  

ERIC Educational Resources Information Center

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.…

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

2012-01-01

12

Identifying Associations between Student Achievement and Parental Involvement Activities  

ERIC Educational Resources Information Center

The revision and renewal of the Elementary and Secondary Education Act of 1965 will likely expand its parental involvement component to engage educators, parents, and community partners in supporting public education for children. This revisions call for best practices, but current literature fails to identify specific activities associated…

Waddle, Ann R.

2011-01-01

13

Involving Intelligent Assistants in Active Human Communication Donald J. Patterson  

E-print Network

phones, the typical IM-enabled distinc- tions of being online/offline no longer give enough informa- tionInvolving Intelligent Assistants in Active Human Communication Donald J. Patterson University of California Irvine Abstract Intelligent assistants that support human communication need to respect

Yorke-Smith, Neil

14

Conformational Changes Involved in G Protein-coupled Receptor Activation  

PubMed Central

Little is known about the nature of the conformational changes that convert G protein-coupled receptors (GPCRs), which bind diffusible ligands, from their resting into their active states. To gain structural insight into this process, various laboratories have used disulfide cross-linking strategies involving cysteine-substituted mutant GPCRs. Several recent disulfide cross-linking studies using the M3 muscarinic acetylcholine receptor as a model system have led to novel insights into the conformational changes associated with the activation of this prototypical class I GPCR. These structural changes are predicted to involve multiple receptor regions, primarily distinct segments of transmembrane helices III, VI, and VII, as well as helix 8. Given the high degree of structural homology found among most GPCRs, it is likely that these findings will be of considerable general relevance. A better understanding of the molecular mechanisms underlying GPCR activation may lead to novel strategies aimed at modulating GPCR function for therapeutic purposes. PMID:18838178

Wess, Jurgen; Han, Sung-Jun; Kim, Soo-Kyung; Jacobson, Kenneth A.; Li, Jian Hua

2012-01-01

15

Involvement in 12-step activities and treatment outcomes.  

PubMed

This study addresses the relative importance of specific 12-step activities to recovery, and how treatment affects participation in those activities. Data were from a clinical trial testing a 12-step facilitation intervention called MAAEZ (Making AA [Alcohol Anonymous] Easier). Participants (N = 508) were recruited at treatment entry. Analyses examined 8 activities measured at baseline, 7 weeks, 6 months, and 12 months. In simultaneous equations, meeting attendance and having a sponsor were the only strong and consistent predictors of abstinence across time points, though other activities (i.e., use of a home group, befriending members, service work, and reading the literature) were significant in some analyses. Treatment involvement had mixed effects on activity participation over time. Contradicting research suggesting that meeting attendance contributes little beyond other 12-step activities, the current results highlight the importance of consistent meeting attendance and sponsorship in recovery. The results suggest a need for enhanced facilitation of key activities even in typical 12-step-oriented treatment. PMID:23327505

Zemore, Sarah E; Subbaraman, Meenakshi; Tonigan, J Scott

2013-01-01

16

A novel receptor involved in T-cell activation  

Microsoft Academic Search

OPTIMAL T-cell activation and T-cell expansion require triggering by T-cell antigen receptors and co-stimulatory signals provided by accessory cells1á¤-3. A major co-stimulatory pathway involves crosslinking the CD28 molecule on T cells by its ligands CD80 or CD86 expressed on antigen-presenting cells4á¤-7. But recent studies8,9 on CD28-deficient mice have indicated that CD28 is not required for all T-cell responses and that

Benjamin G. Cocks; Chia-Chun J. Chang; Hans Yssel; Jan E. de Vries; Gregorio Aversa

1995-01-01

17

Cellular signaling events involved in thrombin activation of vascular endothelium  

SciTech Connect

Although cytosolic calcium ((Ca))/sub I/), inositol trisphosphate (IP/sub 3/) and diacylglycerol (DAG) are important second messengers involved in stimulus-response coupling to certain hormones, little information is available regarding their role in the activation of vascular endothelial cells (EC) during coagulation. The authors have used cultured human umbilical vein EC to examine thrombin effects on (Ca)/sub I/ and on IP/sub 3/ and DAG formation. Thrombin (1 U/ml) induces a rapid (peak < 15 sec) increase in (Ca)/sub I/ (300% basal levels) in suspensions of fura-2 (fluorescent Ca/sup 2 +/ indicator)-loaded EC. In addition thrombin stimulates concentration-dependent (.001-1 U/ml) increases in calcium efflux and IP/sub 3/ formation in EC prelabeled with /sup 45/Ca or /sup 3/H-myoinositol. Peak IP/sub 3/ (182+/-14% control) is rapid (<15 sec) and temporally similar to the rise in (Ca)/sub I/. In /sup 3/H-arachidonic acid-labeled EC, thrombin increases DAG (protein kinase C activator) at 15 sec (133+/-8% control), as well as 5 min (148+/-12% control). EC preincubation with 4..beta..-phorbol 12-myristate 13-acetate (10/sup -7/M, 5 min), a potent activator of protein kinase C, blocks thrombin (1 U/ml)-induced increases in (Ca)/sub I/ and IP/sub 3/. Thus, thrombin may trigger at least two distinct signaling pathways (IP/sub 3//calcium; DAG/protein kinase C) in EC. In addition, DAG stimulation of protein kinase C may influence this mediator's action in vascular EC.

Brock, T.A.; Capasso, E.L.; Gimbrone, M.A. Jr.

1986-03-05

18

[Health management of Saipem workers with projects involving abroad activities].  

PubMed

In remote areas and in developing countries, where adequate health-care structures are few and sparse, Occupational Medicine contributes to guaranteeing workers' health. Companies like Saipem, involved in activities that are carried out in remote, inhospitable areas must ensure the safety and guarantee the health conditions of workers in relation to the risk factors connected with the job as well as with the environment in which it is performed. In such situations, Occupational Medicine addresses both the health aspects of the workplace and of the community, and is the pivot around which revolves the health-care support of workers employed abroad in the sense of protection and enhancement of health. The risks connected with work abroad are of three main types: 1) job-related risks; 2) risks connected with the environment; 3) risks related to the organization of work and the changes in the worker's daily life. The job-related risks are similar to those connected with analogous jobs performed elsewhere. The risks connected with the environment are related to adverse climatic conditions, extreme temperatures and unknown and often dangerous flora and fauna. The occupational physician is called upon to assess the suitability of workers for jobs that are based in remote areas. The main clinical conditions that can prevent issue of the Medical Fitness Certificate to workers for long-stay jobs abroad are discussed. PMID:18409664

Nicosia, V; De Sanctis, S; Mika, F; Consentino, M; Mascheroni, G

2007-01-01

19

Cues to Parent Involvement in Drug Prevention and School Activities.  

ERIC Educational Resources Information Center

Guided by the Health Belief Model, focus groups identified strategies to promote parent involvement with their children's substance abuse education. Low-income parents and school personnel identified cues to action and necessary requirements (child care, transportation, incentives) as important in promoting parent involvement. Children's…

Hahn, Ellen J.; And Others

1996-01-01

20

15 CFR 712.2 - Restrictions on activities involving Schedule 1 chemicals.  

Code of Federal Regulations, 2012 CFR

...on activities involving Schedule 1 chemicals. 712.2 Section 712.2 Commerce...SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.2 Restrictions on...

2012-01-01

21

15 CFR 712.2 - Restrictions on activities involving Schedule 1 chemicals.  

Code of Federal Regulations, 2013 CFR

...on activities involving Schedule 1 chemicals. 712.2 Section 712.2 Commerce...SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.2 Restrictions on...

2013-01-01

22

15 CFR 712.2 - Restrictions on activities involving Schedule 1 chemicals.  

...on activities involving Schedule 1 chemicals. 712.2 Section 712.2 Commerce...SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.2 Restrictions on...

2014-01-01

23

Antithrombin Regulates Matriptase Activity Involved in Plasmin Generation, Syndecan Shedding, and HGF Activation in Keratinocytes  

PubMed Central

Matriptase, a membrane-associated serine protease, plays an essential role in epidermal barrier function through activation of the glycosylphosphatidylinositol (GPI)-anchored serine protease prostasin. The matriptase-prostasin proteolytic cascade is tightly regulated by hepatocyte growth factor activator inhibitor (HAI)-1 such that matriptase autoactivation and prostasin activation occur simultaneously and are followed immediately by the inhibition of both enzymes by HAI-1. However, the mechanisms whereby matriptase acts on extracellular substrates remain elusive. Here we report that some active matriptase can escape HAI-1 inhibition by being rapidly shed from the cell surface. In the pericellular environment, shed active matriptase is able to activate hepatocyte growth factor (HGF), accelerate plasminogen activation, and shed syndecan 1. The amount of active matriptase shed is inversely correlated with the amount of antithrombin (AT) bound to the surface of the keratinocytes. Binding of AT to the surface of keratinocytes is dependent on a functional heparin binding site, Lys-125, and that the N-glycosylation site Asn-135 be unglycosylated. This suggests that ?-AT, and not ?-AT, is responsible for regulation of pericellular matriptase activity in keratinocytes. Keratinocytes appear to rely on AT to regulate the level of pericellular active matriptase much more than breast and prostate epithelial cells in which AT regulation of matriptase activity occurs at much lower levels than keratinocytes. These results suggest that keratinocytes employ two distinct serine protease inhibitors to control the activation and processing of two different sets of matriptase substrates leading to different biological events: 1) HAI-1 for prostasin activation/inhibition, and 2) AT for the pericellular proteolysis involved in HGF activation, accelerating plasminogen activation, and shedding of syndecans. PMID:23675430

Chen, Ya-Wen; Xu, Zhenghong; Baksh, Adrienne N. H.; Wang, Jehng-Kang; Chen, Chiu-Yuan; Swanson, Richard; Olson, Steve T.; Kataoka, Hiroaki; Johnson, Michael D.; Lin, Chen-Yong

2013-01-01

24

Educational Activities The Department is strongly involved in the  

E-print Network

Toft Sørensen Ongoing PhD Projects Lotte Gottschalck Andersen `Structural properties of superconducting at different levels. The involvement ranges from postgraduate and undergraduate research projects, in colla students. Several of the projects are carried out in collaboration with industrial companies, both through

25

Extracurricular Activity Involvement and Adolescent Self-Esteem  

ERIC Educational Resources Information Center

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…

Kort-Butler, Lisa A.

2012-01-01

26

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

Microsoft Academic Search

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 involvement as a social setting variable and a differential factor. Certain activities

Siu Kwong Wong

2005-01-01

27

Activation and Involvement of Ral GTPases in Colorectal Cancer  

PubMed Central

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

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

2010-01-01

28

Involvement of Hypothalamic AMP-Activated Protein Kinase in Leptin-Induced Sympathetic Nerve Activation  

PubMed Central

In mammals, leptin released from the white adipose tissue acts on the central nervous system to control feeding behavior, cardiovascular function, and energy metabolism. Central leptin activates sympathetic nerves that innervate the kidney, adipose tissue, and some abdominal organs in rats. AMP-activated protein kinase (AMPK) is essential in the intracellular signaling pathway involving the activation of leptin receptors (ObRb). We investigated the potential of AMPK?2 in the sympathetic effects of leptin using in vivo siRNA injection to knockdown AMPK?2 in rats, to produce reduced hypothalamic AMPK?2 expression. Leptin effects on body weight, food intake, and blood FFA levels were eliminated in AMPK?2 siRNA-treated rats. Leptin-evoked enhancements of the sympathetic nerve outflows to the kidney, brown and white adipose tissues were attenuated in AMPK?2 siRNA-treated rats. To check whether AMPK?2 was specific to sympathetic changes induced by leptin, we examined the effects of injecting MT-II, a melanocortin-3 and -4 receptor agonist, on the sympathetic nerve outflows to the kidney and adipose tissue. MT-II-induced sympatho-excitation in the kidney was unchanged in AMPK?2 siRNA-treated rats. However, responses of neural activities involving adipose tissue to MT-II were attenuated in AMPK?2 siRNA-treated rats. These results suggest that hypothalamic AMPK?2 is involved not only in appetite and body weight regulation but also in the regulation of sympathetic nerve discharges to the kidney and adipose tissue. Thus, AMPK might function not only as an energy sensor, but as a key molecule in the cardiovascular, thermogenic, and lipolytic effects of leptin through the sympathetic nervous system. PMID:23418591

Tanida, Mamoru; Yamamoto, Naoki; Shibamoto, Toshishige; Rahmouni, Kamal

2013-01-01

29

Exercise and youth: Physical activity,sport involvement, and development  

Microsoft Academic Search

This article summarizes Plenary Session I, “Exercise and Youth,” at the 6th Annual Congress of the European College of Sport Science (Cologne, 24–28 July 2001). The session provided a broad overview of current knowledge and progress in the field. Using the results of cross-sectional studies, Dietrich Kurz of Germany demonstrated associations between sport activity and personal attributes of psychosocial and

Ulrike Wigger

2001-01-01

30

Hemolysis-induced lethality involves inflammasome activation by heme.  

PubMed

The increase of extracellular heme is a hallmark of hemolysis or extensive cell damage. Heme has prooxidant, cytotoxic, and inflammatory effects, playing a central role in the pathogenesis of malaria, sepsis, and sickle cell disease. However, the mechanisms by which heme is sensed by innate immune cells contributing to these diseases are not fully characterized. We found that heme, but not porphyrins without iron, activated LPS-primed macrophages promoting the processing of IL-1? dependent on nucleotide-binding domain and leucine rich repeat containing family, pyrin domain containing 3 (NLRP3). The activation of NLRP3 by heme required spleen tyrosine kinase, NADPH oxidase-2, mitochondrial reactive oxygen species, and K(+) efflux, whereas it was independent of heme internalization, lysosomal damage, ATP release, the purinergic receptor P2X7, and cell death. Importantly, our results indicated the participation of macrophages, NLRP3 inflammasome components, and IL-1R in the lethality caused by sterile hemolysis. Thus, understanding the molecular pathways affected by heme in innate immune cells might prove useful to identify new therapeutic targets for diseases that have heme release. PMID:25225402

Dutra, Fabianno F; Alves, Letícia S; Rodrigues, Danielle; Fernandez, Patricia L; de Oliveira, Rosane B; Golenbock, Douglas T; Zamboni, Dario S; Bozza, Marcelo T

2014-09-30

31

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

PubMed Central

Longitudinal associations among different types of organized activity involvement, problem peer associations, and cigarette smoking were examined in a sample of 1,040 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 tested longitudinal paths between three categories of involvement (team sports, school clubs and activities, and religious activities, measured at baseline and 15 months), problem peer associations (baseline and 15 months), and cigarette smoking behavior (baseline and 24 months). Multi-group analyses indicated pathways differed by type of activity and adolescent gender. Boys’ baseline team sports and religious involvement predicted lower levels of smoking at 24 months via continued activity involvement at 15 months. Girls’ involvement in school clubs and activities and religious activities indirectly predicted lower levels of smoking at 24 months via reduced exposure to problem peers at 15 months. PMID:21603061

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

2010-01-01

32

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

PubMed

The aim of this study was to examine whether street gang membership, psychological factors, and social factors such as preprison experiences could predict young offenders' involvement in prison gang activity. Data were collected via individual interviews with 188 young offenders held in a Young Offenders Institution in the United Kingdom. Results showed that psychological factors such as the value individuals attached to social status, a social dominance orientation, and antiauthority attitudes were important in predicting young offenders' involvement in prison gang activity. Further important predictors included preimprisonment events such as levels of threat, levels of individual delinquency, and levels of involvement in group crime. Longer current sentences also predicted involvement in prison gang activity. However, street gang membership was not an important predictor of involvement in prison gang activity. These findings have implications for identifying prisoners involved in prison gang activity and for considering the role of psychological factors and group processes in gang research. PMID:24127897

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

2014-06-01

33

Urokinase-type plasminogen activator and arthritis progression: role in systemic disease with immune complex involvement  

Microsoft Academic Search

INTRODUCTION: Urokinase-type plasminogen activator (u-PA) has been implicated in fibrinolysis, cell migration, latent cytokine activation, cell activation, T-cell activation, and tissue remodeling, all of which are involved in the development of rheumatoid arthritis. Previously, u-PA has been reported to play a protective role in monoarticular arthritis models involving mBSA as the antigen, but a deleterious role in the systemic polyarticular

Andrew D Cook; Christine M De Nardo; Emma L Braine; Amanda L Turner; Ross Vlahos; S Kaye Beckman; Jason C Lenzo; John A Hamilton

2010-01-01

34

Organized Activity Involvement, Depressive Symptoms, and Social Adjustment in Adolescents: Ethnicity and Socioeconomic Status as Moderators  

ERIC Educational Resources Information Center

The current cross-sectional study investigated the links between various dimensions of organized activity involvement and depressive symptoms, loneliness, and peer victimization in an ethnically and economically diverse sample of adolescents (N = 152; 58% female). Results indicate that adolescents who were involved in organized activities for more…

Randall, Edin T.; Bohnert, Amy M.

2009-01-01

35

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

ERIC Educational Resources Information Center

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…

Busseri, Michael A.; Rose-Krasnor, Linda

2009-01-01

36

Investigations on the Involvement of the Lectin Pathway of Complement Activation in Anaphylaxis  

Microsoft Academic Search

Background: Systemic anaphylaxis is the most severe form of immediate hypersensitivity reaction. The activation of the complement system occurs during anaphylactic shock. The purpose of this study was to determine in a mouse model whether the lectin pathway of complement activation is involved in anaphylaxis. Methods: To see whether the lectin pathway is involved in anaphylactic shock, serum mannan-binding lectin

Michaela Windbichler; Bernd Echtenacher; Kazue Takahashi; R. Alan B. Ezekowitz; Wilhelm J. Schwaeble; Jens C. Jenseniuis; Daniela N. Männel

2006-01-01

37

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

ERIC Educational Resources Information Center

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)…

Bohnert, Amy; Fredricks, Jennifer; Randall, Edin

2010-01-01

38

Behavioral Adaptation of Alpine Skiers to Climate Change: Examining Activity Involvement and Place Loyalty  

Microsoft Academic Search

This study employed a visitor survey to analyze the influence that changing climatic conditions have on the substitution behaviors of alpine skiers (activity, spatial, temporal). It further focuses on the role that activity involvement plays in influencing behavioral adaptations (i.e., substitution) and also the extent to which place loyalty is affected. The Modified Involvement Scale (MIS) was used to segment

Jackie Dawson; Mark Havitz; Daniel Scott

2011-01-01

39

Ego Strength Development of Adolescents Involved in Adult-Sponsored Structured Activities.  

ERIC Educational Resources Information Center

A psychosocial conception of ego strengths is presented in relation to adolescent involvement in adult-sponsored structured youth activities. Five-hundred and seventeen high school students completed measures on their involvement in structured activities and on 8 ego strengths. Gender, age, and SES were controlled in a MANCOVA procedure and it was…

Markstrom, Carol A.; Li, Xaioming; Blackshire, Shana L.; Wilfong, Juanita J.

2005-01-01

40

Regulation of Amyloid Precursor Protein Catabolism Involves the Mitogen-Activated Protein Kinase Signal Transduction Pathway  

Microsoft Academic Search

Catabolic processing of the amyloid precursor protein (APP) is subject to regulatory control by protein kinases. We hypothe- sized that this regulation involves sequential activation of the enzymes mitogen-activated protein kinase kinase (MEK) and extracellular signal-regulated protein kinase (ERK). In the present investigation, we provide evidence that MEK is critically involved in regulating APP processing by both nerve growth factor

Julia Mills; David Laurent Charest; Fred Lam; Konrad Beyreuther; Nobuo Ida; Steven L. Pelech; Peter B. Reiner

1997-01-01

41

Finding enzymes that are actively involved in cancer Matthew Bogyo1  

E-print Network

Finding enzymes that are actively involved in cancer Matthew Bogyo1 Department of Pathology and translation and at the level of enzyme activity. Thus many now-common "-omic" methods fail to provide in­4). The activity-based proteomic approach makes use of small molecule probes that bind to enzymes in an activity

Bogyo, Matthew

42

Involvement of AP1 proteins in pancreatic stellate cell activation in vitro  

Microsoft Academic Search

Background and aims Pancreatic stellate cells (PSCs) play a key role in the development of pancreatic fibrosis. The molecular mechanisms underlying their activation in response to profibrogenic mediators, however, are largely unknown. Extending previous studies on the transcriptional regulation of PSC activation, we have now focused on the involvement of activator protein (AP)-1. Materials and methods Using cultured rat PSCs,

Brit Fitzner; Gisela Sparmann; Jörg Emmrich; Stefan Liebe; Robert Jaster

2004-01-01

43

Male involvement in child care activities: a review of the literature in Botswana.  

PubMed

Engaging men as partners in childrearing is critical because of the positive aspects on the child's development and reduction of childhood illnesses. The paper presents findings from a literature review whose aim was to assess the extent to which males are involved in child care activities. Findings revealed a limited number of studies conducted in the area of male involvement. Sociocultural factors have a negative influence on men's participation on child care activities. In addition, some laws were prohibitive to male involvement. It was difficult to assess the extent to which males were involved due to inadequate data collection tools. Recommendations include a study on male involvement, review of the existing Sexual and Reproductive Health data collection tools, development of a policy on paternity leave, strengthening training on male involvement; community sensitization on cultural stereotypes and harmonization of customary and common laws. PMID:24558780

Jorosi-Tshiamo, Wananani B; Mogobe, Keitshokile D; Mokotedi, Mosidi T

2013-12-01

44

24 CFR 1000.501 - Who is involved in monitoring activities under NAHASDA?  

...CONTINUED) OFFICE OF ASSISTANT SECRETARY FOR PUBLIC AND INDIAN HOUSING, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT NATIVE AMERICAN HOUSING ACTIVITIES Recipient Monitoring, Oversight and Accountability § 1000.501 Who is involved in...

2014-04-01

45

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

PubMed Central

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

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

2014-01-01

46

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

SciTech Connect

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.

Neff, Michael M.

2011-06-23

47

Involvement of tissue plasminogen activator in stress responsivity during acute cocaine withdrawal in mice  

E-print Network

Involvement of tissue plasminogen activator in stress responsivity during acute cocaine withdrawal to stress responsivity during cocaine withdrawal (WD). Recent studies suggest that tissue plasminogen activator (tPA) in the CeA is a downstream effector protein for CRF after acute "binge" cocaine

48

Premature aging in mice activates a systemic metabolic response involving autophagy induction  

Microsoft Academic Search

Autophagy is a highly regulated intracellular process involved in the turnover of most cellular constituents and in the maintenance of cellular homeostasis. It is well-established that the basal autophagic activity of living cells decreases with age, thus contributing to the accumulation of damaged macromolecules during aging. Conversely, the activity of this catabolic pathway is required for lifespan extension in animal

G. Mariño; Alejandro P. Ugalde; Natalia Salvador-Montoliu; Ignacio Varela; P. M. Quirós; J. Cadiñanos; Pluijm van der I; J. M. P. Freije; C. López-Otín

2008-01-01

49

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

ERIC Educational Resources Information Center

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…

Randall, Edin T.; Bohnert, Amy M.

2012-01-01

50

Civil Society, Physical Activity, and the Involvement of Sport Sociologists in the Preparation of Physical Activity Professionals.  

ERIC Educational Resources Information Center

Civil society is important for enhancing quality of life, but it is weakening in the U.S. and elsewhere, with formidable obstacles to expanding it. This paper examines strategies for reinvigorating it; considers relationships between civil society, physical activity, and physical-activity professionals; and discusses involvement of sport…

Harris, Janet C.

1998-01-01

51

An Experiment with Active Involvement in the Teaching of General Physics  

NASA Astrophysics Data System (ADS)

This is a report on an experiment using several active involvement teaching techniques in a general physics course involving some 250 students in two semesters. Included were peer instruction, collaborative worksheets, web-based practice tests, web-based notes, homework submitted on the web, and conceptual emphasis. Student performance was measured with and without the techniques using the Force Concept Inventory and the Mechanics Baseline Test. Results will be reported along with student reaction.

Miner, George

2001-10-01

52

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

Code of Federal Regulations, 2013 CFR

...to activities involving Schedule 1 chemicals. 712.1 Section 712.1 Commerce...SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.1 Round to zero...

2013-01-01

53

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

Code of Federal Regulations, 2012 CFR

...to activities involving Schedule 1 chemicals. 712.1 Section 712.1 Commerce...SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.1 Round to zero...

2012-01-01

54

Parental support and pressure and children's extracurricular activities: relationships with amount of involvement and affective experience of participation  

Microsoft Academic Search

This study examined children's perceptions of their parents' involvement in all types of extracurricular activities, extending research beyond the sports domain. The Parental Involvement in Activities Scale (PIAS) was developed to measure children's perceptions of their parents' involvement. The PIAS resulted in a 16-item measure with 2 factors, “support” and “pressure.” The amount of time children spend in their activities

Jennifer C Anderson; Jeanne B Funk; Robert Elliott; Peg Hull Smith

2003-01-01

55

Activator-Dependent Transcription from Chromatin In Vitro Involving Targeted Histone Acetylation by p300  

Microsoft Academic Search

The transcriptional coactivator p300 shows physical and functional interactions with a diverse group of activators and contains an intrinsic acetyltransferase activity whose exact coactivator functions in the acetylation of nucleosomal histones versus other factors are poorly documented. Here, we show that p300 mediates acetyl-CoA-dependent transcription by GAL4-VP16 from a nucleosomal array template, that this involves p300 targeting by GAL4-VP16 and

Tapas K. Kundu; Vikas B. Palhan; Zhengxin Wang; Woojin An; Philip A. Cole; Robert G. Roeder

2000-01-01

56

Mechanical stress activates angiotensin II type 1 receptor without the involvement of angiotensin II  

Microsoft Academic Search

The angiotensin II type 1 (AT1) receptor has a crucial role in load-induced cardiac hypertrophy. Here we show that the AT1 receptor can be activated by mechanical stress through an angiotensin-II-independent mechanism. Without the involvement of angiotensin II, mechanical stress not only activates extracellular-signal-regulated kinases and increases phosphoinositide production in vitro, but also induces cardiac hypertrophy in vivo. Mechanical stretch

Yunzeng Zou; Hiroshi Akazawa; Yingjie Qin; Masanori Sano; Hiroyuki Takano; Tohru Minamino; Noriko Makita; Koji Iwanaga; Weidong Zhu; Sumiyo Kudoh; Haruhiro Toko; Koichi Tamura; Minoru Kihara; Toshio Nagai; Akiyoshi Fukamizu; Satoshi Umemura; Taroh Iiri; Toshiro Fujita; Issei Komuro

2004-01-01

57

Carbohydrate in the mouth enhances activation of brain circuitry involved in motor performance and sensory perception.  

PubMed

The presence of carbohydrate in the human mouth has been associated with the facilitation of motor output and improvements in physical performance. Oral receptors have been identified as a potential mode of afferent transduction for this novel form of nutrient signalling that is distinct from taste. In the current study oral exposure to carbohydrate was combined with a motor task in a neuroimaging environment to identify areas of the brain involved in this phenomenon. A mouth-rinsing protocol was conducted whilst carbohydrate (CHO) and taste-matched placebo (PLA) solutions were delivered and recovered from the mouths of 10 healthy volunteers within a double-blind, counterbalanced design. This protocol eliminates post-oral factors and controls for the perceptual qualities of solutions. Functional magnetic resonance imaging of the brain was used to identify cortical areas responsive to oral carbohydrate during rest and activity phases of a hand-grip motor task. Mean blood-oxygen-level dependent signal change experienced in the contralateral primary sensorimotor cortex was larger for CHO compared with PLA during the motor task when contrasted with a control condition. Areas of activation associated with CHO exclusively were observed over the primary taste cortex and regions involved in visual perception. Regions in the limbic system associated with reward were also significantly more active with CHO. This is the first demonstration that oral carbohydrate signalling can increase activation within the primary sensorimotor cortex during physical activity and enhance activation of neural networks involved in sensory perception. PMID:24858834

Turner, Clare E; Byblow, Winston D; Stinear, Cathy M; Gant, Nicholas

2014-09-01

58

Electronics is the branch of physics, engineering and technology dealing with electrical circuits that involve active  

E-print Network

28/04/14 1 Electronics is the branch of physics, engineering and technology dealing with electrical circuits that involve active electrical components such as vacuum tubes, transistors, diodes and integrated computers, tablets, internet... · Mobile devices: iPhones, mp3 players... · Solar cells, led displays

Ã?nay, Devrim

59

Structural Model of Employee Involvement in Skill Development Activity: The Role of Individual Differences  

ERIC Educational Resources Information Center

We extend prior research on involvement in employee development activity by including prominent individual difference constructs that have been previously ignored in this area of research. These include two important personality characteristics (conscientiousness and openness to experience), mental ability and goal orientation constructs. We…

Maurer, Todd J.; Lippstreu, Michael; Judge, Timothy A.

2008-01-01

60

Perceived community environment and physical activity involvement in a northern-rural Aboriginal community  

Microsoft Academic Search

BACKGROUND: Type 2 diabetes disproportionately affects Aboriginal peoples in Canada. Ample evidence shows that regular physical activity (PA) plays an important role in the prevention and treatment of type 2 diabetes. Evidence is beginning to emerge linking PA to the physical environment but little is known about the relationship between remote rural environments and PA involvement in Aboriginal peoples. This

Allison M. Kirby; Lucie Lévesque; Virginia Wabano; Jennifer Robertson-Wilson

2007-01-01

61

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

ERIC Educational Resources Information Center

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)

Savage, William; Storer, Graeme

1992-01-01

62

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

ERIC Educational Resources Information Center

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…

White, Amanda M.; Gager, Constance T.

2007-01-01

63

Magnesium Ion-dependent Activation of the RecA Protein Involves the C Terminus*  

E-print Network

Magnesium Ion-dependent Activation of the RecA Protein Involves the C Terminus* Received with ATP. We provide evi- dence that the free magnesium ion is required to medi- ate a conformational at low magnesium ion concentrations. The RecA protein of Escherichia coli plays a central role

Cox, Michael M.

64

814 Journal of Lipid Research Volume 41, 2000 Involvement of the peroxisome proliferator-activated  

E-print Network

814 Journal of Lipid Research Volume 41, 2000 Involvement of the peroxisome proliferator of peroxisome proliferator-induced genes en- coding cytosolic (CTE-I), mitochondrial (MTE-I), and peroxi- somal of the peroxisome proliferator-activated receptor in regu- lating long-chain acyl-CoA thioesterases. J. Lipid Res

Omiecinski, Curtis

65

Extracurricular Activity and Parental Involvement Predict Positive Outcomes in Elementary School Children  

ERIC Educational Resources Information Center

The main goal of this study was to explore if parental involvement and extracurricular activity participation could predict well-being and academic competence in elementary school children. Seventy-two children (mean age = 10.9 years, SD = 0.85) and their parents participated. Results revealed that parental pressure and support, when paired with…

Lagace-Seguin, Daniel G.; Case, Emily

2010-01-01

66

A Handbook on How to Involve Parents in School Activities: Hawaii Follow Through Project.  

ERIC Educational Resources Information Center

This handbook on how to involve parents in school activities, includes ideas and techniques which were used by Hawaii's kindergarten and elementary school teachers to (1) help parents understand how learning takes place; (2) provide parents with opportunities to observe and participate in classroom activites; and (3) work with parents and…

Hawaii State Dept. of Education, Honolulu. Office of Instructional Services.

67

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

ERIC Educational Resources Information Center

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…

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

2011-01-01

68

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

ERIC Educational Resources Information Center

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…

Jiang, Xin; Peterson, Ruth D.

2012-01-01

69

Calanquinone A induces anti-glioblastoma activity through glutathione-involved DNA damage and AMPK activation.  

PubMed

Glioblastoma, a highly malignant glioma, is resistant to both radiation and chemotherapy and is an intractable problem in clinical treatment. New therapeutic approaches are in urgent need. Calanquinone A, an herbal constituent, displayed anti-proliferative activity against glioblastoma cells, including A172, T98 and U87. Flow cytometric analysis showed an S phase arrest and a subsequent apoptosis to calanquinone A action. Further identification demonstrated a rapid increase of ?H2A.X formation at S phase. The data together with comet tail formation and Chk1 activation indicated DNA damage response. N-acetyl cysteine (an antioxidant and a glutathione precursor) and exogenously applied glutathione, but not trolox (an antioxidant), completely abolished calanquinone A-induced effects. Immunofluorescence assay revealed that calanquinone A decreased the intracellular glutathione levels in both A172 and T98 cells. However, calanquinone A, by itself, did not conjugate glutathione. The data suggested that the decrease of cellular glutathione predominantly contributed to the anticancer mechanism. Furthermore, calanquinone A induced the activation of AMP-activated protein kinase (AMPK) and the inhibition of p70S6K activity. Rhodamine efflux assay showed that calanquinone A did not block efflux activity, indicating that calanquinone A was not a P-glycoprotein substrate. In summary, the data suggest that calanquinone A displays anti-glioblastoma activity through a decrease of cellular glutathione levels that subsequently induces DNA damage stress and AMPK activation, leading to cell cycle arrest at S-phase and apoptotic cell death. Furthermore, calanquinone A does not serve as a P-glycoprotein substrate, suggesting a potential for further development in anti-glioblastoma therapy. PMID:24607408

Liu, Fan-Lun; Hsu, Jui-Ling; Lee, Yean-Jang; Dong, Yu-Shun; Kung, Fan-Lu; Chen, Ching-Shih; Guh, Jih-Hwa

2014-05-01

70

Involvement of Macromolecule Biosynthesis in Auxin and Fusicoccin Enhancement of ?-Glucan Synthase Activity in Pea 1  

PubMed Central

In pea stem segments whose cuticle has been made permeable by abrading it, actinomycin D (ActD) and 80S ribosomal protein synthesis inhibitors such as cycloheximide (CHI) inhibit enhancement by indole 3-acetic acid (IAA) of the activity of the cell wall biosynthetic enzyme, glucan synthase I (GS). This supersedes earlier, negative results with inhibitors, obtained with segments having an intact cuticle, which prevents adequate inhibitor uptake. Since these inhibitors also block IAA-stimulated H+ extrusion, which according to earlier results is involved in the GS response, the significance of these inhibitions would be ambiguous without additional evidence. ActD does not inhibit fusicoccin (FC) enhancement of GS activity, which indicates existence of a post-transcriptional control mechanism for GS, but does not preclude involvement of transcription in the GS response to IAA. Although protein synthesis inhibitors such as CHI do not block FC-stimulated H+ extrusion, they do inhibit FC enhancement of GS activity, indicating an involvement of protein synthesis in the GS response to FC, and presumably also to IAA. However, protein synthesis inhibitors (but not ActD) by themselves paradoxically elevate GS activity, less strongly than IAA does but resembling the IAA enhancement in several characteristics. These results suggest that IAA may enhance GS activity at least in part by inhibiting the synthesis or action of a labile repressor of the transcription of, or a labile destabilizer of, mRNA for GS or some polypeptide that enhances GS activity. However, resemblances between the IAA and FC effects on GS suggest that IAA also has a posttranscriptional GS-enhancing action like that of FC. Lipid biosynthesis may be involved in this aspect of the response since both IAA and FC enhancements of GS activity are inhibited by cerulenin. PMID:16665730

Ray, Peter M.

1987-01-01

71

Labdane diterpenes protect against anoxia/reperfusion injury in cardiomyocytes: involvement of AKT activation  

PubMed Central

Several labdane diterpenes exert anti-inflammatory and cytoprotective actions; therefore, we have investigated whether these molecules protect cardiomyocytes in an anoxia/reperfusion (A/R) model, establishing the molecular mechanisms involved in the process. The cardioprotective activity of three diterpenes (T1, T2 and T3) was studied in the H9c2 cell line and in isolated rat cardiomyocyte subjected to A/R injury. In both cases, treatment with diterpenes T1 and T2 protected from A/R-induced apoptosis, as deduced by a decrease in the percentage of apoptotic and caspase-3 active positive cells, a decrease in the Bcl-2/Bax ratio and an increase in the expression of antiapoptotic proteins. Analysis of cell survival signaling pathways showed that diterpenes T1 and T2 added after A/R increased phospho-AKT and phospho-ERK 1/2 levels. These cardioprotective effects were lost when AKT activity was pharmacologically inhibited. Moreover, the labdane-induced cardioprotection involves activation of AMPK, suggesting a role for energy homeostasis in their mechanism of action. Labdane diterpenes (T1 and T2) also exerted cardioprotective effects against A/R-induced injury in isolated cardiomyocytes and the mechanisms involved activation of specific survival signals (PI3K/AKT pathways, ERK1/2 and AMPK) and inhibition of apoptosis. PMID:22071634

Cuadrado, I; Fernandez-Velasco, M; Bosca, L; de las Heras, B

2011-01-01

72

Violence Involvement, Substance Use, and Sexual Activity among Mexican American and European American Adolescents  

PubMed Central

Purpose This study examined longitudinal associations between violence involvement, substance use, and sexual activity. Methods 302 urban Mexican American and European American adolescents were randomly selected and recruited from the membership lists of a large health maintenance organization. Data were obtained from interviews conducted when the mean ages of adolescents were 15, 18, and 19 years. Results Independent of age, gender, ethnicity, family socioeconomic status, and previous levels of health risk behavior, adolescents who had been victimized by violence at age 15 were more likely to use tobacco at age 19. Adolescents who had been victimized by or perpetrated violence at age 18 had a greater number of sexual partners and were more likely to use marijuana at age 19. In addition, adolescents who had perpetrated violence at age 18 engaged in greater alcohol use at age 19. A second set of analyses showed that independent of demographics and previous violence involvement, adolescents who had used marijuana at age 15 were more likely to report violence involvement at age 19. Adolescents who had used tobacco or who had a greater number of sexual partners at ages 15 or 18 were more likely to report violent victimization at age 19. Conclusions Associations between violence involvement and other forms of health risk behavior are bidirectional. Adolescents involved with violence are at risk for increases in substance use and sexual behavior over time. Adolescents who engage in substance use and sexual behavior with multiple partners are also at risk for later violence involvement. PMID:18710684

Brady, Sonya S.; Tschann, Jeanne M.; Pasch, Lauri A.; Flores, Elena; Ozer, Emily J.

2008-01-01

73

EMERGING ADULTS' TREATMENT OUTCOMES IN RELATION TO 12-STEP MUTUAL-HELP ATTENDANCE AND ACTIVE INVOLVEMENT  

PubMed Central

Background Participation in Alcoholics Anonymous (AA) and Narcotics Anonymous (NA) during and following treatment has been found to confer recovery-related benefit among adults and adolescents, but little is known about emerging adults (18–24yrs). This transitional life-stage is distinctive for greater distress, higher density of psychopathology, and poorer treatment and continuing care compliance. Greater knowledge would inform the utility of treatment referrals to 12-step organizations for this age-group. Methods Emerging adults (N=303; 18–24yrs; 26% female; 95% White; 51% comorbid [SCID-derived] axis I disorders) enrolled in a naturalistic study of residential treatment effectiveness assessed at intake, 3, 6, and 12 months on 12-step attendance and involvement and treatment outcomes (Percent Days Abstinent [PDA]; Percent Days Heavy Drinking [PDHD]). Lagged hierarchical linear models (HLMs) tested whether attendance and involvement conferred recovery benefits, controlling for a variety of confounds. Results The percentage attending 12-step meetings prior to treatment (36%) rose sharply at 3months (89%), was maintained at 6 months (82%), but declined at 12 months (76%). Average attendance peaked at about 3 times per week at 3 months dropping to just over once per week at 12 months. Initially high, but similarly diminishing, levels of active 12-step involvement were also observed. Lagged HLMs found beneficial effects for attendance, but stronger effects, which increased over time, for active involvement. Several active 12-step involvement indices were associated individually with outcome benefits. Conclusions Ubiquitous 12-step organizations may provide a supportive recovery context for this high-risk population at a developmental stage where non-using/sober peers are at a premium. PMID:23122600

Kelly, John F.; Stout, Robert L.; Slaymaker, Valerie

2012-01-01

74

Involvement of Mitogen-Activated Protein Kinase in Hippocampal Long-Term Potentiation  

Microsoft Academic Search

Mitogen-activated protein kinase (MAPK) cascade classically is thought to be involved in cellular transformation, including proliferation and differentiation. Recent behavioral studies suggest that MAPK may also have a role in learning and memory. Long-term potentiation (LTP), a candidate mechanism for learning and memory, has at least two distinct temporal phases: an early phase (E-LTP) which lasts for 1–2 h and

Shang-Peng Wu; Kwok-Tung Lu; Wen-Chang Chang; Po-Wu Gean

1999-01-01

75

Involvement of Regulatory and Catalytic Subunits of Phosphoinositide 3Kinase in NF-kappa B Activation  

Microsoft Academic Search

Hypoxia, reoxygenation, and the tyrosine phosphatase inhibitor pervanadate activate the transcription factor NF-kappa B involving phosphorylation of its inhibitor Ikappa B-alpha on tyrosine 42. This modification does not lead to degradation of Ikappa B by the proteasome\\/ubiquitin pathway, as is seen on stimulation of cells with proinflammatory cytokines. It is currently unknown how tyrosine-phosphorylated Ikappa B is removed from NF-kappa

Christophe Beraud; William J. Henzel; Patrick A. Baeuerle

1999-01-01

76

Aluminum Hydroxide Adjuvant Differentially Activates the Three Complement Pathways with Major Involvement of the Alternative Pathway  

PubMed Central

Al(OH)3 is the most common adjuvant in human vaccines, but its mode of action remains poorly understood. Complement involvement in the adjuvant properties of Al(OH)3 has been suggested in several reports together with a depot effect. It is here confirmed that Al(OH)3 treatment of serum depletes complement components and activates the complement system. We show that complement activation by Al(OH)3 involves the three major pathways by monitoring complement components in Al(OH)3-treated serum and in Al(OH)3-containing precipitates. Al(OH)3 activation of complement results in deposition of C3 cleavage products and membrane attack complex (MAC) and in generation of the anaphylatoxins C3a and C5a. Complement activation was time dependent and inhibited by chelation with EDTA but not EGTA+Mg2+. We thus confirm that Al(OH)3 activates the complement system and show that the alternative pathway is of major importance. PMID:24040248

Guven, Esin; Duus, Karen; Laursen, Inga; H?jrup, Peter; Houen, Gunnar

2013-01-01

77

Extracurricular activities in young applicants' résumés: what are the motives behind their involvement?  

PubMed

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

Roulin, Nicolas; Bangerter, Adrian

2013-01-01

78

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

PubMed

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

Jiang, Xin; Peterson, Ruth D

2012-03-01

79

Antinociceptive Activity of Methanol Extract of Muntingia calabura Leaves and the Mechanisms of Action Involved  

PubMed Central

Muntingia calabura L. (family Elaeocarpaceae) has been traditionally used to relieve various pain-related ailments. The present study aimed to determine the antinociceptive activity of methanol extract of M. calabura leaves (MEMC) and to elucidate the possible mechanism of antinociception involved. The in vivo chemicals (acetic acid-induced abdominal constriction and formalin-, capsaicin-, glutamate-, serotonin-induced paw licking test) and thermal (hot plate test) models of nociception were used to evaluate the extract antinociceptive activity. The extract (100, 250, and 500?mg/kg) was administered orally 60?min prior to subjection to the respective test. The results obtained demonstrated that MEMC produced significant (P < 0.05) antinociceptive response in all the chemical- and thermal-induced nociception models, which was reversed after pretreatment with 5?mg/kg naloxone, a non-selective opioid antagonist. Furthermore, pretreatment with L-arginine (a nitric oxide (NO) donor), NG-nitro-L-arginine methyl esters (L-NAME; an inhibitor of NO synthase (NOS)), methylene blue (MB; an inhibitor of cyclic-guanosine monophosphate (cGMP) pathway), or their combination also caused significant (P < 0.05) change in the intensity of the MEMC antinociception. In conclusion, the MEMC antinociceptive activity involves activation of the peripheral and central mechanisms, and modulation via, partly, the opioid receptors and NO/cGMP pathway. PMID:22611437

Sani, M. H. Mohd.; Zakaria, Z. A.; Balan, T.; Teh, L. K.; Salleh, M. Z.

2012-01-01

80

Involvement of the SATB1/F-actin complex in chromatin reorganization during active cell death  

PubMed Central

Over the past years, confirmations on the presence of actin and/or its polymerized form, F-actin, in the cell nucleus are progressively accumulating. Nevertheless, the function and localization of F-actin in the nucleus is still not fully characterized. Thus, the aim of the present study was to evaluate the association between F-actin and sequence-binding protein 1 (SATB1) and their involvement in chromatin remodeling associated with active cell death. Both SATB1 and F-actin were colocalized in the transcriptional active regions of the cell nucleus and a functional interaction was observed between SATB1 and higher-organized nuclear F-actin structures at the border between condensed and decondensed chromatin. These results extend the knowledge on the role of SATB1 and nuclear F-actin in three-dimensional chromatin organization and their functions during active cell death. Additionally, this study opens the discussion on the involvement of the SATB1/F-actin functional complex in active cell death; further studies are required to fully elucidate these issues. PMID:24676287

GRZANKA, DARIUSZ; GAGAT, MACIEJ; IZDEBSKA, MAGDALENA

2014-01-01

81

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

PubMed Central

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

Russell, Stephen T.

2012-01-01

82

von Hippel-Lindau tumor suppressor protein stimulation by thrombin involves RhoA activation.  

PubMed

Inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene is associated with the development of vascular tumors including renal cell carcinoma. Aside from the role played by the VHL protein (pVHL) in negative regulation of hypoxia-inducible factor, 41F-1alpha, pVHL also takes part in cytoskeletal organization. Thrombin is a serine protease involved in angiogenesis and in cancer progression and its action is mediated by the protease-activated receptors (PARs). In several cell types, thrombin induces reorganization of the cytoskeleton along with RhoA activation. Thus, we conducted an investigation on the capacity of thrombin to regulate pVHL expression. Our results demonstrated that VHL mRNA and protein levels were increased by thrombin in cultured renal cancer cells. Cytoplasmic pVHL was redistributed to perinuclear regions and membrane fractions following thrombin treatments. Stimulation of Caki-1 cells with PAR1, PAR2 and PAR4 agonist peptides demonstrated that PAR1 was the receptor involved in thrombin-induced pVHL expression. Western blot analysis confirmed that these cells express PAR1 and that its expression was increased by thrombin. PAR1 activation by both thrombin and an agonist peptide stimulated renal cancer cell invasion through Matrigel. Interestingly, the upregulation of pVHL was dependent on RhoA because C3 exotoxin abolished pVHL induction. However, the pharmacological Rho kinase inhibitor, Y27632, did not influence pVHL expression in the presence of thrombin, suggesting that other RhoA effectors were involved in the process. Together, these results demonstrate that thrombin induces both pVHL expression via PAR1/RhoA activation as well as the stimulation of renal cancer cell invasion suggesting a role for thrombin in tumor invasion. PMID:15386385

Turcotte, Sandra; Desrosiers, Richard R; Brand, Geneviève; Béliveau, Richard

2004-12-10

83

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

SciTech Connect

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.

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

1986-01-01

84

Activated K-ras is involved in regulation of integrin expression in human colon carcinoma cells.  

PubMed

Integrins participate in controlling proliferation and migration. Therefore, changes in integrin expression might be responsible for unrestrained proliferation and invasiveness of tumor cells. Alterations of integrin subunit expression have been observed in human colon carcinoma, especially loss or reduction of the alpha5 subunit, which was observed consistently. The mechanisms responsible for reduction of alpha5 expression and alteration of expression of other integrins are not fully understood. Circumstantial evidence from previous investigations points to an involvement of activated ras oncogenes in repression of integrin expression. The K-ras protooncogene is activated by point mutation in 50% of human colon carcinomas. Thus, we choose an antisense approach for specific inactivation of activated K-ras in the human colon carcinoma cell line SW 480 in order to test whether activated K-ras contributes to changes in integrin expression on colon carcinoma cells. Cell surface expression of the alpha1 and the alpha5 subunit was increased in K-ras antisense transfected clones, cell surface expression of the alpha3 subunit and the alphav subunit was decreased. This shows, in a human system, that activated K-ras is involved in diminishing cell surface expression of the alpha1beta1 collagen/laminin receptor and the alpha5beta1 fibronectin receptor, both of which are implicated in maintenance of a non-transformed phenotype. Moreover, activated K-ras contributes to increased cell surface expression of the alpha3beta1 laminin/collagen/fibronectin receptor and the alphavbeta5 vitronectin receptor, which might play a role in metastatic behavior of tumor cells. PMID:10861468

Schramm, K; Krause, K; Bittroff-Leben, A; Goldin-Lang, P; Thiel, E; Kreuser, E D

2000-07-15

85

Activated Hair Follicle Stem Cells and Wnt/?-catenin Signaling Involve in Pathnogenesis of Sebaceous Neoplasms  

PubMed Central

Sebaceous glands (SGs) undergo cyclic renewal independent of hair follicle stem cells (HFSCs) activation while HFSCs have the potential to differentiate into sebaceous gland cells, hair follicle and epidermal keratinocytes. Abnormalities of sebaceous gland progenitor cells contribute to the development of sebaceous neoplasms, but little is known about the role of HFSCs during sebaceous neoplasm development. Here, using dimethylbenzanthracene (DMBA) plus 12-o-tetradecanoyl phorbol-13-acetate (TPA) treatment developing sebaceous neoplasms (SNs) were identified with H&E and Oil red O staining. And then the molecular expression and activation of HFSCs and was characterized by immunostaining. Wnt10b/?-catenin signaling molecular which is important for activation of HFSCs were detected by immunostaining. We found hair follicle and epidermal cell markers were expressed in sebaceous neoplasms. Furthermore, SOX-9 and CD34-positive HFSCs were located in the basal layer of sebaceous lobules within the sebaceous neoplasms. Many appear to be in an active state. Finally, Wnt10b/?-catenin signaling was activated within the basal cells of sebaceous lobules in the sebaceous neoplasms. Collectively, our findings suggest that the abnormal activation of both HFSCs and Wnt10b/?-catenin signaling involves in the development of sebaceous neoplasms. PMID:25076848

Qiu, Weiming; Lei, Mingxing; Li, Jin; Wang, Ning; Lian, Xiaohua

2014-01-01

86

Involvement of TREK-1 activity in astrocyte function and neuroprotection under simulated ischemia conditions.  

PubMed

Astrocytes play a fundamental role in the pathogenesis of ischemic neuronal death. The optimal operation of electrogenic astrocytic transporters and exchangers for some well-defined astrocyte brain homeostatic functions depends on the presence of K(+) channels in the cell membranes and the hyperpolarized membrane potential. Our previous study showed that astrocytes functionally express two-pore domain K(+) channel TREK-1, which helps to set the negative resting membrane potential. However, the roles of TREK-1 on astrocytic function under normal and ischemic conditions remain unclear. In this study, we investigated the expression of TREK-1 protein on cultured astrocytes and the effect of TREK-1 activity on astrocytic glutamate clearance capacity and release of s100? after simulated ischemic insult. TREK-1 immunoreactivity was up-regulated after hypoxia. Suppression of TREK-1 activity inhibited the glutamate clearance capability, enhanced the inflammatory secretion of astrocytes derived s100? and led to increased neuronal apoptosis after ischemic insult. Our results suggest that TREK-1 activity is involved in astrocytic function and neuronal survival. This would provide evidence showing astrocytic TREK-1 involvement in ischemia pathology which may serve as a potential therapeutic target in stroke. PMID:22895843

Wu, Xiao; Liu, Yang; Chen, Xiaojing; Sun, Qian; Tang, Ronghua; Wang, Wei; Yu, Zhiyuan; Xie, Minjie

2013-03-01

87

Zebrafish reporter lines reveal in vivo signaling pathway activities involved in pancreatic cancer.  

PubMed

Pancreatic adenocarcinoma, one of the worst malignancies of the exocrine pancreas, is a solid tumor with increasing incidence and mortality in industrialized countries. This condition is usually driven by oncogenic KRAS point mutations and evolves into a highly aggressive metastatic carcinoma due to secondary gene mutations and unbalanced expression of genes involved in the specific signaling pathways. To examine in vivo the effects of KRAS(G12D) during pancreatic cancer progression and time correlation with cancer signaling pathway activities, we have generated a zebrafish model of pancreatic adenocarcinoma in which eGFP-KRAS(G12D) expression was specifically driven to the pancreatic tissue by using the GAL4/UAS conditional expression system. Outcrossing the inducible oncogenic KRAS(G12D) line with transgenic zebrafish reporters, harboring specific signaling responsive elements of transcriptional effectors, we were able to follow TGF?, Notch, Bmp and Shh activities during tumor development. Zebrafish transgenic lines expressing eGFP-KRAS(G12D) showed normal exocrine pancreas development until 3 weeks post fertilization (wpf). From 4 to 24 wpf we observed several degrees of acinar lesions, characterized by an increase in mesenchymal cells and mixed acinar/ductal features, followed by progressive bowel and liver infiltrations and, finally, highly aggressive carcinoma. Moreover, live imaging analysis of the exocrine pancreatic tissue revealed an increasing number of KRAS-positive cells and progressive activation of TGF? and Notch pathways. Increase in TGF?, following KRAS(G12D) activation, was confirmed in a concomitant model of medulloblastoma (MDB). Notch and Shh signaling activities during tumor onset were different between MDB and pancreatic adenocarcinoma, indicating a tissue-specific regulation of cell signaling pathways. Moreover, our results show that a living model of pancreatic adenocarcinoma joined with cell signaling reporters is a suitable tool for describing in vivo the signaling cascades and molecular mechanisms involved in tumor development and a potential platform to screen for novel oncostatic drugs. PMID:24878567

Schiavone, Marco; Rampazzo, Elena; Casari, Alessandro; Battilana, Giusy; Persano, Luca; Moro, Enrico; Liu, Shu; Leach, Steve D; Tiso, Natascia; Argenton, Francesco

2014-07-01

88

Involvement of multiple elements in FXR-mediated transcriptional activation of FGF19.  

PubMed

The intestinal endocrine hormone human fibroblast growth factor 19 (FGF19) is involved in the regulation of not only hepatic bile acid metabolism but also carbohydrate and lipid metabolism. In the present study, bile acid/farnesoid X receptor (FXR) responsiveness in the FGF19 promoter region was investigated by a reporter assay using the human colon carcinoma cell line LS174T. The assay revealed the presence of bile acid/FXR-responsive elements in the 5'-flanking region up to 8.8 kb of FGF19. Deletion analysis indicated that regions from -1866 to -1833, from -1427 to -1353, and from -75 to +262 were involved in FXR responsiveness. Four, four, and two consecutive half-sites of nuclear receptors were observed in the three regions, respectively. An electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay revealed FXR/retinoid X receptor ? (RXR?) heterodimer binding in these three regions. EMSA and reporter assays using mutated constructs indicated that the nuclear receptor IR1, ER2, and DR8 motifs in the 5'-flanking region were involved in FXR responsiveness of FGF19. Lithocholic acid (LCA) (10 ?M), chenodeoxycholic acid (CDCA) (10 ?M), or GW4064 (0.1 ?M) treatment increased reporter activity in a construct including the three motifs under FXR-expressing conditions whereas LCA and not CDCA or GW4064 treatment increased the reporter activity under pregnane X receptor (PXR)-expressing conditions. These results suggest that FGF19 is transcriptionally activated through multiple FXR-responsive elements in the promoter region. PMID:22561792

Miyata, Masaaki; Hata, Tatsuya; Yamakawa, Hiroki; Kagawa, Tatehiro; Yoshinari, Kouichi; Yamazoe, Yasushi

2012-10-01

89

Urokinase-type plasminogen activator and arthritis progression: role in systemic disease with immune complex involvement  

PubMed Central

Introduction Urokinase-type plasminogen activator (u-PA) has been implicated in fibrinolysis, cell migration, latent cytokine activation, cell activation, T-cell activation, and tissue remodeling, all of which are involved in the development of rheumatoid arthritis. Previously, u-PA has been reported to play a protective role in monoarticular arthritis models involving mBSA as the antigen, but a deleterious role in the systemic polyarticular collagen-induced arthritis (CIA) model. The aim of the current study is to determine how u-PA might be acting in systemic arthritis models. Methods The CIA model and bone marrow chimeras were used to determine the cellular source of u-PA required for the arthritis development. Gene expression of inflammatory and destructive mediators was measured in joint tissue by quantitiative PCR and protein levels by ELISA. The requirement for u-PA in the type II collagen mAb-induced arthritis (CAIA) and K/BxN serum transfer arthritis models was determined using u-PA-/- mice. Neutrophilia was induced in the peritoneal cavity using either ovalbumin/anti-ovalbumin or the complement component C5a. Results u-PA from a bone marrow-derived cell was required for the full development of CIA. The disease in u-PA-/- mice reconstituted with bone marrrow from C57BL/6 mice was indistinguishable from that in C57BL/6 mice, in terms of clincal score, histologic features, and protein and gene expression of key mediators. u-PA-/- mice were resistant to both CAIA and K/BxN serum transfer arthritis development. u-PA-/- mice developed a reduced neutrophilia and chemokine production in the peritoneal cavity following ovalbumin/anti-ovalbumin injection; in contrast, the peritoneal neutrophilia in response to C5a was u-PA independent. Conclusions u-PA is required for the full development of systemic arthritis models involving immune complex formation and deposition. The cellular source of u-PA required for CIA is bone marrow derived and likely to be of myeloid origin. For immune complex-mediated peritonitis, and perhaps some other inflammatory responses, it is suggested that the u-PA involvement may be upstream of C5a signaling. PMID:20196869

2010-01-01

90

Norcantharidin induces apoptosis of breast cancer cells: Involvement of activities of mitogen activated protein kinases and signal transducers and activators of transcription  

Microsoft Academic Search

Involvement of activities of mitogen-activated protein kinases (MAPKs) and signal transducers and activators of transcription (STATs) remains unsolved in norcantharidin-associated breast cancer cell apoptosis. This study investigated the anti-cancer effect of norcantharidin and its underlying mechanism in two human breast cancer cell lines, estrogen receptor (ER)? HS-578T and ER+ MCF-7 cells. Norcantharidin induced potent cytotoxicity and arrested cell growth through

Pei-Yu Yang; Ming-Feng Chen; Ying-Hsien Kao; Dan-Ning Hu; Fang-Rong Chang; Yang-Chang Wu

2011-01-01

91

Involvement of Autonomic Nervous Activity Changes in Gastroesophageal Reflux in Neonates during Sleep and Wakefulness  

PubMed Central

Background It has been suggested that disturbed activity of the autonomic nervous system is one of the factors involved in gastroesophageal reflux (GER) in adults. We sought to establish whether transient ANS dysfunction (as assessed by heart rate variability) is associated with the occurrence of GER events in neonates during sleep and wakefulness. Methods Nineteen neonates with suspected GER underwent simultaneous, synchronized 12-hour polysomnography and esophageal multichannel impedance-pH monitoring. We compared changes in HRV parameters during three types of periods (control and prior to and during reflux) with respect to the vigilance state. Results The vigilance state influenced the distribution of GER events (P<0.001), with 53.4% observed during wakefulness, 37.6% observed during active sleep and only 9% observed during quiet sleep. A significant increase in the sympathovagal ratio (+32%, P=0.013) was observed in the period immediately prior to reflux (due to a 15% reduction in parasympathetic activity (P=0.017)), relative to the control period. This phenomenon was observed during both wakefulness and active sleep. Conclusion Our results showed that GER events were preceded by a vigilance-state-independent decrease in parasympathetic tone. This suggests that a pre-reflux change in ANS activity is one of the factors contributing to the mechanism of reflux in neonates. PMID:24349512

Djeddi, Djamal-Dine; Kongolo, Guy; Stephan-Blanchard, Erwan; Ammari, Mohamed; Leke, Andre; Delanaud, Stephane; Bach, Veronique; Telliez, Frederic

2013-01-01

92

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

PubMed Central

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

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

93

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

ERIC Educational Resources Information Center

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…

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

2007-01-01

94

Activation of an AMP-activated protein kinase is involved in post-diapause development of Artemia franciscana encysted embryos  

PubMed Central

Background Cysts of Artemia can remain in a dormant state for long periods with a very low metabolic rate, and only resume their development with the approach of favorable conditions. The post-diapause development is a very complicated process involving a variety of metabolic and biochemical events. However, the intrinsic mechanisms that regulate this process are unclear. Results Herein we report the specific activation of an AMP-activated protein kinase (AMPK) in the post-diapause developmental process of Artemia. Using a phospho-AMPK? antibody, AMPK was shown to be phosphorylated in the post-diapause developmental process. Results of kinase assay analysis showed that this phosphorylation is essential for AMPK activation. Using whole-mount immunohistochemistry, phosphorylated AMPK was shown to be predominantly located in the ectoderm of the early developed embryos in a ring shape; however, the location and shape of the activation region changed as development proceeded. Additionally, Western blotting analysis on different portions of the cyst extracts showed that phosphorylated AMPK? localized to the nuclei and this location was not affected by intracellular pH. Confocal microscopy analysis of immunofluorescent stained cyst nuclei further showed that AMPK? localized to the nuclei when activated. Moreover, cellular AMP, ADP, and ATP levels in developing cysts were determined by HPLC, and the results showed that the activation of Artemia AMPK may not be associated with cellular AMP:ATP ratios, suggesting other pathways for regulation of Artemia AMPK activity. Conclusion Together, we report evidence demonstrating the activation of AMPK in Artemia developing cysts and present an argument for its role in the development-related gene expression and energy control in certain cells during post-diapause development of Artemia. PMID:19284883

Zhu, Xiao-Jing; Dai, Jie-Qiong; Tan, Xin; Zhao, Yang; Yang, Wei-Jun

2009-01-01

95

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

PubMed

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

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

96

Neuronal activity in macaque SEF and ACC during performance of tasks involving conflict.  

PubMed

It has been suggested on the basis of previous studies involving functional MRI (fMRI) and single-neuron recording that neurons of the supplementary eye field (SEF) and anterior cingulate cortex (ACC) monitor conflict. To test this idea, we carried out microelectrode recording in monkeys performing a color-conditional eye movement task in which red and green cues instructed leftward and rightward saccades, respectively. In a variant inducing conflict by spatial incompatibility, the cue was presented either at the location of the target (no conflict) or opposite the location of the target (conflict). In a variant inducing conflict by reversal, the foveal cue either remained one color (no conflict) or reversed color after 100 ms (conflict), with the monkey required to follow the instruction conveyed by the second color. In both tasks, conflict was evident in behavioral measures (reduced percent correct and slowed reaction time) and in physiological measures (reduced strength of directional activity among direction-selective neurons). In the SEF, there was a tendency for neurons to fire more strongly on trials involving conflict, but this effect took the form of modulation of task-related activity among direction-selective neurons, not of a pure conflict-monitoring signal. In the ACC, there was no conflict-related enhancement. These results are incompatible with the idea that the SEF and ACC contain populations of neurons specialized for monitoring conflict. PMID:15295008

Nakamura, Kae; Roesch, Matthew R; Olson, Carl R

2005-02-01

97

Study of Possible Mechanisms Involved in the Inhibitory Effects of Coumarin Derivatives on Neutrophil Activity  

PubMed Central

To specify the site of action of the synthetic coumarin derivatives 7-hydroxy-3-(4?-hydroxyphenyl) coumarin (HHC) and 7-hydroxy-3-(4?-hydroxyphenyl) dihydrocoumarin (HHDC), we evaluated their effects on extra- and intracellular reactive oxygen species (ROS) formation in phorbol-myristate-13-acetate (PMA) stimulated human neutrophils. We studied also the effects of HHC and HHDC on possible molecular mechanisms which participate in the activation of NADPH oxidase, that is, on PKC activity, on phosphorylation of some PKC isoforms (?, ?II, and ?), and on phosphorylation of the NADPH oxidase subunit p40phox. Without affecting cytotoxicity, both coumarines tested were effective inhibitors/scavengers of ROS produced by neutrophils on extracellular level. HHC markedly diminished oxidant production and also, intracellularly, decreased PKC activity and partly phosphorylation of PKC?, ?II. On the other hand, we did not observe any effect of coumarin derivatives on phosphorylation of PKC? and on phosphorylation of the NADPH oxidase subunit p40phox, which were suggested to be involved in the PMA-dependent intracellular activation process. In agreement with our previous findings, we assume that the different molecular structures of HHC and HHDC with their different physicochemical and free radical scavenging characteristics are responsible for their diverse effects on the parameters tested. PMID:24349608

Drabikova, Katarina; Perecko, Tomas; Nosal', Radomir; Harmatha, Juraj; Smidrkal, Jan; Jancinova, Viera

2013-01-01

98

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

PubMed

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

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

2014-01-01

99

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

PubMed Central

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

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

2014-01-01

100

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

NASA Astrophysics Data System (ADS)

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.

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

2008-07-01

101

BRCA1-induced apoptosis involves inactivation of ERK1/2 activities.  

PubMed

Mutation in the BRCA1 gene is associated with an increased risk of breast and ovarian cancer. Recent studies have shown that the BRCA1 gene product may be important in mediating responses to DNA damage and genomic instability. Previous studies have indicated that overexpression of BRCA1 can induce apoptosis or cell cycle arrest at the G(2)/M border in various cell types. Although the activation of JNK kinase has been implicated in BRCA1-induced apoptosis, the role of other members of the mitogen-activated protein kinase family in mediating the cellular response to BRCA1 has not yet been examined. In this study, we monitored the activities of three members of the MAPK family (ERK1/2, JNK, p38) in MCF-7 breast cancer cells and U2OS osteosarcoma cells after their exposure to a recombinant adenovirus expressing wild type BRCA1 (Ad.BRCA1). Overexpression of BRCA1 in MCF-7 cells resulted in arrest at the G(2)/M border; however, BRCA1 expression in U2OS cells induced apoptosis. Although BRCA1 induced JNK activation in both cell lines, there were marked differences in ERK1/2 activation in response to BRCA1 expression in these two cell lines. BRCA1-induced apoptosis in U2OS cells was associated with no activation of ERK1/2. In contrast, BRCA1 expression in MCF-7 cells resulted in the activation of both ERK1/2 and JNK. To directly assess the role of ERK1/2 in determining the cellular response to BRCA1, we used dominant negative mutants of MEK1 as well as MEK1/2 inhibitor PD98059. Our results indicate that inhibition of ERK1/2 activation resulted in increased apoptosis after BRCA1 expression in MCF-7 cells. Furthermore, BRCA1-induced apoptosis involved activation of JNK, induction of Fas-L/Fas interaction, and activation of caspases 8 and 9. The studies presented in this report indicate that the response to BRCA1 expression is determined by the regulation of both the JNK and ERK1/2 signaling pathways in cells. PMID:12082091

Yan, Ying; Haas, John P; Kim, Min; Sgagias, Magdalene K; Cowan, Kenneth H

2002-09-01

102

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

PubMed Central

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

Tai, Phang C.

2012-01-01

103

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

PubMed Central

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

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

2014-01-01

104

The Orosomucoid 1 protein is involved in the vitamin D – mediated macrophage de-activation process  

SciTech Connect

Orosomucoid 1 (ORM1), also named Alpha 1 acid glycoprotein A (AGP-A), is an abundant plasma protein characterized by anti-inflammatory and immune-modulating properties. The present study was designed to identify a possible correlation between ORM1 and Vitamin D3 (1,25(OH)2D3), a hormone exerting a widespread effect on cell proliferation, differentiation and regulation of the immune system. In particular, the data described here indicated that ORM1 is a 1,25(OH)2D3 primary response gene, characterized by the presence of a VDRE element inside the 1 kb sequence of its proximal promoter region. This finding was demonstrated with gene expression studies, Chromatin Immunoprecipitation and luciferase transactivation experiments and confirmed by VDR full length and dominant negative over-expression. In addition, several experiments carried out in human normal monocytes demonstrated that the 1,25(OH)2D3 – VDR – ORM1 pathway plays a functional role inside the macrophage de-activation process and that ORM1 may be considered as a signaling molecule involved in the maintenance of tissue homeostasis and remodeling. - Highlights: • ORM1 is a Vitamin D primary response gene. • VD and its receptor VDR are involved in the de-activation process mediated by human resident macrophages. • The signaling pathway VD-VDR-ORM1 plays an important role in the control of macrophage de-activation process. • ORM1 may be defined as a signaling molecule implicated in the maintenance of tissue homeostasis and remodeling.

Gemelli, Claudia, E-mail: claudia.gemelli@unimore.it [Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 287, 41125 Modena (Italy); Center for Regenerative Medicine, University of Modena and Reggio Emilia, Via Gottardi 100, 41125 Modena (Italy); Martello, Andrea; Montanari, Monica; Zanocco Marani, Tommaso; Salsi, Valentina; Zappavigna, Vincenzo; Parenti, Sandra; Vignudelli, Tatiana; Selmi, Tommaso; Ferrari, Sergio; Grande, Alexis [Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 287, 41125 Modena (Italy)

2013-12-10

105

Hepatic microsomal thiol methyltransferase is involved in stereoselective methylation of pharmacologically active metabolite of prasugrel.  

PubMed

Prasugrel, a thienopyridine antiplatelet drug, is converted in animals and humans to the pharmacologically active metabolite R-138727 [(2Z)-{1-[(1RS)-2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4-sulfanylpiperidin-3-ylidene}ethanoic acid], which has two chiral centers, occurring as a mixture of four isomers. The RS and RR isomers are more active than the SS and SR isomers (RS > RR > > SR = SS). The pharmacologically active metabolite is further metabolized to an S-methylated metabolite that is the major identified inactive metabolite in humans. In rat, dog, and human liver microsomes supplemented with S-adenosyl methione, the SS and SR isomers of the active metabolite were extensively S-methylated while the RS and RR isomers were not. Addition of 2,3-dichloromethyl benzylamine (50 µM) completely inhibited the S-methylation reaction, indicating that the microsomal and cytosolic thiol methyltransferase but not the cytosolic thiopurine S-methyltransferase is involved in the methylation. The hepatic intrinsic clearance values for methylation of the RS, RR, SS, and SR isomers (ml/min/kg) were 0, 0, 40.4, and 37.6, respectively, in rat liver microsomes, 0, 0, 11.6, and 2.5, respectively, in dog liver microsomes, and 0, 0, 17.3, and 17.7, respectively, in human liver microsomes, indicating that the RS and RR isomers are not methylated in vitro and that the methylation of SS and SR isomers is high with rat > human > dog. This finding in vitro agreed well with the in vivo observation in rats and dogs, where the S-methylated SS and SR isomers were the major metabolites in the plasma whereas negligible amounts of S-methylated RS and RR isomers were detected after intravenous administration of the pharmacologically active metabolites. PMID:24733788

Kazui, Miho; Hagihara, Katsunobu; Izumi, Takashi; Ikeda, Toshihiko; Kurihara, Atsushi

2014-07-01

106

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

SciTech Connect

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.

Yu Zengli [Department of Nutrition and Food Hygiene, School of Public Health, Zhengzhou University, No. 40 Daxue Road, Zhengzhou 450052 (China)]. E-mail: yuzengli@263.net; Xing Ying [Stem Cell Research Center, Zhengzhou University, 40 Daxue Road, Zhengzhou 450052 (China)]. E-mail: xingy@zzu.edu.cn

2006-08-15

107

Activation of PPARgamma is not involved in butyrate-induced epithelial cell differentiation.  

PubMed

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 (PPARgamma) or vitamin D receptor (VDR). While activation of VDR by butyrate mainly seems to be responsible for cellular differentiation, the activation of PPARgamma in intestinal cells remains to be elucidated. The aim of this study was to determine the role of PPARgamma in butyrate-induced cell growth inhibition and differentiation induction in Caco-2 cells. Treatment with PPARgamma 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 PPARgamma ligands rosiglitazone and MCC-555. Experiments were further performed in dominant-negative PPARgamma mutant cells leading to an increase in cell growth whereas butyrate-induced cell differentiation was again unaffected. The present study clearly demonstrated that PPARgamma is involved in butyrate-induced inhibition of cell growth, but seems not to play an essential role in butyrate-induced cell differentiation. PMID:16112107

Ulrich, S; Wächtershäuser, A; Loitsch, S; von Knethen, A; Brüne, B; Stein, J

2005-10-15

108

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

PubMed Central

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

2013-01-01

109

Tumor necrosis factor restricts hematopoietic stem cell activity in mice: involvement of two distinct receptors  

PubMed Central

Whereas maintenance of hematopoietic stem cells (HSCs) is a requisite for life, uncontrolled expansion of HSCs might enhance the propensity for leukemic transformation. Accordingly, HSC numbers are tightly regulated. The identification of physical cellular HSC niches has underscored the importance of extrinsic regulators of HSC homeostasis. However, whereas extrinsic positive regulators of HSCs have been identified, opposing extrinsic repressors of HSC expansion in vivo have yet to be described. Like many other acute and chronic inflammatory diseases, bone marrow (BM) failure syndromes are associated with tumor necrosis factor-? (TNF) overexpression. However, the in vivo relevance of TNF in the regulation of HSCs has remained unclear. Of considerable relevance for normal hematopoiesis and in particular BM failure syndromes, we herein demonstrate that TNF is a cell-extrinsic and potent endogenous suppressor of normal HSC activity in vivo in mice. These effects of TNF involve two distinct TNF receptors. PMID:21768269

Pronk, Cornelis J.H.; Veiby, Ole Petter; Bryder, David

2011-01-01

110

Molecular Mechanisms Involved in the Antitumor Activity of Cannabinoids on Gliomas: Role for Oxidative Stress  

PubMed Central

Cannabinoids, the active components of Cannabis sativa, have been shown to exert antiproliferative and proapoptotic effects on a wide spectrum of tumor cells and tissues. Of interest, cannabinoids have displayed great potency in reducing the growth of glioma tumors, one of the most aggressive CNS tumors, either in vitro or in animal experimental models curbing the growth of xenografts generated by subcutaneous or intrathecal injection of glioma cells in immune-deficient mice. Cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of non-transformed cells. This review will summarize the anti-cancer properties that cannabinoids exert on gliomas and discuss their potential action mechanisms that appear complex, involving modulation of multiple key cell signaling pathways and induction of oxidative stress in glioma cells. PMID:24281104

Massi, Paola; Valenti, Marta; Solinas, Marta; Parolaro, Daniela

2010-01-01

111

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

PubMed Central

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 ?-citraurin (3-hydroxy-?-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 ?-citraurin content and CCD4b1 transcript levels. These results point to the involvement of CCD4b1 in ?-citraurin formation and indicate that the accumulation of this compound is determined by the availability of the presumed precursors zeaxanthin and ?-cryptoxanthin. Functional analysis of CCD4b1 by in vitro assays unequivocally demonstrated the asymmetric cleavage activity at the 7?,8? double bond in zeaxanthin and ?-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

Rodrigo, Maria J.; Alquezar, Berta; Al-Babili, Salim

2013-01-01

112

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

PubMed

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 IRE1?, 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

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

2014-12-01

113

CaMKK? Is Involved in AMP-Activated Protein Kinase Activation by Baicalin in LKB1 Deficient Cell Lines  

PubMed Central

AMP-activated protein kinase (AMPK) plays an important role in mediating energy metabolism and is controlled mainly by two upstream kinases, LKB1 or Ca2+/calmodulin-dependent protein kinase kinase-? (CaMKK?). Previously, we found that baicalin, one of the major flavonoids in a traditional Chinese herb medicine, Scutellaria baicalensis, protects against the development of hepatic steatosis in rats feeding with a high-fat diet by the activation of AMPK, but, the underlying mechanism for AMPK activation is unknown. Here we show that in two LKB1-deficient cells, HeLa and A549 cells, baicalin activates AMPK by ? Thr-172 phosphorylation and subsequent phosphorylation of its downstream target, acetyl CoA carboxylase, at Ser-79, to a similar degree as does in HepG2 cells (that express LKB1). Pharmacologic inhibition of CaMKK? by its selective inhibitor STO-609 markedly inhibits baicalin-induced AMPK activation in both HeLa and HepG2 cells, indicating that CaMKK? is the responsible AMPK kinase. We also show that treatment of baicalin causes a larger increase in intracellular Ca2+ concentration ([Ca2+]i), although the maximal level of [Ca2+]i is lower in HepG2 cells compared to HeLa cells. Chelation of intracellular free Ca2+ by EDTA and EGTA, or depletion of intracellular Ca2+ stores by the endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin abrogates baicalin-induced activation of AMPK in HeLa cells. Neither cellular ATP nor the production of reactive oxygen species is altered by baicalin. Finally, in HeLa cells, baicalin treatment no longer decreases intracellular lipid accumulation caused by oleic acid after inhibition of CaMKK? by STO-609. These results demonstrate that a potential Ca2+/CaMKK? dependent pathway is involved in the activation of AMPK by baicalin and suggest that CaMKK? likely acts as an upstream kinase of AMPK in response to baicalin. PMID:23110126

Wang, Ying; Du, Zhiyan; Liu, Daihua; Guo, Hongxia; Shen, Jingkang; Peng, Hongli

2012-01-01

114

Plasminogen Activator Inhibitor-1 Is Involved in Streptozotocin-Induced Bone Loss in Female Mice  

PubMed Central

In diabetic patients, the risk of fracture is high because of impaired bone formation. However, the details of the mechanisms in the development of diabetic osteoporosis remain unclear. In the current study, we investigated the role of plasminogen activator inhibitor (PAI)-1 in the pathogenesis of type 1 diabetic osteoporosis by using PAI-1–deficient mice. Quantitative computed tomography analysis showed that PAI-1 deficiency protected against streptozotocin-induced bone loss in female mice but not in male mice. PAI-1 deficiency blunted the changes in the levels of Runx2, osterix, and alkaline phosphatase in tibia as well as serum osteocalcin levels suppressed by the diabetic state in female mice only. Furthermore, the osteoclast levels in tibia, suppressed in diabetes, were also blunted by PAI-1 deficiency in female mice. Streptozotocin markedly elevated the levels of PAI-1 mRNA in liver in female mice only. In vitro study demonstrated that treatment with active PAI-1 suppressed the levels of osteogenic genes and mineralization in primary osteoblasts from female mouse calvaria. In conclusion, the current study indicates that PAI-1 is involved in the pathogenesis of type 1 diabetic osteoporosis in females. The expression of PAI-1 in the liver and the sensitivity of bone cells to PAI-1 may be an underlying mechanism. PMID:23715621

Tamura, Yukinori; Kawao, Naoyuki; Okada, Kiyotaka; Yano, Masato; Okumoto, Katsumi; Matsuo, Osamu; Kaji, Hiroshi

2013-01-01

115

Protein kinase and phosphatase activities are involved in fructan synthesis initiation mediated by sugars.  

PubMed

The induction of fructosylsucrose-synthesizing activity (FSS) by sugars was tested using detached primary leaf blades of several wheat (Triticum aestivum L.) cultivars, immersed in different sugars solutions for 24 h in the dark. The highest induction was brought about by sucrose, while glucose, fructose and maltose also caused significant induction. 5-Ketofructose, 3-methylglucose and 6-deoxyglucose, which cannot be metabolized by plants, produced no induction at all. The fact that mannose also failed to induce FSS and that mannoheptulose did not inhibit the induction by sucrose suggests that the hexokinase-sensing system may not be involved. The protein phosphatase inhibitor okadaic acid and the calmodulin-dependent protein kinase antagonist W7 inhibited FSS induction while some types of protein kinase inhibitors, such as staurosporine and genistein, had less or no effect, respectively. Cycloheximide and cordycepin completely inhibited the induction response, indicating that transcription and translation are necessary for the FSS induction. Northern blot experiments using a sucrose:fructan-6-fructosyl transferase probe gave a clear indication that the mRNA for this enzyme, which is almost absent in control leaves, is dramatically increased after a 24-h treatment with 500 mM sucrose, and confirmed the inhibition produced by protein kinase and protein phosphatase inhibitors. Our data indicate that protein kinase and protein phosphatase activities take part in the chain of events that intervenes in the induction of fructan synthesis by sugars. PMID:11556797

Noël, G M; Tognetti, J A; Pontis, H G

2001-08-01

116

Involvement of pituitary adenylate cyclase-activating peptide in opossum internal anal sphincter relaxation.  

PubMed

Despite its widespread distribution and significance in the gut, the role of pituitary adenylate cyclase-activating peptide (PACAP) in internal anal sphincter (IAS) relaxation has not been examined. This study examined the role of PACAP in nonadrenergic noncholinergic (NANC) nerve-mediated relaxation of IAS smooth muscle. Circular smooth muscle strips from the opossum IAS were prepared for measurement of isometric tension. The influence of PACAP and vasoactive intestinal peptide (VIP) antagonists and tachyphylaxis on the neurally mediated IAS relaxation was examined either separately or in combination. The release of these neuropeptides in response to NANC nerve stimulation before and after the nitric oxide (NO) synthase inhibitor Nomega-nitro-L-arginine and NO was also investigated. Both PACAP and VIP antagonists caused significant attenuation of IAS relaxation by NANC nerve stimulation. The combination of the antagonists, however, did not have an additive effect on IAS relaxation. VIP tachyphylaxis caused significant suppression of IAS relaxation by NANC nerve stimulation. PACAP and VIP were found to be released by NANC nerve stimulation and exogenous NO. The data suggest the involvement of PACAP in IAS relaxation primarily by the activation of PACAP1/VIP receptor and lack of its independent role in the relaxation. Furthermore, NO may regulate the presynaptic release of PACAP and VIP. PMID:9756508

Chakder, S; Rattan, S

1998-10-01

117

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

PubMed

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

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

2014-10-01

118

Calmodulin-dependent phosphatase, kinases, and transcriptional corepressors involved in T-cell activation  

PubMed Central

Summary The second messenger calcium plays an essential role in mediating the TCR signaling pathway leading to cytokine production and T cell clonal expansion. The immunosuppressive drugs cyclosproin A (CsA) and FK506 have served both as therapeutic agents and as molecular probes for unraveling the protein phosphatase calcineurin as a rate-limiting enzyme involved in the transmission of calcium signal from the cytosol into the nucleus to reprogram gene expression. The use of mouse knockout models has helped to verify and further elucidate the functions of different isoforms of calcineurin in both helper T cell activation and thymocyte development. In addition to calcineurin, three other classes of calmodulin-binding proteins have also been shown to play important roles in calcium signaling in T cells. Thus, Cabin1 and class II HDACs have been found to constitute a novel calcium-signaling module in conjunction with the transcription factor myocyte enhance factor family and the transcriptional coactivator p300 to suppress and activate cytokine gene transcription in a calcium-dependent manner. The calmodulin-dependent protein kinases (CaMK) II and IV were also shown to play negative and positive regulatory functions, respectively, in TCR-mediated cytokine production. The crosstalks among these and other signal transducers in T cells form an extensive non-linear signaling network that dictates the final outcome of the TCR signaling pathway. PMID:19290928

Liu, Jun O.

2009-01-01

119

Modulation of NCC activity by low and high K+ intake: insights into the signaling pathways involved  

PubMed Central

Modulation of Na+-Cl? cotransporter (NCC) activity is essential to adjust K+ excretion in the face of changes in dietary K+ intake. We used previously characterized genetic mouse models to assess the role of Ste20-related proline-alanine-rich kinase (SPAK) and with-no-lysine kinase (WNK)4 in the modulation of NCC by K+ diets. SPAK knockin and WNK4 knockout mice were placed on normal-, low-, or high-K+-citrate diets for 4 days. The low-K+ diet decreased and high-K+ diet increased plasma aldosterone levels, but both diets were associated with increased phosphorylation of NCC (phospho-NCC, Thr44/Thr48/Thr53) and phosphorylation of SPAK/oxidative stress responsive kinase 1 (phospho-SPAK/OSR1, Ser383/Ser325). The effect of the low-K+ diet on SPAK phosphorylation persisted in WNK4 knockout and SPAK knockin mice, whereas the effects of ANG II on NCC and SPAK were lost in both mouse colonies. This suggests that for NCC activation by ANG II, integrity of the WNK4/SPAK pathway is required, whereas for the low-K+ diet, SPAK phosphorylation occurred despite the absence of WNK4, suggesting the involvement of another WNK (WNK1 or WNK3). Additionally, because NCC activation also occurred in SPAK knockin mice, it is possible that loss of SPAK was compensated by OSR1. The positive effect of the high-K+ diet was observed when the accompanying anion was citrate, whereas the high-KCl diet reduced NCC phosphorylation. However, the effect of the high-K+-citrate diet was aldosterone dependent, and neither metabolic alkalosis induced by bicarbonate, nor citrate administration in the absence of K+ increased NCC phosphorylation, suggesting that it was not due to citrate-induced metabolic alkalosis. Thus, the accompanying anion might modulate the NCC response to the high-K+ diet. PMID:24761002

Castaneda-Bueno, Maria; Cervantes-Perez, Luz Graciela; Rojas-Vega, Lorena; Arroyo-Garza, Isidora; Vazquez, Norma; Moreno, Erika

2014-01-01

120

Modulation of NCC activity by low and high K(+) intake: insights into the signaling pathways involved.  

PubMed

Modulation of Na(+)-Cl(-) cotransporter (NCC) activity is essential to adjust K(+) excretion in the face of changes in dietary K(+) intake. We used previously characterized genetic mouse models to assess the role of Ste20-related proline-alanine-rich kinase (SPAK) and with-no-lysine kinase (WNK)4 in the modulation of NCC by K(+) diets. SPAK knockin and WNK4 knockout mice were placed on normal-, low-, or high-K(+)-citrate diets for 4 days. The low-K(+) diet decreased and high-K(+) diet increased plasma aldosterone levels, but both diets were associated with increased phosphorylation of NCC (phospho-NCC, Thr(44)/Thr(48)/Thr(53)) and phosphorylation of SPAK/oxidative stress responsive kinase 1 (phospho-SPAK/OSR1, Ser(383)/Ser(325)). The effect of the low-K(+) diet on SPAK phosphorylation persisted in WNK4 knockout and SPAK knockin mice, whereas the effects of ANG II on NCC and SPAK were lost in both mouse colonies. This suggests that for NCC activation by ANG II, integrity of the WNK4/SPAK pathway is required, whereas for the low-K(+) diet, SPAK phosphorylation occurred despite the absence of WNK4, suggesting the involvement of another WNK (WNK1 or WNK3). Additionally, because NCC activation also occurred in SPAK knockin mice, it is possible that loss of SPAK was compensated by OSR1. The positive effect of the high-K(+) diet was observed when the accompanying anion was citrate, whereas the high-KCl diet reduced NCC phosphorylation. However, the effect of the high-K(+)-citrate diet was aldosterone dependent, and neither metabolic alkalosis induced by bicarbonate, nor citrate administration in the absence of K(+) increased NCC phosphorylation, suggesting that it was not due to citrate-induced metabolic alkalosis. Thus, the accompanying anion might modulate the NCC response to the high-K(+) diet. PMID:24761002

Castañeda-Bueno, María; Cervantes-Perez, Luz Graciela; Rojas-Vega, Lorena; Arroyo-Garza, Isidora; Vázquez, Norma; Moreno, Erika; Gamba, Gerardo

2014-06-15

121

Gastric stimulation in obese subjects activates the hippocampus and other regions involved in brain reward circuitry.  

PubMed

The neurobiological mechanisms underlying overeating in obesity are not understood. Here, we assessed the neurobiological responses to an Implantable Gastric Stimulator (IGS), which induces stomach expansion via electrical stimulation of the vagus nerve to identify the brain circuits responsible for its effects in decreasing food intake. Brain metabolism was measured with positron emission tomography and 2-deoxy-2[18F]fluoro-D-glucose in seven obese subjects who had the IGS implanted for 1-2 years. Brain metabolism was evaluated twice during activation (on) and during deactivation (off) of the IGS. The Three-Factor Eating Questionnaire was obtained to measure the behavioral components of eating (cognitive restraint, uncontrolled eating, and emotional eating). The largest difference was in the right hippocampus, where metabolism was 18% higher (P < 0.01) during the "on" than "off" condition, and these changes were associated with scores on "emotional eating," which was lower during the on than off condition and with "uncontrolled eating," which did not differ between conditions. Metabolism also was significantly higher in right anterior cerebellum, orbitofrontal cortex, and striatum during the on condition. These findings corroborate the role of the vagus nerve in regulating hippocampal activity and the importance of the hippocampus in modulating eating behaviors linked to emotional eating and lack of control. IGS-induced activation of regions previously shown to be involved in drug craving in addicted subjects (orbitofrontal cortex, hippocampus, cerebellum, and striatum) suggests that similar brain circuits underlie the enhanced motivational drive for food and drugs seen in obese and drug-addicted subjects, respectively. PMID:17023542

Wang, Gene-Jack; Yang, Julia; Volkow, Nora D; Telang, Frank; Ma, Yeming; Zhu, Wei; Wong, Christopher T; Tomasi, Dardo; Thanos, Panayotis K; Fowler, Joanna S

2006-10-17

122

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

ERIC Educational Resources Information Center

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…

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

2013-01-01

123

Get active. Get involved. Get competitive. Welcome to the 2013 review of City University London's programme of sport, including  

E-print Network

CitySports 2013 Get active. Get involved. Get competitive. #12;Welcome to the 2013 review of City University London's programme of sport, including information about our new sports and how to get involved. We had much to celebrate during the 2012/13 sporting year with fantastic performances

Weyde, Tillman

124

A Mediational Model Predicting Adjustment in Affluent Adolescents: The Role of Parental Perfectionism, Perceived Parental Pressure, and Organized Activity Involvement.  

E-print Network

?? The current cross-sectional study evaluated the relative contributions of parental perfectionism (i.e., self-oriented, other-oriented, and socially prescribed), perceived parental pressure, and organized activity involvement… (more)

Randall, Edin

2012-01-01

125

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

ERIC Educational Resources Information Center

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…

Wong, Siu Kwong

2005-01-01

126

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

PubMed Central

Proteins that are post-translationally adducted with 2-(?-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

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

127

Involvement of TRPA1 activation in acute pain induced by cadmium in mice  

PubMed Central

Background Cadmium (Cd) is an environmental pollutant and acute exposure to it causes symptoms related to pain and inflammation in the airway and gastrointestinal tract, but the underlying mechanisms are still unclear. TRPA1 is a nonselective cation channel expressed in sensory neurons and acts as a nociceptive receptor. Some metal ions such as Ca, Mg, Ba and Zn are reported to modulate TRPA1 channel activity. In the present study, we investigated the effect of Cd on cultured mouse dorsal root ganglion neurons and a heterologous expression system to analyze the effect of Cd at the molecular level. In addition, we examined whether Cd caused acute pain in vivo. Results In wild-type mouse sensory neurons, Cd evoked an elevation of the intracellular Ca concentration ([Ca2+]i) that was inhibited by external Ca removal and TRPA1 blockers. Most of the Cd-sensitive neurons were also sensitive to cinnamaldehyde (a TRPA1 agonist) and [Ca2+]i responses to Cd were absent in TRPA1(?/?) mouse neurons. Heterologous expression of TRPA1 mutant channels that were less sensitive to Zn showed attenuation of Cd sensitivity. Intracellular Cd imaging revealed that Cd entered sensory neurons through TRPA1. The stimulatory effects of Cd were confirmed in TRPA1-expressing rat pancreatic cancer cells (RIN-14B). Intraplantar injection of Cd induced pain-related behaviors that were largely attenuated in TRPA1(?/?) mice. Conclusions Cd excites sensory neurons via activation of TRPA1 and causes acute pain, the mechanism of which may be similar to that of Zn. The present results indicate that TRPA1 is involved in the nociceptive or inflammatory effects of Cd. PMID:23448290

2013-01-01

128

Involvement of bone morphogenetic protein activity in somatostatin actions on ovarian steroidogenesis.  

PubMed

Somatostatin is expressed in the hypothalamus, pancreas and gastrointestinal tracts and it inhibits the secretion of various hormones in vivo. In the rodent ovary, somatostatin receptor (SSTR) subtypes 2 and 5 are expressed in granulosa cells and oocytes. Somatostatin analogs have been clinically used for treatment of endocrine tumors. For this purpose, relatively high-dose or long-term treatments of somatostatin analogs are necessary; however, the direct and continuous impact of somatostatin analogs on gonadal functions has yet to be elucidated. In the present study, we investigated the effects of somatostatin analogs (octreotide and pasireotide) on ovarian steroidogenesis by rat primary granulosa cell culture. The expression levels of SSTR2 and SSTR5 in granulosa cells were upregulated by FSH treatment. Treatment with somatostatin analogs decreased FSH-induced estradiol production with reduction in aromatase mRNA expression, while the treatment also suppressed FSH-induced progesterone production with reduction of mRNAs levels of StAR, P450scc and 3?HSD2 in granulosa cells. This trend was also observed in a granulosa/oocyte co-culture condition. The effect of pasireotide was more potent than that of octreotide. FSH-induced synthesis of steroids and cAMP was also suppressed by somatostatin analog treatment. Notably, pretreatment with a BMP-binding protein, noggin reversed the suppressive effects of somatostatin analogs on progesterone and cAMP production, suggesting that the endogenous BMP system is functionally involved in the SSTR effects in granulosa cells. Treatment with BMP-2, -4, -6 and -7 decreased the mRNA expression of inhibitory Smads6 and 7, leading to enhancement of BMP actions detected by Id-1 transcription in granulosa cells. Collectively, the results revealed that SSTR activation modulates ovarian steroidogenesis by upregulating endogenous BMP activity in growing follicles. PMID:23137853

Nakamura, Eri; Otsuka, Fumio; Inagaki, Kenichi; Tsukamoto, Naoko; Ogura-Ochi, Kanako; Miyoshi, Tomoko; Toma, Kishio; Takeda, Masaya; Makino, Hirofumi

2013-03-01

129

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

PubMed

Proteins that are post-translationally adducted with 2-(?-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

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

130

The Orosomucoid 1 protein is involved in the vitamin D - mediated macrophage de-activation process.  

PubMed

Orosomucoid 1 (ORM1), also named Alpha 1 acid glycoprotein A (AGP-A), is an abundant plasma protein characterized by anti-inflammatory and immune-modulating properties. The present study was designed to identify a possible correlation between ORM1 and Vitamin D3 (1,25(OH)2D3), a hormone exerting a widespread effect on cell proliferation, differentiation and regulation of the immune system. In particular, the data described here indicated that ORM1 is a 1,25(OH)2D3 primary response gene, characterized by the presence of a VDRE element inside the 1kb sequence of its proximal promoter region. This finding was demonstrated with gene expression studies, Chromatin Immunoprecipitation and luciferase transactivation experiments and confirmed by VDR full length and dominant negative over-expression. In addition, several experiments carried out in human normal monocytes demonstrated that the 1,25(OH)2D3--VDR--ORM1 pathway plays a functional role inside the macrophage de-activation process and that ORM1 may be considered as a signaling molecule involved in the maintenance of tissue homeostasis and remodeling. PMID:23973664

Gemelli, Claudia; Martello, Andrea; Montanari, Monica; Zanocco Marani, Tommaso; Salsi, Valentina; Zappavigna, Vincenzo; Parenti, Sandra; Vignudelli, Tatiana; Selmi, Tommaso; Ferrari, Sergio; Grande, Alexis

2013-12-10

131

MASP-2 Activation is Involved in Ischemia-related Necrotic Myocardial Injury in Humans  

PubMed Central

Background/Objectives Insufficient blood supply to the heart results in ischemic injury manifested clinically as myocardial infarction (MI). Following ischemia, inflammation is provoked and related to the clinical outcomes. A recent basic science study indicates that complement factor MASP-2 plays an important role in animal models of ischemia/reperfusion injury. We investigated the role of MASP-2 in human acute myocardial ischemia in two clinical settings: (1) Acute MI, and (2) Open heart surgery. Methods A total of 187 human subjects were enrolled in this study, including 50 healthy individuals, 27 patients who were diagnosed of coronary artery disease (CAD) but without acute MI, 29 patients with acute MI referred for coronary angiography, and 81 cardiac surgery patients with surgically-induced global heart ischemia. Circulating MASP-2 levels were measured by ELISA. Results MASP-2 levels in the peripheral circulation were significantly reduced in MI patients compared with those of healthy individuals or of CAD patients without acute MI. The hypothesis that MASP-2 was activated during acute myocardial ischemia was evaluated in cardiac patients undergoing surgically-induced global heart ischemia. MASP-2 was found to be significantly reduced in the coronary circulation of such patients, and the reduction of MASP-2 levels correlated independently with the increase of the myocardial necrosis marker, cardiac troponin I. Conclusions These results indicate an involvement of MASP-2 in ischemia-related necrotic myocardial injury in humans. PMID:22178059

Zhang, Ming; Hou, Yunfang; Cavusoglu, Erdal; Lee, Daniel C.; Steffensen, Rudi; Yang, Liming; Bashari, Daniel; Villamil, Jose; Moussa, Motaz; Fernaine, George; Jensenius, Jens C.; Marmur, Jonathan D.; Ko, Wilson; Shevde, Ketan

2011-01-01

132

Involvement of Trichoderma Trichothecenes in the Biocontrol Activity and Induction of Plant Defense-Related Genes  

PubMed Central

Trichoderma species produce trichothecenes, most notably trichodermin and harzianum A (HA), by a biosynthetic pathway in which several of the involved proteins have significant differences in functionality compared to their Fusarium orthologues. In addition, the genes encoding these proteins show a genomic organization differing from that of the Fusarium tri clusters. Here we describe the isolation of Trichoderma arundinaceum IBT 40837 transformants which have a disrupted or silenced tri4 gene, a gene encoding a cytochrome P450 monooxygenase that oxygenates trichodiene to give rise to isotrichodiol, and the effect of tri4 gene disruption and silencing on the expression of other tri genes. Our results indicate that the tri4 gene disruption resulted in a reduced antifungal activity against Botrytis cinerea and Rhizoctonia solani and also in a reduced ability to induce the expression of tomato plant defense-related genes belonging to the salicylic acid (SA) and jasmonate (JA) pathways against B. cinerea, in comparison to the wild-type strain, indicating that HA plays an important function in the sensitization of Trichoderma-pretreated plants against this fungal pathogen. Additionally, the effect of the interaction of T. arundinaceum with B. cinerea or R. solani and with tomato seedlings on the expressions of the tri genes was studied. PMID:22562989

Malmierca, M. G.; Cardoza, R. E.; Alexander, N. J.; McCormick, S. P.; Hermosa, R.; Monte, E.

2012-01-01

133

Involvement of Trichoderma trichothecenes in the biocontrol activity and induction of plant defense-related genes.  

PubMed

Trichoderma species produce trichothecenes, most notably trichodermin and harzianum A (HA), by a biosynthetic pathway in which several of the involved proteins have significant differences in functionality compared to their Fusarium orthologues. In addition, the genes encoding these proteins show a genomic organization differing from that of the Fusarium tri clusters. Here we describe the isolation of Trichoderma arundinaceum IBT 40837 transformants which have a disrupted or silenced tri4 gene, a gene encoding a cytochrome P450 monooxygenase that oxygenates trichodiene to give rise to isotrichodiol, and the effect of tri4 gene disruption and silencing on the expression of other tri genes. Our results indicate that the tri4 gene disruption resulted in a reduced antifungal activity against Botrytis cinerea and Rhizoctonia solani and also in a reduced ability to induce the expression of tomato plant defense-related genes belonging to the salicylic acid (SA) and jasmonate (JA) pathways against B. cinerea, in comparison to the wild-type strain, indicating that HA plays an important function in the sensitization of Trichoderma-pretreated plants against this fungal pathogen. Additionally, the effect of the interaction of T. arundinaceum with B. cinerea or R. solani and with tomato seedlings on the expressions of the tri genes was studied. PMID:22562989

Malmierca, M G; Cardoza, R E; Alexander, N J; McCormick, S P; Hermosa, R; Monte, E; Gutiérrez, S

2012-07-01

134

Residual NADPH Oxidase Activity and Isolated Lung Involvement in X-Linked Chronic Granulomatous Disease  

PubMed Central

Chronic granulomatous disease (CGD) is characterized by inherited immune defects resulting from mutations in the NADPH oxidase complex genes. The X-linked type of CGD is caused by defects in the CYBB gene that encodes gp91-phox, a fundamental component of the NADPH oxidase complex. This mutation originates the most common and severe form of CGD, which typically has absence of NADPH oxidase function and aggressive multisystemic infections. We present the case of a 9-year-old child with a rare CYBB mutation that preserves some NADPH oxidase activity, resulting in an atypical mild form of X-linked CGD with isolated lung involvement. Although the clinical picture and partially preserved oxidase function suggested an autosomal recessive form of CGD, genetic testing demonstrated a mutation in the exon 3 of CYBB gene (c.252 G>A, p.Ala84Ala), an uncommon X-linked CGD variant that affects splicing. Atypical presentation and diagnostic difficulties are discussed. This case highlights that the diagnosis of mild forms of X-linked CGD caused by rare CYBB mutations and partially preserved NADPH function should be considered early in the evaluation of atypical and recurrent lung infections. PMID:23193493

Gutierrez, Maria J.; McSherry, George D.; Ishmael, Faoud T.; Horwitz, Alexandra A.; Nino, Gustavo

2012-01-01

135

Norcantharidin induces apoptosis of breast cancer cells: involvement of activities of mitogen activated protein kinases and signal transducers and activators of transcription.  

PubMed

Involvement of activities of mitogen-activated protein kinases (MAPKs) and signal transducers and activators of transcription (STATs) remains unsolved in norcantharidin-associated breast cancer cell apoptosis. This study investigated the anti-cancer effect of norcantharidin and its underlying mechanism in two human breast cancer cell lines, estrogen receptor (ER)- HS-578T and ER+ MCF-7 cells. Norcantharidin induced potent cytotoxicity and arrested cell growth through increasing phosphorylation of Chk1, Chk2 and total p21(Waf1/Cip1) and reducing cyclin B and cdc25c expression. It also induced apoptosis through extrinsic death receptor and intrinsic mitochondrial pathways by cytochrome c release, caspase activation, oligonucleosome appearance, PARP cleavage, and aberration of Bcl-2 family protein expression and phosphorylation. Although norcantharidin did not affect STAT1, STAT3, and STAT5 protein expression, it suppressed STAT3 and STAT5 phosphorylation in HS-578T cells, whereas it up-regulated STAT1 phosphorylation and down-regulated STAT5 phosphorylation in MCF-7 cells. Moreover, norcantharidin activated MAPK family member proteins, extracellular signal-regulated kinase (ERK), p38(MAPK) and c-Jun N-terminal kinase (JNK), were all phosphorylated by treatment. Pretreatment with selective kinase inhibitors significantly attenuated the norcantharidin-induced cytotoxicity in breast cancer cells. These findings suggest the potential involvement of MAPK and STAT pathways in norcantharidin-induced apoptogenesis. Norcantharidin may be an effective anti-cancer drug against breast cancer. PMID:21266192

Yang, Pei-Yu; Chen, Ming-Feng; Kao, Ying-Hsien; Hu, Dan-Ning; Chang, Fang-Rong; Wu, Yang-Chang

2011-04-01

136

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

ERIC Educational Resources Information Center

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…

Lowe, Cynthia Louise Altman

2010-01-01

137

Mothers' and fathers' involvement with school-age children's care and academic activities in Navajo Indian families.  

PubMed

This exploratory study examined mothers' and fathers' reports of time involvement in their school-age children's care and academic activities. The study also explored the relationship between parents' socioeconomic status (SES) variables (age, education, income, work hours, and length of marriage) and their relative involvement with children. Mother and father dyads from 34 two-parent Navajo (Diné) Indian families with a second- or third-grade child participated in the study. Repeated measures analysis of variance showed that mothers invested significantly more time in children's care on demand and academic activities than fathers, but the differences in maternal and paternal perceptions of time involvement in routine care were not significant. The gender of the child did not influence the amount of time parents invested in children's care and academic activities. Mothers' involvement with children was not related to any of the SES variables. Fathers' involvement was significantly associated with work hours and length of marriage, and work hours produced significant interaction with fathers' involvement with children. Findings are discussed in light of gender role differences in parental involvement with children within Navajo families. PMID:18426283

Hossain, Ziarat; Anziano, Michael C

2008-04-01

138

Is activated hemocyanin instead of phenoloxidase involved in immune response in woodlice?  

Microsoft Academic Search

In the Common woodlouse Porcellio scaber (Crustacea: Isopoda: Oniscidea), experimental immune challenge did not induce the expression of pro-phenoloxidase that, in most other invertebrates studied thus far, can be activated into phenoloxidase via an activation cascade upon immune challenge. Instead, Porcellio hemocyanin proved to exhibit catecholoxidase activity upon activation. However, none of the activating factors known from other invertebrates other

Elmar Jaenicke; Sebastian Fraune; Sandra May; Pinar Irmak; Rene Augustin; Christian Meesters; Heinz Decker; Martin Zimmer

2009-01-01

139

Radiation-induced Activation of Nuclear Factor-B Involves Selective Degradation of Plasma Membrane associated IB  

Microsoft Academic Search

In contrast to nuclear factor-B (NF-B) activation by tumor necrosis factor- (TNF-), the specific processes involved in the activation of this transcription factor by ionizing radiation (IR) have not been completely defined. According to the classical paradigm, a critical event in NF-B activation is the degradation of IB. Data presented herein show that, in contrast to treatment with TNF-, IR-induced

Jeffery S. Russell; Philip J. Tofilon

2002-01-01

140

Plasminogen Activator Inhibitor-1 Is Involved in Impaired Bone Repair Associated with Diabetes in Female Mice  

PubMed Central

Previous studies suggest that fracture healing is impaired in diabetes; however, the underlying mechanism remains unclear. Here, we investigated the roles of plasminogen activator inhibitor-1 (PAI-1) in the impaired bone repair process by using streptozotocin (STZ)-induced diabetic female wild-type (PAI-1+/+) and PAI-1-deficient (PAI-1?/?) mice. Bone repair and the number of alkaline phosphatase (ALP)-positive cells at the site of a femoral bone damage were comparable in PAI-1+/+ and PAI-1?/? mice without STZ treatment. Although the bone repair process was delayed by STZ treatment in PAI-1+/+ mice, this delayed bone repair was blunted in PAI-1?/? mice. The reduction in the number of ALP-positive cells at the site of bone damage induced by STZ treatment was attenuated in PAI-1?/? mice compared to PAI-1+/+ mice. On the other hand, PAI-1 deficiency increased the levels of ALP and type I collagen mRNA in female mice with or without STZ treatment, and the levels of Osterix and osteocalcin mRNA, suppressed by diabetic state in PAI-1+/+ mice, were partially protected in PAI-1?/? mice. PAI-1 deficiency did not affect formation of the cartilage matrix and the levels of types II and X collagen and aggrecan mRNA suppressed by STZ treatment, although PAI-1 deficiency increased the expression of chondrogenic markers in mice without STZ treatment. The present study indicates that PAI-1 is involved in the impaired bone repair process induced by the diabetic state in part through a decrease in the number of ALP-positive cells. PMID:24651693

Mao, Li; Kawao, Naoyuki; Tamura, Yukinori; Okumoto, Katsumi; Okada, Kiyotaka; Yano, Masato; Matsuo, Osamu; Kaji, Hiroshi

2014-01-01

141

Massive calcium-activated endocytosis without involvement of classical endocytic proteins.  

PubMed

We describe rapid massive endocytosis (MEND) of >50% of the plasmalemma in baby hamster kidney (BHK) and HEK293 cells in response to large Ca transients. Constitutively expressed Na/Ca exchangers (NCX1) are used to generate Ca transients, whereas capacitance recording and a membrane tracer dye, FM 4-64, are used to monitor endocytosis. With high cytoplasmic adenosine triphosphate (ATP; >5 mM), Ca influx causes exocytosis followed by MEND. Without ATP, Ca transients cause only exocytosis. MEND can then be initiated by pipette perfusion of ATP, and multiple results indicate that ATP acts via phosphatidylinositol-bis 4,5-phosphate (PIP(2)) synthesis: PIP(2) substitutes for ATP to induce MEND. ATP-activated MEND is blocked by an inositol 5-phosphatase and by guanosine 5'-[?-thio]triphosphate (GTP?S). Block by GTP?S is overcome by the phospholipase C inhibitor, U73122, and PIP(2) induces MEND in the presence of GTP?S. MEND can occur in the absence of ATP and PIP(2) when cytoplasmic free Ca is clamped to 10 µM or more by Ca-buffered solutions. ATP-independent MEND occurs within seconds during Ca transients when cytoplasmic solutions contain polyamines (e.g., spermidine) or the membrane is enriched in cholesterol. Although PIP(2) and cholesterol can induce MEND minutes after Ca transients have subsided, polyamines must be present during Ca transients. MEND can reverse over minutes in an ATP-dependent fashion. It is blocked by brief ?-methylcyclodextrin treatments, and tests for involvement of clathrin, dynamins, calcineurin, and actin cytoskeleton were negative. Therefore, we turned to the roles of lipids. Bacterial sphingomyelinases (SMases) cause similar MEND responses within seconds, suggesting that ceramide may be important. However, Ca-activated MEND is not blocked by reagents that inhibit SMases. MEND is abolished by the alkylating phospholipase A(2) inhibitor, bromoenol lactone, whereas exocytosis remains robust, and Ca influx causes MEND in cardiac myocytes without preceding exocytosis. Thus, exocytosis is not prerequisite for MEND. From these results and two companion studies, we suggest that Ca promotes the formation of membrane domains that spontaneously vesiculate to the cytoplasmic side. PMID:21187336

Lariccia, Vincenzo; Fine, Michael; Magi, Simona; Lin, Mei-Jung; Yaradanakul, Alp; Llaguno, Marc C; Hilgemann, Donald W

2011-01-01

142

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

PubMed Central

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 P2-5 implies that inhibitory GABAergic activity linked with gap-junction participates in the maturation of ACx. PMID:22986170

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

2012-01-01

143

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

PubMed Central

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

Greene, Kathryn

2013-01-01

144

The theory of active involvement: processes underlying interventions that engage adolescents in message planning and/or production.  

PubMed

Adolescence is a time of increased risk taking, and recent intervention strategies have included adolescents planning or producing antirisk 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. This article 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 article provides valuable insight into how active involvement strategies function and how to best design these interventions, particularly those targeting adolescents. PMID:23980581

Greene, Kathryn

2013-01-01

145

Embryonic liver fodrin involved in hepatic stellate cell activation and formation of regenerative nodule in liver cirrhosis.  

PubMed

Transforming growth factor (TGF) ?(1) plays a critical role in liver fibrosis. Previous studies demonstrated embryonic liver fodrin (ELF), a ?-spectrin was involved in TGF-?/Smad signalling pathway as Smad3/4 adaptor. Here we investigate the role of ELF in pathogenesis of liver cirrhosis. In carbon tetrachloride (CCl(4))-induced mice model of liver cirrhosis, ELF is up-regulated in activated hepatic stellate cells (HSCs), and down-regulated in regenerative hepatocytes of cirrhotic nodules. In activated HSCs in vitro, reduction of ELF expression mediated by siRNA leads to the inhibition of HSC activation and procollagen I expression. BrdU assay demonstrates that down-regulation of ELF expression does not inhibit proliferation of activated HSCs in vitro. Immunostaining of cytokeratin 19 and Ki67 indicates that regenerative hepatocytes in cirrhotic liver are derived from hepatic progenitor cells (HPC). Further study reveals that HPC expansion occurs as an initial phase, before the reduction of ELF expression in regenerative hepatocytes. Regenerative hepatocytes in cirrhotic liver show the change in proliferative activity and expression pattern of proteins involved in G1/S transition, which suggests the deregulation of cell cycle in regenerative hepatocytes. Finally, we find that ELF participates in TGF-?/Smad signal in activated HSCs and hepatocytes through regulating the localization of Smad3/4. These data reveal that ELF is involved in HSC activation and the formation of regenerative nodules derived from HPC in cirrhotic liver. PMID:21388516

Wang, Zhijun; Liu, Fang; Tu, Wei; Chang, Ying; Yao, Jinjian; Wu, Wei; Jiang, Xiang; He, Xingxing; Lin, Jusheng; Song, Yuhu

2012-01-01

146

Parent Involvement  

E-print Network

To be successful, a 4-H program must have parent involvement. Although 4-H leaders and Extension agents may interest young people in becoming members, they need the parents' goodwill and support to keep them interested, enthusiastic and active. Here...

Howard, Jeff W.

2005-05-10

147

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

ERIC Educational Resources Information Center

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)

Creasey, Gary L; Myers, Barbara J

1986-01-01

148

5Hydroxytryptamine involvement in the locomotor activity suppressant effects of amphetamine in the mouse  

Microsoft Academic Search

d-Amphetamine, in doses lower than required to increase motor activity, reduced mouse spontaneous locomotor activity when this was assessed using cages equipped with photocell units, using treadwheels, or the measurement of spontaneous climbing behaviour. Actue treatments with the serotonergic agonists quipazine and 5-hydroxy-dl-tryptophan also reduced wheel running activity, spontaneous locomotor activity assessed using photocell cages, and spontaneous climbing behaviour; fenfluramine

A. J. Bradbury; B. Costall; R. J. Naylor; E. S. Onaivi

1987-01-01

149

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

ERIC Educational Resources Information Center

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.…

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

150

Human 8-oxoguanine DNA glycosylase increases resistance to hyperoxic cytotoxicity in lung epithelial cells and involvement with altered MAPK activity  

Microsoft Academic Search

It is unknown whether base excision DNA repair (BER) proteins interact with mitogen-activated protein kinases (MAPK) under oxidation. Here, we explored roles of BER proteins in signaling transduction involving MAPK during hyperoxia. We demonstrated that ERK1\\/2 phosphorylation in A549 cells was increased in 95% O2. p38 activity in A549 cells was also increased by exposure to 95% O2. To evaluate

S Kannan; H Pang; D C Foster; Z Rao; M Wu

2006-01-01

151

Early Peroxisome proliferator-activated receptor gamma regulated genes involved in expansion of pancreatic beta cell mass  

E-print Network

RESEARCH ARTICLE Open Access Early peroxisome proliferator-activated receptor gamma regulated genes involved in expansion of pancreatic beta cell mass Yurena Vivas1, Cristina Martínez-García1, Adriana Izquierdo1, Francisco Garcia-Garcia2, Sergio... validated variants associated with insulin-secretory defects in the general population and showed little if any relationship to insulin resistance [5-9]. Peroxisome proliferator-activated receptor gamma (PPARg) is a member of the nuclear receptor superfam...

Vivas, Yurena; Martinez-Garcia, Cristina; Izquierdo, Adriana; Garcia-Garcia, Francisco; Callejas, Sergio; Velasco, Ismael; Campbell, Mark; Ros, Manuel; Dopazo, Ana; Dopazo, Joaquin; Vidal-Puig, Antonio; Medina-Gomez, Gema

2011-12-30

152

Reduction of scale invariance of activity fluctuations with aging and Alzheimer's disease: Involvement of the circadian pacemaker  

Microsoft Academic Search

Human motor control systems orchestrate complex scale-invariant patterns of activity over a wide range of time scales (minutes to hours). The neural mechanisms underlying scale-invariance are unknown in humans. In rats, the master circadian pacemaker [suprachiasmatic nucleus (SCN)] is crucially involved in scale-invariant activity fluctuations over multiple time scales from minutes to 24 h. Aging and Alzheimer's disease (AD) are

Kun Hu; Eus J. W. van Someren; Steven A. Shea; Frank A. J. L. Scheer

2009-01-01

153

Expression of Genes Involved in Lipid Metabolism Correlate with Peroxisome Proliferator-Activated Receptor g Expression in Human Skeletal Muscle  

Microsoft Academic Search

Peroxisome proliferator-activated receptor g (PPAR-g) activation in adipose tissue is known to regulate genes involved in adipocyte differentiation and lipid metabolism. However, the role of PPAR-g in muscle remains unclear. To examine the potential regulation of genes by PPAR-g in human skeletal muscle, we used semiquantitative RT- PCR to determine the expression of PPAR-g, lipoprotein lipase (LPL), muscle carnitine palmitoyl

NARAS M. LAPSYS; ADAMANDIA D. KRIKETOS; MEGAN LIM-FRASER; ANN M. POYNTEN; ANDREW LOWY; STUART M. FURLER; DONALD J. CHISHOLM; GREGORY J. COONEY

154

To provide guidelines for the presence of children in the work place for other than official University activities involving children.  

E-print Network

Purpose To provide guidelines for the presence of children in the work place for other than official University activities involving children. Policy Employees with dependent children are expected to make regular arrangements for proper care of their children while at work. The University must consider

Hutcheon, James M.

155

Title : Involvement of D1 dopamine receptor in MDMA-induced locomotor activity and striatal gene expression in mice.  

E-print Network

Title : Involvement of D1 dopamine receptor in MDMA-induced locomotor activity and striatal gene, France Abstract 3,4-Methylenedioxymethamphetamine (MDMA), a widely used recreational drug with psychoactive properties, induces both serotonin and dopamine release in the brain. In rats and mice MDMA

Paris-Sud XI, Université de

156

162 Electrical and Computer Engineering 163 Courses and projects that actively involve them in their own education and  

E-print Network

162 Electrical and Computer Engineering 163 · Courses and projects that actively involve them of technology Graduate and undergraduate programs in electrical and computer engineering offer concentrations in electrical and computer engineering that the student can build upon to construct a custom program. Because

Richards-Kortum, Rebecca

157

Sp1/Sp3 involved in activation of GATA-1 Cell Research | Vol 18 No 2 | February 2008  

E-print Network

that is essential for the terminal maturation of proerythroblasts, megakaryocytic cells and mast cells is restricted to erythroid cells, megakaryocytes, eosinophils and mast cells, as well as to Sertoli cellsSp1/Sp3 involved in activation of GATA-1 302 npg Cell Research | Vol 18 No 2 | February 2008

Tian, Weidong

158

Endothelial Cell Costimulation of T Cell Activation Through CD58-CD2 Interactions Involves Lipid Raft Aggregation1  

E-print Network

Endothelial Cell Costimulation of T Cell Activation Through CD58-CD2 Interactions Involves Lipid Raft Aggregation1 Javier Mestas and Christopher C. W. Hughes2 Human endothelial cells (EC) costimulate lipid raft aggregation, thus amplifying TCR signaling. Soluble CD2 mAbs block EC-induced raft

Hughes, Christopher C. W.

159

Atmospheric science is the study of short-term weather and long-term climate, involving activities such as weather  

E-print Network

Atmospheric science is the study of short-term weather and long-term climate, involving activities such as weather forecasting, climate projections, air quality modeling, data analysis, and basic and applied. The program maintains strong ties with regional employers in both the private sector and the National Weather

Saldin, Dilano

160

Regulation of the Ste20-like kinase, SLK: involvement of activation segment phosphorylation.  

PubMed

Expression and activation of the Ste20-like kinase, SLK, is increased during kidney development and recovery from ischemic acute kidney injury. SLK promotes apoptosis, and it may regulate cell survival during injury or repair. This study addresses the role of phosphorylation in the regulation of kinase activity. We mutated serine and threonine residues in the putative activation segment of the SLK catalytic domain and expressed wild type (WT) and mutant proteins in COS-1 or glomerular epithelial cells. Compared with SLK WT, the T183A, S189A, and T183A/S189A mutants showed reduced in vitro kinase activity. SLK WT, but not mutants, increased activation-specific phosphorylation of c-Jun N-terminal kinase (JNK) and p38 kinase. Similarly, SLK WT stimulated activator protein-1 reporter activity, but activation of activator protein-1 by the three SLK mutants was ineffective. To test if homodimerization of SLK affects phosphorylation, the cDNA encoding SLK amino acids 1-373 (which include the catalytic domain) was fused with a cDNA for a modified FK506-binding protein, Fv (Fv-SLK 1-373). After transfection, the addition of AP20187 (an FK506 analog) induced regulated dimerization of Fv-SLK 1-373. AP20187-stimulated dimerization enhanced the kinase activity of Fv-SLK 1-373 WT. In contrast, kinase activity of Fv-SLK 1-373 T183A/S189A was weak and was not enhanced after dimerization. Finally, apoptosis was increased after expression of Fv-SLK 1-373 WT but not T183A/S189A. Thus, phosphorylation of Thr-183 and Ser-189 plays a key role in the activation and signaling of SLK and could represent a target for novel therapeutic approaches to renal injury. PMID:22203681

Luhovy, Artem Y; Jaberi, Aala; Papillon, Joan; Guillemette, Julie; Cybulsky, Andrey V

2012-02-17

161

Belinostat-induced apoptosis and growth inhibition in pancreatic cancer cells involve activation of TAK1-AMPK signaling axis  

SciTech Connect

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-?-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.

Wang, Bing, E-mail: wangbin69@yahoo.com; Wang, Xin-bao; Chen, Li-yu; Huang, Ling; Dong, Rui-zen

2013-07-19

162

Activated spinal astrocytes are involved in the maintenance of chronic widespread mechanical hyperalgesia after cast immobilization  

PubMed Central

Background In the present study, we examined spinal glial cell activation as a central nervous system mechanism of widespread mechanical hyperalgesia in rats that experienced chronic post-cast pain (CPCP) 2 weeks after cast immobilization. Activated spinal microglia and astrocytes were investigated immunohistologically in lumbar and coccygeal spinal cord segments 1 day, 5 weeks, and 13 weeks following cast removal. Results In the lumbar cord, astrocytes were activated after microglia. Astrocytes also were activated after microglia in the coccygeal cord, but with a delay that was longer than that observed in the lumbar cord. This activation pattern paralleled the observation that mechanical hyperalgesia occurred in the hindleg or the hindpaw before the tail. The activating transcription factor 3 (ATF3) immune response in dorsal root ganglia (DRG) on the last day of cast immobilization suggested that nerve damage might not occur in CPCP rats. The neural activation assessed by the phosphorylated extracellular signal-regulated kinase (pERK) immune response in DRG arose 1 day after cast removal. In addition, L-?-aminoadipate (L-?-AA), an inhibitor of astrocyte activation administered intrathecally 5 weeks after cast removal, inhibited mechanical hyperalgesia in several body parts including the lower leg skin and muscles bilaterally, hindpaws, and tail. Conclusions These findings suggest that activation of lumbar cord astrocytes is an important factor in widespread mechanical hyperalgesia in CPCP. PMID:24456903

2014-01-01

163

Activation of AMPK by Bitter Melon Triterpenoids Involves CaMKK?  

PubMed Central

We recently showed that bitter melon-derived triterpenoids (BMTs) activate AMPK and increase GLUT4 translocation to the plasma membrane in vitro, and improve glucose disposal in insulin resistant models in vivo. Here we interrogated the mechanism by which these novel compounds activate AMPK, a leading anti-diabetic drug target. BMTs did not activate AMPK directly in an allosteric manner as AMP or the Abbott compound (A-769662) does, nor did they activate AMPK by inhibiting cellular respiration like many commonly used anti-diabetic medications. BMTs increased AMPK activity in both L6 myotubes and LKB1-deficient HeLa cells by 20–35%. Incubation with the CaMKK? inhibitor, STO-609, completely attenuated this effect suggesting a key role for CaMKK? in this activation. Incubation of L6 myotubes with the calcium chelator EGTA-AM did not alter this activation suggesting that the BMT-dependent activation was Ca2+-independent. We therefore propose that CaMKK? is a key upstream kinase for BMT-induced activation of AMPK. PMID:23638033

Iseli, Tristan J.; Turner, Nigel; Zeng, Xiao-Yi; Cooney, Gregory J.; Kraegen, Edward W.; Yao, Sheng; Ye, Yang; James, David E.; Ye, Ji-Ming

2013-01-01

164

Activation of legumain involves proteolytic and conformational events, resulting in a context- and substrate-dependent activity profile.  

PubMed

Localized mainly to endo/lysosomes, legumain plays an important role in exogenous antigen processing and presentation. The cysteine protease legumain, also known as asparaginyl endopepetidase AEP, is synthesized as a zymogen and is known to undergo pH-dependent autoproteolytic activation whereby N-terminal and C-terminal propeptides are released. However, important mechanistic details of this pH-dependent activation as well as the characteristic pH activity profile remain unclear. Here, it is shown that all but one of the autocatalytic cleavage events occur in trans, with only the release of the C-terminal propeptide being relevant to enzymatic activity. An intriguing super-activation event that appears to be exclusively conformational in nature and enhances the enzymatic activity of proteolytically fully processed legumain by about twofold was also found. Accepting asparagines and, to lesser extent, aspartic acid in P1, super-activated legumain exhibits a marked pH dependence that is governed by the P1 residue of its substrate and conformationally stabilizing factors such as temperature or ligands. The crystallization and preliminary diffraction data analysis of active legumain are presented, which form an important basis for further studies that should clarify fundamental aspects of activation, activity and inactivation of legumain, which is a key target in (auto-)immunity and cancer. PMID:22232165

Dall, Elfriede; Brandstetter, Hans

2012-01-01

165

Discovering the Thermodynamics of Simultaneous Equilibria: An Entropy Analysis Activity Involving Consecutive Equilibria  

ERIC Educational Resources Information Center

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…

Bindel, Thomas H.

2007-01-01

166

Involvement of Cot activity in the proliferation of ALCL lymphoma cells  

SciTech Connect

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.

Fernandez, Margarita, E-mail: mfernandez@iib.uam.es [Instituto de Investigaciones Biomedicas 'Alberto Sols', CSIC-UAM, Madrid and Departamento de Bioquimica, Facultad de Medicina de la Universidad Autonoma de Madrid (Spain)] [Instituto de Investigaciones Biomedicas 'Alberto Sols', CSIC-UAM, Madrid and Departamento de Bioquimica, Facultad de Medicina de la Universidad Autonoma de Madrid (Spain); Manso, Rebeca; Bernaldez, Flavia; Lopez, Pilar; Martin-Duce, Antonio; Alemany, Susana [Instituto de Investigaciones Biomedicas 'Alberto Sols', CSIC-UAM, Madrid and Departamento de Bioquimica, Facultad de Medicina de la Universidad Autonoma de Madrid (Spain)] [Instituto de Investigaciones Biomedicas 'Alberto Sols', CSIC-UAM, Madrid and Departamento de Bioquimica, Facultad de Medicina de la Universidad Autonoma de Madrid (Spain)

2011-08-12

167

Evidence for antithrombin III involvement in the anticoagulant activity of cellulose sulphate.  

PubMed Central

1 Cellulose sulphate, like heparin, prolonged the clotting time in partial thromboplastin time (PTT) assays, inhibited the amidolytic activity of thrombin, was without effect on amidolysis catalysed by activated coagulation factor X(Xa), and potentiated the inhibition of both thrombin and Xa by antithrombin III (AT). 2 The anticoagulant activity of cellulose sulphate in PTT assays was, like that of heparin and heparin sulphate, but unlike that of dermatan sulphate, reduced by prior incubation of plasma with antiserum specific for AT. 3 These results, which suggest that the anticoagulant activity of cellulose sulphate is at least partially mediated through AT, are discussed in terms of the structural features of polysaccharides required for AT activation. PMID:7378640

Kindness, G.; Long, W. F.; Williamson, F. B.

1980-01-01

168

Glucose-inhibition of glucagon secretion involves activation of GABAA-receptor chloride channels  

Microsoft Academic Search

THE endocrine part of the pancreas plays a central role in blood-glucose regulation. It is well established that an elevation of glucose concentration reduces secretion of the hyperglycaemia-associated hormone glucagon from pancreatic alpha2 cells. The mechanisms involved, however, remain unknown. Electrophysio-logical studies have demonstrated that alpha2 cells generate Ca2+-dependent action potentials. The frequency of these action poten-tials, which increases under

Patrik Rorsman; Per-Olof Berggren; Krister Bokvist; Hans Ericson; Hanns Möhler; Claes-Göran Östenson; Paul A. Smith

1989-01-01

169

Involvement of cytochrome P-450 enzyme activity in the selectivity and safening action of pyrazosulfuron-ethyl.  

PubMed

To investigate the selectivity and safening action of the sulfonylurea herbicide pyrazosulfuron-ethyl (PSE), pyrazosulfuron-ethyl O-demethylase (PSEOD) activity involving oxidative metabolism by cytochrome P-450 was studied in rice (Oryza sativa L cv Nipponbare) and Cyperus serotinus Rottb. Cytochrome P-450-dependent activity was demonstrated by the use of the inducers 1,8-naphthalic anhydride and ethanol, the herbicides PSE, bensulfuron-methyl, dimepiperate and dymron, or the inhibitor piperonyl butoxide (PBO). Growth inhibition in C serotinus seedlings was more severe than that in rice seedlings. O-Dealkylation activities of PSE were induced differently in rice and in C serotinus, with distinctly higher activity in rice seedlings. The induced PSEOD activities were slightly inhibited by PBO in rice seedlings, whereas they were strongly inhibited in C serotinus seedlings. Dimepiperate and dymron were effective safeners of rice against PSE treatment. Treatments with herbicide alone resulted in less induction of PSEOD activity compared with combined treatments of the herbicide and safener. PSEOD activity in rice seedlings induced with herbicide alone was strongly inhibited by PBO, whereas it was weakly inhibited in rice seedlings induced with combinations of PSE and two safeners. These results suggest that O-demethylation by cytochrome P-450 enzymes may be involved in the metabolism of PSE and may contribute to its selectivity and safening action. Furthermore, these results suggest the existence of a multiple form of cytochrome P-450 in plants. PMID:11455659

Yun, M S; Shim, I S; Usui, K

2001-03-01

170

Directory of DOE and contractor personnel involved in non-government standards activities  

SciTech Connect

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.

NONE

1995-08-01

171

Factors involved in drug interference on enzyme activities of three mitochondrial populations from rat hippocampus.  

PubMed

The maximal rate (Vmax) of some mitochondrial enzyme activities related to energy transduction (citrate synthase, alpha-ketoglutarate dehydrogenase, malate dehydrogenase, succinate dehydrogenase, NADH-cytochrome c reductase, cytochrome oxidase) and amino acid metabolism (glutamate dehydrogenase, glutamate-pyruvate transaminase and glutamate-oxaloacetate transaminase) are evaluated in non synaptic ("free") and intrasynaptic mitochondria from brain hippocampus. The different mitochondrial populations were isolated from rat subjected to single i.p. treatment with saline solution, almitrine (30 mg/kg) and delta-yohimbine (10 mg/kg). In control rats, the mitochondrial populations exhibit different enzymatic patterns. Acute treatment with almitrine decreases cytochrome oxidase activity in intra-synaptic mitochondria, while acute treatment with delta-yohimbine decreases succinate dehydrogenase activity in both types of free and intra-synaptic mitochondria. NADH-cytochrome c reductase activity is also decreased by acute treatment with almitrine ("free" and "synaptic" mitochondria) and delta-yohimbine (synaptic mitochondria only). PMID:1801934

Villa, R F; Ghigini, B; Arnaboldi, R; Geroldi, D; Gorini, A

1991-01-01

172

Mutational analysis of the major soybean UreF paralogue involved in urease activation  

PubMed Central

The soybean genome duplicated ?14 and 45 million years ago and has many paralogous genes, including those in urease activation (emplacement of Ni and CO2 in the active site). Activation requires the UreD and UreF proteins, each encoded by two paralogues. UreG, a third essential activation protein, is encoded by the single-copy Eu3, and eu3 mutants lack activity of both urease isozymes. eu2 has the same urease-negative phenotype, consistent with Eu2 being a single-copy gene, possibly encoding a Ni carrier. Unexpectedly, two eu2 alleles co-segregated with missense mutations in the chromosome 2 UreF paralogue (Ch02UreF), suggesting lack of expression/function of Ch14UreF. However, Ch02UreF and Ch14UreF transcripts accumulate at the same level. Further, it had been shown that expression of the Ch14UreF ORF complemented a fungal ureF mutant. A third, nonsense (Q2*) allelic mutant, eu2-c, exhibited 5- to 10-fold more residual urease activity than missense eu2-a or eu2-b, though eu2-c should lack all Ch02UreF protein. It is hypothesized that low-level activation by Ch14UreF is ‘spoiled’ by the altered missense Ch02UreF proteins (‘epistatic dominant-negative’). In agreement with active ‘spoiling’ by eu2-b-encoded Ch02UreF (G31D), eu2-b/eu2-c heterozygotes had less than half the urease activity of eu2-c/eu2-c siblings. Ch02UreF (G31D) could spoil activation by Chr14UreF because of higher affinity for the activation complex, or because Ch02UreF (G31D) is more abundant than Ch14UreF. Here, the latter is favoured, consistent with a reported in-frame AUG in the 5' leader of Chr14UreF transcript. Translational inhibition could represent a form of ‘functional divergence’ of duplicated genes. PMID:21430294

Polacco, Joe C.; Hyten, David L.; Medeiros-Silva, Monica; Sleper, David A.; Bilyeu, Kristin D.

2011-01-01

173

Involvement of secretory phospholipase A2 activity in the zymosan rat air pouch model of inflammation.  

PubMed Central

1. In the zymosan rat air pouch model of inflammation we have assessed the time dependence of phospholipase A2 (PLA2) accumulation in the inflammatory exudates as well as cell migration, myeloperoxidase activity, prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) levels. 2. A significant increase in PLA2 activity was detected in 1,200 g supernatants of exudates 8 h after injection of zymosan into rat air pouch. This event coincided with peaks in cell accumulation (mainly neutrophils) and myeloperoxidase activity in exudates and was preceded by a rise in eicosanoid levels. 3. This enzyme (without further purification) behaved as a secretory type II PLA2 with an optimum pH at 7-8 units, lack of selectivity for arachidonate release and dependence on mM calcium concentrations for maximal activity. 4. The PLA2 inhibitors manoalide and scalaradial inhibited this enzyme activity in vitro in a concentration-dependent manner. Scalaradial also inhibited zymosan stimulated myeloperoxidase release in vitro. 5. Injection of the marine PLA2 inhibitor scalaradial together with zymosan into the pouch at doses of 0.5, 1 and 5 mumol per pouch resulted in a dose-dependent inhibition of PLA2 activity in exudates collected 8 h later. Myeloperoxidase levels and cell migration were also decreased, while eicosanoid levels were not modified. 6. Colchicine administration to rats prevented infiltration and decreased PLA2 levels in the 8 h zymosan-injected air pouch. 7. These results indicate that during inflammatory response to zymosan in the rat air pouch a secretory PLA2 activity is released into the exudates. The source of this activity is mainly the neutrophil which migrates into the pouch. 8. Scalaradial exerts anti-inflammatory effects in the zymosan air pouch. Images Figure 2 PMID:8732290

Paya, M.; Terencio, M. C.; Ferrandiz, M. L.; Alcaraz, M. J.

1996-01-01

174

Helminth 2Cys peroxiredoxin drives Th2 responses through a mechanism involving alternatively activated macrophages  

Microsoft Academic Search

During helminth infections, alternatively activated macrophages (AAMacs) are key to promoting Th2 responses and suppressing Th1-driven inflamma- tory pathology. Th2 cytokines IL-4 and\\/or IL-13 are believed to be important in the induction and activation of AAMacs. Using murine models for the helminth infections caused by Fasciola hepatica (Fh) and Schisto- soma mansoni (Sm), we show that a secreted antioxidant, peroxiredoxin

Sheila Donnelly; Colin M. Stack; Sandra M. O'Neill; Ahmed A. Sayed; David L. Williams; John P. Dalton

2008-01-01

175

Stretch-induced uterine myocyte differentiation during rat pregnancy: involvement of caspase activation.  

PubMed

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

Shynlova, Oksana; Dorogin, Anna; Lye, Stephen J

2010-06-01

176

Is activated hemocyanin instead of phenoloxidase involved in immune response in woodlice?  

PubMed

In the Common woodlouse Porcellio scaber (Crustacea: Isopoda: Oniscidea), experimental immune challenge did not induce the expression of pro-phenoloxidase that, in most other invertebrates studied thus far, can be activated into phenoloxidase via an activation cascade upon immune challenge. Instead, Porcellio hemocyanin proved to exhibit catecholoxidase activity upon activation. However, none of the activating factors known from other invertebrates other than SDS-treatment resulted in activation of hemocyanin into a functional phenoloxidase in vitro. The distinct characteristics of isopod hemocyanin are reflected by the quaternary structure of the hemocyanin dodecamers that differs from that of other crustacean hemocyanins in that the two hexamers share a common 3-fold rotation axis and have an angular offset of 60 degrees against each other. Accordingly, the sequence of Porcellio hemocyanin can be distinguished clearly from other crustacean hemocyanins and in a phylogenetic analysis forms a cluster with other isopod and amphipod hemocyanins. We propose a peracarid-type hemocyanin that may have evolved in response to its required multiple functions in respiration and immune response, while phenoloxidase sensu strictu is lacking. PMID:19447131

Jaenicke, Elmar; Fraune, Sebastian; May, Sandra; Irmak, Pinar; Augustin, Rene; Meesters, Christian; Decker, Heinz; Zimmer, Martin

2009-10-01

177

Induction of the rat prodynorphin gene through Gs-coupled receptors may involve phosphorylation-dependent derepression and activation.  

PubMed Central

Prodynorphin transcription is activated via Gs-coupled receptors through a cyclic AMP (cAMP)-dependent pathway. Four cAMP response elements (CREs) are present within the rat prodynorphin (RD) control region, and all four CREs appear to function in RD regulation. Three CREs located upstream between -1860 and -1504 are critical for receptor-responsive activity, but their function is distance dependent unless they act together with a fourth CRE found in exon 1. Regulation of RD also appears to involve multiple CRE-binding proteins. Both CRE-binding protein (CREB) and activator protein 1 (AP-1) can regulate RD, but their effects are in opposite directions; CREB represses and AP-1 activates RD. CREB-induced repression and AP-1 activation require distinct elements within the control region, but their binding and functions overlap at CRE-3. While CREB repression is dependent on CRE-3, AP-1 activation (and cAMP induction) of RD requires additional CREs (CRE-1, -2, and -4). CREB repression blocks AP-1 activation in unstimulated cells. However, phosphorylation relieves CREB-induced repression and enhances AP-1 activation. Gs-coupled receptor activation of RD may require phosphorylation-dependent derepression and activation steps. Images PMID:8164647

Collins-Hicok, J; Lin, L; Spiro, C; Laybourn, P J; Tschumper, R; Rapacz, B; McMurray, C T

1994-01-01

178

NIK is involved in constitutive activation of the alternative NF-{kappa}B pathway and proliferation of pancreatic cancer cells  

SciTech Connect

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.

Nishina, Takashi [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan)] [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Yamaguchi, Noritaka [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan) [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 513 Wasedatsurumaki-cho, Shinjuku-ku, Tokyo 162-0041 (Japan); Gohda, Jin [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan)] [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Semba, Kentaro [Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 513 Wasedatsurumaki-cho, Shinjuku-ku, Tokyo 162-0041 (Japan) [Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 513 Wasedatsurumaki-cho, Shinjuku-ku, Tokyo 162-0041 (Japan); Department of Life Science and Medical Bio-science, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480 (Japan); Inoue, Jun-ichiro, E-mail: jun-i@ims.u-tokyo.ac.jp [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan)] [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan)

2009-10-09

179

Phospholipase A{sub 2} is involved in the mechanism of activation of neutrophils by polychlorinated biphenyls  

SciTech Connect

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.

Tithof, P.K.; Schiamberg, E.; Ganey, P.E. [Univ. of Michigan, Ann Arbor, MI (United States); Peters-Golden, M. [Michigan State Univ., East Lansing, MI (United States)

1996-01-01

180

Hydroxycinnamic acid decarboxylase activity of Brettanomyces bruxellensis involved in volatile phenol production: relationship with cell viability.  

PubMed

Brettanomyces bruxellensis populations have been correlated with an increase in phenolic off-flavors in wine. The volatile phenols causing the olfactory defect result from the successive decarboxylation and reduction of hydroxycinnamic acids that are normal components of red wines. The growth of B. bruxellensis is preventable by adding sulfur dioxide (SO(2)), with variable effectiveness. Moreover, it was hypothesized that SO(2) was responsible for the entry of B. bruxellensis into a viable but non-culturable (VBNC) state. The aim of this project was to investigate the effects of SO(2) on the remaining enzyme activities of B. bruxellensis populations according to their viability and cultivability, focusing on the hydroxycinnamate decarboxylase enzyme, the first enzyme needed, rather than the metabolites produced. Enzyme activity was determined both in cell-free extracts and resting cells after various SO(2) treatments in synthetic media. After slight sulfiting (around 50 mg/L total SO(2)), the yeasts had lost part of their enzyme activity but not their cultivability. At higher doses (at least 75 mg/L total SO(2)) the majority of yeasts had lost their cultivability but still retained part of their enzyme activity. These results suggested that non culturable cells retained some enzyme activity. PMID:22986185

Laforgue, R; Lonvaud-Funel, A

2012-12-01

181

Activity involvement as an ecological asset: profiles of participation and youth outcomes.  

PubMed

Prior research has demonstrated that participation in out-of-school time activities is associated with positive and healthy development among adolescents. However, fewer studies have examined how trajectories of participation across multiple activities can impact developmental outcomes. Using data from Wave 3 (approximately Grade 7) through Wave 8 (approximately Grade 12) of the 4-H Study of Positive Youth Development, this study examined patterns of breadth in out-of-school time participation in activities and associated outcomes in positive youth development (PYD), Contribution to self and community, risk behaviors, and depressive symptoms. We assessed 927 students (on average across waves, 65.4% female) from a relatively racially and ethnically homogeneous sample (about 74% European American, across waves) with a mean age in Wave 3 of 12.98 years (SD = 0.52). The results indicated that high likelihood of participation in activities was consistently associated with fewer negative outcomes and higher scores on PYD and Contribution, as compared to low likelihood of participation in activities. Changes in the breadth of participation (in particular, moving from a high to a low likelihood of participation) were associated with increased substance use, depressive symptoms, and risk behaviors. Limitations of the current study, implications for future research, and applications to youth programs are discussed. PMID:24510166

Agans, Jennifer P; Champine, Robey B; DeSouza, Lisette M; Mueller, Megan Kiely; Johnson, Sara Kassie; Lerner, Richard M

2014-06-01

182

Teacher management behaviors and pupil task involvement during small group laboratory activities  

NASA Astrophysics Data System (ADS)

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.

Beasley, Warren

183

Assembly of melleolide antibiotics involves a polyketide synthase with cross-coupling activity.  

PubMed

Little is known about polyketide biosynthesis in mushrooms (basidiomycota). In this study, we investigated the iterative type I polyketide synthase (PKS) ArmB of the tree pathogen Armillaria mellea, a producer of cytotoxic melleolides (i.e., polyketides esterified with various sesquiterpene alcohols). Heterologously produced ArmB showed orsellinic acid (OA) synthase activity in vitro. Further, we demonstrate cross-coupling activity of ArmB, which forms OA esters with various alcohols. Using a tricyclic Armillaria sesquiterpene alcohol, we reconstituted the biosynthesis of melledonol. Intermolecular transesterification reactions may represent a general mechanism of fungal PKSs to create structural diversity of small molecules. Phylogenetic network construction of thioesterase domains of both basidiomycetes and ascomycetes suggests that the fungal nonreducing PKS family has likely evolved from an ancient OA synthase and has gained versatility by adopting Claisen-like cyclase or transferase activity. PMID:23993460

Lackner, Gerald; Bohnert, Markus; Wick, Jonas; Hoffmeister, Dirk

2013-09-19

184

Parent-adolescent joint projects involving leisure time and activities during the transition to high school.  

PubMed

Leisure research to date has generally overlooked planning and organizing of leisure time and activities between parents and adolescents. This investigation examined how a sample of Canadian adolescents and their parents jointly constructed and acted on goals related to adolescents' leisure time during the move from elementary to high school. Using the Qualitative Action-Project Method, data were collected over an 8-10 month period from 26 parent-adolescent dyads located in two urban sites, through video-taped conversations about leisure time, video recall interviews, and telephone monitoring interviews. Analysis of the data revealed that the joint projects of the 26 dyads could be grouped into three clusters: a) governance transfer or attempts to shift, from parent to adolescent, responsibility over academic demands, organizing leisure time, and safety with peers, b) balancing extra-curricular activities with family life, academics, and social activities, and c) relationship adjustment or maintenance. PMID:25134071

Marshall, Sheila K; Young, Richard A; Wozniak, Agnieszka; Lollis, Susan; Tilton-Weaver, Lauree; Nelson, Margo; Goessling, Kristen

2014-10-01

185

Involvement of Caspase Activation in Azaspiracid-Induced Neurotoxicity in Neocortical Neurons  

PubMed Central

Azaspiracids (AZAs) are a novel group of marine phycotoxins that have been associated with severe human intoxication. We found that AZA-1 exposure increased lactate dehydrogense (LDH) efflux in murine neocortical neurons. AZA-1 also produced nuclear condensation and stimulated caspase-3 activity with an half maximal effective concentration (EC50) value of 25.8nM. These data indicate that AZA-1 triggers neuronal death in neocortical neurons by both necrotic and apoptotic mechanisms. An evaluation of the structure-activity relationships of AZA analogs on LDH efflux and caspase-3 activation demonstrated that the full structure of AZAs was required to produce necrotic or apoptotic cell death. The similar potencies of AZA-1 to stimulate LDH efflux and caspase-3 activation and the parallel structure-activity relationships of azaspiracid analogs in the two assays are consistent with a common molecular target for both responses. To explore the molecular mechanism for AZA-1–induced neurotoxicity, we assessed the influence of AZA-1 on Ca2+ homeostasis. AZA-1 suppressed spontaneous Ca2+ oscillations (EC50 = 445nM) in neocortical neurons. A distinct structure-activity profile was found for inhibition of Ca2+ oscillations where both the full structure as well as analogs containing only the FGHI domain attached to a phenyl glycine methyl ester moiety were potent inhibitors. The molecular targets for inhibition of spontaneous Ca2+ oscillations and neurotoxicity may therefore differ. The caspase protease inhibitor Z-VAD-FMK produced a complete elimination of AZA-1–induced LDH efflux and nuclear condensation in neocortical neurons. Although the molecular target for AZA-induced neurotoxicity remains to be established, these results demonstrate that the observed neurotoxicity is dependent on a caspase signaling pathway. PMID:20047973

Cao, Zhengyu; LePage, Keith T.; Frederick, Michael O.; Nicolaou, Kyriacos C.; Murray, Thomas F.

2010-01-01

186

Selective Localization of Arc mRNA in Dendrites Involves Activity- and Translation-Dependent mRNA Degradation  

PubMed Central

Arc is an immediate early gene that is unique among neuronal mRNAs because its transcripts are transported into dendrites and accumulate near activated synapses, presumably to be translated locally. These qualities pose Arc as playing an important, yet not fully understood, role in the activity-dependent modifications of synapses that are thought to underlie memory storage. Here we show in vivo in rats that newly synthesized Arc mRNA accumulates at activated synapses and that synaptic activity simultaneously triggers mRNA decay that eliminates Arc mRNA from inactive dendritic domains. Arc mRNA degradation occurs throughout the dendrite and requires both NMDA receptor activation and active translation. Synaptic activation did not lead to decreases in another dendritic mRNA (?CaMKII), indicating that there is not a general activation of mRNA degradation in dendrites. These data reveal a novel mechanism for controlling mRNA distribution within dendrites and highlight activity-dependent mRNA degradation as a regulatory process involved in synaptic plasticity. PMID:24671994

Farris, Shannon; Lewandowski, Gail; Cox, Conor D.

2014-01-01

187

Selective localization of arc mRNA in dendrites involves activity- and translation-dependent mRNA degradation.  

PubMed

Arc is an immediate early gene that is unique among neuronal mRNAs because its transcripts are transported into dendrites and accumulate near activated synapses, presumably to be translated locally. These qualities pose Arc as playing an important, yet not fully understood, role in the activity-dependent modifications of synapses that are thought to underlie memory storage. Here we show in vivo in rats that newly synthesized Arc mRNA accumulates at activated synapses and that synaptic activity simultaneously triggers mRNA decay that eliminates Arc mRNA from inactive dendritic domains. Arc mRNA degradation occurs throughout the dendrite and requires both NMDA receptor activation and active translation. Synaptic activation did not lead to decreases in another dendritic mRNA (?CaMKII), indicating that there is not a general activation of mRNA degradation in dendrites. These data reveal a novel mechanism for controlling mRNA distribution within dendrites and highlight activity-dependent mRNA degradation as a regulatory process involved in synaptic plasticity. PMID:24671994

Farris, Shannon; Lewandowski, Gail; Cox, Conor D; Steward, Oswald

2014-03-26

188

Physical Activity Based Professional Development for Teachers: The Importance of Whole School Involvement  

ERIC Educational Resources Information Center

Objective: This study sought to investigate teachers' perceptions of a physical activity-related professional development intervention. Design: Interview-based qualitative approach founded on the interpretive paradigm. Setting: Purposive selection of one high-rated independent, and one low-rated public primary school from Auckland, New Zealand.…

Till, Jude; Ferkins, Lesley; Handcock, Phil

2011-01-01

189

Enhanced Spontaneous Locomotor Activity in Bovine GH Transgenic Mice Involves Peripheral Mechanisms  

Microsoft Academic Search

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 spon- taneous locomotor activity. In the present study, we investi- gated whether this behavioral change is owing to a direct action of GH in the central nervous system

MOHAMMAD BOHLOOLY-Y; BOB OLSSON; AMEL GRITLI-LINDE; OLA BRUSEHED; OLLE G. P. ISAKSSON; CLAES OHLSSON; BO SODERPALM; JAN TORNELL

2010-01-01

190

Temporal-Order Judgment of Audiovisual Events Involves Network Activity Between Parietal and Prefrontal Cortices  

PubMed Central

Abstract Our perception of the temporal order of everyday external events depends on the integrated sensory information in the brain. Our understanding of the brain mechanism for temporal-order judgment (TOJ) of unisensory events, particularly in the visual domain, is advanced. In case of multisensory events, however, there are unanswered questions. Here, by using physically synchronous and asynchronous auditory–visual events in functional magnetic resonance imaging (fMRI) experiments, we identified the brain network that is associated with the perception of the temporal order of multisensory events. The activation in the right temporo-parietal junction was modulated by the perception of asynchronous audiovisual events. During this perception of temporal order, the right dorsolateral prefrontal cortex coordinated activity with the right temporo-parietal and the left inferior parietal cortices. These results suggest that the TOJ in the multisensory domain underlies a network activity between parietal and prefrontal cortices unlike the regional activity in the right temporo-parietal junction in the unisensory visual domain. PMID:23988147

Goshorn, Eli S.; Lamichhane, Bidhan; Dhamala, Mukesh

2013-01-01

191

Mechanism of activation of methyltransferases involved in translation by the Trm112 'hub' protein  

PubMed Central

Methylation is a common modification encountered in DNA, RNA and proteins. It plays a central role in gene expression, protein function and mRNA translation. Prokaryotic and eukaryotic class I translation termination factors are methylated on the glutamine of the essential and universally conserved GGQ motif, in line with an important cellular role. In eukaryotes, this modification is performed by the Mtq2-Trm112 holoenzyme. Trm112 activates not only the Mtq2 catalytic subunit but also two other tRNA methyltransferases (Trm9 and Trm11). To understand the molecular mechanisms underlying methyltransferase activation by Trm112, we have determined the 3D structure of the Mtq2-Trm112 complex and mapped its active site. Using site-directed mutagenesis and in vivo functional experiments, we show that this structure can also serve as a model for the Trm9-Trm112 complex, supporting our hypothesis that Trm112 uses a common strategy to activate these three methyltransferases. PMID:21478168

Liger, Dominique; Mora, Liliana; Lazar, Noureddine; Figaro, Sabine; Henri, Julien; Scrima, Nathalie; Buckingham, Richard H.; van Tilbeurgh, Herman; Heurgue-Hamard, Valerie; Graille, Marc

2011-01-01

192

Mechanism of activation of methyltransferases involved in translation by the Trm112 'hub' protein.  

PubMed

Methylation is a common modification encountered in DNA, RNA and proteins. It plays a central role in gene expression, protein function and mRNA translation. Prokaryotic and eukaryotic class I translation termination factors are methylated on the glutamine of the essential and universally conserved GGQ motif, in line with an important cellular role. In eukaryotes, this modification is performed by the Mtq2-Trm112 holoenzyme. Trm112 activates not only the Mtq2 catalytic subunit but also two other tRNA methyltransferases (Trm9 and Trm11). To understand the molecular mechanisms underlying methyltransferase activation by Trm112, we have determined the 3D structure of the Mtq2-Trm112 complex and mapped its active site. Using site-directed mutagenesis and in vivo functional experiments, we show that this structure can also serve as a model for the Trm9-Trm112 complex, supporting our hypothesis that Trm112 uses a common strategy to activate these three methyltransferases. PMID:21478168

Liger, Dominique; Mora, Liliana; Lazar, Noureddine; Figaro, Sabine; Henri, Julien; Scrima, Nathalie; Buckingham, Richard H; van Tilbeurgh, Herman; Heurgué-Hamard, Valérie; Graille, Marc

2011-08-01

193

Analyses of isoamylase gene activity in wild-type barley indicate its involvement in starch synthesis  

Microsoft Academic Search

The notion of debranching enzyme activity as a participant in starch synthesis is gaining acceptance. Inconsistent reports from mutant analyses implicate either isoamylase or pullulanase as a determinant in amylopectin formation and whether wild-type plants utilize one or the other, or both, of these debranching enzymes in starch synthesis is unclear. Recent results on the su1 mutant in maize suggest

Chuanxin Sun; P. Sathish; Staffan Ahlandsberg; Christer Jansson

1999-01-01

194

Oxidative stress-mediated iNKT-cell activation is involved in COPD pathogenesis  

PubMed Central

Chronic obstructive pulmonary disease (COPD) is a major clinical challenge mostly due to cigarette smoke (CS) exposure. Invariant natural killer T (iNKT) cells are potent immunoregulatory cells that have a crucial role in inflammation. In the current study, we investigate the role of iNKT cells in COPD pathogenesis. The frequency of activated NKT cells was found to be increased in peripheral blood of COPD patients relative to controls. In mice chronically exposed to CS, activated iNKT cells accumulated in the lungs and strongly contributed to the pathogenesis. The detrimental role of iNKT cells was confirmed in an acute model of oxidative stress, an effect that depended on interleukin (IL)-17. CS extracts directly activated mouse and human dendritic cells (DC) and airway epithelial cells (AECs) to trigger interferon? and/or IL-17 production by iNKT cells, an effect ablated by the anti-oxidant N-acetylcystein. In mice, this treatment abrogates iNKT-cell accumulation in the lung and abolished the development of COPD. Together, activation of iNKT cells by oxidative stress in DC and AECs participates in the development of experimental COPD, a finding that might be exploited at a therapeutic level. PMID:24172846

Pichavant, M; Remy, G; Bekaert, S; Le Rouzic, O; Kervoaze, G; Vilain, E; Just, N; Tillie-Leblond, I; Trottein, F; Cataldo, D; Gosset, P

2014-01-01

195

Cultural Variation in Young Children's Opportunities for Involvement in Adult Activities.  

ERIC Educational Resources Information Center

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…

Morelli, Gilda A.; And Others

196

Marketing Informal Education Institutions in Israel: The Centrality of Customers' Active Involvement in Service Development  

ERIC Educational Resources Information Center

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…

Oplatka, Izhar

2004-01-01

197

Predictors of condom use among sexually active persons involved in compulsory national service in Ibadan, Nigeria  

Microsoft Academic Search

Migration is known to increase the risk of heterosexual transmission of human immuno- deficiency virus (HIV) in sub-Saharan Africa, but little attention has been paid to fresh graduates of tertiary institutions who are on migration for compulsory national assignment in Nigeria. In July and August 2004, a survey was conducted on sexually active men (n 5 344) and women (n

Adegbenga M. Sunmola; Benjamin O. Olley; Grace E. Oso

2006-01-01

198

School-Based Extracurricular Activity Involvement and Adolescent Self-Esteem: A Growth-Curve Analysis  

ERIC Educational Resources Information Center

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…

Kort-Butler, Lisa A.; Hagewen, Kellie J.

2011-01-01

199

Hypnosis Modulates Activity in Brain Structures Involved in the Regulation of Consciousness  

Microsoft Academic Search

The notion of consciousness is at the core of an ongoing debate on the existence and nature of hypnotic states. Previously, we have described changes in brain activity associated with hypnosis (Rainville, Hofbauer, Paus, Duncan, Bushnell, & Price, 1999). Here, we replicate and extend those findings using positron emission tomography (PET) in 10 normal volunteers. Immediately after each of 8

Pierre Rainville; Robert K. Hofbauer; M. Catherine Bushnell; Gary H. Duncan; Donald D. Price

2002-01-01

200

Rap1 promotes VEGFR2 activation and angiogenesis by a mechanism involving integrin ?v?3  

PubMed Central

Vascular endothelial growth factor (VEGF) acting through VEGF receptor 2 (VEGFR2) on endothelial cells (ECs) is a key regulator of angiogenesis, a process essential for wound healing and tumor metastasis. Rap1a and Rap1b, 2 highly homologous small G proteins, are both required for angiogenesis in vivo and for normal EC responses to VEGF. Here we sought to determine the mechanism through which Rap1 promotes VEGF-mediated angiogenesis. Using lineage-restricted Rap1-knockout mice we show that Rap1-deficiency in endothelium leads to defective angiogenesis in vivo, in a dose-dependent manner. Using ECs obtained from Rap1-deficient mice we demonstrate that Rap1b promotes VEGF-VEGFR2 kinase activation and regulates integrin activation. Importantly, the Rap1b-dependent VEGF-VEGFR2 activation is in part mediated via integrin ?v?3. Furthermore, in an in vivo model of zebrafish angiogenesis, we demonstrate that Rap1b is essential for the sprouting of intersomitic vessels, a process known to be dependent on VEGF signaling. Using 2 distinct pharmacologic VEGFR2 inhibitors we show that Rap1b and VEGFR2 act additively to control angiogenesis in vivo. We conclude that Rap1b promotes VEGF-mediated angiogenesis by promoting VEGFR2 activation in ECs via integrin ?v?3. These results provide a novel insight into the role of Rap1 in VEGF signaling in ECs. PMID:21636859

Lakshmikanthan, Sribalaji; Sobczak, Magdalena; Chun, Changzoon; Henschel, Angela; Dargatz, Jillian; Ramchandran, Ramani

2011-01-01

201

Regrouping: Organized Activity Involvement and Social Adjustment across the Transition to High School  

ERIC Educational Resources Information Center

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…

Bohnert, Amy M.; Aikins, Julie Wargo; Arola, Nicole T.

2013-01-01

202

Facilitation handlings induce increase in electromyographic activity of muscles involved in head control of Cerebral Palsy children.  

PubMed

This study aimed to investigate the electromyographic (EMG) activation of the main cervical muscles involved in the head control during two postures widely used for the facilitation of head control in children with Cerebral Palsy (CP). A crossover trial involving 31 children with clinical diagnosis of CP and spastic quadriplegia was conducted. Electromyography was used to measure muscular activity in randomized postures. Three positions were at rest: (a) lateral decubitus, (b) ventral decubitus on the floor and (c) ventral decubitus on the wedge. Handlings for facilitating the head control were performed using the hip joint as key point of control in two postures: (a) lateral decubitus and (b) ventral decubitus on wedge. All children underwent standardized handlings, performed by the same researcher with experience in the neurodevelopmental treatment. EMG signal was recorded from muscles involved in the head control (paraspinal and sternocleidomastoid muscles) in sagittal, frontal and transverse planes, at the fourth cervical vertebra (C4), tenth thoracic vertebra (T10) and sternocleidomastoid muscle (SCM) levels. The results showed a significant increase in muscle activation when handling was performed in the lateral decubitus at C4 (P<0.001), T10 (P<0.001) and SCM (P=0.02) levels. A significant higher muscle activation was observed when handling was performed in lateral decubitus when compared to ventral decubitus at C4 level (P<0.001). Handling in ventral decubitus also induced an increase in EMG activation at T10 (P=0.018) and SCM (P=0.004) levels but not at C4 level (P=0.38). In conclusion, handlings performed in both positions may induce the facilitation of head control, as evaluated by the activity of cervical and upper trunk muscles. Handling performed in lateral decubitus may induce a slightly better facilitation of head control. These findings contribute to evidence-based physiotherapy practice for the rehabilitation of severely spastic quadriplegic CP children. PMID:25010566

Simon, Anelise de Saldanha; do Pinho, Alexandre Severo; Grazziotin Dos Santos, Camila; Pagnussat, Aline de Souza

2014-10-01

203

Bcl?ChemInfo - Qualitative analysis of machine learning models for activation of HSD involved in Alzheimer's Disease  

Microsoft Academic Search

In this case study, a ligand-based virtual high throughput screening suite, bcl?ChemInfo, was applied to screen for activation of the protein target 17-beta hydroxysteroid dehydrogenase type 10 (HSD) involved in Alzheimer's Disease. bcl?ChemInfo implements a diverse set of machine learning techniques such as artificial neural networks (ANN), support vector machines (SVM) with the extension for regression, kappa nearest neighbor (KNN),

Mariusz Butkiewicz; Edward W. Lowe; Jens Meiler

2012-01-01

204

Involvement of ASK1 activation in apoptosis induced by NPe6-PDT  

NASA Astrophysics Data System (ADS)

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.

Liu, Lei; Zhang, Zhen-zhen; Zhang, Zhigang

2010-02-01

205

'Co-active coaching' could help HIV patients. New type of counseling involves goal-setting.  

PubMed

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

Garfinkel, M; Blumenthal, E

2001-08-01

206

Involvement of intracellular Ca 2+ in oxidant-induced NF-?B activation  

Microsoft Academic Search

In human Jurkat T cells and its subclone Wurzburg cells oxidant challenge elevated [Ca2+]i by mobilizing Ca2+ from intracellular stores. In Jurkat cells this effect was rapid and transient, but in Wurzburg cells the response was slow and sustained. H202-induced NF-?B activation in Wurzburg cells was not influenced by the presence of extracellular EGTA but was totally inhibited in cells

Chandan K. Sen; Sashwati Roy; Lester Packer

1996-01-01

207

Protease-activated receptor 1-dependent neuronal damage involves NMDA receptor function  

PubMed Central

Protease-activated receptor 1 (PAR1) is a G-protein coupled receptor that is expressed throughout the central nervous system. PAR1 activation by brain-derived as well as blood-derived proteases has been shown to have variable and complex effects in a variety of animal models of neuronal injury and inflammation. In this study, we have evaluated the effects of PAR1 on lesion volume in wild-type or PAR1?/? C57Bl/6 mice subjected to transient occlusion of the middle cerebral artery or injected with NMDA in the striatum. We found that removal of PAR1 reduced infarct volume following transient focal ischemia to 57% of control. Removal of PAR1 or application of a PAR1 antagonist also reduced the neuronal injury associated with intrastriatal injection of NMDA to 60% of control. To explore whether NMDA receptor potentiation by PAR1 activation contributes to the harmful effects of PAR1, we investigated the effect of NMDA receptor antagonists on the neuroprotective phenotype of PAR1?/? mice. We found that MK801 reduced penumbral but not core neuronal injury in mice subjected to transient middle cerebral artery occlusion or intrastriatal NMDA injection. Lesion volumes in both models were not significantly different between PAR1?/? mice treated with and without MK801. Use of the NMDA receptor antagonist and dissociative anesthetic ketamine also renders NMDA-induced lesion volumes identical in PAR1?/? mice and wild-type mice. These data suggest that the ability of PAR1 activation to potentiate NMDA receptor function may underlie its harmful actions during injury. PMID:19416668

Hamill, Cecily E.; Mannaioni, Guido; Lyuboslavsky, Polina; Sastre, Aristide A.; Traynelis, Stephen F.

2009-01-01

208

Mechanism of glial activation by S100B: involvement of the transcription factor NF?B  

Microsoft Academic Search

Compelling evidence links chronic activation of glia and the subsequent cycle of neuroinflammation and neuronal dysfunction to the progression of neurodegeneration in disorders such as Alzheimer’s disease (AD). S100B, a glial-derived cytokine, is significantly elevated in the brains of AD patients and high concentrations of S100B are believed to be detrimental to brain function. As a first step toward elucidating

Amy G. M Lam; Tanuja Koppal; Keith T Akama; Ling Guo; Jeffrey M Craft; Barat Samy; James P Schavocky; D Martin Watterson; Linda J Van Eldik

2001-01-01

209

Enhanced contractility of rat aorta in DOCA-salt hypertension involves COX2 activation  

Microsoft Academic Search

Responsiveness to many contractile agonists increase in deoxycorticosterone acetate (DOCA)-salt induced hypertension We tested the hypothesis that enhanced contractility of rat aorta to norepinephrine (NE) in DOCA-salt hypertension is causally related to increased expression and activity of COX-2. Thoracic aortic rings were obtained from uninephrectomized rats fed for 3 weeks on either normal (control), or 8% sodium+potassium (experimental) diets. The

Ayotunde S. Adeagbo; Xiaodong Zhang; Yang Wang; Mabayoje A. Oriowo

2001-01-01

210

Involvement of IL32 in activation-induced cell death in T cells  

Microsoft Academic Search

NK cell transcript 4 (NK4), now denoted as IL-32, was originally identified as a transcript whose expression was increased in activated NK cells. It has been very recently demonstrated that NK4 is secreted from several cells upon the stimulation of some inflammatory cytokines such as IL-18, IL-1b, IFN-c and IL-12. Furthermore, NK4 induces production of tumor necrosis factor, macrophage inflammatory

Chiho God; Taisuke Kanaji; Sachiko Kanaji; Go Tanaka; Kazuhiko Arima; Shigeaki Ohno; Kenji Izuhara

2006-01-01

211

A systematic review of weight loss, physical activity and dietary interventions involving African American men.  

PubMed

When compared with men of other racial or ethnic groups, African American men are more likely to experience adverse health conditions. The systematic review objectives were to (i) determine the current evidence base concerning African American men's response to lifestyle behavioural interventions designed to promote weight loss, increase physical activity, and/or improve healthy eating and (ii) determine the next steps for research in these areas. The PubMed, Web of Science, Psych Info and Cochrane databases were searched to identify papers published before January 1, 2013 that reported change in weight, physical activity and/or dietary patterns in African American men aged 18 and older, as a result of behavioural change strategies. The titles and abstracts of 1,403 papers were screened; after removing duplicates, 141 papers were read to determine their eligibility. Seventeen publications from 14 studies reported outcomes for African American men. Eight large multi-centre trials and six community-based studies were identified. African American men were an exclusive sample in only four studies. Five studies showed statistically significant improvements. Although the available evidence appears to show that these interventions produce positive results, the relative and the long-term effectiveness of weight loss, dietary and/or physical activity interventions for this population are unknown. PMID:25196408

Newton, R L; Griffith, D M; Kearney, W B; Bennett, G G

2014-10-01

212

Production of lysophosphatidic acid in blister fluid: involvement of a lysophospholipase D activity  

PubMed Central

Lysophosphatidic acid (LPA) is present in abundance in serum resulting from platelet activation and is also found in other biological fluids. LPA controls numerous cellular responses and plays a role in specific functions such as wound healing, especially in the skin. Nevertheless, its presence in the skin has never been investigated during wound healing, or in other situations. Since re-epithelialization occurs after blister rupture, the presence of LPA in blister fluids was investigated. Using a radioenzymatic assay, LPA was detected in 33 blister fluids originating from 24 bullous dermatoses, and at higher concentrations than in plasma. LPA concentration was independent of the type of dermatoses. In parallel, blister fluids contained a lysophospholipase D (LPLD) activity but no detectable phospholipase A2 activity. The expression of the LPLD autotaxin (ATX) and of LPA1-receptor were greatly increased in blister skin when compared to normal skin. Finally, LPA was found to have a positive effect on the migration of cultured keratinocytes. These results show that LPA is present in blister fluid synthesized by the LPLD ATX. Due to its ability to enhance keratinocyte migration, LPA in blister fluid could, via the LPA1-receptor, play an important role in re-epithelialization occuring after blister rupture. PMID:16117781

Mazereeuw-Hautier, Juliette; Gres, Sandra; Fanguin, Madie; Cariven, Clotilde; Fauvel, Josette; Perret, Bertrand; Chap, Hugues; Salles, Jean-Pierre; Saulnier-Blache, Jean-Sebastien

2005-01-01

213

Nuclear Gating of a Drosophila dCREB2 Activator is involved in Memory Formation  

PubMed Central

The transcription factor CREB is an important regulator of many adaptive processes in neurons, including sleep, cellular homeostasis, and memory formation. The Drosophila dCREB2 family includes multiple protein isoforms generated from a single gene. Overexpression of an activator or blocker isoform has been shown to enhance or block memory formation, but the molecular mechanisms underlying these phenomena remain unclear. In the present study, we generate isoform-specific antibodies and new transgenic flies to track and manipulate the activity of different dCREB2 isoforms during memory formation. We find that nuclear accumulation of a dCREB2 activator-related species, p35+, is dynamically regulated during memory formation. Furthermore, various dCREB2 genetic manipulations that enhance or block memory formation correspondingly increase or decrease p35+ levels in the nucleus. Finally, we show that overexpression of S6K can enhance memory formation and increase p35+ nuclear abundance. Taken together, these results suggest that regulation of dCREB2 localization may be a key molecular convergence point in the coordinated host of events that lead to memory formation. PMID:24076014

Fropf, Robin; Tubon, Thomas C.; Yin, Jerry C. P.

2013-01-01

214

A Novel Accessory Molecule Trim59 Involved in Cytotoxicity of BCG-Activated Macrophages  

PubMed Central

BCG-activated macrophages (BAM) could kill the tumor cells through cell-cell contact. In this process membrane proteins play an important role. However, up to date, few membrane proteins were revealed. In this study, we selected a surface molecule named Trim59, which was specifically expressed on BAM membrane (compared with the negative control). We cloned and prokaryoticly expressed the extracellular domain of Trim59, purified the recombinant protein and generated polyclonal antibodies. Immunohistochemistry showed that Trim59 abundantly expressed in spleen, stomach and ovary; intermediately expressed in brain, lung, kidney, muscle and intestine; but not in thymus, liver, heart, uterus. Using the antibodies to block Trim59 on BAM significantly reduced BAM cytotoxicity against MCA207 cells. This demonstrated that Trim59 serves as an indispensable molecule in maintaining BAM activity. Overexpression of Trim59 in Raw264.7 cell line failed to lyse target MCA207 cells, which potentiated Trim59 per se could not enhance macrophage cytotoxicity; on another hand, overexpression of Trim59 enhance the pinocytosis and Phagocytosis activity of Raw-264.7, which imply Trim59 might mediate the cell-molecule interaction. Our results indicate Trim59 might be an essential accessory molecule in mediating BAM tumoricidal functions; and Trim59 is a phagocytosis-correlated molecule. PMID:22949172

Zhao, Xiangfeng; Liu, Qihui; Du, Baiqiu; Li, Peng; Cui, Qu; Han, Xiao; Du, Bairong; Yan, Dongmei; Zhu, Xun

2012-01-01

215

Endoplasmic reticulum stress-induced PCD and caspase-like activities involved  

PubMed Central

Plant cells, like cells from other kingdoms, have the ability to self-destruct in a genetically controlled manner. This process is defined as Programmed cell death (PCD). PCD can be triggered by various stimuli in plants including by endoplasmic reticulum (ER) stress. Research in the past two decades discovered that disruption of protein homeostasis in the ER could cause ER stress, which when prolonged/unresolved leads cells into PCD. ER stress-induced PCD is part of several plant processes, for instance, drought and heat stress have been found to elicit ER stress-induced PCD. Despite the importance of ER stress-induced PCD in plants, its regulation remains largely unknown, when compared with its counterpart in animal cells. In mammalian cells, several pro-apoptotic proteases called caspases were found to play a crucial role in ER stress-induced PCD. Over the past decade, several key proteases with caspase-like enzymatic activity have been discovered in plants and implicated in PCD regulation. This review covers what is known about caspase-like enzymatic activities during plant ER stress-induced PCD and discusses possible regulation pathways leading to the activation of relevant proteases in plants. PMID:24592269

Cai, Yao-Min; Yu, Jia; Gallois, Patrick

2014-01-01

216

Cisplatin Nephrotoxicity Involves Mitochondrial Injury with Impaired Tubular Mitochondrial Enzyme Activity  

PubMed Central

Cisplatin is a widely used antineoplastic agent. However, its major limitation is dose-dependent nephrotoxicity whose precise mechanism is poorly understood. Recent studies have suggested that mitochondrial dysfunction in tubular epithelium contributes to cisplatin-induced nephrotoxicity. Here the authors extend those findings by describing the role of an important electron transport chain enzyme, cytochrome c oxidase (COX). Immunohistochemistry for COX 1 protein demonstrated that, in response to cisplatin, expression was mostly maintained in focally damaged tubular epithelium. In contrast, COX enzyme activity in proximal tubules (by light microscopy) was decreased. Ultrastructural analysis of the cortex and outer stripe of the outer medulla showed decreased mitochondrial mass, disruption of cristae, and extensive mitochondrial swelling in proximal tubular epithelium. Functional electron microscopy showed that COX enzyme activity was decreased in the remaining mitochondria in the proximal tubules but maintained in distal tubules. In summary, cisplatin-induced nephrotoxicity is associated with structural and functional damage to the mitochondria. More broadly, using functional electron microscopy to measure mitochondrial enzyme activity may generate mechanistic insights across a spectrum of renal disorders. PMID:22511597

Ellezian, Lena; Brown, Dan; Horvath, Bela; Mukhopadhyay, Partha; Kalyanaraman, Balaraman; Parikh, Samir M.; Karumanchi, S. Ananth; Stillman, Isaac E.; Pacher, Pal

2012-01-01

217

A polysaccharide from Armillaria mellea exhibits strong in vitro anticancer activity via apoptosis-involved mechanisms.  

PubMed

Armillaria mellea is a famous traditional Chinese medicinal and edible fungus. In this study, we purified a water-soluble polysaccharide (AMP) from the fruiting bodies of this fungus. AMP contained 94.8% carbohydrate, 2.3% uronic acid and 0.5% protein. Its molecular weight was determined as 4.6 × 10? Da, as determined by high-performance gel-permeation chromatography (HPGPC). Gas chromatography (GC) analysis indicated that AMP was mainly composed of d-glucose. In vitro assay, AMP exhibited a potent tumor growth inhibitory effect on A549 cells, and induced cell cycle disruption in the G0/G1 phase, accompanied by an increment of apoptotic cells. Furthermore, AMP induced the disruption of mitochondrial membrane potential, thus leading to cytochrome c release from mitochondria and activation of caspase-3 and -9. Taken together, our results demonstrate that AMP possesses strong antitumor activities through the mitochondria dependent pathway and activation of caspase cascade through cytochrome c release. PMID:22771925

Wu, Jun; Zhou, Jinxu; Lang, Yaoguo; Yao, Lei; Xu, Hai; Shi, Hubo; Xu, Shidong

2012-11-01

218

Activism and Leadership Development: Examining the Relationship between College Student Activism Involvement and Socially Responsible Leadership Capacity  

ERIC Educational Resources Information Center

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…

Page, Jeremy Dale

2010-01-01

219

Pb-inhibited mitotic activity in onion roots involves DNA damage and disruption of oxidative metabolism.  

PubMed

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

Kaur, Gurpreet; Singh, Harminder Pal; Batish, Daizy Rani; Kohli, Ravinder Kumar

2014-09-01

220

Bilirubin mediated oxidative stress involves antioxidant response activation via Nrf2 pathway.  

PubMed

Unconjugated bilirubin (UCB) is responsible for neonatal jaundice and high level of free bilirubin (Bf) can lead to kernicterus. Previous studies suggest that oxidative stress is a critical component of UCB-induced neurotoxicity. The Nrf2 pathway is a powerful sensor for cellular redox state and is activated directly by oxidative stress and/or indirectly by stress response protein kinases. Activated Nrf2 translocates to nucleus, binds to Antioxidant Response Element (ARE), and enhances the up-regulation of cytoprotective genes that mediate cell survival. The aim of the present study was to investigate the role of Nrf2 pathway in cell response to bilirubin mediated oxidative stress in the neuroblastoma SH-SY5Y cell line. Cells exposed to a toxic concentration of UCB (140 nM Bf) showed an increased intracellular ROS levels and enhanced nuclear accumulation of Nrf2 protein. UCB stimulated transcriptional induction of ARE-GFP reporter gene and induced mRNA expression of multiple antioxidant response genes as: xCT, Gly1, ?GCL-m, ?GCL-c, HO-1, NQO1, FTH, ME1, and ATF3. Nrf2 siRNA decreased UCB induced mRNA expression of HO1 (75%), NQO1 (54%), and FTH (40%). The Nrf2-related HO-1 induction was reduced to 60% in cells pre-treated with antioxidant (NAC) or specific signaling pathway inhibitors for PKC, P38? and MEK1/2 (80, 40 and 25%, respectively). In conclusion, we demonstrated that SH-SY5Y cells undergo an adaptive response against UCB-mediated oxidative stress by activation of multiple antioxidant response, in part through Nrf2 pathway. PMID:24308969

Qaisiya, Mohammed; Coda Zabetta, Carlos Daniel; Bellarosa, Cristina; Tiribelli, Claudio

2014-03-01

221

The gastroprotective effect of menthol: involvement of anti-apoptotic, antioxidant and anti-inflammatory activities.  

PubMed

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-? (TNF-?) 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-? 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

Rozza, Ariane Leite; Meira de Faria, Felipe; Souza Brito, Alba Regina; Pellizzon, Cláudia Helena

2014-01-01

222

Activation mechanism of phospholipase D involved in the generation of lipid mediators in cultured Madin-Darby canine kidney cells.  

PubMed

Addition of 100 nM phorbol 12-myristate 13-acetate (PMA), an active phorbol diester, to quiescent cultured Madin-Darby canine kidney (MDCK) cells caused a maximal stimulation of phosphatidylethanol formation within 1-2 h in the presence of 1% ethanol, indicating the activation of phospholipase D (PLD). The specificity of phorbol diesters for the activation of PLD activation was confirmed by the fact that phorbol 12,13-dibutyrate (PDBu) was effective, whereas 4 alpha-phorbol 12,13-didecanoate (4 alpha-PDD) was without effect. Down-regulation caused by the long-term pretreatment of the cells with active phorbol diesters significantly decreased the production of phosphatidylethanol. Staurosporine, a well known protein kinase (PK)C inhibitor at 1 microM, decreased the activation of PLD. Taken together, these observations suggested the involvement of PKC in the activation of PLD. The cellular PLD activity was found to be selectively localized in the particulate fraction by centrifugation at 12,000 x g. The particulate PLD showed the selective substrate specificity for phosphatidylcholine rather than phosphatidylethanolamine. In response to the addition of 100 nM PMA, 1,2-diacylglycerol (DG) increased in a biphasic fashion. In view of the time course of the activation of PLD, the second increase in the 1,2-DG around 20 min was contributed by the activation of PLD. In response to the simultaneous addition of 100 nM PMA and 100 nM A23187, the cultured MDCK cells activated the arachidonate cascades to form prostaglandin (PG)E2 and PGF2 alpha as major products, requiring slower 24 h to reach maximal levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7670190

Yokota, K; Takeuchi, J; Jisaka, M; Takinami, K

1995-07-01

223

Blockade of T-Cell Activation by Dithiocarbamates Involves Novel Mechanisms of Inhibition of Nuclear Factor of Activated T Cells  

Microsoft Academic Search

Dithiocarbamates (DTCs) have recently been reported as powerful inhibitors of NF-kB activation in a number of cell types. Given the role of this transcription factor in the regulation of gene expression in the inflammatory response, NF-kB inhibitors have been suggested as potential therapeutic drugs for inflammatory diseases. We show here that DTCs inhibited both interleukin 2 (IL-2) synthesis and membrane

SARA MARTINEZ-MARTINEZ; PABLO GOMEZ DEL ARCO; ANGEL LUIS ARMESILLA; CHUN LUO; ANJANA RAO; JUAN MIGUEL REDONDO

1997-01-01

224

Medial Parietal Cortex Activation Related to Attention Control Involving Alcohol Cues  

PubMed Central

Automatic attentional engagement toward and disengagement from alcohol cues play a role in alcohol use and dependence. In the current study, social drinkers performed a spatial cueing task designed to evoke conflict between such automatic processes and task instructions, a potentially important task feature from the perspective of recent dual-process models of addiction. Subjects received instructions either to direct their attention toward pictures of alcoholic beverages, and away from non-alcohol beverages; or to direct their attention toward pictures of non-alcoholic beverages, and away from alcohol beverages. Instructions were varied per block. Activation in medial parietal cortex was found during “approach alcohol” versus “avoid-alcohol” blocks. This region is associated with the, possibly automatic, shifting of attention between stimulus features. Subjects thus appeared to shift attention away from certain features of alcoholic cues when attention had to be directed toward their location. Further, activation in voxels located close to this region was negatively correlated with riskier drinking behavior. A tentative interpretation of the results is that risky drinking may be associated with a reduced automatic tendency to shift attention away from potentially distracting task-irrelevant alcohol cues. Future study is needed to test this interpretation, and to further determine the role of medial posterior regions in automatic alcohol-related attentional processes in general. PMID:24391604

Gladwin, Thomas E.; ter Mors-Schulte, Mieke H. J.; Ridderinkhof, K. Richard; Wiers, Reinout W.

2013-01-01

225

Involvement of caspase and MAPK activities in norcantharidin-induced colorectal cancer cell apoptosis.  

PubMed

Norcantharidin exhibits cytotoxicity in many cancer cell lines, including colorectal cancer (CRC) cells. Its cytotoxic potency on primary CRC cells and other normal constituent cells of the human body remains elusive. This study investigates whether norcantharidin differentially exhibits cytotoxicity on primarily isolated CRC cells and dermal fibroblasts. The in vitro chemosensitivity of norcantharidin was measured using a MTT tetrazolium assay and compared with 73 primary tumor cells from surgically excised colorectal tumors, six human CRC cell lines and dermal fibroblasts. Observations of cytotoxicity to primary tumor cells reveal significant differences among genders and histological types; however, drug-induced chemosensitivity was not correlated with age or clinical stages of CRC patients. Norcantharidin had a similar cytotoxic effect on primary tumor cells and CRC cell lines in a dose-dependent manner. In contrast, normal fibroblasts were more resistant to norcantharidin-induced cytotoxicity than CRC cells. DAPI staining results demonstrated that norcantharidin caused CRC cell apoptosis by nuclear fragmentation and chromatin condensation. The release of cytochrome c and the triggering of caspase-3, -8 and -9 activation mediated apoptotic induction. Conversely, pretreatment with caspases or mitogen-activated protein kinase (MAPK) inhibitors significantly suppressed norcantharidin-induced CRC cytotoxicity. These in vitro results suggest that norcantharidin may be a safe and effective anti-cancer drug for CRC. PMID:20040369

Yang, Pei-Yu; Chen, Ming-Feng; Tsai, Chi-Hong; Hu, Dan-Ning; Chang, Fang-Rong; Wu, Yang-Chang

2010-04-01

226

The involvement of 5-lipoxygenase activating protein in anxiety-like behavior.  

PubMed

The 5-lipoxygenase is an enzyme widely expressed in the central nervous system, where its activity is dependent on the presence the 5-lipoxygenase activating protein (FLAP) for the formation of leukotrienes, potent bioactive lipid mediators. Emerging evidence has shown that the FLAP/leukotriene pathway may play a role in neuropsychiatric disease contexts. In this study we investigated whether genetic deficiency of FLAP (FLAPKO) modulated some behavioral aspects in mice, and if this effect was age-dependent. While we observed that FLAPKO mice at 3 and 6 months of age did not different from wild type animals in the elevated plus maze, at 12 months of age they manifested a significant increase in anxiety-like behavior. By contrast, we observed no differences between FLAPKO mice and their controls at any of the three ages considered when they were tested for working memory in the Y maze paradigm. Additionally, while we found that cFOS protein and message levels were reduced in the brains of animals lacking FLAP, no changes for other transcription factors were detected. Taken together our findings suggest a novel role for FLAP in the pathogenesis of anxiety-like behavior. Future studies of FLAP neurobiology may be attractive for development of anxiolytic therapeutics. PMID:23357209

Joshi, Yash B; Praticò, Domenico

2013-05-01

227

Anti-inflammatory active gold(I) complexes involving 6-substituted-purine derivatives.  

PubMed

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-?, IL-1? 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 ?-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

Trávní?ek, Zden?k; Starha, Pavel; Van?o, Ján; Silha, Tomáš; Hošek, Jan; Suchý, Pavel; Pražanová, Gabriela

2012-05-24

228

Acclimation of microalgae to wastewater environments involves increased oxidative stress tolerance activity.  

PubMed

A wastewater environment can be particularly toxic to eukaryotic microalgae. Microalgae can adapt to these conditions but the specific mechanisms that allow strains to tolerate wastewater environments are unclear. Furthermore, it is unknown whether the ability to acclimate microalgae to tolerate wastewater is an innate or species-specific characteristic. Six different species of microalgae (Chlamydomonas debaryana, Chlorella luteoviridis, Chlorella vulgaris, Desmodesmus intermedius, Hindakia tetrachotoma and Parachlorella kessleri) that had never previously been exposed to wastewater conditions were acclimated over an 8-week period in secondary-treated municipal wastewater. With the exception of C. debaryana, acclimation to wastewater resulted in significantly higher growth rate and biomass productivity. With the exception of C. vulgaris, total chlorophyll content was significantly increased in all acclimated strains, while all acclimated strains showed significantly increased photosynthetic activity. The ability of strains to acclimate was species-specific, with two species, C. luteoviridis and P. kessleri, able to acclimate more efficiently to the stress than C. debaryana and D. intermedius. Metabolic fingerprinting of the acclimated and non-acclimated microalgae using Fourier transform infrared spectroscopy was able to differentiate strains on the basis of metabolic responses to the stress. In particular, strains exhibiting greater stress response and altered accumulation of lipids and carbohydrates could be distinguished. The acclimation to wastewater tolerance was correlated with higher accumulation of carotenoid pigments and increased ascorbate peroxidase activity. PMID:25231961

Osundeko, Olumayowa; Dean, Andrew P; Davies, Helena; Pittman, Jon K

2014-10-01

229

Involvement of protein kinase C in 5-HT-stimulated ciliary activity in Helisoma trivolvis embryos  

PubMed Central

During development, embryos of the pulmonate gastropod, Helisoma trivolvis, undergo a rotation behaviour due to the co-ordinated beating of three bands of ciliated epithelial cells. This behaviour is in part mediated by the neurotransmitter serotonin (5-HT) released from a pair of identified embryonic neurons. Using time-lapse videomicroscopy to measure ciliary beat frequency (CBF) in response to pharmacological manipulations, we determined whether protein kinase C (PKC) is involved in mediating 5-HT-stimulated ciliary beating.Diacylglycerol (DAG) analogues sn-1,2-dioctanoyl glycerol (DiC8; 100 ?M) and 1-oleoyl-2-acetyl-sn-glycerol (OAG; 100 ?M), partially mimicked the 5-HT-induced increase in CBF. In contrast, application of OAG in the absence of extracellular Ca2+ did not result in an increase in CBF.5-HT-stimulated CBF was effectively blocked by PKC inhibitors bisindolylmaleimide (10 and 100 nM) and calphostin C (10 nM). In addition, bisindolylmaleimide (100 nM) inhibited DiC8-induced increases in CBF. At a higher concentration (200 nM), bisindolylmaleimide did not significantly reduce 5-HT-stimulated cilio-excitation.Two different phorbol esters, phorbol 12-myristate 13-acetate (TPA; 0.1, 10 or 1000 nM) and phorbol 12?, 13?-dibenzoate (PDBn; 10 ?M) did not alter basal CBF. TPA (1 ?M) did not alter 5-HT-stimulated CBF. Likewise, the synthetic form of phosphatidylserine, N-(6-phenylhexyl)-5-chloro-1-naphthalenesulphonamide (SC-9; 10 ?M), did not increase CBF, whereas a strong increase in CBF was observed upon exposure to 5-HT.The results suggest that a DAG-dependent, phorbol ester-insensitive isoform of PKC mediates 5-HT-stimulated CBF in ciliated epithelial cells from embryos of Helisoma trivolvis. PMID:10050017

Christopher, Kimberley J; Young, Kevin G; Chang, John P; Goldberg, Jeffrey I

1999-01-01

230

Characterization of Streptococcal Platelet-Activating Factor Acetylhydrolase Variants That Are Involved in Innate Immune Evasion  

PubMed Central

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

Liu, Guanghui; Liu, Mengyao; Xie, Gang

2013-01-01

231

Characterization of 17?-hydroxysteroid dehydrogenase activity (17?-HSD) and its involvement in the biosynthesis of epitestosterone  

PubMed Central

Background Epi-testosterone (epiT) is the 17?-epimer of testosterone. It has been found at similar level as testosterone in human biological fluids. This steroid has thus been used as a natural internal standard for assessing testosterone abuse in sports. EpiT has been also shown to accumulate in mammary cyst fluid and in human prostate. It was found to possess antiandrogenic activity as well as neuroprotective effects. So far, the exact pathway leading to the formation of epiT has not been elucidated. Results In this report, we describe the isolation and characterization of the enzyme 17?-hydroxysteroid dehydrogenase. The name is given according to its most potent activity. Using cells stably expressing the enzyme, we show that 17?-HSD catalyzes efficienty the transformation of 4-androstenedione (4-dione), dehydroepiandrosterone (DHEA), 5?-androstane-3,17-dione (5?-dione) and androsterone (ADT) into their corresponding 17?-hydroxy-steroids : epiT, 5-androstene-3?,17?-diol (epi5diol), 5?-androstane-17?-ol-3-one (epiDHT) and 5?-androstane-3?,17?-diol (epi3?-diol), respectively. Similar to other members of the aldo-keto reductase family that possess the ability to reduce the keto-group into hydroxyl-group at different position on the steroid nucleus, 17?-HSD could also catalyze the transformation of DHT, 5?-dione, and 5?-pregnane-3,20-dione (DHP) into 3?-diol, ADT and 5?-pregnane-3?-ol-20-one (allopregnanolone) through its less potent 3?-HSD activity. We also have over-expressed the 17?-HSD in Escherichia coli and have purified it by affinity chromatography. The purified enzyme exhibits the same catalytic properties that have been observed with cultured HEK-293 stably transfected cells. Using quantitative Realtime-PCR to study tissue distribution of this enzyme in the mouse, we observed that it is expressed at very high levels in the kidney. Conclusion The present study permits to clarify the biosynthesis pathway of epiT. It also offers the opportunity to study gene regulation and function of this enzyme. Further study in human will allow a better comprehension about the use of epiT in drug abuse testing; it will also help to clarify the importance of its accumulation in breast cyst fluid and prostate, as well as its potential role as natural antiandrogen. PMID:16018803

Bellemare, Veronique; Faucher, Frederick; Breton, Rock; Luu-The, Van

2005-01-01

232

DOE Technical Standards List. Directory of DOE and contractor personnel involved in non-government standards activities  

SciTech Connect

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.

NONE

1997-06-01

233

Orexin-A activates hypothalamic AMP-activated protein kinase signaling through a Ca²?-dependent mechanism involving voltage-gated L-type calcium channel.  

PubMed

Hypothalamic AMP-activated protein kinase (AMPK) and orexins/hypocretins are both involved in the control of feeding behavior, but little is known about the interaction between these two signaling systems. Here, we demonstrated that orexin-A elicited significant activation of AMPK in the arcuate nucleus (ARC) of the hypothalamus by elevating cytosolic free Ca²? involving extracellular calcium influx. Electrophysiological results revealed that orexin-A increased the L-type calcium current via the orexin receptor-phospholipase C-protein kinase C signaling pathway in ARC neurons that produce neuropeptide Y, an important downstream effector of orexin-A's orexigenic effect. Furthermore, the L-type calcium channel inhibitor nifedipine attenuated orexin-A-induced AMPK activation in vitro and in vivo. We found that inhibition of AMPK by either compound C (6-[4-[2-(1-piperidinyl)ethoxy]phenyl]-3-(4-pyridinyl)-pyrazolo[1,5-a]pyrimidine) or the ATP-mimetic 9-?-D-arabinofuranoside prevented the appetite-stimulating effect of orexin-A. This action can be mimicked by nifedipine, the blocker of the L-type calcium channel. Our results indicated that orexin-A activates hypothalamic AMPK signaling through a Ca²?-dependent mechanism involving the voltage-gated L-type calcium channel, which may serve as a potential target for regulating feeding behavior. PMID:24068427

Wu, Wen-Ning; Wu, Peng-Fei; Zhou, Jun; Guan, Xin-Lei; Zhang, Zui; Yang, Yuan-Jian; Long, Li-Hong; Xie, Na; Chen, Jian-Guo; Wang, Fang

2013-12-01

234

PhosphoTyrosyl Phosphatase Activator of Plasmodium falciparum: Identification of Its Residues Involved in Binding to and Activation of PP2A  

PubMed Central

In Plasmodium falciparum (Pf), the causative agent of the deadliest form of malaria, a tight regulation of phosphatase activity is crucial for the development of the parasite. In this study, we have identified and characterized PfPTPA homologous to PhosphoTyrosyl Phosphatase Activator, an activator of protein phosphatase 2A which is a major phosphatase involved in many biological processes in eukaryotic cells. The PfPTPA sequence analysis revealed that five out of six amino acids involved in interaction with PP2A in human are conserved in P. falciparum. Localization studies showed that PfPTPA and PfPP2A are present in the same compartment of blood stage parasites, suggesting a possible interaction of both proteins. In vitro binding and functional studies revealed that PfPTPA binds to and activates PP2A. Mutation studies showed that three residues (V283, G292 and M296) of PfPTPA are indispensable for the interaction and that the G292 residue is essential for its activity. In P. falciparum, genetic studies suggested the essentiality of PfPTPA for the completion of intraerythrocytic parasite lifecycle. Using Xenopus oocytes, we showed that PfPTPA blocked the G2/M transition. Taken together, our data suggest that PfPTPA could play a role in the regulation of the P. falciparum cell cycle through its PfPP2A regulatory activity. PMID:24521882

Vandomme, Audrey; Fréville, Aline; Cailliau, Katia; Kalamou, Hadidjatou; Bodart, Jean-François; Khalife, Jamal; Pierrot, Christine

2014-01-01

235

Calmodulin Involvement in Stress-Activated Nuclear Localization of Albumin in JB6 Epithelial Cells.  

SciTech Connect

We report that in response to oxidative stress, albumin is translocated to the nucleus where it binds in concert with known transcription factors to an antioxidant response element (ARE), which controls the expression of glutathione-S-transferase and other antioxidant enzymes, functioning to mediate adaptive cellular responses. To investigate the mechanisms underlying this adaptive cell response, we have identified linkages between calcium signaling and the nuclear translocation of albumin in JB6 epithelial cells. Under resting conditions, albumin and the calcium regulatory protein, calmodulin (CaM), co-immunoprecipitate using antibodies against either protein, indicating a tight association. Calcium activation of CaM disrupts the association between CaM and albumin, suggesting that transient increases in cytosolic calcium levels function to mobilize intracellular albumin to facilitate its translocation into the nucleus. Likewise, nuclear translocation of albumin is induced by exposure of cells to hydrogen peroxide or a phorbol ester, indicating a functional linkage between reactive oxygen species, calcium, and PKC-signaling pathways. Inclusion of an antioxidant enzyme (i.e., superoxide dismutase) blocks nuclear translocation, suggesting that the oxidation of sensitive proteins functions to coordinate the adaptive cellular response. These results suggest that elevated calcium transients, and associated increases in reactive oxygen species, contribute to adaptive cellular responses through the mobilization and nuclear translocation of cellular albumin to mediate the transcriptional regulation of antioxidant responsive elements.

Weber, Thomas J.; Negash, Sewite; Smallwood, Heather S.; Ramos, Kenneth S.; Thrall, Brian D.; Squier, Thomas C.

2004-06-15

236

Genes affecting the activity of nicotinic receptors involved in Caenorhabditis elegans egg-laying behavior.  

PubMed Central

Egg-laying behavior in Caenorhabditis elegans is regulated by multiple neurotransmitters, including acetylcholine and serotonin. Agonists of nicotinic acetylcholine receptors such as nicotine and levamisole stimulate egg laying; however, the genetic and molecular basis for cholinergic neurotransmission in the egg-laying circuitry is not well understood. Here we describe the egg-laying phenotypes of eight levamisole resistance genes, which affect the activity of levamisole-sensitive nicotinic receptors in nematodes. Seven of these genes, including the nicotinic receptor subunit genes unc-29, unc-38, and lev-1, were essential for the stimulation of egg laying by levamisole, though they had only subtle effects on egg-laying behavior in the absence of drug. Thus, these genes appear to encode components of a nicotinic receptor that can promote egg laying but is not necessary for egg-laying muscle contraction. Since the levamisole-receptor mutants responded to other cholinergic drugs, other acetylcholine receptors are likely to function in parallel with the levamisole-sensitive receptors to mediate cholinergic neurotransmission in the egg-laying circuitry. In addition, since expression of functional unc-29 in muscle cells restored levamisole sensitivity under some but not all conditions, both neuronal and muscle cell UNC-29 receptors are likely to contribute to the regulation of egg-laying behavior. Mutations in one levamisole receptor gene, unc-38, also conferred both hypersensitivity and reduced peak response to serotonin; thus nicotinic receptors may play a role in regulating serotonin response pathways in the egg-laying neuromusculature. PMID:11290716

Kim, J; Poole, D S; Waggoner, L E; Kempf, A; Ramirez, D S; Treschow, P A; Schafer, W R

2001-01-01

237

Growth hormone activity in mitochondria depends on GH receptor Box 1 and involves caveolar pathway targeting  

SciTech Connect

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.

Perret-Vivancos, Cecile [CNRS UMR 5123, Bat. R. Dubois, Universite Claude Bernard-Lyon 1, 43 Bd du 11 Novembre 1918, 69622 Villeurbanne cedex (France); Abbate, Aude [CNRS UMR 5123, Bat. R. Dubois, Universite Claude Bernard-Lyon 1, 43 Bd du 11 Novembre 1918, 69622 Villeurbanne cedex (France); Ardail, Dominique [INSERM U189-Faculte de medecine Lyon Sud, 69921 Oullins cedex (France); Raccurt, Mireille [CNRS UMR 5123, Bat. R. Dubois, Universite Claude Bernard-Lyon 1, 43 Bd du 11 Novembre 1918, 69622 Villeurbanne cedex (France); Usson, Yves [UMR 5525 CNRS, Institut de l'Ingenierie de l'Information de Sante (IN3S) Domaine de la Merci, Universite Joseph Fourier, 38706 La Tronche cedex (France); Lobie, Peter E. [Liggins Institute, University of Aukland, 2-6 Park Avenue, Private Bag, Aukland 92019 (New Zealand); Morel, Gerard [CNRS UMR 5123, Bat. R. Dubois, Universite Claude Bernard-Lyon 1, 43 Bd du 11 Novembre 1918, 69622 Villeurbanne cedex (France)]. E-mail: gerard.morel@univ-lyon1.fr

2006-02-01

238

Arsenic decreases antinociceptive activity of paracetamol: Possible involvement of serotonergic and endocannabinoid receptors.  

PubMed

We assessed whether repeated arsenic exposure can decrease paracetamol-mediated antinociception by modulating serotonergic and endocannabinoid pathways. Rats were preexposed to elemental arsenic (4ppm) as sodium arsenite through drinking water for 28 days. Next day paracetamol's (400mg/kg, oral) antinociceptive activity was assessed through formalin-induced nociception. Serotonin content and gene expression of 5-HT1A, 5-HT2A and CB1 receptors were evaluated in brainstem and frontal cortex. Arsenic decreased paracetamol-mediated analgesia. Paracetamol, but not arsenic, increased serotonin content in these regions. Arsenic attenuated paracetamol-mediated increase in serotonin level. Paracetamol did not alter 5-HT1A expression, but caused down-regulation of 5-HT2A and up-regulation of CB1 receptors. Arsenic down-regulated these receptors. However, paracetamol-mediated down-regulation of 5-HT2A was more pronounced. Arsenic did not modify paracetamol's effect on 5-HT1A expression, but reduced paracetamol-mediated down-regulation of 5-HT2A and reversed up-regulation of CB1 receptors. Results suggest arsenic reduced paracetamol-induced analgesia possibly by interfering with pronociceptive 5-HT2A and antinociceptive CB1 receptors. PMID:25128769

Vijayakaran, Karunakaran; Kesavan, Manickam; Kannan, Kandasamy; Sankar, Palanisamy; Tandan, Surendra Kumar; Sarkar, Souvendra Nath

2014-09-01

239

Photosynthetic activity influences cellulose biosynthesis and phosphorylation of proteins involved therein in Arabidopsis leaves.  

PubMed

Cellulose is one of the most important organic compounds in terrestrial ecosystems and represents a major plant structural polymer. However, knowledge of the regulation of cellulose biosynthesis is still rather limited. Recent studies have shown that the phosphorylation of cellulose synthases (CESAs) may represent a key regulatory event in cellulose production. However, the impact of environmental conditions on the carbon flux of cellulose deposition and on phosphorylation levels of CESAs has not been fully elucidated. Here, we took advantage of gas exchange measurements, isotopic techniques, metabolomics, and quantitative phosphoproteomics to investigate the regulation of cellulose production in Arabidopsis rosette leaves in different photosynthetic contexts (different CO2 mole fractions) or upon light/dark transition. We show that the carbon flux to cellulose production increased with photosynthesis, but not proportionally. The phosphorylation level of several phosphopeptides associated with CESA1 and 3, and several enzymes of sugar metabolism was higher in the light and/or increased with photosynthesis. By contrast, a phosphopeptide (Ser126) associated with CESA5 seemed to be more phosphorylated in the dark. Our data suggest that photosynthetic activity affects cellulose deposition through the control of both sucrose metabolism and cellulose synthesis complexes themselves by protein phosphorylation. PMID:25039072

Boex-Fontvieille, Edouard; Davanture, Marlène; Jossier, Mathieu; Zivy, Michel; Hodges, Michael; Tcherkez, Guillaume

2014-09-01

240

Attributes of Dental Trauma in a School Population with Active Sports Involvement  

PubMed Central

Purpose Dental trauma has become an important aspect of dental public health. The primary requisite before actively dealing with such problems is to describe the extent, distribution, and variables associated with the specific condition. The purpose of this study was to assess the prevalence and role of socioeconomic status and anatomic risk factors in traumatic dental injuries (TDI) to permanent anterior teeth in 10 to 16 year old Sainik (Army) school, children in India. Methods A cross-sectional study was conducted. Data was collected through a survey form and clinical examination. The permanent anterior teeth of four hundred and forty six male school children were examined for TDI. The socio-economic status, lip coverage and overjet were recorded. Statistical significance for the association between occurrence of TDI and the various risk factors was carried out. Results The prevalence of TDI to permanent anterior teeth was 23.8%. A large number of injuries occurred during participation in sports. Inadequate lip coverage and a large maxillary overjet were identified as important predictors for dental trauma. Conclusion A high prevalence of dental trauma was observed in the study population suggestive of low awareness regarding the cause, effects and prevention of the condition. PMID:24427477

Prabhu, Anand; Rao, Arun Prasad; Govindarajan, Mohan; Reddy, Venugopal; Krishnakumar, Ramalingam; Kaliyamoorthy, Sugumaran

2013-01-01

241

The ability of thapsigargin and thapsigargicin to activate cells involved in the inflammatory response.  

PubMed Central

The ability of thapsigargin and thapsigargicin to activate mast cells and leukocytes has been investigated. The thapsigargin-induced histamine release from rat peritoneal mast cells was found to be dependent on the concentration of thapsigargin, the purity of the mast cell preparations, and the number of mast cells in suspension. Thapsigargin induced histamine release from human basophil leukocytes. Thapsigargin induced beta-glucuronidase and lysozyme release from human neutrophil leukocytes. Thapsigargin caused a release of histamine from mesentery, lung, and heart mast cells of the rat, but only to a minor extent from the corresponding guinea-pig cells. Thapsigargicin induced histamine release from mesentery, lung, and heart mast cells of the rat at concentrations from 0.1 microM but provoked only a release from the corresponding guinea-pig cells in the concentration-range 0.16 to 1.6 microM. Thapsigargin increased the cytoplasmic free calcium level in intact human blood platelets at concentrations from 3.0 nM. PMID:2411328

Ali, H.; Christensen, S. B.; Foreman, J. C.; Pearce, F. L.; Piotrowski, W.; Thastrup, O.

1985-01-01

242

The ability of thapsigargin and thapsigargicin to activate cells involved in the inflammatory response.  

PubMed

The ability of thapsigargin and thapsigargicin to activate mast cells and leukocytes has been investigated. The thapsigargin-induced histamine release from rat peritoneal mast cells was found to be dependent on the concentration of thapsigargin, the purity of the mast cell preparations, and the number of mast cells in suspension. Thapsigargin induced histamine release from human basophil leukocytes. Thapsigargin induced beta-glucuronidase and lysozyme release from human neutrophil leukocytes. Thapsigargin caused a release of histamine from mesentery, lung, and heart mast cells of the rat, but only to a minor extent from the corresponding guinea-pig cells. Thapsigargicin induced histamine release from mesentery, lung, and heart mast cells of the rat at concentrations from 0.1 microM but provoked only a release from the corresponding guinea-pig cells in the concentration-range 0.16 to 1.6 microM. Thapsigargin increased the cytoplasmic free calcium level in intact human blood platelets at concentrations from 3.0 nM. PMID:2411328

Ali, H; Christensen, S B; Foreman, J C; Pearce, F L; Piotrowski, W; Thastrup, O

1985-07-01

243

Pituitary adenylate cyclase-activating polypeptide is a sympathoadrenal neurotransmitter involved in catecholamine regulation and glucohomeostasis.  

PubMed

The adrenal gland is important for homeostatic responses to metabolic stress: hypoglycemia stimulates the splanchnic nerve, epinephrine is released from adrenomedullary chromaffin cells, and compensatory glucogenesis ensues. Acetylcholine is the primary neurotransmitter mediating catecholamine secretion from the adrenal medulla. Accumulating evidence suggests that a secretin-related neuropeptide also may function as a transmitter at the adrenomedullary synapse. Costaining with highly specific antibodies against the secretin-related neuropeptide pituitary adenylate cyclase-activating peptide (PACAP) and the vesicular acetylcholine transporter (VAChT) revealed that PACAP is found in nerve terminals at all mouse adrenomedullary cholinergic synapses. Mice with a targeted deletion of the PACAP gene had otherwise normal cholinergic innervation and morphology of the adrenal medulla, normal adrenal catecholamine and blood glucose levels, and an intact initial catecholamine secretory response to insulin-induced hypoglycemia. However, insulin-induced hypoglycemia was more profound and longer-lasting in PACAP knock-outs, and was associated with a dose-related lethality absent in wild-type mice. Failure of PACAP-deficient mice to adequately counterregulate plasma glucose levels could be accounted for by impaired long-term secretion of epinephrine, secondary to a lack of induction of tyrosine hydroxylase, normally occurring after insulin hypoglycemia in wild-type mice, and a consequent depletion of adrenomedullary epinephrine stores. Thus, PACAP is needed to couple epinephrine biosynthesis to secretion during metabolic stress. PACAP appears to function as an "emergency response" cotransmitter in the sympathoadrenal axis, where the primary secretory response is controlled by a classical neurotransmitter but sustained under paraphysiological conditions by a neuropeptide. PMID:11756684

Hamelink, Carol; Tjurmina, Olga; Damadzic, Ruslan; Young, W Scott; Weihe, Eberhard; Lee, Hyeon-Woo; Eiden, Lee E

2002-01-01

244

Possible involvement of platelet activating factor in anaphylaxis of passively sensitised, isolated guinea pig hearts.  

PubMed

There is evidence that cardiac tissue may be a target for antigen/antibody reactions. Platelet activating factor (PAF) is released during anaphylaxis and could mediate cardiac damage. To investigate this, guinea pigs were passively sensitised by anti-ovalbumin rabbit serum (6 mg.kg-1 intravenously) and 24 h later their hearts were excised and isolated according to a working heart preparation technique. After a 20 min equilibration period, anaphylactic challenge was induced by a bolus injection of ovalbumin (2 mg in 0.2 ml buffer) via the side arm of the aortic cannula. Heart rate, coronary flow, aortic flow, left ventricular developed pressure (LVDP), its first derivative (LVdp/dtmax) and left ventricular end diastolic pressure (LVEDP) were recorded. After ovalbumin challenge, heart rate and LVEDP were markedly increased, while coronary flow, aortic flow, LVDP, and LVdp/dtmax were profoundly decreased. All these alterations were over within 5 min, and the measured variables returned to approximately the pre-challenge values. BN 52021, a specific PAF receptor antagonist, was dissolved in the perfusion buffer and given in doses of 15, 30 and 60 mumol.litre-1 10 min prior to the induction of anaphylactic challenge until the end of the observation period. BN 52021 inhibited the increase in heart rate and LVEDP and the decrease in coronary and aortic flow, LVDP and LVdp/dtmax in a dose dependent manner. The changes produced by 30 and 60 mumol.litre-1 were statistically significant at the levels of p less than 0.01 and p less than 0.001 when compared to the control values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2557156

Tosaki, A; Koltai, M; Braquet, P; Szekeres, L

1989-08-01

245

A Pathogenic Mechanism in Huntington's Disease Involves Small CAG-Repeated RNAs with Neurotoxic Activity  

PubMed Central

Huntington's disease (HD) is an autosomal dominantly inherited disorder caused by the expansion of CAG repeats in the Huntingtin (HTT) gene. The abnormally extended polyglutamine in the HTT protein encoded by the CAG repeats has toxic effects. Here, we provide evidence to support that the mutant HTT CAG repeats interfere with cell viability at the RNA level. In human neuronal cells, expanded HTT exon-1 mRNA with CAG repeat lengths above the threshold for complete penetrance (40 or greater) induced cell death and increased levels of small CAG-repeated RNAs (sCAGs), of ?21 nucleotides in a Dicer-dependent manner. The severity of the toxic effect of HTT mRNA and sCAG generation correlated with CAG expansion length. Small RNAs obtained from cells expressing mutant HTT and from HD human brains significantly decreased neuronal viability, in an Ago2-dependent mechanism. In both cases, the use of anti-miRs specific for sCAGs efficiently blocked the toxic effect, supporting a key role of sCAGs in HTT-mediated toxicity. Luciferase-reporter assays showed that expanded HTT silences the expression of CTG-containing genes that are down-regulated in HD. These results suggest a possible link between HD and sCAG expression with an aberrant activation of the siRNA/miRNA gene silencing machinery, which may trigger a detrimental response. The identification of the specific cellular processes affected by sCAGs may provide insights into the pathogenic mechanisms underlying HD, offering opportunities to develop new therapeutic approaches. PMID:22383888

Banez-Coronel, Monica; Porta, Silvia; Kagerbauer, Birgit; Mateu-Huertas, Elisabet; Pantano, Lorena; Ferrer, Isidre; Guzman, Manuel; Estivill, Xavier; Marti, Eulalia

2012-01-01

246

Esophageal cancer tumorspheres involve cancer stem-like populations with elevated aldehyde dehydrogenase enzymatic activity.  

PubMed

Cancer stem cells (CSCs) form spheres in vitro in serum-free suspension culture. Sphere formation is particularly useful to enrich the potential CSC subpopulations as a functional approach. Few reports are currently available on tumorspheres in esophageal cancer (EC). The present study focused on evaluating the cancer stem-like properties and analyzing the difference between spheroid and adherent cells of the Eca109 human EC cell line. Immunofluorescence and immunoblotting analysis revealed that EC tumorspheres expressed the stem cell markers Nanog and Oct4 more highly, but showed a decreased expression of the differentiation marker CK5/6. The spheroids were chemoresistant to cisplatin compared to the adherent cells (32.5 vs. 135.8 µM in IC50). Side population cells increased in tumorspheres compared to adherent cells (0.7 vs. 5.6%). A marked upregulation of drug-resistant genes (ABCG2 and MDR1) was observed in sphere-forming cells. We compared the profiles of adherent and spheroid cells by microarrays and obtained one representative differentially expressed gene, aldehyde dehydrogenase (ALDH). We also verified that the cancer stem-like cells of EC contained a high ALDH enzymatic activity. ALDH-positive cells were enriched by 11- to 12-fold in spheroids, compared to adherent cells (2.5 vs. 28.6%). Immunofluorescence and immunoblotting analysis also revealed a higher expression of ALDH in EC tumorspheres. In conclusion, our study verified that sphere-forming culturing can be utilized to demonstrate the putative esophageal CSCs, and identified a potential esophageal CSC surface marker, ALDH. PMID:22684859

Zhang, Gong; Ma, Lei; Xie, You-Ke; Miao, Xiao-Bo; Jin, Chuan

2012-09-01

247

Understanding Scientists' Involvement in Education--Their Interests, Activities, and Needs: Research Results from the ReSciPE Project  

NASA Astrophysics Data System (ADS)

The involvement of scientists in education has been cited by national leaders as essential for strengthening US science education at the K-12 and higher levels. While many individuals and groups have developed expertise in designing and implementing programs that engage scientists with students or teachers, there is little research evidence that helps us understand what motivates or discourages scientists from such involvement, the benefits and costs to them of participating, and the barriers they face that must be addressed to involve them effectively. The ReSciPE Project (Resources for Scientists in Partnership with Education) has offered a workshop on "Scientific Inquiry in the K-12 Classroom" to over 300 scientists and science educators across the US. These workshops have reached a wide audience of science professionals who undertake activities in science education, whether individual or institution-based work, for work or as a volunteer. The project aims to help these "education-engaged scientists" pursue their education work more effectively, but has also drawn on this group as a research sample for an evaluation-with-research study to investigate scientists' involvement in education. Pre- and post-surveys have enabled us to characterize the demographics of the participants and measure their self-reported knowledge and learning about education, especially inquiry-based science. Follow- up interviews have provided insight into their education activities, motivations, interests, difficulties, and needs. We will report on recent research findings from this study and place them in context of national needs and efforts to engage scientists in education.

Thiry, H.; Hunter, A.; Laursen, S.; Melton, G.

2006-12-01

248

Differential Pro-Inflammatory Responses of Astrocytes and Microglia Involve STAT3 Activation in Response to 1800 MHz Radiofrequency Fields  

PubMed Central

Microglia and astrocytes play important role in maintaining the homeostasis of central nervous system (CNS). Several CNS impacts have been postulated to be associated with radiofrequency (RF) electromagnetic fields exposure. Given the important role of inflammation in neural physiopathologic processes, we investigated the pro-inflammatory responses of microglia and astrocytes and the involved mechanism in response to RF fields. Microglial N9 and astroglial C8-D1A cells were exposed to 1800 MHz RF for different time with or without pretreatment with STAT3 inhibitor. Microglia and astrocytes were activated by RF exposure indicated by up-regulated CD11b and glial fibrillary acidic protein (GFAP). However, RF exposure induced differential pro-inflammatory responses in astrocytes and microglia, characterized by different expression and release profiles of IL-1?, TNF-?, IL-6, PGE2, nitric oxide (NO), inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2). Moreover, the RF exposure activated STAT3 in microglia but not in astrocytes. Furthermore, the STAT3 inhibitor Stattic ameliorated the RF-induced release of pro-inflammatory cytokines in microglia but not in astrocytes. Our results demonstrated that RF exposure differentially induced pro-inflammatory responses in microglia and astrocytes, which involved differential activation of STAT3 in microglia and astrocytes. Our data provide novel insights into the potential mechanisms of the reported CNS impacts associated with mobile phone use and present STAT3 as a promising target to protect humans against increasing RF exposure. PMID:25275372

Lu, Yonghui; He, Mindi; Zhang, Yang; Xu, Shangcheng; Zhang, Lei; He, Yue; Chen, Chunhai; Liu, Chuan; Pi, Huifeng; Yu, Zhengping; Zhou, Zhou

2014-01-01

249

Modulation of Pineal Melatonin Synthesis by Glutamate Involves Paracrine Interactions between Pinealocytes and Astrocytes through NF-?B Activation  

PubMed Central

The glutamatergic modulation of melatonin synthesis is well known, along with the importance of astrocytes in mediating glutamatergic signaling in the central nervous system. Pinealocytes and astrocytes are the main cell types in the pineal gland. The objective of this work was to investigate the interactions between astrocytes and pinealocytes as a part of the glutamate inhibitory effect on melatonin synthesis. Rat pinealocytes isolated or in coculture with astrocytes were incubated with glutamate in the presence of norepinephrine, and the melatonin content, was quantified. The expression of glutamate receptors, the intracellular calcium content and the NF-?B activation were analyzed in astrocytes and pinealocytes. TNF-?'s possible mediation of the effect of glutamate was also investigated. The results showed that glutamate's inhibitory effect on melatonin synthesis involves interactions between astrocytes and pinealocytes, possibly through the release of TNF-?. Moreover, the activation of the astrocytic NF-?B seems to be a necessary step. In astrocytes and pinealocytes, AMPA, NMDA, and group I metabotropic glutamate receptors were observed, as well as the intracellular calcium elevation. In conclusion, there is evidence that the modulation of melatonin synthesis by glutamate involves paracrine interactions between pinealocytes and astrocytes through the activation of the astrocytic NF-?B transcription factor and possibly by subsequent TNF-? release. PMID:23984387

Atherino, Victoria Fairbanks; Lima, Larissa de Sá; Moutinho, Anderson Augusto; do Amaral, Fernanda Gaspar; Peres, Rafael; Martins de Lima, Thais; Torrão, Andréa da Silva; Cipolla-Neto, José; Scavone, Cristóforo; Afeche, Solange Castro

2013-01-01

250

Mapping of the RXRalpha binding elements involved in retinoic acid induced transcriptional activation of the human SOX3 gene.  

PubMed

Sox3/SOX3 gene is implicated in the control of nervous system development and is considered to be one of the earliest neural markers. Expression of human SOX3 gene is modulated during the RA-induced neuronal differentiation cascade of NT2/D1 cells. Our present results demonstrate that the sequences responsible for RA-induced activation of SOX3 gene are localized within the 0.4 kb of its 5'-flanking region and implicate RXRalpha involvement in this regulation. The active RA/RXRalpha responsive region is pinned down to two regulatory elements. Only in the presence of both elements full RA/RXRalpha inducibility is achieved, suggesting they act synergistically. These elements comprise two unique G-rich boxes, separated by 49 bp, that could be considered as a novel, atypical RA-response element. Here, for the first time, we have demonstrated direct interaction of RXRalpha and SOX3 control elements. Furthermore, the functional in vivo analysis revealed that liganded RXRalpha is a potent activator of endogenous SOX3 protein expression. Since it is proven that Sox3 is critical determinant of neurogenesis our data may help in providing new insight into complex regulatory networks involved in retinoic acid induced neural differentiation of NT2/D1 cells. PMID:17005281

Mojsin, Marija; Grujici?, Natasa Kovacevi?; Nikcevi?, Gordana; Krsti?, Aleksandar; Savi?, Tijana; Stevanovi?, Milena

2006-12-01

251

Differential Pro-Inflammatory Responses of Astrocytes and Microglia Involve STAT3 Activation in Response to 1800 MHz Radiofrequency Fields.  

PubMed

Microglia and astrocytes play important role in maintaining the homeostasis of central nervous system (CNS). Several CNS impacts have been postulated to be associated with radiofrequency (RF) electromagnetic fields exposure. Given the important role of inflammation in neural physiopathologic processes, we investigated the pro-inflammatory responses of microglia and astrocytes and the involved mechanism in response to RF fields. Microglial N9 and astroglial C8-D1A cells were exposed to 1800 MHz RF for different time with or without pretreatment with STAT3 inhibitor. Microglia and astrocytes were activated by RF exposure indicated by up-regulated CD11b and glial fibrillary acidic protein (GFAP). However, RF exposure induced differential pro-inflammatory responses in astrocytes and microglia, characterized by different expression and release profiles of IL-1?, TNF-?, IL-6, PGE2, nitric oxide (NO), inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2). Moreover, the RF exposure activated STAT3 in microglia but not in astrocytes. Furthermore, the STAT3 inhibitor Stattic ameliorated the RF-induced release of pro-inflammatory cytokines in microglia but not in astrocytes. Our results demonstrated that RF exposure differentially induced pro-inflammatory responses in microglia and astrocytes, which involved differential activation of STAT3 in microglia and astrocytes. Our data provide novel insights into the potential mechanisms of the reported CNS impacts associated with mobile phone use and present STAT3 as a promising target to protect humans against increasing RF exposure. PMID:25275372

Lu, Yonghui; He, Mindi; Zhang, Yang; Xu, Shangcheng; Zhang, Lei; He, Yue; Chen, Chunhai; Liu, Chuan; Pi, Huifeng; Yu, Zhengping; Zhou, Zhou

2014-01-01

252

Public involvement in the priority setting activities of a wait time management initiative: a qualitative case study  

PubMed Central

Background As no health system can afford to provide all possible services and treatments for the people it serves, each system must set priorities. Priority setting decision makers are increasingly involving the public in policy making. This study focuses on public engagement in a key priority setting context that plagues every health system around the world: wait list management. The purpose of this study is to describe and evaluate priority setting for the Ontario Wait Time Strategy, with special attention to public engagement. Methods This study was conducted at the Ontario Wait Time Strategy in Ontario, Canada which is part of a Federal-Territorial-Provincial initiative to improve access and reduce wait times in five areas: cancer, cardiac, sight restoration, joint replacements, and diagnostic imaging. There were two sources of data: (1) over 25 documents (e.g. strategic planning reports, public updates), and (2) 28 one-on-one interviews with informants (e.g. OWTS participants, MOHLTC representatives, clinicians, patient advocates). Analysis used a modified thematic technique in three phases: open coding, axial coding, and evaluation. Results The Ontario Wait Time Strategy partially meets the four conditions of 'accountability for reasonableness'. The public was not directly involved in the priority setting activities of the Ontario Wait Time Strategy. Study participants identified both benefits (supporting the initiative, experts of the lived experience, a publicly funded system and sustainability of the healthcare system) and concerns (personal biases, lack of interest to be involved, time constraints, and level of technicality) for public involvement in the Ontario Wait Time Strategy. Additionally, the participants identified concern for the consequences (sustainability, cannibalism, and a class system) resulting from the Ontario Wait Times Strategy. Conclusion We described and evaluated a wait time management initiative (the Ontario Wait Time Strategy) with special attention to public engagement, and provided a concrete plan to operationalize a strategy for improving public involvement in this, and other, wait time initiatives. PMID:18021393

Bruni, Rebecca A; Laupacis, Andreas; Levinson, Wendy; Martin, Douglas K

2007-01-01

253

Ventricular tachyarrhythmias in rats with acute myocardial infarction involves activation of small-conductance Ca2+-activated K+ channels.  

PubMed

In vitro experiments have shown that the upregulation of small-conductance Ca(2+)-activated K(+) (SK) channels in ventricular epicardial myocytes is responsible for spontaneous ventricular fibrillation (VF) in failing ventricles. However, the role of SK channels in regulating VF has not yet been described in in vivo acute myocardial infarction (AMI) animals. The present study determined the role of SK channels in regulating spontaneous sustained ventricular tachycardia (SVT) and VF, the inducibility of ventricular tachyarrhythmias, and the effect of inhibition of SK channels on spontaneous SVT/VF and electrical ventricular instability in AMI rats. AMI was induced by ligation of the left anterior descending coronary artery in anesthetized rats. Spontaneous SVT/VF was analyzed, and programmed electrical stimulation was performed to evaluate the inducibility of ventricular tachyarrhythmias, ventricular effective refractory period (VERP), and VF threshold (VFT). In AMI, the duration and episodes of spontaneous SVT/VF were increased, and the inducibility of ventricular tachyarrhythmias was elevated. Pretreatment in the AMI group with the SK channel blocker apamin or UCL-1684 significantly reduced SVT/VF and inducibility of ventricular tachyarrhythmias (P < 0.05). Various doses of apamin (7.5, 22.5, 37.5, and 75.0 ?g/kg iv) inhibited SVT/VF and the inducibility of ventricular tachyarrhythmias in a dose-dependent manner. Notably, no effects were observed in sham-operated controls. Additionally, VERP was shortened in AMI animals. Pretreatment in AMI animals with the SK channel blocker significantly prolonged VERP (P < 0.05). No effects were observed in sham-operated controls. Furthermore, VFT was reduced in AMI animals, and block of SK channels increased VFT in AMI animals, but, again, this was without effect in sham-operated controls. Finally, the monophasic action potential duration at 90% repolarization (MAPD(90)) was examined in the myocardial infarcted (MI) and nonmyocardial infarcted areas (NMI) of the left ventricular epicardium. Electrophysiology recordings showed that MAPD(90) in the MI area was shortened in AMI animals, and pretreatment with SK channel blocker apamin or UCL-1684 significantly prolonged MAPD(90) (P < 0.05) in the MI area but was without effect in the NMI area or in sham-operated controls. We conclude that the activation of SK channels may underlie the mechanisms of spontaneous SVT/VF and susceptibility to ventricular tachyarrhythmias in AMI. Inhibition of SK channels normalized the shortening of MAPD(90) in the MI area, which may contribute to the inhibitory effect on spontaneous SVT/VF and inducibility of ventricular tachyarrhythmias in AMI. PMID:23086994

Gui, Le; Bao, Zhiwei; Jia, Yinyu; Qin, Xiaotong; Cheng, Zixi Jack; Zhu, Jianhua; Chen, Qing-Hui

2013-01-01

254

Active involvement of micro-lipid droplets and lipid-droplet-associated proteins in hormone-stimulated lipolysis in adipocytes.  

PubMed

The regulation of lipolysis in adipocytes involves coordinated actions of many lipid droplet (LD)-associated proteins such as perilipin, hormone sensitive lipase (HSL), adipose triglyceride lipase (ATGL), and its activator protein, CGI-58. Here, we describe the cellular origin and physiological significance of micro LDs (mLDs) that emerge in the cytoplasm during active lipolysis, as well as the roles of key lipolytic proteins on mLDs in differentiated 3T3-L1 adipocytes. Multiplex coherent anti-Stokes Raman scattering (CARS) microscopy demonstrated that mLDs receive the fatty acid (FA) moiety of triglyceride from pre-existing LDs during lipolysis. However, when FA re-esterification was blocked, mLDs did not emerge. Time-lapse imaging of GFP-tagged LD-associated proteins and immunocytochemical analyses showed that particulate structures carrying LD-associated proteins emerged throughout the cells upon lipolytic stimulation, but not when FA re-esterification was blocked. Overall lipolysis, as estimated by glycerol release, was significantly lowered by blocking re-esterification, whereas release of free FAs was enhanced. ATGL was co-immunoprecipitated with CGI-58 from the homogenates of lipolytically stimulated cells. Following CGI-58 knockdown or ATGL inhibition with bromoenol lactone, release of both glycerol and FA was significantly lowered. AICAR, an activator of AMP-activated protein kinase, significantly increased FA release, in accordance with increased expression of ATGL, even in the absence of CGI-58. These results suggest that, besides on the surface of pre-existing central LDs, LD-associated proteins are actively involved in lipolysis on mLDs that are formed by FA re-esterification. Regulation of mLDs and LD-associated proteins may be an attractive therapeutic target against lipid-associated metabolic diseases. PMID:23108672

Hashimoto, Takeshi; Segawa, Hiroki; Okuno, Masanari; Kano, Hideaki; Hamaguchi, Hiro-o; Haraguchi, Tokuko; Hiraoka, Yasushi; Hasui, Shiho; Yamaguchi, Tomohiro; Hirose, Fumiko; Osumi, Takashi

2012-12-15

255

The C-terminal domain of Escherichia coli MutY is involved in DNA binding and glycosylase activities  

PubMed Central

Escherichia coli MutY is an adenine and a weak guanine DNA glycosylase involved in reducing mutagenic effects of 7,8-dihydro-8-oxo-guanine (8-oxoG). The C-terminal domain of MutY is required for 8-oxoG recognition and is critical for mutation avoidance of oxidative damage. To determine which residues of this domain are involved in 8-oxoG recognition, we constructed four MutY mutants based on similarities to MutT, which hydrolyzes specifically 8-oxo-dGTP to 8-oxo-dGMP. F294A-MutY has a slightly reduced binding affinity to A/G mismatch but has a severe defect in A/8-oxoG binding at 20°C. The catalytic activity of F294A-MutY is much weaker than that of the wild-type MutY. The DNA binding activity of R249A-MutY is comparable to that of the wild-type enzyme but the catalytic activity is reduced with both A/G and A/8-oxoG mismatches. The biochemical activities of F261A-MutY are nearly similar to those of the wild-type enzyme. The solubility of P262A-MutY was improved as a fusion protein containing streptococcal protein G (GB1 domain) at its N-terminus. The binding of GB1-P262A-MutY with both A/G and A/8-oxoG mismatches are slightly weaker than those of the wild-type protein. The catalytic activity of GB1-P262A-MutY is weaker than that of the wild-type enzyme at lower enzyme concentrations. Importantly, all four mutants can complement mutY mutants in vivo when expressed at high levels; however, F294A, R249A and P262A, but not F261A, are partially defective in vivo when they are expressed at low levels. These results strongly support that the C-terminal domain of MutY is involved not only in 8-oxoG recognition, but also affects the binding and catalytic activities toward A/G mismatches. PMID:12799430

Li, Lina; Lu, A-Lien

2003-01-01

256

Ginseng Gintonin Activates the Human Cardiac Delayed Rectifier K+ Channel: Involvement of Ca2+/Calmodulin Binding Sites  

PubMed Central

Gintonin, a novel, ginseng-derived G protein-coupled lysophosphatidic acid (LPA) receptor ligand, elicits [Ca2+]i transients in neuronal and non-neuronal cells via pertussis toxin-sensitive and pertussis toxin-insensitive G proteins. The slowly activating delayed rectifier K+ (IKs) channel is a cardiac K+ channel composed of KCNQ1 and KCNE1 subunits. The C terminus of the KCNQ1 channel protein has two calmodulin-binding sites that are involved in regulating IKs channels. In this study, we investigated the molecular mechanisms of gintonin-mediated activation of human IKs channel activity by expressing human IKs channels in Xenopus oocytes. We found that gintonin enhances IKs channel currents in concentration- and voltage-dependent manners. The EC50 for the IKs channel was 0.05 ± 0.01 ?g/ml. Gintonin-mediated activation of the IKs channels was blocked by an LPA1/3 receptor antagonist, an active phospholipase C inhibitor, an IP3 receptor antagonist, and the calcium chelator BAPTA. Gintonin-mediated activation of both the IKs channel was also blocked by the calmodulin (CaM) blocker calmidazolium. Mutations in the KCNQ1 [Ca2+]i/CaM-binding IQ motif sites (S373P, W392R, or R539W)blocked the action of gintonin on IKs channel. However, gintonin had no effect on hERG K+ channel activity. These results show that gintonin-mediated enhancement of IKs channel currents is achieved through binding of the [Ca2+]i/CaM complex to the C terminus of KCNQ1 subunit. PMID:25234465

Choi, Sun-Hye; Lee, Byung-Hwan; Kim, Hyeon-Joong; Jung, Seok-Won; Kim, Hyun-Sook; Shin, Ho-Chul; Lee, Jun-Hee; Kim, Hyoung-Chun; Rhim, Hyewhon; Hwang, Sung-Hee; Ha, Tal soo; Kim, Hyun-Ji; Cho, Hana; Nah, Seung-Yeol

2014-01-01

257

CD66 nonspecific cross-reacting antigens are involved in neutrophil adherence to cytokine-activated endothelial cells  

PubMed Central

Neutrophil adherence to cytokine-activated endothelial cell (EC) monolayers depends on the expression of the endothelial leukocyte adhesion molecule-1 (ELAM-1). The ligand for ELAM-1 is the sialylated Lewis-x antigen (SLe(x)) structure. The selectin LAM-1 (or LECAM-1) has been described as one of the SLe(x)-presenting glycoproteins involved in neutrophil binding to ELAM-1. Other presenter molecules have not yet been described. Our data demonstrate that the carcinoembryonic antigen (CEA)-like surface molecules on neutrophils--known as the nonspecific cross-reacting antigens (NCAs)--are involved in neutrophil adherence to monolayers of IL-1-beta-activated EC. The NCAs are recognized by CD66 (NCA-160 and NCA-90) and CD67 (NCA-95). Because NCA-95 and NCA-90 have previously been found to be phosphatidylinositol (PI)-linked, paroxysmal nocturnal hemoglobinuria (PNH) neutrophils (which lack PI- linked surface proteins) were tested as well. PNH neutrophils showed a diminished binding to activated EC. CD66 (on PNH cells still recognizing the transmembrane NCA-160 form) still inhibited the adherence of PNH cells to IL-1-beta-activated EC, but to a limited extent. Soluble CEA(-related) antigens inhibited normal neutrophil adherence as well, whereas neutrophil transmigration was unaffected. Sialidase-treatment as well as CD66 preclearing abolished the inhibitory capacity of the CEA(-related) antigens. The binding of soluble CEA antigens to IL-1-beta-pretreated EC was blocked by anti- ELAM-1. These soluble antigens, as well as the neutrophil NCA-160 and NCA-90, both recognized by CD66 antibodies, presented the SLe(x) determinant. Together, these findings indicate that the CD66 antigens (i.e., NCA-160/NCA-90) function as presenter molecules of the SLe(x) oligosaccharide structures on neutrophils that bind to ELAM-1 on EC. PMID:1378450

1992-01-01

258

Metatranscriptome of an anaerobic benzene-degrading, nitrate-reducing enrichment culture reveals involvement of carboxylation in benzene ring activation.  

PubMed

The enzymes involved in the initial steps of anaerobic benzene catabolism are not known. To try to elucidate this critical step, a metatranscriptomic analysis was conducted to compare the genes transcribed during the metabolism of benzene and benzoate by an anaerobic benzene-degrading, nitrate-reducing enrichment culture. RNA was extracted from the mixed culture and sequenced without prior mRNA enrichment, allowing simultaneous examination of the active community composition and the differential gene expression between the two treatments. Ribosomal and mRNA sequences attributed to a member of the family Peptococcaceae from the order Clostridiales were essentially only detected in the benzene-amended culture samples, implicating this group in the initial catabolism of benzene. Genes similar to each of two subunits of a proposed benzene-carboxylating enzyme were transcribed when the culture was amended with benzene. Anaerobic benzoate degradation genes from strict anaerobes were transcribed only when the culture was amended with benzene. Genes for other benzoate catabolic enzymes and for nitrate respiration were transcribed in both samples, with those attributed to an Azoarcus species being most abundant. These findings indicate that the mineralization of benzene starts with its activation by a strict anaerobe belonging to the Peptococcaceae, involving a carboxylation step to form benzoate. These data confirm the previously hypothesized syntrophic association between a benzene-degrading Peptococcaceae strain and a benzoate-degrading denitrifying Azoarcus strain for the complete catabolism of benzene with nitrate as the terminal electron acceptor. PMID:24795366

Luo, Fei; Gitiafroz, Roya; Devine, Cheryl E; Gong, Yunchen; Hug, Laura A; Raskin, Lutgarde; Edwards, Elizabeth A

2014-07-01

259

The neuropeptide Y Y1 receptor knockdown modulates activator protein 1-involved feeding behavior in amphetamine-treated rats  

PubMed Central

Background Hypothalamic neuropeptide Y (NPY) and two immediate early genes, c-fos and c-jun, have been found to be involved in regulating the appetite-suppressing effect of amphetamine (AMPH). The present study investigated whether cerebral catecholamine (CA) might regulate NPY and POMC expression and whether NPY Y1 receptor (Y1R) participated in activator protein-1 (AP-1)–mediated feeding. Methods Rats were given AMPH daily for 4 days. Changes in the expression of NPY, Y1R, c-Fos, c-Jun, and AP-1 were assessed and compared. Results Decreased CA could modulate NPY and melanocortin receptor 4 (MC4R) expressions. NPY and food intake decreased the most on Day 2, but Y1R, c-Fos, and c-Jun increased by approximately 350%, 280%, and 300%, respectively, on Day 2. Similarly, AP-1/DNA binding activity was increased by about 180% on Day 2. The expression patterns in Y1R, c-Fos, c-Jun, and AP-1/DNA binding were opposite to those in NPY during AMPH treatment. Y1R knockdown was found to modulate the opposite regulation between NPY and AP-1, revealing an involvement of Y1R in regulating NPY/AP-1–mediated feeding. Conclusions These results point to a molecular mechanism of CA/NPY/Y1R/AP-1 signaling in the control of AMPH-mediated anorexia and may advance the medical research of anorectic and anti-obesity drugs. PMID:24225225

2013-01-01

260

GABA/sub B/ receptor activation inhibits Ca/sup 2 +/-activated potassium channels in synaptosomes: involvement of G-proteins  

SciTech Connect

/sup 86/Rb-efflux assay from preloaded synaptosomes of rat cerebral cortex was developed to study the effect of GABA/sub B/ receptor agonist baclofen on Ca/sup 2 +/-activated K/sup +/-channels. Depolarization of /sup 86/Rb-loaded synaptosomes in physiological buffer increased Ca/sup 2 +/-activated /sup 86/Rb-efflux by 400%. The /sup 86/Rb-efflux was blocked by quinine sulfate, tetraethylammonium, and La/sup 3 +/ indicating the involvement of Ca/sup 2 +/-activated K/sup +/-channels. (-)Baclofen inhibited Ca/sup 2 +/-activated /sup 86/Rb-efflux in a stereospecific manner. The inhibitory effect of (-)baclofen was mediated by GABA/sub B/ receptor activation, since it was blocked by GABA/sub B/ antagonist phaclofen, but not by bicuculline. Further, pertussis toxin also blocked the ability of baclofen or depolarizing action to affect Ca/sup 2 +/-activated K/sup +/-channels. These results suggest that baclofen inhibits Ca/sup 2 +/-activated K/sup +/-channels in synaptosomes and these channels are regulated by G-proteins. This assay may provide an ideal in vitro model to study GABA/sub B/ receptor pharmacology.

Ticku, M.K.; Delgado, A.

1989-01-01

261

Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2  

PubMed Central

Lectin pathway activation of C3 is known to involve target recognition by mannan-binding lectin (MBL) or ficolins and generation of classical pathway C3 convertase via cleavage of C4 and C2 by MBL-associated serine protease 2 (MASP-2). We investigated C3 activation in C2-deficient human sera and in sera with other defined defects of complement to assess other mechanisms through which MBL might recruit complement. The capacity of serum to support C3 deposition was examined by ELISA using microtiter plates coated with O antigen–specific oligosaccharides derived from Salmonella typhimurium, S. thompson, and S. enteritidis corresponding to serogroups B, C, and D (BO, CO, and DO). MBL bound to CO, but not to BO and DO, and efficiently supported C3 deposition in the absence of C2, C4, or MASP-2. The existence of an MBL-dependent C2 bypass mechanism for alternative pathway–mediated C3 activation was clearly demonstrated using CO, solid-phase mannan, and E. coli LPS. MASP-1 might contribute, but was not required for C3 deposition in the model used. Independent of MBL, specific antibodies to CO supported C3 deposition through classical and alternative pathways. MBL-dependent C2 bypass activation could be particularly important in various inherited and acquired complement deficiency states. PMID:16670774

Selander, Barbro; Martensson, Ulla; Weintraub, Andrej; Holmstrom, Eva; Matsushita, Misao; Thiel, Steffen; Jensenius, Jens C.; Truedsson, Lennart; Sjoholm, Anders G.

2006-01-01

262

Acrolein activates cell survival and apoptotic death responses involving the endoplasmic reticulum in A549 lung cells.  

PubMed

Acrolein, a highly reactive ?,?-unsaturated aldehyde, is a product of endogenous lipid peroxidation. It is a ubiquitous environmental pollutant that is generated mainly by smoke, overheated cooking oil and vehicle exhaust. Acrolein damages cellular proteins, which could lead to accumulation of aberrantly-folded proteins in the endoplasmic reticulum (ER). This study determines the mechanisms involved in acrolein-induced apoptosis mediated by the ER and possible links with the ER stress response in human A549 lung cells. The exposure of cells to acrolein (15-50?M) for shorter times of 15 to 30min activated several ER stress markers. These included the ER chaperone protein BiP and the three ER sensors: (i) the survival/rescue molecules protein kinase RNA (PKR)-like ER kinase (PERK) and eukaryotic initiation factor 2 alpha (eIF2?) were phosphorylated; (ii) cleavage of activating transcription factor 6 (ATF6) occurred, and (iii) inositol-requiring protein-1 alpha (IRE1?) was phosphorylated. Acrolein (25-50?M) caused apoptotic cell death mediated by the ER after 2h, which was characterised by the induction of CHOP and activation of ER proteases calpain and caspase-4. Calpain and caspase-7 were the initiating factors for caspase-4 activation in acrolein-induced apoptosis. These results increase our knowledge about cellular responses to acrolein in lung cells, which have implications for human health. PMID:24373849

Tanel, André; Pallepati, Pragathi; Bettaieb, Ahmed; Morin, Patrick; Averill-Bates, Diana A

2014-05-01

263

PmPPAF is a pro-phenoloxidase activating factor involved in innate immunity response of the shrimp Penaeus monodon.  

PubMed

One of the major steps in the innate immune response of shrimp includes the activation of serine proteinases of the pro-phenoloxidase pathway by the prophenoloxidase activation enzyme (PPAF). In this study, the cDNA encoding a serine proteinase homologue (SPH) with prophenoloxidase activating activity of Penaeus monodon (PmPPAF) was cloned and characterized. PmPPAF cDNA consists of 1444 nucleotides encoding a protein with 394 amino acid residues. The estimated molecular weight of PmPPAF is 43.5 kDa with an isoelectric point of 5.19. PmPPAF consists of a signal peptide, a CLIP domain and a carboxyl-terminal trypsin-like serine protease domain. It is highly similar to the masquerade-like protein 2A (61% similarity) of the crayfish Pacifastacus leniusculus, other serine proteases (42.9-67% identity) of P. monodon, and the PPAF of the crab (61% similarity). Unlike other SPH of P. monodon, which express mainly in the hemocytes, PmPPAF transcripts were detected in the hemocytes, eyestalk, hypodermis, gill, swimming leg and brain. Similar to the crab PPAF, PmPPAF transcript level is high in shrimp at the premolt stages and PmPPAF expression is up-regulated in shrimp infected with white spot syndrome virus (WSSV). Gene silencing of PmPPAF decreased expression of a prophenoloxidase-like gene and injection of Anti-PmPPAF antibody causes a decrease in PO activity. Taken together, these results provided evidence that PmPPAF is a serine proteinase homologue, and is involved in the pro-PO activation pathway of the shrimp innate immune system. PMID:24345607

Ma, Tracy H T; Benzie, John A H; He, Jian-Guo; Sun, Cheng-Bo; Chan, Siuming F

2014-05-01

264

Ras-related C3 botulinum toxin substrate 1 activation is involved in the pathogenesis of diabetic retinopathy  

PubMed Central

This study used a streptozotocin (STZ)-induced rat model of diabetes to investigate whether Ras-related C3 botulinum toxin substrate 1 (Rac1) was involved in the pathogenesis of diabetic retinopathy. The effects of Rac1 inhibition on vascular endothelial (VE)-cadherin and ?-catenin expression in high glucose-induced rat retinal endothelial cells (RRECs) were additionally examined. Rac1 activation in the retinas from STZ-induced diabetic rats and in high glucose-induced RRECs was measured by reverse transcription-quantitative polymerase chain reaction analysis, immunohistochemistry and western blot analysis. The expression levels of VE-cadherin and ?-catenin were also examined with or without Rac1 inhibition through small interfering (si)RNA transfection. STZ-induced diabetes was associated with an increase in the vascular permeability of the retina. Furthermore, Rac1 activation was increased in the retina of STZ-induced diabetic rats and in high glucose-induced RRECs compared with that in the controls. Immunohistochemistry showed that immunostaining of Rac1 was localized in the outer plexiform, inner nuclear, inner plexiform and ganglion cell layers and in the retinal microvasculature of rats. The expression of ?-catenin was increased in the retinas of the diabetic rats at four, eight and 12 weeks after the induction of diabetes compared with that in the controls. Additionally, Rac1 activation was required for the high glucose-induced VE-cadherin expression decrease and for ?-catenin expression in high glucose-induced RRECs. Rac1 inhibition by Rac1-siRNA transfection effectively prevented hyperpermeability, ?-catenin expression and the VE-cadherin expression decrease in high glucose-induced RRECs. In conclusion, diabetes affects the expression of Rac1 in the retina. Rac1 may be involved in the diabetes-induced damage and/or alterations to the blood-retinal barrier through changes in VE-cadherin and ?-catenin expression.

LI, YANG-JUN; ZHANG, JIE; HAN, JING; DU, ZHAO-JIANG; WANG, PING; GUO, YONG

2015-01-01

265

Sympathoexcitation and pressor responses induced by ethanol in the central nucleus of amygdala involves activation of NMDA receptors in rats.  

PubMed

The central nervous system plays an important role in regulating sympathetic outflow and arterial pressure in response to ethanol exposure. However, the underlying neural mechanisms have not been fully understood. In the present study, we tested the hypothesis that injection of ethanol in the central nucleus of the amygdala (CeA) increases sympathetic outflow, which may require the activation of local ionotropic excitatory amino acid receptors. In anesthetized rats, CeA injection of ethanol (0, 0.17, and 1.7 ?mol) increased splanchnic sympathetic nerve activity (SSNA), lumbar sympathetic nerve activity (LSNA), and mean arterial pressure (MAP) in a dose-dependent manner. A cocktail containing ethanol (1.7 ?mol) and kynurenate (KYN), an ionotropic excitatory amino acid receptor blocker, showed significantly blunted sympathoexcitatory and pressor responses compared with those elicited by CeA-injected ethanol alone (P < 0.01). A cocktail containing ethanol and d-2-amino-5-phosphonovalerate, an N-methyl-d-aspartate (NMDA) receptor antagonist, elicited attenuated sympathoexcitatory and pressor responses that were significantly less than ethanol alone (P < 0.01). In addition, CeA injection of acetate (0.20 ?mol, n = 7), an ethanol metabolite, consistently elicited sympathoexcitatory and pressor responses, which were effectively blocked by d-2-amino-5-phosphonovalerate (n = 9, P < 0.05). Inhibition of neuronal activity of the rostral ventrolateral medulla (RVLM) with KYN significantly (P < 0.01) attenuated sympathoexcitatory responses elicited by CeA-injected ethanol. Double labeling of immune fluorescence showed NMDA NR1 receptor expression in CeA neurons projecting to the RVLM. We conclude that ethanol and acetate increase sympathetic outflow and arterial pressure, which may involve the activation of NMDA receptors in CeA neurons projecting to the RVLM. PMID:24993048

Chapp, Andrew D; Gui, Le; Huber, Michael J; Liu, Jinling; Larson, Robert A; Zhu, Jianhua; Carter, Jason R; Chen, Qing-Hui

2014-09-01

266

Antimicrobial activity of plant essential oils against bacterial and fungal species involved in food poisoning and/or food decay.  

PubMed

The currative properties of aromatic and medicinal plants have been recognized since ancient times and, more recently, the antimicrobial activity of plant essential oils has been used in several applications, including food preservation. The purpose of this study was to create directly comparable, quantitative data on the antimicrobial activity of some plant essential oils prepared in the National Institute of Research-Development for Chemistry and Petrochemistry, Bucharest to be used for the further development of food packaging technology, based on their antibacterial and antifungal activity. The essential oils extracted from thyme (Thymus vulgaris L.), basil (Ocimum basilicum L.), coriander (Coriandrum sativum L.), rosemary (Rosmarinus officinalis L.), sage (Salvia officinalis L.), fennel (Foeniculum vulgare L.), spearmint (Mentha spicata L.) and carraway (Carum carvi L.) were investigated for their antimicrobial activity against eleven different bacterial and three fungal strains belonging to species reported to be involved in food poisoning and/or food decay: S. aureus ATCC 25923, S. aureus ATCC 6538, S. aureus ATCC 25913, E. coli ATCC 25922, E. coli ATCC 35218, Salmonella enterica serovar Enteritidis Cantacuzino Institute Culture Collection (CICC) 10878, Listeria monocytogenes ATCC 19112, Bacillus cereus CIP 5127, Bacillus cereus ATCC 11778, Candida albicans ATCC 10231, Aspergillus niger ATCC 16404, Penicillium spp. CICC 251 and two E. coli and Salmonella enterica serovar Enteritidis clinical isolates. The majority of the tested essential oils exibited considerable inhibitory capacity against all the organisms tested, as supported by growth inhibition zone diameters, MICs and MBC's. Thyme, coriander and basil oils proved the best antibacterial activity, while thyme and spearmint oils better inhibited the fungal species. PMID:21462837

Lixandru, Brîndu?a-Elena; Dr?cea, Nicoleta Olgu?a; Dragomirescu, Cristiana Cerasella; Dr?gulescu, Elena Carmina; Coldea, Ileana Lumini?a; Anton, Liliana; Dobre, Elena; Rovinaru, Camelia; Codi??, Irina

2010-01-01

267

Intrinsic factors involved in the depression of neuronal activity induced by temperature increase in rat hippocampal neurons.  

PubMed

The intrinsic factors involved in the temperature-dependent impairment of neuronal activity in hippocampal CA2-CA1 regions were investigated using optical recording techniques. At 32 degrees C, stimulation of the Schaffer collaterals in the hippocampal CA2 region evoked depolarizing optical responses that spread toward the CA1 region. The optical response was characterized by fast and slow components that were mainly related to the presynaptic action potentials and excitatory postsynaptic response, respectively. The increase of the temperature to 38 degrees C was associated with a reversible depression of the neuronal activity in the hippocampal brain preparations. The depression of neuronal activity was irreversible when the temperature was increased to 40 degrees C. In the presence of 22 mM glucose, the depression of the neuronal activity at 38 degrees C was significantly attenuated. Pyruvate (22 mM), but not lactate (22 mM), also improved the depression of neuronal activity induced by the temperature increase. Adenosine (200 microM) strongly depressed the excitatory postsynaptic response, but not presynaptic action potentials. 8-Cyclopentyl-1,3-dimethylxanthine (8-CPT) (10 microM), an adenosine A1 receptor blocker, attenuated the adenosine-induced depression of the excitatory postsynaptic response. 8-CPT (10 microM) prevented the impairment of the excitatory postsynaptic response induced by the increase of the temperature to 38 degrees C. In contrast, the depression of presynaptic action potential at 38 degrees C was not prevented by 8-CPT (10 microM). N omega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, and methylcobalamin (10 microM), a vitamin B12 analogue, attenuated the inhibition of pre- and postsynaptic activities induced by the increase of the temperature to 38 degrees C. Glibenclamide, a KATP channel blocker, did not protect neuronal activity from the effects of the increase of the temperature. These results suggest that the heat-induced depression of neuronal activity is mediated by multiple factors, such as impairment of energy metabolism and increase in extracellular adenosine and nitric oxide (NO) levels in hippocampal neurons. PMID:11830930

Takeya, M

2001-01-01

268

The production of VEGF involving MAP kinase activation by low level laser therapy in human granulosa cells  

PubMed Central

Objective: The function of granulosa cells is regulated by various hormones and growth factors. Our aim is to clarify the regulation of vascular endothelial growth factor (VEGF) production via mitogen-activated protein kinase (MAPK) induced by low level laser therapy (LLLT) in human granulosa cells. Methods: A human granulosa cell line, KGN cells, were cultured and incubated after LLLT (60mW, GaAlAs 830nm). The levels of VEGF in the culture media were determined by an enzyme-linked immunosorbent assay. The activation of MAP kinase in KGN cells was detected by western blot analysis. Results: VEGF production was significantly increased by LLLT in a time-dependent manner. MAP kinase activity was increased by LLLT. In addition it was enhanced by LLLT and follicle-stimulating hormone (FSH) stimulation. Conclusions: The results suggested that VEGF is induced by LLLT through mechanisms involving MAPK. The increase in VEGF may contribute to neovascularization, which in turn would promote various ovulation phenomena as well as follicular growth. PMID:24511196

Utsunomiya-Kai, Yufuko; Kai, Kentaro; Miyakawa, Isao; Ohshiro, Toshio; Narahara, Hisashi

2012-01-01

269

Possible Involvement of TLRs and Hemichannels in Stress-Induced CNS Dysfunction via Mastocytes, and Glia Activation  

PubMed Central

In the central nervous system (CNS), mastocytes and glial cells (microglia, astrocytes and oligodendrocytes) function as sensors of neuroinflammatory conditions, responding to stress triggers or becoming sensitized to subsequent proinflammatory challenges. The corticotropin-releasing hormone and glucocorticoids are critical players in stress-induced mastocyte degranulation and potentiation of glial inflammatory responses, respectively. Mastocytes and glial cells express different toll-like receptor (TLR) family members, and their activation via proinflammatory molecules can increase the expression of connexin hemichannels and pannexin channels in glial cells. These membrane pores are oligohexamers of the corresponding protein subunits located in the cell surface. They allow ATP release and Ca2+ influx, which are two important elements of inflammation. Consequently, activated microglia and astrocytes release ATP and glutamate, affecting myelinization, neuronal development, and survival. Binding of ligands to TLRs induces a cascade of intracellular events leading to activation of several transcription factors that regulate the expression of many genes involved in inflammation. During pregnancy, the previous responses promoted by viral infections and other proinflammatory conditions are common and might predispose the offspring to develop psychiatric disorders and neurological diseases. Such disorders could eventually be potentiated by stress and might be part of the etiopathogenesis of CNS dysfunctions including autism spectrum disorders and schizophrenia. PMID:23935250

Aguirre, Adam; Maturana, Carola J.; Harcha, Paloma A.; Saez, Juan C.

2013-01-01

270

Retinal cell death induced by TRPV1 activation involves NMDA signaling and upregulation of nitric oxide synthases.  

PubMed

The activation of the transient receptor potential vanilloid type 1 channel (TRPV1) has been correlated with oxidative and nitrosative stress and cell death in the nervous system. Our previous results indicate that TRPV1 activation in the adult retina can lead to constitutive and inducible nitric oxide synthase-dependent protein nitration and apoptosis. In this report, we have investigated the potential effects of TRPV1 channel activation on nitric oxide synthase (NOS) expression and function, and the putative participation of ionotropic glutamate receptors in retinal TRPV1-induced protein nitration, lipid peroxidation, and DNA fragmentation. Intravitreal injections of the classical TRPV1 agonist capsaicin up-regulated the protein expression of the inducible and endothelial NOS isoforms. Using 4,5-diaminofluorescein diacetate for nitric oxide (NO) imaging, we found that capsaicin also increased the production of NO in retinal blood vessels. Processes and perikarya of TRPV1-expressing neurons in the inner nuclear layer of the retina were found in the vicinity of nNOS-positive neurons, but those two proteins did not colocalize. Retinal explants exposed to capsaicin presented high protein nitration, lipid peroxidation, and cell death, which were observed in the inner nuclear and plexiform layers and in ganglion cells. This effect was partially blocked by AP-5, a NMDA glutamate receptor antagonist, but not by CNQX, an AMPA/kainate receptor antagonist. These data support a potential role for TRPV1 channels in physiopathological retinal processes mediated by NO, which at least in part involve glutamate release. PMID:23324998

Leonelli, Mauro; Martins, Daniel O; Britto, Luiz R G

2013-04-01

271

Development of the parents' perception of their involvement in their child's tennis activity questionnaire (Q-PPICTA).  

PubMed

The purpose of this study was to develop and validate a questionnaire for assessing parents' perception of their involvement in their children's tennis activity (Q-PPICTA). The validation required four successive studies. In study 1, a preliminary version of the questionnaire was formulated after selecting and adapting items taken from existing questionnaires and interviews conducted with the parents of 36 young tennis players. Three factors for measuring parental involvement in sport were identified and retained: emotional, logistic, and informational supports. In study 2, exploratory factor analyses were performed on data collected from 214 parents of tennis players. Results attested the questionnaire's three-factor structure and ascertained its internal consistency. In study 3, a confirmatory factor analysis as well as tests on convergent and discriminant validity were carried out on data gathered from a different sample of 220 parents of tennis players. Statistics confirmed the questionnaire's three-factor structure and reliability. In study 4, the questionnaire's external construct validity was compared with another sample consisting of 192 parents and their children. Overall, results underlined satisfactory psychometric properties for the Q-PPICTA. Nevertheless, further studies are required to confirm the questionnaire's accuracy, reliability, and temporal validity. PMID:23438202

Hurtel, V; Lacassagne, M-F

2013-08-01

272

The activation of protein degradation in muscle by Ca2+ or muscle injury does not involve a lysosomal mechanism.  

PubMed Central

By use of different inhibitors, we distinguished three proteolytic processes in rat skeletal muscle. When soleus muscles maintained under tension were exposed to the calcium ionophore A23187 or were incubated under no tension in the presence of Ca2+, net protein breakdown increased by 50-80%. Although leupeptin and E-64 inhibit this acceleration of protein breakdown almost completely, other agents that prevent lysosomal function, such as methylamine or leucine methyl ester, did not inhibit this effect. A similar increase in net proteolysis occurred in muscle fibres injured by cutting, and this response was also inhibited by leupeptin, but not by methylamine. In contrast, all these inhibitors markedly decreased the 2-fold increase in protein breakdown induced by incubating muscles without insulin and leucine, isoleucine and valine. In addition, the low rate of proteolysis seen in muscles under passive tension in complete medium was not affected by any of these inhibitors. Thus the basal degradative process in muscle does not involve lysosomes or thiol proteinases, and muscle can enhance protein breakdown by two mechanisms: lack of insulin and nutrients enhances a lysosomal process in muscle, as in other cells, whereas Ca2+ and muscle injury activate a distinct pathway involving cytosolic thiol proteinase(s). PMID:3099758

Furuno, K; Goldberg, A L

1986-01-01

273

Involvement of Dopamine Receptors in Binge Methamphetamine-Induced Activation of Endoplasmic Reticulum and Mitochondrial Stress Pathways  

PubMed Central

Single large doses of methamphetamine (METH) cause endoplasmic reticulum (ER) stress and mitochondrial dysfunctions in rodent striata. The dopamine D1 receptor appears to be involved in these METH-mediated stresses. The purpose of this study was to investigate if dopamine D1 and D2 receptors are involved in ER and mitochondrial stresses caused by single-day METH binges in the rat striatum. Male Sprague-Dawley rats received 4 injections of 10 mg/kg of METH alone or in combination with a putative D1 or D2 receptor antagonist, SCH23390 or raclopride, respectively, given 30 min prior to each METH injection. Rats were euthanized at various timepoints afterwards. Striatal tissues were used in quantitative RT-PCR and western blot analyses. We found that binge METH injections caused increased expression of the pro-survival genes, BiP/GRP-78 and P58IPK, in a SCH23390-sensitive manner. METH also caused up-regulation of ER-stress genes, Atf2, Atf3, Atf4, CHOP/Gadd153 and Gadd34. The expression of heat shock proteins (HSPs) was increased after METH injections. SCH23390 completely blocked induction in all analyzed ER stress-related proteins that included ATF3, ATF4, CHOP/Gadd153, HSPs and caspase-12. The dopamine D2-like antagonist, raclopride, exerted small to moderate inhibitory influence on some METH-induced changes in ER stress proteins. Importantly, METH caused decreases in the mitochondrial anti-apoptotic protein, Bcl-2, but increases in the pro-apoptotic proteins, Bax, Bad and cytochrome c, in a SCH23390-sensitive fashion. In contrast, raclopride provided only small inhibition of METH-induced changes in mitochondrial proteins. These findings indicate that METH-induced activation of striatal ER and mitochondrial stress pathways might be more related to activation of SCH23390-sensitive receptors. PMID:22174933

Beauvais, Genevieve; Atwell, Kenisha; Jayanthi, Subramaniam; Ladenheim, Bruce; Cadet, Jean Lud

2011-01-01

274

Peroxisome proliferator-activated receptor-? and thymic stromal lymphopoietin are involved in the pathophysiology of childhood coeliac disease.  

PubMed

Celiac disease (CD) is a chronic autoimmune enteropathy caused by exposure to dietary gluten in genetically predisposed individuals. The transcription factor peroxisome proliferator-activated receptor gamma (PPAR?) was shown to exert protective effects in several immune-mediated disorders. Activation of PPAR? suppressed the expression of thymic stromal lymphopoietin (TSLP), an inducer of proinflammatory cytokines. Since the role of TSLP in gluten-sensitive enteropathy is completely unknown, we investigated the involvement of TSLP and its regulator PPAR? in childhood CD. We collected duodenal biopsy specimens from 19 children with newly diagnosed CD, 6 children with treated CD (gluten-free diet, GFD), and 10 controls. Expression of mRNA and protein levels of PPAR?, TSLP, and TSLP receptor were determined by real-time RT-PCR and Western blot, respectively. Duodenal localization of PPAR? and TSLP was studied by immunohistochemistry. In duodenal mucosa of children with CD, the amount of PPAR? was significantly lower and simultaneously that of TSLP significantly higher compared to controls (p?involved in the pathophysiology of CD. We hypothesize that PPAR? may be an inhibitory regulator of TSLP-stimulated inflammatory processes in CD. PMID:25187315

Sziksz, Erna; Molnár, Kriszta; Lippai, Rita; Pap, Domonkos; Onody, Anna; Veres-Székely, Apor; Vörös, Péter; Szabó, Dolóresz; Gy?rffy, Hajnalka; Veres, Gábor; Tulassay, Tivadar; Vannay, Adám; Arató, András

2014-10-01

275

Effect of game format on heart rate, activity profile, and player involvement in elite and recreational youth players.  

PubMed

The purpose of this study was to evaluate activity profile, aerobic load, and player involvement in two game formats of recreational and elite youth football for two age groups. A total of 152 youth players participated, with 45 U10 players playing 5v5 and 8v8 games, and 41 U13 players playing 8v8 and 11v11 (20 min) games. Activity profile, heart rate (HR), and technical actions were measured during all games using 10 Hz GPS, video filming, and HR monitors. For U10, no difference was found in total distance covered (1754 ± 237 vs 1771 ± 314 m, P = 0.650, d = 0.06), whereas mean HR (174 ± 10 vs 168 ± 12 bpm, P = 0.001, d = 0.59) and number of technical actions (65.1 ± 24.0 vs 36.9 ± 20.4, P? ? 0.001, d = 1.27) were higher in 5v5 than in 8v8. For U13, lower total distance covered (1821 ± 325 vs 2038 ± 328 m, P < 0.001, d = 0.66) and higher number of technical actions (36.2 ± 14.9 vs 26.9 ± 14.1, P < 0.001, d = 0.64) were observed in 8v8 than in 11v11, with no difference in mean HR (170 ± 10 vs 171 ± 10 bpm, P = 0.679, d = 0.10). In conclusion, HR is high in youth football matches irrespective of the level of play and the game format. Playing with fewer players on smaller pitches results in minor changes to the physical loading but elevates the technical involvement of youth players both at elite level and recreational level. PMID:24944130

Randers, M B; Andersen, T B; Rasmussen, L S; Larsen, M N; Krustrup, P

2014-08-01

276

Involvement of the Serine Protease Inhibitor, SERPINE2, and the Urokinase Plasminogen Activator in Cumulus Expansion and Oocyte Maturation  

PubMed Central

The serpin peptidase inhibitor, clade E, member 2 (SERPINE2) inhibits urokinase-type plasminogen activator (PLAU) and tissue-type plasminogen activator. Higher SERPINE2 expression levels were detected in cumulus cells of human immature oocytes than in those of mature oocytes. The objective of this study was to evaluate whether high SERPINE2 levels in cumulus cells are associated with oocyte immaturity. Using the mouse cumulus–oocyte complex as an experimental model, the effects of elimination and overexpression of SERPINE2 in cumulus cells on cumulus expansion and oocyte maturation were assayed by in vitro maturation. Serpine2 and PLAU transcripts were the most highly expressed serpins and plasminogen activators, respectively. Their expression was coordinately regulated in cumulus cells during gonadotropin-induced oocyte maturation. Silencing of Serpine2 expression using small interfering RNAs or blockage of SERPINE2 protein using a specific antibody had no effect on oocyte maturation. However, overexpression of Serpine2 or exogenous supplementation with high levels of SERPINE2 impaired cumulus expansion and oocyte maturation, probably by decreasing hyaluronan synthase 2 (Has2) and versican (Vcan) mRNA expression. Amiloride, a specific PLAU inhibitor, also suppressed these processes. PLAU supplementation of the oocyte in vitro maturation medium caused earlier and more extensive expansion of cumulus cells and oocyte maturation that may be mediated by increased Has2 mRNA expression. However, these effects were neutralized by coincubation with SERPINE2 or amiloride and PLAU. In conclusion, SERPINE2 and PLAU are involved in cumulus expansion and oocyte maturation. High SERPINE2 levels impair these processes, probably by decreasing cumulus matrix gene expression as well as reducing cumulus hyaluronan contents and inhibiting PLAU activity. These findings may explain why cumulus cells surrounding immature human oocytes express high SERPINE2 levels. PMID:24023701

Hwu, Yuh-Ming; Lin, Ming-Huei; Yeh, Ling-Yu; Chen, Ying-Jie; Lin, Shau-Ping; Li, Sheng-Hsiang

2013-01-01

277

Hypoxia downregulates the expression of activating receptors involved in NK-cell-mediated target cell killing without affecting ADCC.  

PubMed

In certain infection sites or tumor tissues, the disruption of homeostasis can give rise to a hypoxic microenvironment, which, in turn, can alter the function of different immune cell types and favor the progression of the disease. Natural killer (NK) cells are directly involved in the elimination of virus-infected or transformed cells, however it is unknown whether their function is affected by hypoxia or not. In this study, we show that NK cells adapt to a hypoxic environment by upregulating the hypoxia-inducible factor 1?. However, NK cells lose their ability to upregulate the surface expression of the major activating NK-cell receptors (NKp46, NKp30, NKp44, and NKG2D) in response to IL-2 (or other activating cytokines, including IL-15, IL-12, and IL-21). These altered phenotypic features correlate with reduced responses to triggering signals resulting in impaired capability of killing infected or tumor target cells. Remarkably, hypoxia does not significantly alter the surface density and the triggering function of the Fc-? receptor CD16, thus allowing NK cells to maintain their capability of killing target cells via antibody-dependent cellular cytotoxicity. This finding offers an important clue for exploitation of NK cell in antibody-based immunotherapy of cancer. PMID:23913266

Balsamo, Mirna; Manzini, Claudia; Pietra, Gabriella; Raggi, Federica; Blengio, Fabiola; Mingari, Maria Cristina; Varesio, Luigi; Moretta, Lorenzo; Bosco, Maria Carla; Vitale, Massimo

2013-10-01

278

Transient accumulation of 5-carboxylcytosine indicates involvement of active demethylation in lineage specification of neural stem cells.  

PubMed

5-Methylcytosine (5mC) is an epigenetic modification involved in regulation of gene activity during differentiation. Tet dioxygenases oxidize 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Both 5fC and 5caC can be excised from DNA by thymine-DNA glycosylase (TDG) followed by regeneration of unmodified cytosine via the base excision repair pathway. Despite evidence that this mechanism is operative in embryonic stem cells, the role of TDG-dependent demethylation in differentiation and development is currently unclear. Here, we demonstrate that widespread oxidation of 5hmC to 5caC occurs in postimplantation mouse embryos. We show that 5fC and 5caC are transiently accumulated during lineage specification of neural stem cells (NSCs) in culture and in vivo. Moreover, 5caC is enriched at the cell-type-specific promoters during differentiation of NSCs, and TDG knockdown leads to increased 5fC/5caC levels in differentiating NSCs. Our data suggest that active demethylation contributes to epigenetic reprogramming determining lineage specification in embryonic brain. PMID:24882006

Wheldon, Lee M; Abakir, Abdulkadir; Ferjentsik, Zoltan; Dudnakova, Tatiana; Strohbuecker, Stephanie; Christie, Denise; Dai, Nan; Guan, Shengxi; Foster, Jeremy M; Corrêa, Ivan R; Loose, Matthew; Dixon, James E; Sottile, Virginie; Johnson, Andrew D; Ruzov, Alexey

2014-06-12

279

Morus alba and active compound oxyresveratrol exert anti-inflammatory activity via inhibition of leukocyte migration involving MEK/ERK signaling  

PubMed Central

Background Morus alba has long been used in traditional Chinese medicine to treat inflammatory diseases; however, the scientific basis for such usage and the mechanism of action are not well understood. This study investigated the action of M. alba on leukocyte migration, one key step in inflammation. Methods Gas chromatography-mass spectrometry (GC-MS) and cluster analyses of supercritical CO2 extracts of three Morus species were performed for chemotaxonomy-aided plant authentication. Phytochemistry and CXCR4-mediated chemotaxis assays were used to characterize the chemical and biological properties of M. alba and its active compound, oxyresveratrol. fluorescence-activated cell sorting (FACS) and Western blot analyses were conducted to determine the mode of action of oxyresveratrol. Results Chemotaxonomy was used to help authenticate M. alba. Chemotaxis-based isolation identified oxyresveratrol as an active component in M. alba. Phytochemical and chemotaxis assays showed that the crude extract, ethyl acetate fraction and oxyresveratrol from M. alba suppressed cell migration of Jurkat T cells in response to SDF-1. Mechanistic study indicated that oxyresveratrol diminished CXCR4-mediated T-cell migration via inhibition of the MEK/ERK signaling cascade. Conclusions A combination of GC-MS and cluster analysis techniques are applicable for authentication of the Morus species. Anti-inflammatory benefits of M. alba and its active compound, oxyresveratrol, may involve the inhibition of CXCR-4-mediated chemotaxis and MEK/ERK pathway in T and other immune cells. PMID:23433072

2013-01-01

280

Hindbrain medulla catecholamine cell group involvement in lactate-sensitive hypoglycemia-associated patterns of hypothalamic norepinephrine and epinephrine activity.  

PubMed

Cell-type compartmentation of glucose metabolism in the brain involves trafficking of the oxidizable glycolytic end product, l-lactate, by astrocytes to fuel neuronal mitochondrial aerobic respiration. Lactate availability within the hindbrain medulla is a monitored function that regulates systemic glucostasis as insulin-induced hypoglycemia (IIH) is exacerbated by lactate repletion of that brain region. A2 noradrenergic neurons are a plausible source of lactoprivic input to the neural gluco-regulatory circuit as caudal fourth ventricular (CV4) lactate infusion normalizes IIH-associated activation, e.g. phosphorylation of the high-sensitivity energy sensor, adenosine 5'-monophosphate-activated protein kinase (AMPK), in these cells. Here, we investigated the hypothesis that A2 neurons are unique among medullary catecholamine cells in directly screening lactate-derived energy. Adult male rats were injected with insulin or vehicle following initiation of continuous l-lactate infusion into the CV4. Two hours after injections, A1, C1, A2, and C2 neurons were collected by laser-microdissection for Western blot analysis of AMPK?1/2 and phosphoAMPK?1/2 proteins. Results show that AMPK is expressed in each cell group, but only a subset, e.g. A1, C1, and A2 neurons, exhibit increased sensor activity in response to IIH. Moreover, hindbrain lactate repletion reversed hypoglycemic augmentation of pAMPK?1/2 content in A2 and C1 but not A1 cells, and normalized hypothalamic norepinephrine and epinephrine content in a site-specific manner. The present evidence for discriminative reactivity of AMPK-expressing medullary catecholamine neurons to the screened energy substrate lactate implies that that lactoprivation is selectively signaled to the hypothalamus by A2 noradrenergic and C1 adrenergic cells. PMID:25084049

Shrestha, P K; Tamrakar, P; Ibrahim, B A; Briski, K P

2014-10-10

281

The Department of Kinesiology and Physical Education offers courses in theoretical perspectives of the study of human movement and the practical application of physical activity involvement. A  

E-print Network

dimensions of Kinesiology. Recreational, educational and high performance aspects of sport, play and physical leadership, early childhood and youth sport/physical activity program involvement, teachingThe Department of Kinesiology and Physical Education offers courses in theoretical perspectives

Seldin, Jonathan P.

282

Luteinizing hormone stimulation of in vitro ovulation in brook trout (Salvelinus fontinalis) involves follicle contraction and activation of proteolytic genes.  

PubMed

Luteinizing hormone (LH) is an essential hormone for the stimulation of the ovulatory process in vertebrates. However, little is known in fish regarding the different mechanisms induced by LH during ovulation that facilitate the rupture of the follicle wall and the subsequent expulsion of the mature oocyte. In this study, the effects of salmon LH (sLH) on in vitro ovulation were investigated in brook trout (Salvelinus fontinalis) isolated follicles. sLH significantly stimulated in vitro ovulation and contraction of brook trout preovulatory follicles. In order to investigate the possible involvement of proteolytic events in the ovulatory action of LH, the expression of genes known to have a crucial role in the degradation of follicle wall structure was examined. Our results show that sLH clearly stimulated the mRNA expression levels of matrix metalloproteinases (MMPs; including mmp2 and mmp19) and other enzymes with proteolytic action during ovulation, such as a disintegrin and metalloproteinase with thrombospondin-like motifs 1 (adamts1) and plasminogen (plg), in brook trout preovulatory follicles. In addition, the expression of mmp2, adamts1 and plg increased in brook trout follicles during the progression of LH-induced ovulation. Interestingly, the expression of tissue inhibitor of matrix metalloproteinase 2 (timp2), a known regulator of MMP2 activity, paralleled that of mmp2, suggesting the existence of a controlled mechanism of MMP2 action. Therefore, the known increase in proteolytic activity during ovulation in fish could be the result of the stimulation of the expression of proteolytic enzymes by LH in preovulatory follicles. We propose that LH may stimulate ovulation in brook trout follicles by stimulating proteolysis of the follicle wall and by stimulating follicle contraction. PMID:23500674

Crespo, Diego; Pramanick, Kousik; Goetz, Frederick W; Planas, Josep V

2013-07-01

283

Hippocampal dysfunction and cognitive impairments provoked by chronic early-life stress involve excessive activation of CRH receptors  

PubMed Central

Chronic stress impairs learning and memory in humans and rodents and disrupts long-term potentiation (LTP) in animal models. These effects are associated with structural changes in hippocampal neurons, including reduced dendritic arborization. Unlike the generally reversible effects of chronic stress on adult rat hippocampus, we have previously found that the effects of early-life stress endure and worsen during adulthood, yet the mechanisms for these clinically important sequelae are poorly understood. Stress promotes secretion of the neuropeptide corticotropin-releasing hormone (CRH) from hippocampal interneurons, activating receptors (CRF1) located on pyramidal cell dendrites. Additionally, chronic CRF1 occupancy negatively affects dendritic arborization in mouse organotypic slice cultures, similar to the pattern observed in middle-aged, early-stressed (CES) rats. Here we found that CRH-expression is augmented in hippocampus of middle-aged CES rats, and then tested if the morphological defects and poor memory performance in these animals involve excessive activation of CRF1 receptors. Central or peripheral administration of a CRF1 blocker following the stress period improved memory performance of CES rats in novel object recognition tests and in the Morris water maze. Consonant with these effects, the antagonist also prevented dendritic atrophy and LTP attenuation in CA1 Schaffer collateral synapses. Together, these data suggest that persistently elevated hippocampal CRH-CRF1 interaction contributes importantly to the structural and cognitive impairments associated with early-life stress. Reducing CRF1 occupancy post-hoc normalized hippocampal function during middle-age, thus offering potential mechanism-based therapeutic interventions for children affected by chronic stress. PMID:20881118

Ivy, Autumn S.; Rex, Christopher S.; Chen, Yuncai; Dube, Celine; Maras, Pamela M.; Grigoriadis, Dimitri E.; Gall, Christine M.; Lynch, Gary; Baram, Tallie Z.

2010-01-01

284

Involvement of the amino-terminal ?-hairpin of the Aspergillus ribotoxins on the interaction with membrances and nonspecific ribonuclease activity  

PubMed Central

Ribotoxins are a family of potent cytotoxic proteins from Aspergillus whose members display a high sequence identity (85% for about 150 amino acid residues). The three-dimensional structures of two of these proteins, ?-sarcin and restrictocin, are known. They interact with phospholipid bilayers, according to their ability to enter cells, and cleave a specific phosphodiester bond in the large subunit of ribosome thus inhibiting protein biosynthesis. Two nonconservative sequence changes between these proteins are located at the amino-terminal ?-hairpin of ?-sarcin, a characteristic structure that is absent in other nontoxic structurally related microbial RNases. These two residues of ?-sarcin, Lys 11 and Thr 20, have been substituted with the equivalent amino acids in restrictocin. The single mutants (K11L and T20D) and the corresponding K11L/T20D double mutant have been produced in Escherichia coli and purified to homogeneity. The spectroscopic characterization of the purified proteins reveals that the overall native structure is preserved. The ribonuclease and lipid-perturbing activities of the three mutants and restrictocin have been evaluated and compared with those of ?-sarcin. These proteins exhibit the same ability to specifically inactivate ribosomes, although they show different activity against nonspecific substrate analogs such as poly(A). The mutant variant K11L and restrictocin display a lower phospholipid-interacting ability correlated with a decreased cytotoxicity. The results obtained are interpreted in terms of the involvement of the amino-terminal ?-hairpin in the interaction with both membranes and polyadenylic acid. PMID:11468362

García-ortega, Lucía; Lacadena, Javier; Mancheño, José M.; Oñaderra, Mercedes; Kao, Richard; Davies, Julian; Olmo, Nieves; Pozo, Álvaro Martínez Del; Gavilanes, José G.

2001-01-01

285

Tumor necrosis factor-? downregulates sodium current in skeletal muscle by protein kinase C activation: involvement in critical illness polyneuromyopathy.  

PubMed

Sepsis is involved in the decrease of membrane excitability of skeletal muscle, leading to polyneuromyopathy. This effect is mediated by alterations of the properties of voltage-gated sodium channels (Na(V)), but the exact mechanism is still unknown. The aim of the present study was to check whether tumor necrosis factor (TNF-?), a cytokine released during sepsis, exerts a rapid effect on Na(V). Sodium current (I(Na)) was recorded by macropatch clamp in skeletal muscle fibers isolated from rat peroneus longus muscle, in control conditions and after TNF-? addition. Analyses of dose-effect and time-effect relationships were carried out. Effect of chelerythrine, a PKC inhibitor, was also studied to determine the way of action of TNF-?. TNF-? induced a reversible dose- and time-dependent inhibition of I(Na). A maximum inhibition of 75% of the control current was observed. A shift toward more negative potentials of activation and inactivation curves of I(Na) was also noticed. These effects were prevented by chelerythrine pretreatment. TNF-? is a cytokine released in the early stages of sepsis. Besides a possible transcriptional role, i.e., modification of the channel type and/or number, we demonstrated the existence of a rapid, posttranscriptional inhibition of Na(V) by TNF-?. The downregulation of the sodium current could be mediated by a PKC-induced phosphorylation of the sodium channel, thus leading to a significant decrease in muscle excitability. PMID:21795525

Guillouet, Maité; Gueret, Gildas; Rannou, Fabrice; Giroux-Metges, Marie-Agnès; Gioux, Maxime; Arvieux, Charles C; Pennec, Jean-Pierre

2011-11-01

286

Involvement of uptake1 and uptake2 in terminating the cardiovascular activity of noradrenaline in normotensive and genetically hypertensive rats.  

PubMed Central

1. In pithed, pancuronium-treated rats, inhibition of Uptake1 with desmethylimipramine (2.5 mg/kg i.v.) increased the time course of the pressor response to vasomotor nerve stimulation (1 and 5 Hz for 5 sec) but not the time course of the pressor response to injected noradrenaline (10 and 50 ng i.v.). 2. Subsequent inhibition of Uptake2 with metanephrine (3 mg/kg, i.v.) did not affect the time course of responses to either vasomotor nerve stimulation or injected noradrenaline. 3. It is concluded that Uptake1 but not Uptake2 is important in terminating the activity of noradrenaline released from rat vasomotor nerves and that neither process inactivates intraluminal catecholamine. 4. By contrast, chronotropic responses of rat atria to adrenergic nerve stimulation were prolonged by blockade of both Uptake1 and Uptake2, in agreement with previous evidence for involvement of both processes in terminating sino-atrial adrenergic responses. 5. Animals from the Otago strain of genetically hypertensive animals were identical to normotensives in their vascular handling of catecholamine. However, they lacked an atrial Uptake2 process. 6. This defect may be related to the high resting heart rate and abnormal cardiac catecholamine turnover observed to exist in the Otago hypertensive rats. PMID:722583

Bell, C; Kushinsky, R

1978-01-01

287

Enzymatic activities involved in the DNA resynthesis step of nucleotide excision repair are firmly attached to chromatin.  

PubMed Central

In this study the role of nuclear architecture in nucleotide excision repair (NER) was investigated by gentle dismantling of the cell and probing the capability of chromatin to carry out repair in vitro. The rationale behind this approach is that compartmentalization of NER at nuclear structures would make the enzymatic activities refractory to extraction by buffers that solubilize cellular membranes. In order to obtain intact chromatin primary human fibroblasts were encapsulated in agarose microbeads and lysed in isotonic buffers containing the non-ionic detergent Triton X-100. Under these conditions the majority of cellular proteins diffuse out of the beads, but the remaining chromatin is able to replicate and to transcribe DNA in the presence of triphosphates and Mg2+. UV irradiation of confluent repair-proficient human fibroblasts prior to lysis stimulated the incorporation of deoxynucleotide triphosphates in Triton X-100-isolated chromatin, even under stringent lysis conditions. In addition, experiments with UV-sensitive xeroderma pigmentosum (complementation groups A and C) and Cockayne's syndrome fibroblasts (complementation group A) revealed that this repair synthesis was due to global genome repair activity. Transcription-coupled repair was only detectable in cells permeabilized by streptolysin O (SLO). Repair synthesis in Triton X-100-isolated chromatin amounted to 15% of the total repair synthesis as measured in SLO-permeabilized cells. To allow the detection of these activities in vitro, presynthesis complexes have to be formed in intact cells, indicating that chromatin from Triton X-100-lysed cells is unable to initiate NER in vitro. Our data indicate that the components involved in the resynthesis step of NER are tightly associated with chromatin. A substantial fraction of total proliferating cell nuclear antigen (PCNA), which is required for the resynthesis step in NER, has been reported to become Triton X-100 non-extractable and tightly associated with nuclear structures after UV irradiation of cells. We propose that Triton X-100-resistant repair synthesis might be mediated by this chromatin-bound fraction of total PCNA. PMID:9023118

Bouayadi, K; van der Leer-van Hoffen, A; Balajee, A S; Natarajan, A T; van Zeeland, A A; Mullenders, L H

1997-01-01

288

Active and Avoidant Coping and Coping Efficacy as Mediators of the Relation of Maternal Involvement to Depressive Symptoms among Urban Adolescents  

ERIC Educational Resources Information Center

Our study tested an extension of the social resource model in an urban sample of 129 African American and 114 European American adolescents. Maternal involvement was positively related to the use of active and avoidant coping strategies among youth of both ethnicities. Additionally, use of active coping strategies was related to greater coping…

Mosher, Catherine E.; Prelow, Hazel M.

2007-01-01

289

America Goes Back to School: A Place for Families and the Community. An Initiative of the Family Involvement Partnership for Learning. Partners' Activity Guide.  

ERIC Educational Resources Information Center

Noting the improvement in the quality of schools and education that occurs when parents are actively involved in their children's schools, this activity guide provides ways that parents can forge partnerships with schools on a variety of levels. Following an invitation from the United States Secretary of Education for parents to participate in the…

Family Involvement Partnership for Learning, Washington, DC.

290

Induction of Id-1 by FGF-2 involves activity of EGR-1 and sensitizes neuroblastoma cells to cell death.  

PubMed

Inhibitor of differentiation-1 (Id-1) is a member of helix-loop-helix (HLH) family of proteins that regulate gene transcription through their inhibitory binding to basic-HLH transcription factors. Similarly to other members of this family, Id-1 is involved in the repression of cell differentiation and activation of cell growth. The dual function of Id-1, inhibition of differentiation, and stimulation of cell proliferation, might be interdependent, as cell differentiation is generally coupled with the exit from the cell cycle. Fibroblast growth factor-2 (FGF-2) has been reported to play multiple roles in different biological processes during development of the central nervous system (CNS). In addition, FGF-2 has been described to induce "neuronal-like" differentiation and trigger apoptosis in neuroblastoma SK-N-MC cells. Although regulation of Id-1 protein by several mitogenic factors is well-established, little is known about the role of FGF-2 in the regulation of Id-1. Using human neuroblastoma cell line, SK-N-MC, we found that treatment of these cells with FGF-2 resulted in early induction of both Id-1 mRNA and protein. The induction occurs within 1 h from FGF-2 treatment and is mediated by ERK1/2 pathway, which in turn stimulates expression of the early growth response-1 (Egr-1) transcription factor. We also demonstrate direct interaction of Egr-1 with Id-1 promoter in vitro and in cell culture. Finally, inhibition of Id-1 expression results in G(2) /M accumulation of FGF-2-treated cells and delayed cell death. PMID:21506108

Passiatore, Giovanni; Gentilella, Antonio; Rom, Slava; Pacifici, Marco; Bergonzini, Valeria; Peruzzi, Francesca

2011-07-01

291

Activation of a positive feedback loop involving IL-6 and aromatase promotes intratumoral 17?-estradiol biosynthesis in endometrial carcinoma microenvironment.  

PubMed

Tumor-stroma interactions contribute greatly to intratumoral estrogen biosynthesis in endometrial carcinoma, but the mechanisms involved remain largely unknown. Previous study demonstrated that intratumoral aromatase upregulation in stromal cells participated in this process, but the specific aromatase-regulators have not been reported. In the present study, we found that aromatase expression in intratumoral stroma, but not in tumor epithelium, correlated positively with interleukin 6 (IL-6) expression in cancer epithelial cells by immunohistochemistry, which was confirmed using laser capture microdissection/real-time reverse transcription-PCR. With stimulation by exogenous IL-6, aromarase expression was increased in stromal cells not but not in cancer cells. Aromatase mRNA levels in endometrial cancer cells were not influenced by cocultivation with intratumoral stromal cells. When cocultured with 17?-estradiol (E2 )-treated cancer cells, aromatase mRNA in stromal cells was significantly elevated and increased IL-6 protein levels were detected in E2 -treated culture medium. Next, we demonstrated that E2 -induced IL-6 production was through cooperation between estrogen receptor ? and nuclear factor-kappa B. Furthermore, an IL-6 receptor blocking antibody could attenuate the upregulation of aromatase expression in stromal cells and the E2 concentration in coculture systems of cancer and stromal cells. The results were confirmed by an orthotopic nude endometrial carcinoma model in vivo. These studies elucidated the activation of a positive feedback loop, that is, IL-6 stimulated by E2 in endometrial cancer cells induced aromatase expression in stromal cells, promoting enhanced intratumoral E2 synthesis. Blocking of this tumor-stroma interaction may be a therapeutic strategy to overcome in situ estrogen biosynthesis in endometrial carcinoma. PMID:24347287

Che, Qi; Liu, Bin-Ya; Liao, Yun; Zhang, Hui-Juan; Yang, Ting-Ting; He, Yin-Yan; Xia, Yu-Hong; Lu, Wen; He, Xiao-Ying; Chen, Zheng; Wang, Fang-Yuan; Wan, Xiao-Ping

2014-07-15

292

The tef1 box, a ubiquitous cis -acting element involved in the activation of plant genes that are highly expressed in cycling cells  

Microsoft Academic Search

InArabidopsis thaliana, thetef1 box is acis-acting promoter element of the EF-1? A1 gene involved in the activation of transcription in meristematic tissues. The initiation of rootcalli in transgenicArabidopsis by 2,4-D shows that thetef1-dependent expression of theGUS reporter gene is not restricted to meristematic regions but involves all of the cycling cells. Hybridization experiments conducted usingArabidopsis cDNA clones organized in a

Farid Regad; Christine Hervé; Olivier Marinx; Bernard Lescure; Catherine Bergounioux; Dominique Tremousaygue

1995-01-01

293

The use of parent involved take-home science activities during student teaching: Understanding the challenges of implementation  

NASA Astrophysics Data System (ADS)

The purpose of this study was to identify student teachers use and implementation of Science in a Bag when it was no longer a required course-based assessment. This take-home science activity acted as the elaboration component of the 5Es lesson teacher candidates designed and taught in the classroom, utilized household items, and directly involved parents in their child's education. The purposeful sample was comprised of six teacher candidates during their student teaching practicum, the last semester of the childhood education teacher certification program. This collective case study centered on student teachers' use of the focused activity, Science in a Bag, in order to gain knowledge of challenges faced in applying take-home science kits and working with parents. Data collection was comprised of student teacher and parent interviews, candidate reflections, as well as in-class observations and discussions carried out during weekly seminars. Data collection occurred throughout the seven-week student teaching practicum. The four research questions were: 1) What factors do teacher candidates identify as interfering with their ability to implement Science in a Bag during student teaching placements? 2) What factors do teacher candidates identify as enhancing their ability to carry out Science in a Bag? 3) What forms of support do teacher candidates believe are important to their success in implementing Science in a Bag during student teaching? 4) How do teacher candidates deal with obstacles when implementing Science in a Bag? Despite the fact that no student teacher was prohibited from implementing Science in a Bag, the level to which candidates valued and utilized this instructional strategy varied compared to how they were taught and practiced it during the science methods course. Some student teachers attempted to hide their feelings toward Science in a Bag, however their actions revealed that they were simply carrying out the instructional strategy because they had agreed to implement it, not because they appreciated its worth to students and their families. Altering candidate beliefs in one semester prior to student teaching proved difficult, especially when cooperating teachers were demonstrating and encouraging methodologies which were frowned upon during the science methods coursework. Therefore, this study also raised issues with teacher education and identified the need to better align educational philosophies taught throughout the program and those showcased by cooperating teachers if science education reform is to transpire. Teacher candidates very often abandoned the inquiry-based modes of instruction taught to them during the science methods course prior to student teaching and replaced them with ideas and suggestions from their cooperating teacher, approaches which were more traditional and teacher-centered. Cooperating teacher opinions and suggestions appeared to take precedence over what was taught and practiced during their preparation coursework. Candidates' prior beliefs and experiences with education appeared to dominate their teaching repertoire. The culmination of their own K-12 education and much of their undergraduate courses made altering their beliefs toward inquiry-based methodologies difficult during only one semester prior to student teaching. Therefore, all candidates reverted back to some level of teacher-centered, recipe-like science lessons and tasks. It was also noted that the candidates' understanding of hands-on versus inquiry learning was often blurred. Hands-on learning was often demonstrated and applauded by cooperating teachers, as well as parents, once they responded to Science in a Bag surveys and interviews, further supporting this misconception by praising hands-on learning and in some cases stating it was the way students learned best. Most parents were willing to and enjoyed performing these take-home family activities. Some of the most frequent parent comments related to family time, being informed about the content their child was learning in school and the child taking on

Zarazinski, Jill

294

Tibia tumor-induced cancer pain involves spinal p38 mitogen-activated protein kinase activation via TLR4-dependent mechanisms.  

PubMed

Molecular mechanisms underlying bone cancer pain are poorly understood. Recently, p38 mitogen-activated protein kinase (MAPK) activation was shown to play a major role not only in the production of proinflammatory cytokines but also in the progression of inflammatory and neuropathic pain. We have demonstrated that tactile allodynia and spontaneous pain of female rats with tibia tumors were correlated with the increase of both phosphorylated-p38MAPK (p-p38MAPK) and proinflammatory cytokines (IL-1beta and TNF-alpha) in the spinal cord 6 days after Walker 256 cells' inoculation. This change was specific to bone cancer pain because rats without tibia tumors failed to show such an increase. On the other hand, a 3-day administration [4 microg/rat/day, intrathecally (i.t.)] of 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole (SB203580), an inhibitor of p38MAPK, could suppress tactile allodynia and spontaneous pain of the bone cancer pain rats and decrease the phosphorylation of p38 as well as the expression of IL-1beta and TNF-alpha. To characterize the cellular events upstream of p38MAPK, we have examined the role of the toll-like receptor 4 (TLR4), which had been suggested to be involved in pain hypersensitivity. We found that prolonged knockdown of TLR4 during the 3-day administration of TLR4 small interfering RNA (siRNA; 2 microg/rat/day, i.t.) could attenuate hyperalgesia developed by Walker 256 cells' inoculation and decrease the phosphorylation of p38 as well as the increase of IL-1beta and TNF-alpha expression. These results demonstrate that TLR4-dependent phosphorylation of p38MAPK in spinal cord of rats might contribute to the development and maintenance of bone cancer pain, and p38MAPK and TLR4 would possibly be the potential targets for pain therapy. PMID:20478276

Liu, Silan; Yang, Jianping; Wang, Lina; Jiang, Miao; Qiu, Qiaocheng; Ma, Zhenni; Liu, Lei; Li, Caifang; Ren, Chunguang; Zhou, Jin; Li, Wei

2010-07-30

295

75 FR 10526 - In the Matter of Mr. Lawrence E. Grimm; Order Prohibiting Involvement in NRC-Licensed Activities  

Federal Register 2010, 2011, 2012, 2013

...identified, with two examples, involving the dosimetry program and the security of materials...These procedures included NIST's Dosimetry Program Procedures HPI 2-1 through...was no program in place for providing dosimetry to frequent users of the...

2010-03-08

296

Estrous cycle-dependent activity of neutrophils in the porcine endometrium: possible involvement of heat shock protein 27 and lactoferrin.  

PubMed

Neutrophil infiltration into the porcine endometrium is thought to be a specific feature during the follicular phase of the estrous cycle. To specify the localization and distribution of neutrophil granulocytes at different stages of the estrous cycle, porcine uterine samples were evaluated by immunohistochemical methods using anti-bovine lactoferrin (LF) antibody. Additionally, blood samples were collected from 30 pigs at different stages of the estrous cycle with a special focus on peri-estrous phase. Manual 100-cell differential counts were performed on routinely stained blood smears and evaluated statistically. Finally, the expression of granulocyte-colony-stimulating factor (G-CSF) and heat shock protein 27 (HSP 27), which are known to influence activation of the neutrophilic granulocytic lineage, was analyzed in porcine uteri using immunohistochemistry. Results show that LF is expressed regularly in the cytoplasm of neutrophil granulocytes. An increasing infiltration of subepithelial neutrophils was detected in the follicular phase. The highest number of intra- and subepithelial LF-positive cells was found on d 2 of the estrous cycle. Maximum level was followed by a strong decrease on d 3. Blood analysis revealed that the percentage of neutrophil granulocytes was significantly lower at d 2 (26.2+/-11.1%) than d 1 (42.1+/-11%) of the estrous cycle. HSP 27 staining was predominantly localized to luminal epithelium (LE) and glandular epithelium (GE) depending on stage of the estrous cycle. Strong immunostaining of HSP 27 is only found in LE during estrus. At d 2 of the estrous cycle, HSP 27 immunoreactivity in LE and superficial GE is reduced but moderate staining is found in deep GE. G-CSF immunostaining is uniformly not detected in endometrial cells of cyclic pigs. In conclusion, there is a clinically relevant relationship between neutrophil count in the blood and neutrophil infiltrate in the endometrium of the pig during the estrous cycle. This association may reflect the possibility of translocation of neutrophils from the blood to the endometrium up to d 2 of the estrous cycle. Additionally, HSP 27 could be a good candidate involved in migration and/or function of neutrophils within the porcine endometrium. PMID:20541878

Steffl, M; Telgen, L; Schweiger, M; Amselgruber, W M

2010-08-01

297

In vitro and in vivo biological activity screening of Ru(III) complexes involving 6-benzylaminopurine derivatives with higher pro-apoptotic activity than NAMI-A.  

PubMed

A series of novel octahedral ruthenium(III) complexes involving 6-benzylaminopurine (L) derivatives as N-donor ligands has been prepared by the reaction of [(DMSO)(2)H][trans-RuCl(4)(DMSO)(2)] with the corresponding L derivative. The complexes 1-12 have the general compositions trans-[RuCl(4)(DMSO)(n-Cl-LH)]?xSol (1-3), trans-[RuCl(4)(DMSO)(n-Br-LH)]·xSol (4-6), trans-[RuCl(4)(DMSO)(n-OMe-LH)]·xSol (7-9) and trans-[RuCl(4)(DMSO)(n-OH-LH)]·xSol (10-12); n=2, 3, and 4, x=0-1.5; and Sol = H(2)O, DMSO, EtOH and/or (Me)(2)CO. The complexes have been thoroughly characterized by elemental analysis, UV-visible, FTIR, Raman, and EPR spectroscopy, ES+(positive ionization electrospray) mass spectrometry, thermal analysis, cyclic voltammetry, magnetic and conductivity measurements. The X-ray molecular structure of trans-[RuCl(4)(DMSO)(3-Br-LH)]?(Me)(2)CO (5) revealed the distorted octahedral coordination in the vicinity of the central atom, and also confirmed that the 3-Br-L ligand is present as the N3-protonated N7-H tautomer and is coordinated to Ru(III) through the N9 atom of the purine moiety. The tested complexes have been found to be in vitro non-cytotoxic against K562, G361, HOS and MCF7 human cancer cell lines with IC(50)>100?M in contrast to the moderate results regarding the antiradical activity with IC(50)?10(-3)M. On the contrary, in vivo antitumor activity screening showed that the prepared Ru(III) complexes possess higher pro-apoptotic activity than NAMI-A. The reduction of Ru(III) to Ru(II) and Ru(II)-species formation in tumor tissues was confirmed by means of a simple method of detection and visualization of intracellular Ru(II) by fluorescence microscopy. The originality of this method is based on the preparation of a Ru(II)-bipyridine complex in situ. PMID:21536006

Trávní?ek, Zden?k; Matiková-Mal'arová, Miroslava; Novotná, Radka; Van?o, Ján; St?pánková, Kamila; Suchý, Pavel

2011-07-01

298

Lung involvement at presentation predicts disease activity and permanent organ damage at 6, 12 and 24 months follow?-?up in ANCA?-?associated vasculitis  

PubMed Central

Background Antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV) may present with pulmonary involvement ranging from mild to life-threatening disease such as diffuse alveolar hemorrhage. There is a paucity of information regarding morbidity outcomes for AAV subjects presenting with lung involvement. This study determines the relationship between disease activity and damage in these subjects using the Birmingham Vasculitis Activity Score v 3 (BVAS 3) and Vasculitis Damage Index (VDI) respectively. Results 151 patients with AAV were included with 59 presenting initially with pulmonary involvement. The initial BVAS scores recorded at time of diagnosis were positively correlated with the final VDI scores at 24 months (p?involvement group only, BVAS scores were significantly higher at 6, 12 and 24 months whilst the VDI scores were significantly higher at 12 and 24 months. Subjects presenting with pulmonary involvement had an increased likelihood for cardiovascular (OR 1.31, 95% CI 0.89, 1.54; p?=?0.032) and renal (OR 1.32, 95% CI 1.22, 1.39; p?=?0.005) involvement. Subjects presenting with lung involvement with granulomatosis with polyangiitis and microscopic polyangiitis had 24-month VDI scores that were significantly higher (p?=?0.027, p?=?0.045), and more likely to develop pulmonary fibrosis (OR 1.79, 95% CI 1.48, 2.12; p?involvement at presentation had a higher disease activity and damage scores at 6, 12 and 24 months follow-up representing a considerable burden of disease despite improvement in overall survival due to the introduction of immunosuppressive therapy. PMID:24884372

2014-01-01

299

Differential Involvement of Excitatory and Inhibitory Neurons of Cat Motor Cortex in Coincident Spike Activity Related to Behavioral Context  

E-print Network

To assess temporal associations in spike activity between pairs of neurons in the primary motor cortex (MI) related to different behaviors, we compared the incidence of coincident spiking activity of task-related (TR) and ...

Putrino, David F.

300

Involvement of the paraventricular nucleus of the hypothalamus in the pressor response to chemoreflex activation in awake rats  

Microsoft Academic Search

Chemoreflex activation with potassium cyanide (KCN, i.v.) produces pressor and bradycardic responses in awake rats in addition to the tachypneic response. In the present study we evaluated the role of the paraventricular nucleus of the hypothalamus (PVN) in the cardiovascular responses to chemoreflex activation in awake rats. Bilateral electrolytic lesion of the PVN was performed 1 day before chemoreflex activation

Marcelo V. Olivan; Leni G. H. Bonagamba; Benedito H. Machado

2001-01-01

301

41 CFR 102-74.495 - If a permit involves demonstrations or activities that may lead to civil disturbances, what...  

Code of Federal Regulations, 2010 CFR

...or activities that may lead to civil disturbances, what action must a Federal agency...or activities that may lead to civil disturbances, what action must a Federal agency...or activities that may lead to civil disturbances. Disapproval of Applications...

2010-07-01

302

Cyclooxygenase pathway is involved in the vascular reactivity and inhibition of the Na +, K +ATPase activity in the tail artery from L-NAME-treated rats  

Microsoft Academic Search

L-NAME (LN) induces hypertension by blocking nitric oxide (NO) synthesis. It produces vascular hyperreactivity to phenylephrine (PHE) associated with a reduced vascular Na+, K+-ATPase activity. The aim of this work was to investigate whether products of the cyclooxygenase pathway are involved in alterations of vascular reactivity and Na+-pump activity in the tail artery from LN-induced hypertension rats. Four groups of

Leonardo dos Santos; Fabiano E Xavier; Dalton V Vassallo; Luciana V Rossoni

2003-01-01

303

Exercise-induced changes in expression and activity of proteins involved in insulin signal transduction in skeletal muscle: Differential effects on insulin-receptor substrates 1 and 2  

Microsoft Academic Search

Level of physical activity is linked to improved glucose homeostasis. We determined whether exercise alters the expression and\\/or activity of proteins involved in insulin-signal transduction in skeletal muscle. Wistar rats swam 6 h per day for 1 or 5 days. Epitrochlearis muscles were excised 16 h after the last exercise bout, and were incubated with or without insulin (120 nM).

Alexander V. Chibalin; Mei Yu; Jeffrey W. Ryder; Xiao Mei Song; Dana Galuska; Anna Krook; Harriet Wallberg-Henriksson; Juleen R. Zierath

2000-01-01

304

EGF receptor is involved in WNT3a-mediated proliferation and motility of NIH3T3 cells via ERK pathway activation.  

PubMed

WNT3a stimulates proliferation of NIH3T3 cells via activation of the extracellular signal-regulated kinase (ERK) pathway. The RAF-1-->MEK-->ERK cascade was immediately increased by WNT3a treatment, however, the upstream event triggering ERK pathway activation by WNT3a is not clear. WNT3a activated RAS and WNT3a-induced ERK activation was blocked by dominant-negative RAS, indicating that WNT3a might act upstream of RAS. WNT3a-induced ERK pathway activations were blocked by AG1478, the epidermal growth factor receptor (EGFR) inhibitor, and EGFR siRNA. The WNT3a-induced ERK pathway activation was not observed in fibroblasts retaining defective EGFR, but the WNT3a effect was restored by EGFR reconstitution. These results indicate involvement of EGFR in the WNT3a-induced ERK pathway activation. WNT3a-induced motility and cytoskeletal rearrangement as well as proliferation of NIH3T3 cells were blocked by AG1478 and EGFR siRNA or abolished in EGFR knock-out fibroblasts, indicating involvement of EGFR in those cellular processes. WNT3a-induced ERK pathway activation was not affected by Dickkoff-1 (DKK-1), although WNT3a-induced activations of the WNT/beta-catenin pathway and proliferation were reduced by DKK-1. EGFR is involved in WNT3a-induced proliferation via both routes dependent on and independent of the WNT/beta-catenin pathway. These results indicate that WNT3a stimulates proliferation and motility of NIH3T3 fibroblasts via EGFR-mediated ERK pathway activation. PMID:17374561

Kim, Sung-Eun; Choi, Kang-Yell

2007-07-01

305

On Involvement.  

ERIC Educational Resources Information Center

Involvement Ratings In Settings (IRIS), a multi-dimensional non-verbal scale of involvement adaptable to a time-sampling method of data collection, was constructed with the aid of the videotapes of second-grade Follow Through classrooms made by CCEP. Scales were defined through observations of involved and alienated behavior, and the IRIS was…

Greene, Michael B.

306

Spatial working memory learning in young male and female rats: Involvement of different limbic system regions revealed by cytochrome oxidase activity  

Microsoft Academic Search

Sex differences have been found in the spatial memory which involve several regions of the limbic system. The Morris water maze (MWM) is one of the most widely used tasks in behavioral neuroscience to explore spatial and episodic memory in rats. We evaluated the oxidative metabolic activity of the prefrontal cortex, dorsal hippocampus, anterior thalamic nuclei and mammillary region following

Magdalena Méndez-López; Marta Méndez; Laudino López; Jorge L. Arias

2009-01-01

307

Active site characterization of RNase Rs from Rhizopus stolonifer: involvement of histidine and lysine in catalysis and carboxylate in substrate binding  

Microsoft Academic Search

Chemical modification studies on purified RNase Rs revealed the involvement of a single histidine, lysine and carboxylate residue in the catalytic activity of the enzyme. RNA could not protect the enzyme against DEP- and TNBS-mediated inactivation whereas, substrate protection was observed in case of EDAC-mediated inactivation of the enzyme. Km and kcat values of the partially inactivated enzyme samples suggested

Srinivasan Rangarajan; Rohini Chacko; Vepatu Shankar

1999-01-01

308

The Association of Attendance at Religious Services and Involvement in Church/Religious Activities and Youth Assets, by Gender, with Youths Engagement in Sexual Intercourse  

ERIC Educational Resources Information Center

Purpose: Previous research has shown that religion plays a role in the lives of many youths. This paper aims to extend previous research and examine attendance at religious services and involvement in religious/church activities as separate items to determine if one aspect was more strongly associated with never having had sexual intercourse among…

Mueller, Trisha; Bensyl, Diana; Vesely, Sara K.; Oman, Roy F.; Aspy, Cheryl B.

2010-01-01

309

The Memory-Impairing Effects of Septal GABA Receptor Activation Involve GABAergic Septo-Hippocampal Projection Neurons  

ERIC Educational Resources Information Center

Septal infusions of the [gamma]-aminobutyric acid (GABA)[subscript A] agonist muscimol impair memory, and the effect likely involves the hippocampus. GABA[subscript A] receptors are present on the perikarya of cholinergic and GABAergic septo-hippocampal (SH) projections. The current experiments determined whether GABAergic SH projections are…

Krebs-Kraft, Desiree L.; Wheeler, Marina G.; Parent, Marise B.

2007-01-01

310

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

...applicants or other non-Federal entities, require some form of Federal approval. Pursuant to the Export-Import Bank Act of 1945, as amended, Eximbank is asked to provide financing for transactions involving exports of U.S. goods and services for...

2014-01-01

311

Contractile Activity Regulates Isoform Expression and Polysialylation of NCAM in Cultured Myotubes: Involvement of Ca 2+ and Protein Kinase C  

Microsoft Academic Search

Muscle development involves a series of complex cell-cell interactions that are mediated, at least in part, by several different cell adhesion mole- cules. Previous work from this lab showed that the dif- ferent isoforms of NCAM and its level of polysialyla- tion are developmentally regulated during chick myogenesis in vivo and that this regulation is important for normal muscle development.

Victor F. Rafuse; Lynn Landmesser

1996-01-01

312

Mechanisms Involved in the Pathogenesis of Sepsis Are Not Necessarily Reflected by In Vitro Cell Activation Studies  

Microsoft Academic Search

It is thought that lipopolysaccharide (LPS) from gram-negative bacteria contributes significantly to the pathogenesis of septic shock. In vitro studies to address the mechanisms involved in this process have often investigated human monocytes or mouse macrophages, since these cells produce many of the mediators found in septic patients. Targeting of these mediators, especially tumor necrosis factor alpha (TNF-a), has been

CLAUDIA R. AMURA; R. SILVERSTEIN; D. C. MORRISON

1998-01-01

313

The involvement of hydrogen peroxide in abscisic acid-induced activities of ascorbate peroxidase and glutathione reductase in rice roots  

Microsoft Academic Search

We have monitored the changes in antioxidant enzyme activities and H2O2 concentrations in roots of rice (Oryza sativa L., cv. Taichung Native 1) seedlings treated with exogenous abscisic acid(ABA). Decrease in superoxide dismutase (SOD) and catalase (CAT) activities was observed in rice roots in the presence of ABA. However, ascorbate peroxide (APX) and glutathione reductase (GR) activities were increased after

Yu-Chang Tsai; Ching Huei Kao

2004-01-01

314

Possible mechanisms of the involvement of dopaminergic cells and cholinergic interneurons in the striatum in the conditioned-reflex selection of motor activity.  

PubMed

A possible mechanism for the involvement of cholinergic interneurons in the striatum and dopaminergic cells in the substantia nigra in the selection from among several types of motor activity during learning is proposed. Selection is triggered by simultaneous increases in the activity of dopaminergic neurons and a pause in the activity of cholinergic interneurons in response to the conditioned signal. The appearance of the pause may facilitate activation of GABAergic interneurons in the striatum and the action of dopamine on D2 receptors on cholinergic interneurons. Differently directed changes in dopamine and acetylcholine levels synergistically modulate the efficiency of corticostriatal inputs, such that the rules for modulation of the "strong" and "weak" inputs are opposite in sign. The subsequent reorganization of neuron activity in the cortex-basal ganglia-thalamus-cortex circuit leads to increased activity in those cortical neurons providing "strong" innervation to the striatum with simultaneous decreases in the activity of neurons providing "weak" innervation to the striatum, which may underlie the selection of the movement reaction, in which the neocortex is involved. It follows from this model that if the delay between the conditioned and unconditioned stimuli is not longer than the latent period of the reactions of dopaminergic and cholinergic cells (about 100 msec), selection of movement activity in response to the conditioned signal and learning is hindered. PMID:16380830

Sil'kis, I G

2006-02-01

315

Effects of pituitary adenylate cyclase polypeptide (PACAP) on extinction of active avoidance learning in rats: involvement of neurotransmitters  

Microsoft Academic Search

The effects of PACAP-38 on the extinction of active avoidance learning were studied in rats. The action of transmitter mediation was followed by pretreating the animals with appropriate receptor antagonists.PACAP-38 administered into the lateral brain ventricle caused a transitory facilitation of the extinction of a learned active avoidance response at 3 and 6 h following extinction, which had returned to

Agnes Adamik; Gyula Telegdy

2005-01-01

316

Peroxisomal localization and activation by bivalent metal ions of ureidoglycolate lyase, the enzyme involved in urate degradation in Candida tropicalis  

SciTech Connect

Ureidoglycolate lyase was found only in the peroxisomes in urate-induced Candida tropicalis. The enzyme was markedly activated by the bivalent metal ions Mn/sup 2 +/, Fe/sup 2 +/, and Ni/sup 2 +/. The activation by Mn/sup 2 +/ was suggested to be the result of its binding to the apoenzyme.

Takada, Y.; Tsukiji, N.

1987-05-01

317

The Role of Intentional Self Regulation, Lower Neighborhood Ecological Assets, and Activity Involvement in Youth Developmental Outcomes  

ERIC Educational Resources Information Center

Extracurricular activities provide a key context for youth development, and participation has been linked with positive developmental outcomes. Using data from the 4-H Study of Positive Youth Development (PYD), this study explored how the intentional self regulation ability of youth interacted with participation in extracurricular activities to…

Urban, Jennifer Brown; Lewin-Bizan, Selva; Lerner, Richard M.

2010-01-01

318

Involvement of cAMP/EPAC/TRPM2 activation in glucose- and incretin-induced insulin secretion.  

PubMed

In pancreatic ?-cells, closure of the ATP-sensitive K(+) (K(ATP)) channel is an initial process triggering glucose-stimulated insulin secretion. In addition, constitutive opening of background nonselective cation channels (NSCCs) is essentially required to effectively evoke depolarization as a consequence of K(ATP) channel closure. Thus, it is hypothesized that further opening of NSCC facilitates membrane excitability. We identified a class of NSCC that was activated by exendin (ex)-4, GLP-1, and its analog liraglutide at picomolar levels. This NSCC was also activated by increasing the glucose concentration. NSCC activation by glucose and GLP-1 was a consequence of the activated cAMP/EPAC-mediated pathway and was attenuated in TRPM2-deficient mice. The NSCC was not activated by protein kinase A (PKA) activators and was activated by ex-4 in the presence of PKA inhibitors. These results suggest that glucose- and incretin-activated NSCC (TRPM2) works in concert with closure of the KATP channel to effectively induce membrane depolarization to initiate insulin secretion. The current study reveals a new mechanism for regulating electrical excitability in ?-cells and for mediating the action of glucose and incretin to evoke insulin secretion, thereby providing an innovative target for the treatment of type 2 diabetes. PMID:24824430

Yosida, Masashi; Dezaki, Katsuya; Uchida, Kunitoshi; Kodera, Shiho; Lam, Nien V; Ito, Kiyonori; Rita, Rauza S; Yamada, Hodaka; Shimomura, Kenju; Ishikawa, San-e; Sugawara, Hitoshi; Kawakami, Masanobu; Tominaga, Makoto; Yada, Toshihiko; Kakei, Masafumi

2014-10-01

319

Youth Activity Involvement, Neighborhood Adult Support, Individual Decision Making Skills, and Early Adolescent Delinquent Behaviors: Testing a Conceptual Model  

ERIC Educational Resources Information Center

This study examines a cross-sectional structural equation model of participation in youth activities, neighborhood adult support, individual decision making skills, and delinquent behavior in urban middle school youths (n = 2611). Results indicate extracurricular activity participation had both direct and indirect associations with delinquent…

Crean, Hugh F.

2012-01-01

320

Involvement in Campus Activities and the Retention of First-Year College Students. The First-Year Experience Monograph Series.  

ERIC Educational Resources Information Center

The chapters of this monograph offer insights into educationally purposeful out-of-class activities and the impact they have on the student experience. It also provides future directions for the campus activities field and identifies ways to improve the educational experience of first-year students to enhance their scholarly experience and to…

Skipper, Tracy L., Ed.; Argo, Roxanne, Ed.

321

Inclusion of selected higher excitations involving active orbitals in the state-specific multireference coupled-cluster theory.  

PubMed

The parent state-specific multireference coupled-cluster (SS-MRCC) theory proposed by Mukherjee et al. [J. Chem. Phys. 110, 6171 (1999)], though rigorously size-extensive and also size-consistent with localized orbitals, has some deficiencies in the minimal truncation scheme, viz. at the singles and doubles (SD) level (SS-MRCCSD). SS-MRCCSD does not involve the direct coupling of all the model functions with a given virtual function belonging to the uncontracted multiconfiguration CISD space. It also does not involve, even in the linear power of a cluster operator T(?), the direct coupling of the virtual functions ?(l(?)), which are up to doubly excited with respect to a model function ?(?) to the other virtual functions of the MRCISD space which can be generated by triple and quadruple excitations from ?(?). We argue that inclusion of a selection of triples and quadruples involving at most two inactive orbital excitations from every ?(?) would ameliorate the shortcoming of the incomplete coupling of the triply and quadruply excited virtual functions which can couple with the singly and doubly excited ones. This extended ansatz for our SS-MRCC theory, to be called SS-MRCCSDtq by us, would still miss the direct coupling of the manifold of the model functions {?(?),? ? ?} to singly and doubly excited virtual functions. However, this effect is expected to be less significant than the lack of the more complete virtual space couplings, these functions being many more numerous, suggesting the new methods to be significantly improved schemes. Excellent results on the potential energy surfaces of small molecules involving single, double, and triple bond dissociation bear out our expectations fully. PMID:21186861

Das, Sanghamitra; Kállay, Mihály; Mukherjee, Debashis

2010-12-21

322

Support for harmful treatment and reduction of empathy toward blacks: “Remnants” of stereotype activation involving Hurricane Katrina and “Lil’ Kim”  

Microsoft Academic Search

Two experiments involving White participants tested the influence of media-based Black stereotypes on subsequent responses to Black and White persons-in-need. Experiment 1 showed that priming the “Black criminal” stereotype through exposure to photographs of Blacks looting after Hurricane Katrina produced greater application of the criminal stereotype and support for harmful treatment toward Black evacuees-in-need (i.e., police firing gun shots directly

James D. Johnson; Brad J. Bushman; John F. Dovidio

2008-01-01

323

The effect of celery and parsley juices on pharmacodynamic activity of drugs involving cytochrome P450 in their metabolism  

Microsoft Academic Search

Summary  Celery (Apium graveolens) and parsley (Petroselinum sativum), plants used worldwide in human nutrition, are the natural sources\\u000a of methoxsalen. In this study we investigated the effect of mice pretreatment with juices of this plants on the hypnotic action\\u000a of pentobarbital and analgesic action of paracetamol and aminopyrine, the drugs involving cytochrome P450 superfamily in their\\u000a metabolism. In mice pretreated with

V. Jakovljevic; A. Raskovic; M. Popovic; J. Sabo

2002-01-01

324

Involvement of mitogen-activated protein kinases and NF{kappa}B in LPS-induced CD40 expression on human monocytic cells  

SciTech Connect

CD40 is a costimulatory molecule linking innate and adaptive immune responses to bacterial stimuli, as well as a critical regulator of functions of other costimulatory molecules. The mechanisms regulating lipopolysaccharide (LPS)-induced CD40 expression have not been adequately characterized in human monocytic cells. In this study we used a human monocytic cell line, THP-1, to investigate the possible mechanisms of CD40 expression following LPS exposure. Exposure to LPS resulted in a dose- and time-dependent increase in CD40 expression. Further studies using immunoblotting and pharmacological inhibitors revealed that mitogen-activated protein kinases (MAPKs) and NF{kappa}B were activated by LPS exposure and involved in LPS-induced CD40 expression. Activation of MAPKs was not responsible for LPS-induced NF{kappa}B activation. TLR4 was expressed on THP-1 cells and pretreatment of cells with a Toll-like receptor 4 (TLR4) neutralizing antibody (HTA125) significantly blunted LPS-induced MAPK and NF{kappa}B activation and ensuing CD40 expression. Additional studies with murine macrophages expressing wild type and mutated TLR4 showed that TLR4 was implicated in LPS-induced ERK and NF{kappa}B activation, and CD40 expression. Moreover, blockage of MAPK and NF{kappa}B activation inhibited LPS-induced TLR4 expression. In summary, LPS-induced CD40 expression in monocytic cells involves MAPKs and NF{kappa}B.

Wu Weidong [Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina, Chapel Hill, North Carolina 27599 (United States)]|[Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina 27599 (United States)], E-mail: Weidong_Wu@med.unc.edu; Alexis, Neil E. [Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina, Chapel Hill, North Carolina 27599 (United States)]|[Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina 27599 (United States); Chen Xian [Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599 (United States)]|[Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599 (United States); Bromberg, Philip A. [Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina, Chapel Hill, North Carolina 27599 (United States)]|[Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599 (United States); Peden, David B. [Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina, Chapel Hill, North Carolina 27599 (United States)]|[Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina 27599 (United States)]|[Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599 (United States)

2008-04-15

325

Domains of the glucocorticoid receptor involved in specific and nonspecific deoxyribonucleic acid binding, hormone activation, and transcriptional enhancement.  

PubMed

We have analyzed the domain structure of the mouse glucocorticoid receptor by expression of in vitro mutated receptor in COS-7 cells. The receptor consists of a core domain rich in Cys, Lys, and Arg amino acids which can bind specific DNA sequences (glucocorticoid response elements) and activate transcription. The activity of this centrally located domain is modulated by the activity of the other two domains. The N-terminal domain of the receptor plays a role in decreasing nonspecific DNA binding and may therefore improve the ability of the protein to discriminate between specific and nonspecific DNA binding sites. This activity maps to a small, highly acidic region of the N-terminal domain. The C-terminal domain of the receptor contains the glucocorticoid binding site and in addition represses the transcriptional activity of the receptor in the absence of hormone. Hormone binding relieves the repression allowing transcription activation. The C-terminal domain contains a short sequence conserved among steroid receptors; its deletion yields a receptor that activates transcription in the absence of hormone. PMID:3153464

Danielsen, M; Northrop, J P; Jonklaas, J; Ringold, G M

1987-11-01

326

Severity of nicotine dependence modulates cue-induced brain activity in regions involved in motor preparation and imagery  

Microsoft Academic Search

Rationale  In nicotine-dependent subjects, cues related to smoking elicit activity in brain regions linked to attention, memory, emotion\\u000a and motivation. Cue-induced brain activation is associated with self-reported craving but further correlates are widely unknown.\\u000a \\u000a \\u000a \\u000a Objectives  This study was conducted to investigate whether brain activity elicited by smoking cues increases with severity of nicotine\\u000a dependence and intensity of cue-elicited craving.\\u000a \\u000a \\u000a \\u000a Methods  Ten healthy male

Michael N. Smolka; Mira Bühler; Sabine Klein; Ulrich Zimmermann; Karl Mann; Andreas Heinz; Dieter F. Braus

2006-01-01

327

Nitric oxide regulation of Na, K-ATPase activity in ocular ciliary epithelium involves Src family kinase.  

PubMed

The nitric oxide (NO) donor sodium nitroprusside (SNP) is known to reduce aqueous humor (AH) secretion in the isolated porcine eye. Previously, SNP was found to inhibit Na,K-ATPase activity in nonpigmented ciliary epithelium (NPE), AH-secreting cells, through a cGMP/protein kinase G (PKG)-mediated pathway. Here we show Src family kinase (SFK) activation in the Na,K-ATPase activity response to SNP. Ouabain-sensitive (86) Rb uptake was reduced by >35% in cultured NPE cells exposed to SNP (100 µM) or exogenously added cGMP (8-Br-cGMP) (100 µM) and the SFK inhibitor PP2 (10 µM) prevented the response. Ouabain-sensitive ATP hydrolysis was reduced by ~40% in samples detected in material obtained from SNP- and 8-Br-cGMP-treated cells following homogenization, pointing to an intrinsic change of Na,K-ATPase activity. Tyrosine-10 phosphorylation of Na,K-ATPase ?1 subunit was detected in SNP and L-arginine-treated cells and the response prevented by PP2. SNP elicited an increase in cell cGMP. Cells exposed to 8-Br-cGMP displayed SFK activation (phosphorylation) and inhibition of both ouabain-sensitive (86) Rb uptake and Na,K-ATPase activity that was prevented by PP2. SFK activation, which also occurred in SNP-treated cells, was suppressed by inhibitors of soluble guanylate cyclase (ODQ; 10 µM) and PKG (KT5823; 1 µM). SNP and 8-Br-cGMP also increased phosphorylation of ERK1/2 and p38 MAPK and the response prevented by PP2. However, U0126 did not prevent SNP or 8-Br-cGMP-induced inhibition of Na,K-ATPase activity. Taken together, the results suggest that NO activates guanylate cyclase to cause a rise in cGMP and subsequent PKG-dependent SFK activation. Inhibition of Na,K-ATPase activity depends on SFK activation. PMID:24037816

Shahidullah, Mohammad; Mandal, Amritlal; Wei, Guojun; Delamere, Nicholas A

2014-03-01

328

78 FR 66968 - In the Matter of Landon E. Brittain; Order Prohibiting Involvement In NRC-Licensed Activities...  

Federal Register 2010, 2011, 2012, 2013

...exhibiting unusual or aberrant behavior. Despite these requirements...coworker's unusual or aberrant behavior to his supervisor. III Due...to report the questionable behavior of his fellow employee, and...Mr. Brittain's apparent criminal activities related to the...

2013-11-07

329

“Apathetic, active, or antagonistic”: A history of the American Sociological Association’s involvement in high school sociology  

Microsoft Academic Search

The role that the American Sociological Association (ASA) has historically played in reforming high school sociology courses\\u000a has been alternately apathetic, active, or antagonistic. Apathy marked the time period between 1905 and about 1960, and again\\u000a during most of the 1970s and 1980s. The Association played a much more active role during the New Social Studies movement\\u000a of the 1960s,

Michael DeCesare

2004-01-01

330

Anti-inflammatory effects of ?-galactosylceramide analogs in activated microglia: involvement of the p38 MAPK signaling pathway.  

PubMed

Microglial activation plays a pivotal role in the development and progression of neurodegenerative diseases. Thus, anti-inflammatory agents that control microglial activation can serve as potential therapeutic agents for neurodegenerative diseases. Here, we designed and synthesized ?-galactosylceramide (?-GalCer) analogs to exert anti-inflammatory effects in activated microglia. We performed biological evaluations of 25 ?-GalCer analogs and observed an interesting preliminary structure-activity relationship in their inhibitory influence on NO release and TNF-? production in LPS-stimulated BV2 microglial cells. After identification of 4d and 4e as hit compounds, we further investigated the underlying mechanism of their anti-inflammatory effects using RT-PCR analysis. We confirmed that 4d and 4e regulate the expression of iNOS, COX-2, IL-1?, and IL-6 at the mRNA level and the expression of TNF-? at the post-transcriptional level. In addition, both 4d and 4e inhibited LPS-induced DNA binding activities of NF-?B and AP-1 and phosphorylation of p38 MAPK without affecting other MAP kinases. When we examined the anti-inflammatory effect of a p38 MAPK-specific inhibitor, SB203580, on microglial activation, we observed an identical inhibitory pattern as that of 4d and 4e, not only on NO and TNF-? production but also on the DNA binding activities of NF-?B and AP-1. Taken together, these results suggest that p38 MAPK plays an important role in the anti-inflammatory effects of 4d and 4e via the modulation of NF-?B and AP-1 activities. PMID:24523867

Jeong, Yeon-Hui; Kim, Yongju; Song, Heebum; Chung, Young Sun; Park, Seung Bum; Kim, Hee-Sun

2014-01-01

331

Direct Interaction between Nucleosome Assembly Protein 1 and the Papillomavirus E2 Proteins Involved in Activation of Transcription  

Microsoft Academic Search

Using a yeast two-hybrid screen, we identified human nucleosome assembly protein 1 (hNAP-1) as a protein interacting with the activation domain of the transcriptional activator encoded by papillomaviruses (PVs), the E2 protein. We show that the interaction between E2 and hNAP-1 is direct and not merely mediated by the transcriptional coactivator p300, which is bound by both proteins. Coexpression of

Manuela Rehtanz; Hanns-Martin Schmidt; Ursula Warthorst; Gertrud Steger

2004-01-01

332

Neural and sympathetic activity associated with exploration in decision-making: further evidence for involvement of insula  

PubMed Central

We previously reported that sympathetic activity was associated with exploration in decision-making indexed by entropy, which is a concept in information theory and indexes randomness of choices or the degree of deviation from sticking to recent experiences of gains and losses, and that activation of the anterior insula mediated this association. The current study aims to replicate and to expand these findings in a situation where contingency between options and outcomes is manipulated. Sixteen participants performed a stochastic decision-making task in which we manipulated a condition with low uncertainty of gain/loss (contingent-reward condition) and a condition with high uncertainty of gain/loss (random-reward condition). Regional cerebral blood flow was measured by 15O-water positron emission tomography (PET), and cardiovascular parameters and catecholamine in the peripheral blood were measured, during the task. In the contingent-reward condition, norepinephrine as an index of sympathetic activity was positively correlated with entropy indicating exploration in decision-making. Norepinephrine was negatively correlated with neural activity in the right posterior insula, rostral anterior cingulate cortex, and dorsal pons, suggesting neural bases for detecting changes of bodily states. Furthermore, right anterior insular activity was negatively correlated with entropy, suggesting influences on exploration in decision-making. By contrast, in the random-reward condition, entropy correlated with activity in the dorsolateral prefrontal and parietal cortices but not with sympathetic activity. These findings suggest that influences of sympathetic activity on exploration in decision-making and its underlying neural mechanisms might be dependent on the degree of uncertainty of situations.

Ohira, Hideki; Ichikawa, Naho; Kimura, Kenta; Fukuyama, Seisuke; Shinoda, Jun; Yamada, Jitsuhiro

2014-01-01

333

The Role of Intentional Self Regulation, Lower Neighborhood Ecological Assets, and Activity Involvement in Youth Developmental Outcomes  

Microsoft Academic Search

Extracurricular activities provide a key context for youth development, and participation has been linked with positive developmental\\u000a outcomes. Using data from the 4-H Study of Positive Youth Development (PYD), this study explored how the intentional self\\u000a regulation ability of youth interacted with participation in extracurricular activities to affect PYD among adolescents living\\u000a in neighborhoods with relatively low ecological assets. In

Jennifer Brown Urban; Selva Lewin-Bizan; Richard M. Lerner

2010-01-01

334

The FGL2/fibroleukin prothrombinase is involved in alveolar macrophage activation in COPD through the MAPK pathway  

SciTech Connect

Fibrinogen-like protein 2 (FGL2)/fibroleukin has been reported to play a vital role in the pathogenesis of some critical inflammatory diseases by possessing immunomodulatory activity through the mediation of 'immune coagulation' and the regulation of maturation and proliferation of immune cells. We observed upregulated FGL2 expression in alveolar macrophages from peripheral lungs of chronic obstructive pulmonary disease (COPD) patients and found a correlation between FGL2 expression and increased macrophage activation markers (CD11b and CD14). The role of FGL2 in the activation of macrophages was confirmed by the detection of significantly decreased macrophage activation marker (CD11b, CD11c, and CD71) expression as well as the inhibition of cell migration and inflammatory cytokine (IL-8 and MMP-9) production in an LPS-induced FGL2 knockdown human monocytic leukemia cell line (THP-1). Increased FGL2 expression co-localized with upregulated phosphorylated p38 mitogen-activated protein kinase (p38-MAPK) in the lung tissues from COPD patients. Moreover, FGL2 knockdown in THP-1 cells significantly downregulated LPS-induced phosphorylation of p38-MAPK while upregulating phosphorylation of c-Jun N-terminal kinase (JNK). Thus, we demonstrate that FGL2 plays an important role in macrophage activation in the lungs of COPD patients through MAPK pathway modulation.

Liu, Yanling; Xu, Sanpeng; Xiao, Fei; Xiong, Yan; Wang, Xiaojin; Gao, Sui; Yan, Weiming [Department and Institute of Infectious Disease, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030 (China)] [Department and Institute of Infectious Disease, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030 (China); Ning, Qin, E-mail: qning@tjh.tjmu.edu.cn [Department and Institute of Infectious Disease, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030 (China)] [Department and Institute of Infectious Disease, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030 (China)

2010-05-28

335

Cocoa protective effects against abnormal fat storage and oxidative stress induced by a high-fat diet involve PPAR? signalling activation.  

PubMed

A high-fat (HF) diet increases lipid storage and oxidative stress in mouse liver and this process seems to be mediated by Peroxisome Proliferator-Activated Receptor ? (PPAR?). In this study we evaluated the protective effect of cocoa against hepatic steatosis induced by a HF diet. The HF diet down-regulated PPAR? expression and turned off PPAR?-signalling, deregulated the ?-oxidation (?-Ox) system and catalase (CAT) activity, increased fat storage, reduced expression of enzymatic activity involved in oxidative defence in the liver and doubled the weight gain per calorie consumed compared to animals under the normal diet. In contrast, cocoa improved hepatic ?-Ox, activated PPAR?-signalling and up-regulated both gene and protein expression of SOD1. Moreover, when co-administered with the HF diet, cocoa treatment counteracted lipid storage in the liver, improved the lipid-metabolizing activity and oxidative stress defences and normalized the weight gain per calorie consumed. PMID:25214316

Fidaleo, Marco; Fracassi, Anna; Zuorro, Antonio; Lavecchia, Roberto; Moreno, Sandra; Sartori, Claudia

2014-10-22

336

Signaling through CD5 Activates a Pathway Involving Phosphatidylinositol 3-Kinase, Vav, and Rac1 in Human Mature T Lymphocytes  

PubMed Central

CD5 acts as a coreceptor on T lymphocytes and plays an important role in T-cell signaling and T-cell–B-cell interactions. Costimulation of T lymphocytes with anti-CD5 antibodies results in an increase of the intracellular Ca2+ levels, and subsequently in the activation of Ca2+/calmodulin-dependent (CaM) kinase type IV. In the present study, we have characterized the initial signaling pathway induced by anti-CD5 costimulation. The activation of phosphatidylinositol (PI) 3-kinase through tyrosine phosphorylation of its p85 subunit is a proximal event in the CD5-signaling pathway and leads to the activation of the lipid kinase activity of the p110 subunit. The PI 3-kinase inhibitors wortmannin and LY294002 inhibit the CD5-induced response as assessed in interleukin-2 (IL-2) secretion experiments. The expression of an inactivated Rac1 mutant (Rac1 · N17) in T lymphocytes transfected with an IL-2 promoter-driven reporter construct also abrogates the response to CD5 costimulation, while the expression of a constitutively active Rac1 mutant (Rac1-V12) completely replaces the CD5 costimulatory signal. The Rac1-specific guanine nucleotide exchange factor Vav is heavily phosphorylated on tyrosine residues upon CD5 costimulation, which is a prerequisite for its activation. A role for Vav in the CD5-induced signaling pathway is further supported by the findings that the expression of a dominant negative Vav mutant (Vav-C) completely abolishes the response to CD5 costimulation while the expression of a constitutively active Vav mutant [Vav(?1–65)] makes the CD5 costimulation signal superfluous. Wortmannin is unable to block the Vav(?1–65)- or Rac1 · V12-induced signals, indicating that both Vav and Rac1 function downstream from PI 3-kinase. Vav and Rac1 both act upstream from the CD5-induced activation of CaM kinase IV, since KN-62, an inhibitor of CaM kinases, and a dominant negative CaM kinase IV mutant block the Vav(?1–65)-and Rac1 · V12-mediated signals. We propose a model for the CD5-induced signaling pathway in which the PI 3-kinase lipid products, together with tyrosine phosphorylation, activate Vav, resulting in the activation of Rac1 by the Vav-mediated exchange of GDP for GTP. PMID:9488489

Gringhuis, Sonja I.; de Leij, Lou F. M. H.; Coffer, Paul J.; Vellenga, Edo

1998-01-01

337

Anesthetic activation of central respiratory chemoreceptor neurons involves inhibition of a THIK-1-like background K(+) current.  

PubMed

At surgical depths of anesthesia, inhalational anesthetics cause a loss of motor response to painful stimuli (i.e., immobilization) that is characterized by profound inhibition of spinal motor circuits. Yet, although clearly depressed, the respiratory motor system continues to provide adequate ventilation under these same conditions. Here, we show that isoflurane causes robust activation of CO(2)/pH-sensitive, Phox2b-expressing neurons located in the retrotrapezoid nucleus (RTN) of the rodent brainstem, in vitro and in vivo. In brainstem slices from Phox2b-eGFP mice, the firing of pH-sensitive RTN neurons was strongly increased by isoflurane, independent of prevailing pH conditions. At least two ionic mechanisms contributed to anesthetic activation of RTN neurons: activation of an Na(+)-dependent cationic current and inhibition of a background K(+) current. Single-cell reverse transcription-PCR analysis of dissociated green fluorescent protein-labeled RTN neurons revealed expression of THIK-1 (TWIK-related halothane-inhibited K(+) channel, K(2P)13.1), a channel that shares key properties with the native RTN current (i.e., suppression by inhalational anesthetics, weak rectification, inhibition by extracellular Na(+), and pH-insensitivity). Isoflurane also increased firing rate of RTN chemosensitive neurons in urethane-anesthetized rats, again independent of CO(2) levels. In these animals, isoflurane transiently enhanced activity of the respiratory system, an effect that was most prominent at low levels of respiratory drive and mediated primarily by an increase in respiratory frequency. These data indicate that inhalational anesthetics cause activation of RTN neurons, which serve an important integrative role in respiratory control; the increased drive provided by enhanced RTN neuronal activity may contribute, in part, to maintaining respiratory motor activity under immobilizing anesthetic conditions. PMID:20610767

Lazarenko, Roman M; Fortuna, Michal G; Shi, Yingtang; Mulkey, Daniel K; Takakura, Ana C; Moreira, Thiago S; Guyenet, Patrice G; Bayliss, Douglas A

2010-07-01

338

Light modulated activity of root alkaline/neutral invertase involves the interaction with 14-3-3 proteins.  

PubMed

Alkaline/neutral invertases (A/N-Invs) are now recognized as essential proteins in plant life. They catalyze the irreversible breakdown of sucrose into glucose and fructose and thus supply the cells with energy as well as signaling molecules. In this study we report on a mechanism that affects the activity of the cytosolic invertase AtCINV1 (At-A/N-InvG or AT1G35580). We demonstrate that Ser547 at the extreme C-terminus of the AtCINV1 protein is a substrate of calcium-dependent kinases (CPK3 and 21) and that phosphorylation creates a high-affinity binding site for 14-3-3 proteins. The invertase as such has basal activity, but we provide evidence that interaction with 14-3-3 proteins enhances its activity. The analysis of three quadruple 14-3-3 mutants generated from six T-DNA insertion mutants of the non-epsilon family shows both specificity as well as redundancy for this function of 14-3-3 proteins. The strong reduction in hexose levels in the roots of one 14-3-3 quadruple mutant plant is in line with the activating function of 14-3-3 proteins. The physiological relevance of this mechanism that affects A/N-invertase activity is underscored by the light-induced activation and is another example of the central role of 14-3-3 proteins in mediating dark/light signaling. The nature of the light-induced signal that travels from the shoot to root and the question whether this signal is transmitted via cytosolic Ca(++) changes that activate calcium-dependent kinases, await further study. PMID:25256212

Gao, Jing; van Kleeff, Paula J M; Oecking, Claudia; Li, Ka Wan; Erban, Alexander; Kopka, Joachim; Hincha, Dirk K; de Boer, Albertus H

2014-12-01

339

Arsenic-induced alteration in intracellular calcium homeostasis induces head kidney macrophage apoptosis involving the activation of calpain-2 and ERK in Clarias batrachus  

SciTech Connect

We had earlier shown that exposure to arsenic (0.50 {mu}M) caused caspase-3 mediated head kidney macrophage (HKM) apoptosis involving the p38-JNK pathway in Clarias batrachus. Here we examined the roles of calcium (Ca{sup 2+}) and extra-cellular signal-regulated protein kinase (ERK), the other member of MAPK-pathway on arsenic-induced HKM apoptosis. Arsenic-induced HKM apoptosis involved increased expression of ERK and calpain-2. Nifedipine, verapamil and EGTA pre-treatment inhibited the activation of calpain-2, ERK and reduced arsenic-induced HKM apoptosis as evidenced from reduced caspase-3 activity, Annexin V-FITC-propidium iodide and Hoechst 33342 staining. Pre-incubation with ERK inhibitor U 0126 inhibited the activation of calpain-2 and interfered with arsenic-induced HKM apoptosis. Additionally, pre-incubation with calpain-2 inhibitor also interfered with the activation of ERK and inhibited arsenic-induced HKM apoptosis. The NADPH oxidase inhibitor apocynin and diphenyleneiodonium chloride also inhibited ERK activation indicating activation of ERK in arsenic-exposed HKM also depends on signals from NADPH oxidase pathway. Our study demonstrates the critical role of Ca{sup 2+} homeostasis on arsenic-induced HKM apoptosis. We suggest that arsenic-induced alteration in intracellular Ca{sup 2+} levels initiates pro-apoptotic ERK and calpain-2; the two pathways influence each other positively and induce caspase-3 mediated HKM apoptosis. Besides, our study also indicates the role of ROS in the activation of ERK pathway in arsenic-induced HKM apoptosis in C. batrachus. - Highlights: > Altered Ca{sup 2+} homeostasis leads to arsenic-induced HKM apoptosis. > Calpain-2 plays a critical role in the process. > ERK is pro-apoptotic in arsenic-induced HKM apoptosis. > Arsenic-induced HKM apoptosis involves cross talk between calpain-2 and ERK.

Banerjee, Chaitali [Immunobiology Laboratory, Department of Zoology, University of Delhi, Delhi 110 007 (India); Goswami, Ramansu [Immunobiology Laboratory, Department of Zoology, University of Delhi, Delhi 110 007 (India); Centre for Environmental Studies, Visva-Bharati University, Santiniketan 731 235 (India); Datta, Soma [Immunobiology Laboratory, Department of Zoology, University of Delhi, Delhi 110 007 (India); Rajagopal, R. [Gut Biology Laboratory, Department of Zoology, University of Delhi, Delhi 110 007 (India); Mazumder, Shibnath, E-mail: shibnath1@yahoo.co.in [Immunobiology Laboratory, Department of Zoology, University of Delhi, Delhi 110 007 (India)

2011-10-01

340

Cardioprotection induced by hydrogen sulfide preconditioning involves activation of ERK and PI3K\\/Akt pathways  

Microsoft Academic Search

We previously reported that hydrogen sulfide (H2S) preconditioning (SP) produces cardioprotective effects against ischemia in rat cardiac myocytes. The present study aims\\u000a to elucidate the signaling mechanisms involved in SP-induced cardioprotection by investigating the role of extracellular signal\\u000a regulated kinase (ERK1\\/2) and phosphatidylinositol 3-kinase (PI3K)\\/Akt. We found that preconditioning with NaHS (a H2S donor) for three cycles significantly decreased myocardial

Yeshi Hu; Xin Chen; Ting-Ting Pan; Kay Li Neo; Shiau Wei Lee; Ester Sandar Win Khin; Philip K. Moore; Jin-Song Bian

2008-01-01

341

Human synovial mast cell involvement in rheumatoid arthritis and osteoarthritis. Relationship to disease type, clinical activity, and antirheumatic therapy.  

PubMed

Mast cells were isolated by enzymatic digestion of synovium obtained from 48 patients with rheumatoid arthritis (RA) and 42 patients with osteoarthritis (OA). A significantly lower percentage of stainable synovial mast cells was obtained by tissue digestion from patients with clinically active RA compared with those with less active disease. The 54 patients treated with nonsteroidal antiinflammatory drugs had a significantly lower percentage of stainable synovial mast cells in cell suspension than did the other 36 patients. When anti-IgE antibody was used as a secretagogue in vitro, significantly greater histamine release was observed from synovial mast cells of RA patients compared with OA patients. Greater histamine release in response to anti-IgE was observed in the RA patients with more clinically active disease and those who were treated with prednisone, compared with RA patients without these features. Synovial mast cells of RA patients treated with a disease-modifying antirheumatic drug had a significantly lower mean histamine content than did cells from patients not receiving such treatment. Our data suggest that there are differences between synovial mast cells from tissues of patients with RA and OA and suggest that synovial mast cells may be activated in clinically active RA. In addition, the data indicate an effect of systemic antirheumatic therapy on mast cells isolated from synovium of patients with arthritis. PMID:1930330

Bridges, A J; Malone, D G; Jicinsky, J; Chen, M; Ory, P; Engber, W; Graziano, F M

1991-09-01

342

The Differential Effect of Toxoplasma Gondii Infection on the Stability of BCL2-Family Members Involves Multiple Activities  

PubMed Central

The regulation of mitochondrial permeability, a key event in the initiation of apoptosis is governed by the opposing actions of the pro- and anti-apoptotic members of the BCL2-family of proteins. The BCL2-family can be classified further based on the number of BCL-homology (BH) domains they encode. Pathogen mediated modulation of BCL2-family members play a significant role in their ability to affect the apoptotic pathways in the infected host cell. The protozoan parasite Toxoplasma gondii establishes a profound blockade of apoptosis noted by a requirement for host NF?B activity and correlating with the selective degradation of pro-apoptotic BCL2-family members. In this study, we explore the potential activities associated with the inherent stability of the anti-apoptotic BCL2 as well as the selective degradation of the pro-apoptotic proteins BAX, BAD, and BID. We find that multiple activities govern the relative stability of BCL2-family members suggesting a complex and balanced network of stability-enhancing and–destabilizing activities are perturbed by parasite infection. The data leave open the possibility for both parasite induced host activities as well as the direct consequence of parasite effectors in governing the relative levels of BCL2-proteins in the course of infection. PMID:21716958

Carmen, John Cherrington; Sinai, Anthony Peter

2011-01-01

343

Family Involvement.  

ERIC Educational Resources Information Center

Family involvement in schools will work only when perceived as an enlarged concept focusing on all children, including those from at-risk families. Each publication reviewed here is specifically concerned with family involvement strategies concerned with all children or targeted at primarily high risk students. Susan McAllister Swap looks at three…

Liontos, Lynn Balster

1992-01-01

344

OsPT2, a phosphate transporter, is involved in the active uptake of selenite in rice.  

PubMed

• Selenite is a predominant form of selenium (Se) available to plants, especially in anaerobic soils, but the molecular mechanism of selenite uptake by plants is not well understood. • ltn1, a rice mutant previously shown to have increased phosphate (Pi) uptake, was found to exhibit higher selenite uptake than the wild-type in both concentration- and time-dependent selenite uptake assays. Respiratory inhibitors significantly inhibited selenite uptake in the wildtype and the ltn1 mutant, indicating that selenite uptake was coupled with H(+) and energy-dependent. Selenite uptake was greatly enhanced under Pi-starvation conditions, suggesting that Pi transporters are involved in selenite uptake. • OsPT2, the most abundantly expressed Pi transporter in the roots, is also significantly up-regulated in ltn1 and dramatically induced by Pi starvation. OsPT2-overexpressing and knockdown plants displayed significantly increased and decreased rates of selenite uptake, respectively, suggesting that OsPT2 plays a crucial role in selenite uptake. Se content in rice grains also increased significantly in OsPT2-overexpressing plants. • These data strongly demonstrate that selenite and Pi share similar uptake mechanisms and that OsPT2 is involved in selenite uptake, which provides a potential strategy for breeding Se-enriched rice varieties. PMID:24491113

Zhang, Lianhe; Hu, Bin; Li, Wei; Che, Ronghui; Deng, Kun; Li, Hua; Yu, Feiyan; Ling, Hongqing; Li, Youjun; Chu, Chengcai

2014-03-01

345

Treg-mediated immunosuppression involves activation of the Notch-HES1 axis by membrane-bound TGF-?  

PubMed Central

Studies in humans and mice show an important role for Tregs in the control of immunological disorders. The mechanisms underlying the immunosuppressive functions of Tregs are not well understood. Here, we show that CD4+ T cells expressing Foxp3 and membrane-bound TGF-? (TGF-?m+Foxp3+), previously shown to be immunosuppressive in both allergic and autoimmune diseases, activate the Notch1–hairy and enhancer of split 1 (Notch1-HES1) axis in target cells. Soluble TGF-? and cells secreting similar levels of soluble TGF-? were unable to trigger Notch1 activation. Inhibition of Notch1 activation in vivo reversed the immunosuppressive functions of TGF-?m+Foxp3+ cells, resulting in severe allergic airway inflammation. Integration of the TGF-? and Notch1 pathways may be an important mechanism for the maintenance of immune homeostasis in the periphery. PMID:16543950

Ostroukhova, Marina; Qi, Zengbiao; Oriss, Timothy B.; Dixon-McCarthy, Barbara; Ray, Prabir; Ray, Anuradha

2006-01-01

346

Evidence that the effects of phospholipids on the activity of the Ca(2+)-ATPase do not involve aggregation.  

PubMed Central

The Ca(2+)-ATPase of skeletal-muscle sarcoplasmic reticulum, solubilized in monomeric from in C12E8, has been reconstituted by dialysis into sealed vesicles of dioleoyl phosphatidylcholine [di(C18:1)PC], dimyristoleoyl phosphatidylcholine [di(C14:1)PC], dinervonyl phosphatidylcholine [di(C24:1)PC] or dipalmitoyl phosphatidylcholine [di(C16:0)PC] in the gel phase, at a phospholipid/ATPase molar ratio of 10,000: 1. Cross-linking experiments show that ATPase molecules are present in these reconstituted vesicles as isolated monomeric species. ATPase activities for the reconstituted vesicles are about half of those for the ATPase reconstituted with the same lipid in unsealed membrane fragments, attributed to a close to random orientation for the ATPase molecules in the reconstituted vesicles. ATPase activities for the ATPase in reconstituted vesicles of di(C14:1)PC or di(C24:1)PC are less than in vesicles of di(C18:1)PC, and no activity could be detected for the ATPase in di(C16:0)PC in the gel phase. It is concluded that effects of lipids on the activity of the ATPase are independent of any changes in the state of aggregation of the ATPase. Inhibition of ATPase activity by spermine and by the hydrophilic domain of phospholamban are observed both for the unreconstituted ATPase and for the ATPase in reconstituted vesicles, so that inhibition is independent of any aggregation caused by these polycationic species. Stimulation of ATPase activity by jasmone is also observed both for the unreconstituted ATPase and for the ATPase in reconstituted vesicles, so that stimulation of the ATPase also does not follow from any change in the state of aggregation of the ATPase. Images Figure 1 Figure 2 PMID:7755584

Starling, A P; East, J M; Lee, A G

1995-01-01

347

Kallikrein-related Peptidase-8 (KLK8) Is an Active Serine Protease in Human Epidermis and Sweat and Is Involved in a Skin Barrier Proteolytic Cascade  

PubMed Central

Kallikrein-related peptidase-8 (KLK8) is a relatively uncharacterized epidermal protease. Although proposed to regulate skin-barrier desquamation and recovery, the catalytic activity of KLK8 was never demonstrated in human epidermis, and its regulators and targets remain unknown. Herein, we elucidated for the first time KLK8 activity in human non-palmoplantar stratum corneum and sweat ex vivo. The majority of stratum corneum and sweat KLK8 was catalytically active, displaying optimal activity at pH 8.5 and considerable activity at pH 5. We also showed that KLK8 is a keratinocyte-specific protease, not secreted by human melanocytes or dermal fibroblasts. KLK8 secretion increased significantly upon calcium induction of terminal keratinocyte differentiation, suggesting an active role for this protease in upper epidermis. Potential activators, regulators, and targets of KLK8 activity were identified by in vitro kinetic assays using pro-KLK8 and mature KLK8 recombinant proteins produced in Pichia pastoris. Mature KLK8 activity was enhanced by calcium and magnesium ions and attenuated by zinc ions and by autocleavage after Arg164. Upon screening KLK8 cleavage of a library of FRET-quenched peptides, trypsin-like specificity was observed with the highest preference for (R/K)(S/T)(A/V) at P1-P1?-P2?. We also demonstrated that KLK5 and lysyl endopeptidase activate latent pro-KLK8, whereas active KLK8 targets pro-KLK11, pro-KLK1, and LL-37 antimicrobial peptide activation in vitro. Together, our data identify KLK8 as a new active serine protease in human stratum corneum and sweat, and we propose regulators and targets that augment its involvement in a skin barrier proteolytic cascade. The implications of KLK8 elevation and hyperactivity in desquamatory and inflammatory skin disease conditions remain to be studied. PMID:20940292

Eissa, Azza; Amodeo, Vanessa; Smith, Christopher R.; Diamandis, Eleftherios P.

2011-01-01

348

Fiber composition, fiber size and enzyme activities in vastus lateralis of elite athletes involved in high intensity exercise  

Microsoft Academic Search

Summary  In order to determine the influence of an extensive history of participation in high intensity activity on muscle fiber type, fiber size, and metabolic profile, elite ice hockey players were selected for investigation from three different leagues. Biopsy samples from the vastus lateralis muscle were obtained from different groups of players prior to and following the season and compared with

H. J. Green; J. A. Thomson; W. D. Daub; M. E. Houston; D. A. Ranney

1979-01-01

349

Binding of Human Urokinase-Type Plasminogen Activator to Its Receptor Residues Involved in Species Specificity and Binding  

Microsoft Academic Search

Urokinase-type plasminogen activator (UPA), particularly when bound to its receptor (UPAR), is thought to play a major role in local proteolytic processes, thus facilitating cell migration as may occur during angiogenesis, neointima and atherosclerotic plaque formation, and tumor cell invasion. To facilitate understanding of the need and function of the UPA\\/UPAR interaction in cell migration and vascular remodeling, we changed

Paul H. A. Quax; Jos M. Grimbergen; Mirian Lansink; Arjen H. F. Bakker; Marie-Claude Blatter; Dominique Belin; Victor W. M. van Hinsbergh; Jan H. Verheijen

350

Pathogenic forms of tau inhibit kinesin-dependent axonal transport through a mechanism involving activation of axonal phosphotransferases.  

PubMed

Aggregated filamentous forms of hyperphosphorylated tau (a microtubule-associated protein) represent pathological hallmarks of Alzheimer's disease (AD) and other tauopathies. While axonal transport dysfunction is thought to represent a primary pathogenic factor in AD and other neurodegenerative diseases, the direct molecular link between pathogenic forms of tau and deficits in axonal transport remain unclear. Recently, we demonstrated that filamentous, but not soluble, forms of wild-type tau inhibit anterograde, kinesin-based fast axonal transport (FAT) by activating axonal protein phosphatase 1 (PP1) and glycogen synthase kinase 3 (GSK3), independent of microtubule binding. Here, we demonstrate that amino acids 2-18 of tau, comprising a phosphatase-activating domain (PAD), are necessary and sufficient for activation of this pathway in axoplasms isolated from squid giant axons. Various pathogenic forms of tau displaying increased exposure of PAD inhibited anterograde FAT in squid axoplasm. Importantly, immunohistochemical studies using a novel PAD-specific monoclonal antibody in human postmortem tissue indicated that increased PAD exposure represents an early pathogenic event in AD that closely associates in time with AT8 immunoreactivity, an early marker of pathological tau. We propose a model of pathogenesis in which disease-associated changes in tau conformation lead to increased exposure of PAD, activation of PP1-GSK3, and inhibition of FAT. Results from these studies reveal a novel role for tau in modulating axonal phosphotransferases and provide a molecular basis for a toxic gain-of-function associated with pathogenic forms of tau. PMID:21734277

Kanaan, Nicholas M; Morfini, Gerardo A; LaPointe, Nichole E; Pigino, Gustavo F; Patterson, Kristina R; Song, Yuyu; Andreadis, Athena; Fu, Yifan; Brady, Scott T; Binder, Lester I

2011-07-01

351

Vehicle design and speed and pedestrian injury: Australia's involvement in the International Harmonised Research Activities Pedestrian Safety Expert Group  

Microsoft Academic Search

Australia is contributing to the International Harmonised Research Activities Pedestrian Safety Expert Group (IHRA PSEG) through research undertaken at the Road Accident Research Unit, and funded by the Commonwealth Department of Transport and Regional Services. The IHRA PSEG is charged with the development of test procedures for assessing the protection afforded by the vehicle to a pedestrian in the event

Robert Anderson; Jack McLean

352

A model of involvement in work-related learning and development activity: the effects of individual, situational, motivational, and age variables.  

PubMed

Eight hundred employees from across the U.S. work force participated in a detailed 13-month longitudinal study of involvement in learning and development activities. A new model was posited and tested in which the hypothesized sequence was as follows: worker age --> individual and situational antecedents --> perceived benefits of participation and self-efficacy for development --> attitudes toward development --> intentions to participate --> participation. The results depict a person who is oriented toward employee development as having participated in development activities before, perceiving themselves as possessing qualities needed for learning, having social support for development at work and outside of work, being job involved, having insight into his or her career, and believing in the need for development, in his or her ability to develop skills and to receive intrinsic benefits from participating. Given the aging work force, a detailed treatment of age differences in development is presented. Implications for new ideas in practice and future research are discussed. PMID:12940410

Maurer, Todd J; Weiss, Elizabeth M; Barbeite, Francisco G

2003-08-01

353

The involvement of nitric oxide in the hemodynamic and metabolic activities of the brain and small intestine  

NASA Astrophysics Data System (ADS)

Nitric oxide is a mediator in many physiological processes including vasodilatation of blood vessels, neurotransmission and prevention of platelet aggregation. It has also a role in the pathophysiology of sepsis, hemorrhagic shock, various traumatic events and critical conditions involved with circulatory abnormalities. The last one is accompanied by blood flow redistribution and is considered to be the putative cause of altered oxygen metabolism in various pathophysiological conditions. The present study tested the involvement of NO in the brain as a vital organ versus the small intestine, a less vital organ using the non-specific nitric oxide synthase inhibitor L-NAME and exogenous NO donor - nitrite. The parameters that were simultaneously monitored in both organs included mean arterial blood pressure (MAP), tissue blood flow (TBF), using laser Doppler flowmetery and NADH fluorescence using the fluorometric technique. Three groups were tested. Group 1 - L-NAME +nitrite, group 2 - control L-NAME and group 3 - control nitrite. Following LNAME, MAP significantly increased and remained elevated through the entire experiment. TBF decreased in both organs with full recovery in the brain and no recovery in the intestine, whereas NADH showed no significant changes. Nitrite alone had no significant effect on the parameters in any of the organs. In group 1 the infusion of nitrite decreased the level of elevated MAP earlier induced by L-NAME. Nitrite also recovered the reduced TBF in the brain whereas it had no beneficial effect on intestinal blood flow indicating for its regulatory role in the brain but not in the intestine.

Tolmasov, M.; Barbiro-Michaely, E.; Mayevsky, A.

2009-02-01

354

Identification of active bacteria involved in decomposition of complex maize and soybean residues in a tropical Vertisol using 15N-DNA stable isotope probing  

Microsoft Academic Search

As limited information is available about the relationship between microbial processes and community structure in tropical soils, we used 15N-DNA stable isotope probing (15N-DNA-SIP) to identify bacteria actively involved in decomposition of plant residues of different biochemical quality. 15N-labeled (90atom%) and unlabeled (control) maize (C-to-N ratio: 32; cellulose content: 24.9%) and soybean (15; 15.5%) leaf residues were incubated in a

Mingrelia España; Frank Rasche; Ellen Kandeler; Thomas Brune; Belkis Rodriguez; Gary D. Bending; Georg Cadisch

2011-01-01

355

Involvement of conserved histidine, lysine and tyrosine residues in the mechanism of DNA cleavage by the caspase-3 activated DNase CAD  

Microsoft Academic Search

The caspase-activated DNase (CAD) is involved in DNA degradation during apoptosis. Chemical modifi- cation of murine CAD with the lysine-specific reagent 2,4,6-trinitrobenzenesulphonic acid and the tyrosine- specific reagent N-acetylimidazole leads to inactivation of the nuclease, indicating that lysine and tyrosine residues are important for DNA cleavage by this enzyme. The presence of DNA or the inhibitor ICAD-L protects the enzyme

Christian Korn; Sebastian Richard Scholz; Oleg Gimadutdinow; Alfred Pingoud; Gregor Meiss

2002-01-01

356

Brain oxytocin inhibits the (re)activity of the hypothalamo–pituitary–adrenal axis in male rats: involvement of hypothalamic and limbic brain regions  

Microsoft Academic Search

In response to various stressors, oxytocin is released not only into blood, but also within hypothalamic and extrahypothalamic limbic brain regions. Here, we describe the involvement of intracerebrally released oxytocin in the regulation of the activity of the hypothalamo–pituitary–adrenal (HPA) axis by infusion of the oxytocin receptor antagonist (des Gly-NH2d(CH2)5 [Tyr(Me)2, Thr4] OVT; pH 7.4; Dr. M. Manning, Toledo, OH,

Inga D Neumann; Simone A Krömer; Nicola Toschi; Karl Ebner

2000-01-01

357

Differential Regulation of Sphingosine1Phosphate and VEGF-Induced Endothelial Cell Chemotaxis Involvement of G i ? 2 Linked Rho Kinase Activity  

Microsoft Academic Search

We compared stimulus-coupling pathways involved in bovine pulmonary artery (PA) and lung microvascular endothelial cell migration evoked by sphingosine-1-phosphate (S1P), a potent bioactive lipid released from activated platelets, and by vascu- lar endothelial growth factor (VEGF), a well-recognized angio- genic factor. S1P-induced endothelial cell migration was maxi- mum at 1 ? M ( ? 8-fold increase with PA endothelium) and

Feng Liu; Alexander D. Verin; Peiyi Wang; Regina Day; Robert P. Wersto; Francis J. Chrest; Denis K. English; Joe G. N. Garcia

358

Involvement of NF-?B activation in the cisplatin resistance of human epidermoid carcinoma KCP-4 cells.  

PubMed

cis-Diamminedichloroplatinum II (cisplatin) is one of the most potent antitumor agents for the treatment of various types of cancer. In spite of its therapeutic usefulness, the intrinsic resistance acquired under continuous treatment limits its benefit in cancer therapy. KCP-4, a cisplatin-resistant cell line, was derived from human epidermoid carcinoma KB-3-1 cells. Since the accumulation of cisplatin in KCP-4 cells is markedly reduced by the presence of an efflux pump, this pump is thought to be related to cisplatin resistance of the KCP-4 cells. However, given that KCP-4 cells are tremendously resistant to cisplatin compared with KB-3-1 cells, it is possible that another mechanism exists. The aim of this study was to investigate whether the activation of nuclear factor-kappa B (NF-?B) contributes to the cisplatin resistance of KCP-4 cells. We used the level of translocated NF-?B into the nucleus, determined by immunoblot analysis, as the indicator of NF-?B activation. The activation level of NF-?B was higher in KCP-4 cells than in KB-3-1 cells. KCP-4 cells were treated with a combination of cisplatin and curcumin, an inhibitor of NF-?B activation, and the cell viabilities were subsequently determined by the MTT assay using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. In the presence of 10 µmol/l curcumin, we found that the sensitivity of KCP-4 cells to 100 and 300 µmol/l cisplatin was augmented. Additionally, curcumin reduced the activation levels of NF-?B in KCP-4 cells, and suppressed the expression levels of Bcl-2, Bcl-xL and survivin, which are apoptosis-related proteins regulated by NF-?B. Our results suggest that the high cisplatin resistance of KCP-4 cells compared with KB-3-1 cells results from multiple mechanisms other than increased cisplatin efflux, including the activation of NF-?B. PMID:22562377

Oiso, Shigeru; Ikeda, Ryuji; Nakamura, Kazuo; Takeda, Yasuo; Akiyama, Shin-Ichi; Kariyazono, Hiroko

2012-07-01

359

TLR9 and NF-?B Are Partially Involved in Activation of Human Neutrophils by Helicobacter pylori and Its Purified DNA  

PubMed Central

Helicobacter pylori infection represents one of the most common bacterial infections worldwide. The inflammatory response to this bacterium involves a large influx of neutrophils to the lamina propria of the gastric mucosa. However, little is known about the receptors and molecular mechanisms involved in activation of these neutrophils. In this study, we aimed to determine the role of toll-like receptor 9 (TLR9) in the response of human neutrophils to H. pylori and purified H. pylori DNA (Hp-DNA). Neutrophils were isolated from the blood of adult volunteers and challenged with either H. pylori or Hp-DNA. We found that both, H. pylori and Hp-DNA induced increased expression and release of IL-8. Furthermore, we showed that TLR9 is involved in the induction of IL-8 production by H. pylori and Hp-DNA. IL-8 production induced by H. pylori but not by Hp-DNA was partially mediated by NF-?B. In conclusion, this study showed for first time that both, H. pylori and Hp-DNA activate TLR9 and induce a different inflammatory response that leads to activation of neutrophils. PMID:24987851

Alvarez-Arellano, Lourdes; Cortes-Reynosa, Pedro; Sanchez-Zauco, Norma; Salazar, Eduardo; Torres, Javier; Maldonado-Bernal, Carmen

2014-01-01

360

DOE technical standards list: Directory of DOE and contractor personnel involved in non-government standards activities  

SciTech Connect

The body of 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, which is attached to the end of this document and to DOE Order 1300.2A. Additional names were added from rosters supplied by non-Government standards bodies. The committees or governing bodies in which the person participates is listed after each name. An asterisk preceding the committee notation indicates that the person has identified himself or herself as the DOE representative on that committee. Appendices to this document are also provided to sort the information by the parent employment organization, by non-Government standards activity, and by the proper names of the non-Government standards organizations and committees. DOE employees and contractors listed in this TSL are those recorded as of July 1, 1996.

NONE

1996-08-01

361

DOE technical standards list: Directory of DOE and contractor personnel involved in non-government standards activities  

SciTech Connect

The body of 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, which is attached to the end of this document. Additional names were added from rosters supplied by non-Government standards bodies. The committees or governing bodies in which the person participates is listed after each name. An asterisk preceding the committee notation indicates that the person has identified himself or herself as the DOE representative on that committee. Appendices to this document are also provided to sort the information by the parent employment organization, by non-Government standards activity, and by the proper names of the non-Government standards organizations and committees. DOE employees and contractors listed in this technical standards list are those recorded as of May 1, 1999.

NONE

1999-05-01

362

Activation of STAT3 is involved in malignancy mediated by CXCL12-CXCR4 signaling in human breast cancer.  

PubMed

The chemokine receptor CXCR4 and signal transducer and activator of transcription 3 (STAT3) play an important role in breast cancer malignancy and metastasis. However, it remains unknown whether STAT3 can be activated by CXCR4 in human breast cancer. The expression levels of CXCR4, STAT3 and p-STAT3 in 208 breast cancer tissues and 26 tumor-adjacent tissues were examined by immunohistochemistry. Flow cytometry, western blot analysis and immunoprecipitation were used to study activation of STAT3 by CXCL12-CXCR4 signaling in human breast cancer cell lines. The expression levels of CXCR4, STAT3 and p-STAT3 were higher in the breast cancer samples than these levels in the tumor-adjacent samples. The combined expression of CXCR4 and p-STAT3 was correlated with TNM stage, tumor size, lymph node metastasis and histological grade of breast cancer. In the breast cancer cells, CXCL12 treatment increased the expression of p-STAT3. The CXCR4 antagonist AMD3100 and the Janus kinase 2 (JAK2) antagonist AG490 inhibited the CXCL12-induced increase in the phosphorylation of STAT3. Furthermore, CXCL12 promoted direct binding of JAK2 to CXCR4. Our findings suggest that activation of the JAK2/STAT3 pathway via CXCL12-CXCR4 signaling plays an important role in breast cancer malignancy and metastasis. Targeting the CXCL12-CXCR4/JAK2/STAT3 signaling pathway may be a potential therapeutic strategy for the treatment of breast cancer. PMID:25310198

Liu, Xiaojian; Xiao, Qinghuan; Bai, Xuefeng; Yu, Zhaojin; Sun, Mingli; Zhao, Haishan; Mi, Xiaoyi; Wang, Enhua; Yao, Weifan; Jin, Feng; Zhao, Lin; Ren, Jie; Wei, Minjie

2014-12-01

363

The photoproduction of superoxide radicals and the superoxide dismutase activity of Photosystem II. The possible involvement of cytochrome b559  

Microsoft Academic Search

In the present study the light induced formation of superoxide and intrinsic superoxide dismutase (SOD) activity in PS II membrane fragments and D1\\/D2\\/Cytb559-complexes from spinach have been analyzed by the use of ferricytochrome c (cyt c(III)) reduction and xanthine\\/xanthine oxidase as assay systems. The following results were obtained: 1.) Photoreduction of Cyt c (III) by PS II membrane fragments is

Gennady Ananyev; Gernot Renger; Ulrich Wacker; Vyacheslav Klimov

1994-01-01

364

Involvement of -Glucans in the Wide-Spectrum Antimicrobial Activity of Williopsis saturnus var. mrakii MUCL 41968 Killer Toxin  

Microsoft Academic Search

Background: Williopsis saturnus var. mrakii MUCL 41968 secretes a 85-kDa glycoprotein killer toxin (WmKT) that displays a cytocidal activity against a wide range of microorganisms, making WmKT a promising candidate for the development of new antimicrobial molecules. Although the killing mechanism of WmKT is still unknown, the toxin was recently proposed to bind to the surface of sensitive microorganisms through

Cyril Guyard; Eric Dehecq; Jean-Pierre Tissier; Luciano Polonelli; Eduardo Dei-Cas; Jean-Charles Cailliez; Franco D. Menozzi

365

Calreticulin Is Directly Involved in Anti-?3 Integrin Antibody-Mediated Secretion and Activation of Matrix Metalloprotease-2  

Microsoft Academic Search

Matrix metalloprotease-2 (MMP-2) plays a pivotal role in cancer invasion and metastasis. Invasive human rhabdomyosarcoma cells (RD) secrete proMMP-2. We recently reported that anti-?3 integrin antibody induced the activated form of MMP-2 and enhanced proMMP-2 secretion by RD cells with concomitant enhancement of RD cell invasion. Since recent studies showed that calreticulin interacts with integrin ? subunit, we hypothesized that

Hiromichi Ito; Yousuke Seyama; Shunichiro Kubota

2001-01-01

366

A Ca~+ACTIVATED PROTEASE POSSIBLY INVOLVED IN MYOFIBRILLAR PROTEIN TURNOVER Subcellular Localization of the Protease in Porcine Skeletal Muscle  

Microsoft Academic Search

A study was done to determine whether the Ca2+-activated muscle protease (CAF) that removes Z disks from myofibrils in the presence of Ca ~+ is located in a sedimentable subcellular organelle. Porcine skeletal muscle cells were diced finely with a scalpel and were suspended in 0.25 M sucrose, 4 mM EDTA with a VIRTIS homogenizer. Filtration of the suspended muscle

WILLIAM J. REVILLE; DARREL E. GOLL; MARVIN H. STROMER; RICHARD M. ROBSON; DAYTON WILLIAM R

367

Sugar-induced tolerance to the herbicide atrazine in Arabidopsis seedlings involves activation of oxidative and xenobiotic stress responses  

Microsoft Academic Search

Exogenous sucrose confers to Arabidopsis seedlings a very high level of tolerance to the herbicide atrazine that cannot be ascribed to photoheterotrophic growth.\\u000a Important differences of atrazine tolerance between sucrose and glucose treatments showed that activation of chloroplast biogenesis\\u000a per se could not account for induced tolerance. Sucrose-induced acquisition of defence mechanisms was shown by the gene expression\\u000a pattern of

Cécile Sulmon; Gwenola Gouesbet; Abdelhak El Amrani; Ivan Couée

2006-01-01

368

Metabolic Activity and mRNA Levels of Human Cardiac CYP450s Involved in Drug Metabolism  

Microsoft Academic Search

BackgroundTissue-specific expression of CYP450s can regulate the intracellular concentration of drugs and explain inter-subject variability in drug action. The overall objective of our study was to determine in a large cohort of samples, mRNA levels and CYP450 activity expressed in the human heart.MethodologyCYP450 mRNA levels were determined by RTPCR in left ventricular samples (n = 68) of explanted hearts from

Veronique Michaud; Martin Frappier; Marie-Christine Dumas; Jacques Turgeon; Ulrich M. Zanger

2010-01-01

369

Estrogen modulation of K + channel activity in hypothalamic neurons involved in the control of the reproductive axis  

Microsoft Academic Search

Here we report on the progress we have made in elucidating the mechanisms through which estrogen alters synaptic responses in hypothalamic neurons. We examined the modulation by estrogen of the coupling of various receptor systems to inwardly rectifying and small conductance, Ca2+-activated K+ (SK) channels. We used intracellular sharp-electrode and whole-cell recordings in hypothalamic slices from ovariectomized female guinea pigs.

Martin J. Kelly; Oline K. Rønnekleiv; Nurhadi Ibrahim; Andre H. Lagrange; Edward J. Wagner

2002-01-01

370

Human Deoxyhypusine Hydroxylase, an Enzyme Involved in Regulating Cell Growth, Activates O2 with a Nonheme Diiron Center  

SciTech Connect

Deoxyhypusine hydroxylase is the key enzyme in the biosynthesis of hypusine containing eukaryotic translation initiation factor 5A (eIF5A), which plays an essential role in the regulation of cell proliferation. Recombinant human deoxyhypusine hydroxylase (hDOHH) has been reported to have oxygen- and iron-dependent activity, an estimated iron/holoprotein stoichiometry of 2, and a visible band at 630 nm responsible for the blue color of the as-isolated protein. EPR, Moessbauer, and XAS spectroscopic results presented herein provide direct spectroscopic evidence that hDOHH has an antiferromagnetically coupled diiron center with histidines and carboxylates as likely ligands, as suggested by mutagenesis experiments. Resonance Raman experiments show that its blue chromophore arises from a (e-1,2-peroxo)diiron(III) center that forms in the reaction of the reduced enzyme with O2, so the peroxo form of hDOHH is unusually stable. Nevertheless we demonstrate that it can carry out the hydroxylation of the deoxyhypusine residue present in the elF5A substrate. Despite a lack of sequence similarity, hDOHH has a nonheme diiron active site that resembles both in structure and function those found in methane and toluene monooxygenases, bacterial and mammalian ribonucleotide reductases, and stearoyl acyl carrier protein ?9-desaturase from plants, suggesting that the oxygen-activating diiron motif is a solution arrived at by convergent evolution. Notably, hDOHH is the only example thus far of a human hydroxylase with such a diiron active site.

Vu, V.; Emerson, J; Martinho, M; Kim, Y; Munck, E; Park, M; Que, Jr., L

2009-01-01

371

Redox Mechanisms Involved in the Selective Activation of Nrf2-mediated Resistance Versus p53-dependent Apoptosis in Adenocarcinoma Cells*  

PubMed Central

We have investigated the role of reactive oxygen species and thiol-oxidizing agents in the induction of cell death and have shown that adenocarcinoma gastric (AGS) cells respond differently to the oxidative challenge according to the signaling pathways activated. In particular, apoptosis in AGS cells is induced via the mitochondrial pathway upon treatment with thiol-oxidizing agents, such as diamide. Apoptosis is associated with persistent oxidative damage, as evidenced by the increase in carbonylated proteins and the expression/activation of DNA damage-sensitive proteins histone H2A.X and DNA-dependent protein kinase. Resistance to hydrogen peroxide is instead associated with Keap1 oxidation and rapid translocation of Nrf2 into the nucleus. Sensitivity to diamide and resistance to hydrogen peroxide are correlated with GSH redox changes, with diamide severely increasing GSSG, and hydrogen peroxide transiently inducing protein-GSH mixed disulfides. We show that p53 is activated in response to diamide treatment by the oxidative induction of the Trx1/p38MAPK signaling pathway. Similar results were obtained with another carcinoma cell line, CaCo2, indicating that these findings are not limited to AGS cells. Our data suggest that thiol-oxidizing agents could be exploited as inducers of apoptosis in tumor histotypes resistant to ROS-producing chemotherapeutics. PMID:19643729

Piccirillo, Sara; Filomeni, Giuseppe; Brune, Bernhard; Rotilio, Giuseppe; Ciriolo, Maria R.

2009-01-01

372

Antiangiogenic activity of trabectedin in myxoid liposarcoma: Involvement of host TIMP-1 and TIMP-2 and tumor thrombospondin-1.  

PubMed

Trabectedin is a marine natural product, approved in Europe for the treatment of soft tissue sarcoma and relapsed ovarian cancer. Clinical and experimental evidence indicates that trabectedin is particularly effective against myxoid liposarcomas where response is associated to regression of capillary networks. Here, we investigated the mechanism of the antiangiogenic activity of trabectedin in myxoid liposarcomas. Trabectedin directly targeted endothelial cells, impairing functions relying on extracellular matrix remodeling (invasion and branching morphogenesis) through the upregulation of the inhibitors of matrix metalloproteinases TIMP-1 and TIMP-2. Increased TIMPs synthesis by the tumor microenvironment following trabectedin treatment was confirmed in xenograft models of myxoid liposarcoma. In addition, trabectedin upregulated tumor cell expression of the endogenous inhibitor thrombospondin-1 (TSP-1, a key regulator of angiogenesis-dependent dormancy in sarcoma), in in vivo models of myxoid liposarcomas, in vitro cell lines and primary cell cultures from patients' myxoid liposarcomas. Chromatin Immunoprecipitation analysis showed that trabectedin displaced the master regulator of adipogenesis C/EBP? from the TSP-1 promoter, indicating an association between the up-regulation of TSP-1 and induction of adipocytic differentiation program by trabectedin. We conclude that trabectedin inhibits angiogenesis through multiple mechanisms, including directly affecting endothelial cells in the tumor microenvironment-with a potentially widespread activity-and targeting tumor cells' angiogenic activity, linked to a tumor-specific molecular alteration. PMID:24917554

Dossi, Romina; Frapolli, Roberta; Di Giandomenico, Silvana; Paracchini, Lara; Bozzi, Fabio; Brich, Silvia; Castiglioni, Vittoria; Borsotti, Patrizia; Belotti, Dorina; Uboldi, Sarah; Sanfilippo, Roberta; Erba, Eugenio; Giavazzi, Raffaella; Marchini, Sergio; Pilotti, Silvana; D'Incalci, Maurizio; Taraboletti, Giulia

2015-02-15

373

Tetrahydrocurcumin induces G2/M cell cycle arrest and apoptosis involving p38 MAPK activation in human breast cancer cells.  

PubMed

Curcumin (CUR) is a major naturally-occurring polyphenol of Curcuma species, which is commonly used as a yellow coloring and flavoring agent in foods. In recent years, it has been reported that CUR exhibits significant anti-tumor activity in vivo. However, the pharmacokinetic features of CUR have indicated poor oral bioavailability, which may be related to its extensive metabolism. The CUR metabolites might be responsible for the antitumor pharmacological effects in vivo. Tetrahydrocurcumin (THC) is one of the major metabolites of CUR. In the present study, we examined the efficacy and associated mechanism of action of THC in human breast cancer MCF-7 cells for the first time. Here, THC exhibited significant cell growth inhibition by inducing MCF-7 cells to undergo mitochondrial apoptosis and G2/M arrest. Moreover, co-treatment of MCF-7 cells with THC and p38 MAPK inhibitor, SB203580, effectively reversed the dissipation in mitochondrial membrane potential (??m), and blocked THC-mediated Bax up-regulation, Bcl-2 down-regulation, caspase-3 activation as well as p21 up-regulation, suggesting p38 MAPK might mediate THC-induced apoptosis and G2/M arrest. Taken together, these results indicate THC might be an active antitumor form of CUR in vivo, and it might be selected as a potentially effective agent for treatment of human breast cancer. PMID:24593988

Kang, Ning; Wang, Miao-Miao; Wang, Ying-Hui; Zhang, Zhe-Nan; Cao, Hong-Rui; Lv, Yuan-Hao; Yang, Yang; Fan, Peng-Hui; Qiu, Feng; Gao, Xiu-Mei

2014-05-01

374

Cellular redox state and activating protein-1 are involved in ascorbate effect on calcitriol-induced differentiation.  

PubMed

Ascorbate has been related to the differentiation of several mesenchymal cells including haematopoietic cells. We have previously demonstrated that ascorbate enhances the activity of 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3) on monocytic differentiation of HL-60 cells. Here, we show that ascorbate-mediated modification of cellular redox state and AP-1 (activating protein-1) DNA binding during early phases are related to the enhancing effect of ascorbate on differentiation. Ascorbate, but not its fully oxidized form, dehydroascorbate, or an ascorbate analogue with a low rate of oxidation, ascorbate-2-phosphate, enhanced the differentiation induced by 1 alpha,25(OH)2D3, modified cytosolic reactive oxygen species levels and mitochondrial redox potential (delta psi m), and modulated AP-1 DNA binding in HL-60 cells. Ascorbate itself increased AP-1 binding to DNA in noninduced cells, whereas it inhibited AP-1 binding in 1 alpha,25(OH)2D3-induced cells. However, ascorbate increased the mRNA levels of c-jun, junB, and c-fos in 1 alpha,25(OH)2D3-induced cells. Taken together, these results suggest that the enhancing effect of ascorbate on HL-60 differentiation induced by 1 alpha, 25(OH)2D3 is related to its effect on the cellular redox state and the modulation of AP-1 activity. PMID:11732330

López-Lluch, G; Blázquez, M V; Pérez-Vicente, R; Macho, A; Burón, M I; Alcaín, F J; Muñoz, E; Navas, P

2001-01-01

375

Trypanosoma rangeli: an alkaline ecto-phosphatase activity is involved with survival and growth of the parasite.  

PubMed

The aim of this work was to investigate whether an alkaline ecto-phosphatase activity is present in the surface of Trypanosoma rangeli. Intact short epimastigote forms were assayed for ecto-phosphatase activity to study kinetics and modulators using ?-glycerophosphate (?-GP) and p-nitrophenyl phosphate (pNPP) as substrates. Its role in parasite development and differentiation was also studied. Competition assays using different proportions of ?-GP and pNPP evidenced the existence of independent and non-interacting alkaline and acid phosphatases. Hydrolysis of ?-GP increased progressively with pH, whereas the opposite was evident using pNPP. The alkaline enzyme was inhibited by levamisole in a non-competitive fashion. The Ca(2+) present in the reaction medium was enough for full activity. Pretreatment with PI-PLC decreased the alkaline but not the acid phosphatase evidence that the former is catalyzed by a GPI-anchored enzyme, with potential intracellular signaling ability. ?-GP supported the growth and differentiation of T. rangeli to the same extent as high orthophosphate (Pi). Levamisole at the IC50 spared significantly parasite growth when ?-GP was the sole source of Pi and stopped it in the absence of ?-GP, indicating that the alkaline enzyme can utilize phosphate monoesters present in serum. These results demonstrate the existence of an alkaline ecto-phosphatase in T. rangeli with selective requirements and sensitivity to inhibitors that participates in key metabolic processes in the parasite life cycle. PMID:23994113

Dos-Santos, André L A; Dick, Claudia F; Silveira, Thaís S; Fonseca-de-Souza, André L; Meyer-Fernandes, José R

2013-10-01

376

Two negative cis-regulatory regions involved in fruit-specific promoter activity from watermelon (Citrullus vulgaris S.)  

PubMed Central

A 1.8?kb 5?-flanking region of the large subunit of ADP-glucose pyrophosphorylase, isolated from watermelon (Citrullus vulgaris S.), has fruit-specific promoter activity in transgenic tomato plants. Two negative regulatory regions, from –986 to –959 and from –472 to –424, were identified in this promoter region by fine deletion analyses. Removal of both regions led to constitutive expression in epidermal cells. Gain-of-function experiments showed that these two regions were sufficient to inhibit RFP (red fluorescent protein) expression in transformed epidermal cells when fused to the cauliflower mosaic virus (CaMV) 35S minimal promoter. Gel mobility shift experiments demonstrated the presence of leaf nuclear factors that interact with these two elements. A TCCAAAA motif was identified in these two regions, as well as one in the reverse orientation, which was confirmed to be a novel specific cis-element. A quantitative ?-glucuronidase (GUS) activity assay of stable transgenic tomato plants showed that the activities of chimeric promoters harbouring only one of the two cis-elements, or both, were ?10-fold higher in fruits than in leaves. These data confirm that the TCCAAAA motif functions as a fruit-specific element by inhibiting gene expression in leaves. PMID:19073962

Yin, Tao; Wu, Hanying; Zhang, Shanglong; Liu, Jingmei; Lu, Hongyu; Zhang, Lingxiao; Xu, Yong; Chen, Daming

2009-01-01

377

Trypanosoma brucei variant surface glycoprotein regulation involves coupled activation/inactivation and chromatin remodeling of expression sites.  

PubMed Central

Trypanosoma brucei is an extracellular protozoan parasite that cycles between mammalian hosts and the tsetse vector. In bloodstream-form trypanosomes, only one variant surface glycoprotein gene (VSG) expression site (ES) is active at any time. Transcriptional switching between ESs results in antigenic variation. No VSG is transcribed in the insect procyclic stage. We have used bacteriophage T7 RNA polymerase (T7RNAP) to study the transcriptional accessibility of ES chromatin in vivo. We show that T7RNAP-mediated transcription from chromosomally integrated T7 promoters is repressed along the entire length of the ES in the procyclic form, but not in the bloodstream form, suggesting that the accessible chromatin of inactive bloodstream-form ESs is remodeled upon differentiation to yield a structure that is no longer permissive for T7RNAP-mediated transcription. In the bloodstream form, replacing the active ES promoter with a T7 promoter, which is incapable of sustaining high-level transcription of the entire ES, prompts an ES switch. These data suggest two distinct mechanisms for ES regulation: a chromatin-mediated developmental silencing of the ES in the procyclic form and a rapid coupled mechanism for ES activation and inactivation in the bloodstream form. PMID:10205179

Navarro, M; Cross, G A; Wirtz, E

1999-01-01

378

Timely Activation of Budding Yeast APCCdh1 Involves Degradation of Its Inhibitor, Acm1, by an Unconventional Proteolytic Mechanism  

PubMed Central

Regulated proteolysis mediated by the ubiquitin proteasome system is a fundamental and essential feature of the eukaryotic cell division cycle. Most proteins with cell cycle-regulated stability are targeted for degradation by one of two related ubiquitin ligases, the Skp1-cullin-F box protein (SCF) complex or the anaphase-promoting complex (APC). Here we describe an unconventional cell cycle-regulated proteolytic mechanism that acts on the Acm1 protein, an inhibitor of the APC activator Cdh1 in budding yeast. Although Acm1 can be recognized as a substrate by the Cdc20-activated APC (APCCdc20) in anaphase, APCCdc20 is neither necessary nor sufficient for complete Acm1 degradation at the end of mitosis. An APC-independent, but 26S proteasome-dependent, mechanism is sufficient for complete Acm1 clearance from late mitotic and G1 cells. Surprisingly, this mechanism appears distinct from the canonical ubiquitin targeting pathway, exhibiting several features of ubiquitin-independent proteasomal degradation. For example, Acm1 degradation in G1 requires neither lysine residues in Acm1 nor assembly of polyubiquitin chains. Acm1 was stabilized though by conditional inactivation of the ubiquitin activating enzyme Uba1, implying some requirement for the ubiquitin pathway, either direct or indirect. We identified an amino terminal predicted disordered region in Acm1 that contributes to its proteolysis in G1. Although ubiquitin-independent proteasome substrates have been described, Acm1 appears unique in that its sensitivity to this mechanism is strictly cell cycle-regulated via cyclin-dependent kinase (Cdk) phosphorylation. As a result, Acm1 expression is limited to the cell cycle window in which Cdk is active. We provide evidence that failure to eliminate Acm1 impairs activation of APCCdh1 at mitotic exit, justifying its strict regulation by cell cycle-dependent transcription and proteolytic mechanisms. Importantly, our results reveal that strict cell-cycle expression profiles can be established independent of proteolysis mediated by the APC and SCF enzymes. PMID:25072887

Melesse, Michael; Choi, Eunyoung; Hall, Hana; Walsh, Michael J.; Geer, M. Ariel; Hall, Mark C.

2014-01-01

379

Involvement of tyrosine kinases, Ca2+ and PKC in activation of mitogen-activated protein (MAP) kinase in human polymorphonuclear neutrophils  

PubMed Central

Activation of mitogen-activated protein (MAP) kinase is an early response to a wide variety of stimuli and plays an important role in the regulation of cellular functions. In the present study we investigated the activation of MAP kinase in human polymorphonuclear neutrophils (PMNs).Activity of MAP kinase and protein kinase C (PKC) was measured radiometrically from the rate of phosphorylation of specific peptide substrates. Protein phosphorylation was measured by immunoprecipitation and Western blot analysis.N-Formyl-Met-Leu-Phe (fMLP), phorbol 12-myristate, 13-acetate (PMA) and the Ca2+-ATPase inhibitors thapsigargin (Tg) and cyclopiazonic acid (CPA) increased MAP kinase activity significantly. The tyrosine kinase inhibitors erbstatin and herbimycin A partially inhibited the effects of fMLP and PMA, and completely abolished the effects of both Tg and CPA. The specific PKC inhibitor calphostin C suppressed activation of MAP kinase produced by fMLP and PMA, but had no effect on that produced by Tg and CPA. Tg and CPA were without effect on PKC activity.Immunoprecipitation and Western blot analysis indicated that the 42 and 44 kDa tyrosine-phosphorylated proteins found after stimulation of PMNs were both members of the MAP kinase family. Pretreatment of PMNs with staurosporine, EGTA or erbstatin significantly reduced the tyrosine phosphorylation of MAP kinase(s).These results suggest that in human PMNs, MAP kinase can be stimulated in both a PKC-dependent and a PKC-independent manner. The Ca2+ signal leads to activation of tyrosine kinases, which contribute to the activation of MAP kinase. However, a PMA-sensitive Ca2+-independent pathway also exists. Mobilization of Ca2+ and activation of PKC synergistically induce maximal MAP kinase activation and tyrosine phosphorylation. PMID:9806988

Zhang, Hong; Garlichs, Christoph D; Mugge, Andreas; Daniel, Werner G

1998-01-01

380

Activation of the PI3K/mTOR Pathway Is Involved in Cystic Proliferation of Cholangiocytes of the PCK Rat  

PubMed Central

The polycystic kidney (PCK) rat is an animal model of Caroli’s disease as well as autosomal recessive polycystic kidney disease (ARPKD). The signaling pathways involving the mammalian target of rapamycin (mTOR) are aberrantly activated in ARPKD. This study investigated the effects of inhibitors for the cell signaling pathways including mTOR on cholangiocyte proliferation of the PCK rat. Cultured PCK cholangiocytes were treated with rapamycin and everolimus [inhibitors of mTOR complex 1 (mTOC1)], LY294002 [an inhibitor of phosphatidylinositol 3-kinase (PI3K)] and NVP-BEZ235 (an inhibitor of PI3K and mTORC1/2), and the cell proliferative activity was determined in relation to autophagy and apoptosis. The expression of phosphorylated (p)-mTOR, p-Akt, and PI3K was increased in PCK cholangiocytes compared to normal cholangiocytes. All inhibitors significantly inhibited the cell proliferative activity of PCK cholangiocytes, where NVP-BEZ235 had the most prominent effect. NVP-BEZ235, but not rapamycin and everolimus, further inhibited biliary cyst formation in the three-dimensional cell culture system. Rapamycin and everolimus induced apoptosis in PCK cholangiocytes, whereas NVP-BEZ235 inhibited cholangiocyte apoptosis. Notably, the autophagic response was significantly induced following the treatment with NVP-BEZ235, but not rapamycin and everolimus. Inhibition of autophagy using siRNA against protein-light chain3 and 3-methyladenine significantly increased the cell proliferative activity of PCK cholangiocytes treated with NVP-BEZ235. In vivo, treatment of the PCK rat with NVP-BEZ235 attenuated cystic dilatation of the intrahepatic bile ducts, whereas renal cyst development was unaffected. These results suggest that the aberrant activation of the PI3K/mTOR pathway is involved in cystic proliferation of cholangiocytes of the PCK rat, and inhibition of the pathway can reduce cholangiocyte proliferation via the mechanism involving apoptosis and/or autophagy. PMID:24498161

Ren, Xiang Shan; Sato, Yasunori; Harada, Kenichi; Sasaki, Motoko; Furubo, Shinichi; Song, Jing Yu; Nakanuma, Yasuni

2014-01-01

381

(-)-Epicatechin prevents TNF?-induced activation of signaling cascades involved in inflammation and insulin sensitivity in 3T3-L1 adipocytes  

PubMed Central

Obesity is major public health concern worldwide and obese individuals exhibit a higher risk of chronic diseases such as type 2 diabetes. Inflammation plays a significant role in metabolic regulation and mounting evidence highlight the contribution of adipose tissue to systemic inflammatory state. Food extracts with a high content of (-)-epicatechin have been found to exert systemic anti-inflammatory actions, however the anti-inflammatory actions of (-)-epicatechin on adipose tissue remain to be determined. The aim of this study was to investigate the capacity of (-)-epicatechin to prevent tumor necrosis alpha (TNF?)-induced activation of cell signals involved in inflammation and insulin resistance (NF-?B, mitogen-activated protein kinases (MAPKs), AP-1, and peroxisome proliferator activated receptor ? (PPAR?)) in differentiated white adipocytes (3T3-L1). TNF? triggered the activation of transcription factors NF-?B and AP-1, and MAPKs ERK1/2, JNK, and p38. (-)-Epicatechin caused a dose (0.5-10 ?M)-dependent decrease in TNF?-mediated JNK, ERK1/2, and p-38 phosphorylation, and nuclear AP-1-DNA binding. (-)-Epicatechin also inhibited TNF?-triggered activation of the NF-?B signaling cascade, preventing TNF?-mediated p65 nuclear transport and nuclear NF-?B-DNA binding. (-)-Epicatechin also attenuated the TNF?-mediated downregulation of PPAR? expression and decreased nuclear DNA binding. Accordingly, (-)-epicatechin inhibited TNF?-mediated altered transcription of genes (MCP-1, interleukin-6, TNF?, resistin, and protein-tyrosine phosphatase 1B) involved in inflammation and insulin signaling. In conclusion, (-)-epicatechin can attenuate TNF?-mediated triggering of signaling cascades involved in inflammation and insulin resistance. These findings could be of relevance in the dietary management of obesity and metabolic syndrome. PMID:22425757

Vazquez-Prieto, Marcela A.; Bettaieb, A.; Haj, Fawaz G.; Fraga, Cesar G.; Oteiza, Patricia I.

2012-01-01

382

Duplicate Maize Wrinkled1 Transcription Factors Activate Target Genes Involved in Seed Oil Biosynthesis1[C][W  

PubMed Central

WRINKLED1 (WRI1), a key regulator of seed oil biosynthesis in Arabidopsis (Arabidopsis thaliana), was duplicated during the genome amplification of the cereal ancestor genome 90 million years ago. Both maize (Zea mays) coorthologs ZmWri1a and ZmWri1b show a strong transcriptional induction during the early filling stage of the embryo and complement the reduced fatty acid content of Arabidopsis wri1-4 seeds, suggesting conservation of molecular function. Overexpression of ZmWri1a not only increases the fatty acid content of the mature maize grain but also the content of certain amino acids, of several compounds involved in amino acid biosynthesis, and of two intermediates of the tricarboxylic acid cycle. Transcriptomic experiments identified 18 putative target genes of this transcription factor, 12 of which contain in their upstream regions an AW box, the cis-element bound by AtWRI1. In addition to functions related to late glycolysis and fatty acid biosynthesis in plastids, the target genes also have functions related to coenzyme A biosynthesis in mitochondria and the production of glycerol backbones for triacylglycerol biosynthesis in the cytoplasm. Interestingly, the higher seed oil content in ZmWri1a overexpression lines is not accompanied by a reduction in starch, thus opening possibilities for the use of the transgenic maize lines in breeding programs. PMID:21474435

Pouvreau, Benjamin; Baud, Sebastien; Vernoud, Vanessa; Morin, Valerie; Py, Cyrille; Gendrot, Ghislaine; Pichon, Jean-Philippe; Rouster, Jacques; Paul, Wyatt; Rogowsky, Peter M.

2011-01-01

383

Activity of moxifloxacin on biofilms produced in vitro by bacterial pathogens involved in acute exacerbations of chronic bronchitis.  

PubMed

The aim of this study was to assess whether moxifloxacin is able to inhibit the synthesis of and to disrupt biofilms produced in vitro by bacterial pathogens involved in acute bacterial exacerbations of chronic bronchitis. Three strains each of Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Staphylococcus aureus and Escherichia coli recently isolated from clinical respiratory specimens and capable of slime production were used. Biofilm formation on polystyrene plates was quantified spectrophotometrically by established methodologies. Moxifloxacin (0.5 mg/L) inhibited slime synthesis by >70% in S. aureus, H. influenzae and S. pneumoniae, 45-70% in E. coli and 35-70% in M. catarrhalis. Disruption of pre-formed structures was also promoted by moxifloxacin both for initial (5h) and mature (48 h) biofilms. Drug concentrations reached during therapy (0.5-4 mg/L) resulted in a breakdown of initial biofilm of 60-80% in H. influenzae and S. pneumoniae, 48-86% in S. aureus, 37-69% in M. catarrhalis and 51-71% in E. coli. Mature biofilms were less susceptible to degradation. Moxifloxacin at concentrations that can be achieved in the bronchial mucosa during therapy therefore promotes a significant inhibition of biofilm synthesis and induces slime disruption, a feature that may be instrumental in reducing the exacerbations so frequently observed in this condition. PMID:17768034

Roveta, S; Schito, A M; Marchese, A; Schito, G C

2007-11-01

384

Decolorizing activity of malachite green and its mechanisms involved in dye biodegradation by Achromobacter xylosoxidans MG1.  

PubMed

An Achromobacter xylosoxidans MG1 strainisolated from the effluent treatment plant of a textile and dyeing factory from Yunnan Province in China was found capable of decolorizing the malachite green dye at a high efficacy. Strain MG1 reduced 86% malachite green at the concentration of 2,000 mg/l within 1 h, representing a greater ability for decolorizing and a higher tolerance of this compound than all previously reported bacteria. Color removal was optimal at pH 6 and 38°C. Further experimental evidences demonstrated that both cytoplasmic and extracellular biodegradation contributed to the decolorization of malachite green. Nested PCR was employed to identify the candidate genes responsible for malachite green decolorization, and we identified a cytoplasmic triphenylmethane reductase gene with 100% amino acid similarity to the corresponding gene in Citrobacter sp. strain. In contrast to our expectation, the addition of metyrapone had little effect on the cytoplasmic biodegradation, suggesting that cytochrome P450 was not involved in the high-performance reduction. The extracellular biodegradation was likely attributable to the secretion of extracellular proteases and some heat-resistant compounds. PMID:21865764

Wang, Ji'ai; Qiao, Min; Wei, Kangbi; Ding, Junmei; Liu, Zhongzhong; Zhang, Ke-Qin; Huang, Xiaowei

2011-01-01

385

Gastroprotective activity of Annona muricata leaves against ethanol-induced gastric injury in rats via Hsp70/Bax involvement.  

PubMed

The popular fruit tree of Annona muricata L. (Annonaceae), known as soursop and graviola, is a widely distributed plant in Central and South America and tropical countries. Leaves of A. muricata have been reported to possess antioxidant and anti-inflammatory activities. In this study, the gastroprotective effects of ethyl acetate extract of A. muricata leaves (EEAM) were investigated against ethanol-induced gastric injury models in rats. The acute toxicity test of EEAM in rats, carried out in two doses of 1 g/kg and 2 g/kg, showed the safety of this plant, even at the highest dose of 2 g/kg. The antiulcer study in rats (five groups, n=6) was performed with two doses of EEAM (200 mg/kg and 400 mg/kg) and with omeprazole (20 mg/kg), as a standard antiulcer drug. Gross and histological features showed the antiulcerogenic characterizations of EEAM. There was significant suppression on the ulcer lesion index of rats pretreated with EEAM, which was comparable to the omeprazole effect in the omeprazole control group. Oral administration of EEAM to rats caused a significant increase in the level of nitric oxide and antioxidant activities, including catalase, glutathione, and superoxide dismutase associated with attenuation in gastric acidity, and compensatory effect on the loss of gastric wall mucus. In addition, pretreatment of rats with EEAM caused significant reduction in the level of malondialdehyde, as a marker for oxidative stress, associated with an increase in prostaglandin E2 activity. Immunohistochemical staining also demonstrated that EEAM induced the downregulation of Bax and upregulation of Hsp70 proteins after pretreatment. Collectively, the present results suggest that EEAM has a promising antiulcer potential, which could be attributed to its suppressive effect against oxidative damage and preservative effect toward gastric wall mucus. PMID:25378912

Moghadamtousi, Soheil Zorofchian; Rouhollahi, Elham; Karimian, Hamed; Fadaeinasab, Mehran; Abdulla, Mahmood Ameen; Kadir, Habsah Abdul

2014-01-01

386

Cathepsin K is involved in development of psoriasis-like skin lesions through TLR-dependent Th17 activation.  

PubMed

Cathepsins (CTSs) are lysosomal cysteine proteases that play an important role in the turnover of intracellular proteins and extracellular proteins, such as the degradation of extracellular matrices and the processing of antigenic proteins. A CTS inhibitor, NC-2300, not only suppresses bone erosion by inhibition of cathepsin K (CTSK), but also ameliorates paw swelling at inflamed joints in adjuvant-induced arthritis in rats. It has been demonstrated that the amelioration of joint inflammation by NC-2300 is mediated by the downregulation of cytokine expression in dendritic cells, which are essential for Th17 activation. In this work, we studied the role for CTSs in the pathogenesis of psoriasis-like lesion in K5.Stat3C mice, a mouse model of psoriasis, in which Th17 contributes to lesion development similar to psoriasis. Psoriatic lesions expressed increased levels of Ctsk and Ctss mRNA compared with uninvolved skin and normal control skin. Similarly, the epidermis and dermis in K5.Stat3C mice demonstrated increased CTSK activities, which were sensitive to NC-2300. Topical treatment with NC-2300 significantly ameliorated 12-O-tetradecanoylphorbol-13-acetate-induced psoriasis-like lesions in K5.Stat3C mice, and downregulated the expression of IL-12, IL-23, and Th17 cytokines. In vitro experiments revealed that TLR7 activation of bone marrow-derived myeloid dendritic cells led to increase in IL-23 at mRNA and protein levels, which were downregulated by NC-2300. These results suggest that CTSK plays a role in development of psoriatic lesions through TLR7-dependent Th17 polarization. PMID:23543761

Hirai, Toshitake; Kanda, Takashi; Sato, Kenji; Takaishi, Mikiro; Nakajima, Kimiko; Yamamoto, Mayuko; Kamijima, Reiko; Digiovanni, John; Sano, Shigetoshi

2013-05-01

387

Gastroprotective activity of Annona muricata leaves against ethanol-induced gastric injury in rats via Hsp70/Bax involvement  

PubMed Central

The popular fruit tree of Annona muricata L. (Annonaceae), known as soursop and graviola, is a widely distributed plant in Central and South America and tropical countries. Leaves of A. muricata have been reported to possess antioxidant and anti-inflammatory activities. In this study, the gastroprotective effects of ethyl acetate extract of A. muricata leaves (EEAM) were investigated against ethanol-induced gastric injury models in rats. The acute toxicity test of EEAM in rats, carried out in two doses of 1 g/kg and 2 g/kg, showed the safety of this plant, even at the highest dose of 2 g/kg. The antiulcer study in rats (five groups, n=6) was performed with two doses of EEAM (200 mg/kg and 400 mg/kg) and with omeprazole (20 mg/kg), as a standard antiulcer drug. Gross and histological features showed the antiulcerogenic characterizations of EEAM. There was significant suppression on the ulcer lesion index of rats pretreated with EEAM, which was comparable to the omeprazole effect in the omeprazole control group. Oral administration of EEAM to rats caused a significant increase in the level of nitric oxide and antioxidant activities, including catalase, glutathione, and superoxide dismutase associated with attenuation in gastric acidity, and compensatory effect on the loss of gastric wall mucus. In addition, pretreatment of rats with EEAM caused significant reduction in the level of malondialdehyde, as a marker for oxidative stress, associated with an increase in prostaglandin E2 activity. Immunohistochemical staining also demonstrated that EEAM induced the downregulation of Bax and upregulation of Hsp70 proteins after pretreatment. Collectively, the present results suggest that EEAM has a promising antiulcer potential, which could be attributed to its suppressive effect against oxidative damage and preservative effect toward gastric wall mucus. PMID:25378912

Moghadamtousi, Soheil Zorofchian; Rouhollahi, Elham; Karimian, Hamed; Fadaeinasab, Mehran; Abdulla, Mahmood Ameen; Kadir, Habsah Abdul

2014-01-01

388

Lysophosphatidylcholine from white muscle of bonito Euthynnus pelamis (Linnaeus): involvement of phospholipase A1 activity for its production.  

PubMed

A fairly large amount of lysophosphatidylcholine (LPC) was detected in the fresh muscle of bonito Euthynnus pelamis (Linnaeus). The major fatty acid esterified in LPC were highly unsaturated fatty acids, such as docosahexaenoic and eicosapentaenoic acids, and the form was mainly composed of 1-lyso-2-acyl-sn-glycero-3-phosphocholine (1-LPC). The content of this species continued to increase during 4 months of frozen storage and then decreased. Phospholipase A1 activity detected in the bonito muscle was supposed to be responsible for the accumulation of LPC. PMID:7918613

Satouchi, K; Sakaguchi, M; Shirakawa, M; Hirano, K; Tanaka, T

1994-10-01

389

Involvement of mitogen-activated protein kinases and protein kinase C in regulation of antioxidant response element activity in human keratinocytes  

Microsoft Academic Search

Antioxidant response element (ARE) is a unique cis-acting regulatory sequence located in the upstream regions of many genes encoding anticarcinogenic\\/antioxidant proteins. Induction of ARE dependent genes plays an important role in protection of cells against oxidative damage. However, the signaling mechanism(s) involved in regulating transcription of ARE dependent gene expression has not been clearly defined. In this study, we identified

Ming Zhu; Yuesheng Zhang; G. Tim Bowden

2006-01-01

390

Midazolam induces apoptosis in MA-10 mouse Leydig tumor cells through caspase activation and the involvement of MAPK signaling pathway  

PubMed Central

Purpose The present study aims to investigate how midazolam, a sedative drug for clinical use with cytotoxicity on neuronal and peripheral tissues, induced apoptosis in MA-10 mouse Leydig tumor cells. Methods The apoptotic effect and underlying mechanism of midazolam to MA-10 cells were investigated by flow cytometry assay and Western blotting methods. Results Data showed that midazolam induced the accumulation of the MA-10 cell population in the sub-G1 phase and a reduction in the G2/M phase in a time- and dose-dependent manner, suggesting an apoptotic phenomenon. Midazolam could also induce the activation of caspase-8, -9, and -3 and poly (ADP-ribose) polymerase proteins. There were no changes in the levels of Bax and cytochrome-c, whereas Bid was significantly decreased after midazolam treatment. Moreover, midazolam decreased both pAkt and Akt expression. In addition, midazolam stimulated the phosphorylation of p38 and c-Jun NH2-terminal kinase but not extracellular signal-regulated kinase. Conclusion Midazolam could induce MA-10 cell apoptosis through the activation of caspase cascade, the inhibition of pAkt pathway, and the induction of p38 and c-Jun NH2-terminal kinase pathways. PMID:24611016

So, Edmund Cheung; Lin, Yu-Xuan; Tseng, Chi Hao; Pan, Bo-Syong; Cheng, Ka-Shun; Wong, Kar-Lok; Hao, Lyh-Jyh; Wang, Yang-Kao; Huang, Bu-Miin

2014-01-01

391

Volatile Compounds in Honey: A Review on Their Involvement in Aroma, Botanical Origin Determination and Potential Biomedical Activities  

PubMed Central

Volatile organic compounds (VOCs) in honey are obtained from diverse biosynthetic pathways and extracted by using various methods associated with varying degrees of selectivity and effectiveness. These compounds are grouped into chemical categories such as aldehyde, ketone, acid, alcohol, hydrocarbon, norisoprenoids, terpenes and benzene compounds and their derivatives, furan and pyran derivatives. They represent a fingerprint of a specific honey and therefore could be used to differentiate between monofloral honeys from different floral sources, thus providing valuable information concerning the honey’s botanical and geographical origin. However, only plant derived compounds and their metabolites (terpenes, norisoprenoids and benzene compounds and their derivatives) must be employed to discriminate among floral origins of honey. Notwithstanding, many authors have reported different floral markers for honey of the same floral origin, consequently sensory analysis, in conjunction with analysis of VOCs could help to clear this ambiguity. Furthermore, VOCs influence honey’s aroma described as sweet, citrus, floral, almond, rancid, etc. Clearly, the contribution of a volatile compound to honey aroma is determined by its odor activity value. Elucidation of the aroma compounds along with floral origins of a particular honey can help to standardize its quality and avoid fraudulent labeling of the product. Although only present in low concentrations, VOCS could contribute to biomedical activities of honey, especially the antioxidant effect due to their natural radical scavenging potential. PMID:22272147

Manyi-Loh, Christy E.; Ndip, Roland N.; Clarke, Anna M.

2011-01-01

392

Interstitial chromatin alteration causes persistent p53 activation involved in the radiation-induced senescence-like growth arrest  

SciTech Connect

Various stresses including ionizing radiation give normal human fibroblasts a phenotype of senescence-like growth arrest (SLGA), manifested by p53-dependent irreversible G1 arrest. To determine the mechanism of persistent activation of p53, we examined phosphorylated Ataxia telangiectasia mutated (ATM) and phosphorylated histone H2AX foci formation after X-irradiation. Although the multiple tiny foci, detected soon after (<30 min) irradiation, gradually disappeared, some of these foci changed to large foci and persisted for 5 days. Large foci containing phosphorylated ATM and {gamma}-H2AX co-localized and foci with p53 phosphorylated at serine 15 also showed the same distribution. Interestingly, the signals obtained by telomere fluorescence in situ hybridization (FISH) assay did not co-localize with 90% of the large foci. Our results indicate that chromatin alteration in interstitial chromosomal regions is the most likely cause of continuous activation of p53, which results in the induction of SLGA by ionizing radiation.