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1.
Nurs Sci Q ; 37(3): 286-290, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38836476

RESUMO

The authors, who are nursing faculty members and leaders at a faith-based institution of higher education, discuss their concept of wisdom and how it guides their teaching and practice. Wisdom is seen by them as a universal humanuniverse living experience that is inspired and cocreated with their faith and understanding of God with others. They apply the concept of wisdom in global service experiences that their institution supports. These experiences strengthen their inherent core whatness as they cocreate what is important in the moment while participating in teaching-learning.


Assuntos
Docentes de Enfermagem , Humanos , Ensino , Aprendizagem , Conhecimento
2.
PLoS One ; 17(11): e0275469, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36322519

RESUMO

Standardized cross-cultural databases of the arts are critical to a balanced scientific understanding of the performing arts, and their role in other domains of human society. This paper introduces the Global Jukebox as a resource for comparative and cross-cultural study of the performing arts and culture. The Global Jukebox adds an extensive and detailed global database of the performing arts that enlarges our understanding of human cultural diversity. Initially prototyped by Alan Lomax in the 1980s, its core is the Cantometrics dataset, encompassing standardized codings on 37 aspects of musical style for 5,776 traditional songs from 1,026 societies. The Cantometrics dataset has been cleaned and checked for reliability and accuracy, and includes a full coding guide with audio training examples (https://theglobaljukebox.org/?songsofearth). Also being released are seven additional datasets coding and describing instrumentation, conversation, popular music, vowel and consonant placement, breath management, social factors, and societies. For the first time, all digitized Global Jukebox data are being made available in open-access, downloadable format (https://github.com/theglobaljukebox), linked with streaming audio recordings (theglobaljukebox.org) to the maximum extent allowed while respecting copyright and the wishes of culture-bearers. The data are cross-indexed with the Database of Peoples, Languages, and Cultures (D-PLACE) to allow researchers to test hypotheses about worldwide coevolution of aesthetic patterns and traditions. As an example, we analyze the global relationship between song style and societal complexity, showing that they are robustly related, in contrast to previous critiques claiming that these proposed relationships were an artifact of autocorrelation (though causal mechanisms remain unresolved).


Assuntos
Música , Humanos , Reprodutibilidade dos Testes , Comparação Transcultural , Idioma , Bases de Dados Factuais , Cultura
3.
Br J Radiol ; 95(1139): 20220459, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36063424

RESUMO

OBJECTIVES: To undertake a national survey of the Radiotherapy Dosimetrist workforce within the UK; examining different attributes and experiences, comparing results with published evidence within the literature. METHODS: A national, anonymised survey was undertaken between Dec 2020 and end of Feb 2021; employing a mixed-methods approach and blend of closed, open-ended answer choices and free-text comments. Questions included range of training routes and job titles; registration status; job tasks and engagement with Continuing Professional Development (CPD). RESULTS: A total of 223 individuals responded. Nearly half were trained via therapeutic radiography; approximately, a fifth through a clinical technologist/physics routes. Most (70%) had Dosimetrist in their job title. Nearly 70% were statutorily registered, and almost a fifth were in the voluntary register of Clinical Technologists. Most job tasks were in treatment planning - with 57% spending over 70% of their time there. Most notably, 29% were not involved in any CPD scheme. No published evidence showed the same aspects identified here. CONCLUSIONS: Our survey showed a unique profile of the Radiotherapy Dosimetrist workforce in the UK, with a variety of training routes and statutory registration status. Nearly, a third were not engaged in a CPD scheme - adding to the current discussion that perhaps all Dosimetrists should be statutorily registered, for ensuring safe and effective clinical practice. ADVANCES IN KNOWLEDGE: A novel and unique national survey of Dosimetrists working in Radiotherapy in the UK is presented, leading to new insights into current training routes, registration status, job tasks and CPD engagement and needs.


Assuntos
Radioterapia (Especialidade) , Humanos , Recursos Humanos , Inquéritos e Questionários , Reino Unido
4.
PLoS One ; 14(6): e0218179, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31194794

RESUMO

The Laban Movement Analysis system (LMA) is a widely used system for the description of human movement. Here we present results of an empirical analysis of the reliability of the LMA system. Firstly, we developed a directed graph-based representation for the formalization of LMA. Secondly, we implemented a custom video annotation tool for stimulus presentation and annotation of the formalized LMA. Using these two elements, we conducted an experimental assessment of LMA reliability. In the experimental assessment of the reliability, experts-Certified Movement Analysts (CMA)-were tasked with identifying the differences between a "neutral" movement and the same movement executed with a specific variation in one of the dimensions of the LMA parameter space. The videos represented variations on the pantomimed movement of knocking at a door or giving directions. To be as close as possible to the annotation practice of CMAs, participants were given full control over the number of times and order in which they viewed the videos. The LMA annotation was captured by means of the video annotation tool that guided the participants through the LMA graph by asking them multiple-choice questions at each node. Participants were asked to first annotate the most salient difference (round 1), and then the second most salient one (round 2) between a neutral and gesture and the variation. To quantify the overall reliability of LMA, we computed Krippendorff's α. The quantitative data shows that the reliability, depending on how the two rounds are integrated, ranges between a weak and an acceptable reliability of LMA. The analysis of viewing behavior showed that, despite relatively large differences at the inter-individual level, there is no simple relationship between viewing behavior and individual performance (quantified as the level of agreement of the individual with the dominant rating). This research advances the state of the art in formalizing and implementing a reliability measure for the Laban Movement Analysis system. The experimental study we conducted allows identifying some of the strengths and weaknesses of the widely used movement coding system. Additionally, we have gained useful insights into the assessment procedure itself.


Assuntos
Movimento , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Gravação em Vídeo/métodos
6.
Front Hum Neurosci ; 8: 188, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24782734

RESUMO

Although efforts to characterize human movement through electroencephalography (EEG) have revealed neural activities unique to limb control that can be used to infer movement kinematics, it is still unknown the extent to which EEG can be used to discern the expressive qualities that influence such movements. In this study we used EEG and inertial sensors to record brain activity and movement of five skilled and certified Laban Movement Analysis (LMA) dancers. Each dancer performed whole body movements of three Action types: movements devoid of expressive qualities ("Neutral"), non-expressive movements while thinking about specific expressive qualities ("Think"), and enacted expressive movements ("Do"). The expressive movement qualities that were used in the "Think" and "Do" actions consisted of a sequence of eight Laban Effort qualities as defined by LMA-a notation system and language for describing, visualizing, interpreting and documenting all varieties of human movement. We used delta band (0.2-4 Hz) EEG as input to a machine learning algorithm that computed locality-preserving Fisher's discriminant analysis (LFDA) for dimensionality reduction followed by Gaussian mixture models (GMMs) to decode the type of Action. We also trained our LFDA-GMM models to classify all the possible combinations of Action Type and Laban Effort quality (giving a total of 17 classes). Classification accuracy rates were 59.4 ± 0.6% for Action Type and 88.2 ± 0.7% for Laban Effort quality Type. Ancillary analyses of the potential relations between the EEG and movement kinematics of the dancer's body, indicated that motion-related artifacts did not significantly influence our classification results. In summary, this research demonstrates that EEG has valuable information about the expressive qualities of movement. These results may have applications for advancing the understanding of the neural basis of expressive movements and for the development of neuroprosthetics to restore movements.

9.
AJS ; 114(4): 924-76, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19824299

RESUMO

Data from 44 societies are used to explore sex segregation by field of study. Contrary to accounts linking socioeconomic modernization to a "degendering" of public-sphere institutions, sex typing of curricular fields is stronger in more economically developed contexts. The authors argue that two cultural forces combine in advanced industrial societies to create a new sort of sex segregation regime. The first is gender-essentialist ideology, which has proven to be extremely resilient even in the most liberal-egalitarian of contexts; the second is self-expressive value systems, which create opportunities and incentives for the expression of "gendered selves." Multivariate analyses suggest that structural features of postindustrial labor markets and modern educational systems support the cultivation, realization, and display of gender-specific curricular affinities.


Assuntos
Comparação Transcultural , Currículo/estatística & dados numéricos , Estudantes/estatística & dados numéricos , Escolha da Profissão , Países Desenvolvidos/estatística & dados numéricos , Economia/estatística & dados numéricos , Escolaridade , Feminino , Identidade de Gênero , Humanos , Análise Multivariada , Fatores Sexuais , Estereotipagem
10.
Pediatr Crit Care Med ; 9(1): 40-6, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18477912

RESUMO

OBJECTIVE: Few data exist on successes at reducing pediatric catheter-associated bloodstream infections (CA-BSI). The objective was to eradicate CA-BSI with a multifaceted pediatric-relevant intervention proven effective in adult patients. DESIGN: Prospective cohort of pediatric intensive care (PICU) patients with historical controls. SETTING: Multidisciplinary PICU. PATIENTS/PARTICIPANTS: PICU patients with intervention targeting PICU providers. INTERVENTIONS: Multifaceted intervention involving preintervention staff surveys, provider educational program, creation of central catheter procedure cart, guideline-supported central catheter insertion checklist, nursing staff empowerment to stop procedures that breached guidelines, and real-time data feedback to PICU leadership. MEASUREMENTS AND MAIN RESULTS: We measured rate of CA-BSI per 1000 catheter days from August 2001 through September 2006. Reliable use of evidence-based best practices for insertion of central catheters in our PICU was associated with a statistically and clinically significant decrease in our CA-BSI rate for 24 months postintervention (p < .05). During a portion of this postintervention period, we experienced a dramatic increase in our CA-BSI rate that was ultimately found to be due to the introduction of a new positive displacement mechanical valve intravenous port in April 2004. After removal of this positive displacement mechanical valve, our CA-BSI rate dropped from 5.2 +/- 4.5 CA-BSI per 1000 central catheter days to a rate of 3.0 +/- 1.9 CA-BSI per 1000 central catheter days. Chart review of postintervention CA-BSI cases revealed that these patients acquired CA-BSI weeks after both PICU admission and after insertion of the most recent central catheter. CONCLUSIONS: Our data show that improving practices for insertion of central catheters leads to a reduction of CA-BSI among pediatric patients but not elimination of CA-BSI. More research is needed to identify best practices for maintenance of central catheters for children. In addition, our experience shows that even despite good interventions to control CA-BSI, institutions must remain vigilant to factors such as new technology with apparent advantages but short track records of use.


Assuntos
Bacteriemia/prevenção & controle , Cateterismo Venoso Central/efeitos adversos , Infecção Hospitalar/prevenção & controle , Unidades de Terapia Intensiva Pediátrica , Adolescente , Adulto , Bacteriemia/etiologia , Baltimore , Patógenos Transmitidos pelo Sangue , Criança , Pré-Escolar , Estudos de Coortes , Infecção Hospitalar/epidemiologia , Humanos , Auditoria Médica , Estudos Prospectivos
11.
Obstet Gynecol ; 108(6): 1417-22, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17138775

RESUMO

OBJECTIVE: Modern intrauterine devices (IUDs) are safe, effective, and reversible, but only 2.1% of U.S. women use IUDs. We aimed to estimate young pregnant women's knowledge of IUDs. METHODS: We surveyed 190 women, aged 14-25 years, presenting for prenatal or abortion care about their contraceptive history, plans, and knowledge. We asked if they had heard of IUDs and queried them on IUD characteristics. RESULTS: The women were, on average, 20 years old, 27% had education past high school, and 47% had delivered a child. Half were in prenatal care, and 91% had not planned their current pregnancy. Fifty-two percent wished to wait 4 or more years before their next pregnancy, and 27% did not want to be pregnant ever again. Safety and efficacy were the most important factors in choosing a contraceptive method. Fifty percent had heard of IUDs, 71% did not know about IUDs' safety, and 58% did not know about IUDs' efficacy. Respondents who knew of IUDs were older (21 versus 19 years, P<.001) and more likely to be parous (55% versus 39%, P=.04). CONCLUSION: Young women choosing contraception after a pregnancy would benefit from counseling about the relative safety and effectiveness of IUDs, allowing them to make fully informed contraceptive decisions. LEVEL OF EVIDENCE: II-2.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Dispositivos Intrauterinos , Gravidez/psicologia , Adolescente , Adulto , Anticoncepção , Escolaridade , Feminino , Humanos
12.
Cell Calcium ; 40(5-6): 461-93, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17069885

RESUMO

In smooth muscle, Ca(2+) controls diverse activities including cell division, contraction and cell death. Of particular significance in enabling Ca(2+) to perform these multiple functions is the cell's ability to localize Ca(2+) signals to certain regions by creating high local concentrations of Ca(2+) (microdomains), which differ from the cytoplasmic average. Microdomains arise from Ca(2+) influx across the plasma membrane or release from the sarcoplasmic reticulum (SR) Ca(2+) store. A single Ca(2+) channel can create a microdomain of several micromolar near (approximately 200 nm) the channel. This concentration declines quickly with peak rates of several thousand micromolar per second when influx ends. The high [Ca(2+)] and the rapid rates of decline target Ca(2+) signals to effectors in the microdomain with rapid kinetics and enable the selective activation of cellular processes. Several elements within the cell combine to enable microdomains to develop. These include the brief open time of ion channels, localization of Ca(2+) by buffering, the clustering of ion channels to certain regions of the cell and the presence of membrane barriers, which restrict the free diffusion of Ca(2+). In this review, the generation of microdomains arising from Ca(2+) influx across the plasma membrane and the release of the ion from the SR Ca(2+) store will be discussed and the contribution of mitochondria and the Golgi apparatus as well as endogenous modulators (e.g. cADPR and channel binding proteins) will be considered.


Assuntos
Sinalização do Cálcio/fisiologia , Microdomínios da Membrana/fisiologia , Músculo Liso/fisiologia , Animais , Cálcio/análise , Canais de Cálcio/fisiologia , Membrana Celular/fisiologia , ADP-Ribose Cíclica/fisiologia , Complexo de Golgi/fisiologia , Mitocôndrias Musculares/fisiologia , Músculo Liso/ultraestrutura , Retículo Sarcoplasmático/fisiologia , Proteínas de Ligação a Tacrolimo/fisiologia
13.
Infect Control Hosp Epidemiol ; 27(1): 67-70, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16418990

RESUMO

The technology of intravenous catheter access ports has evolved from open ports covered by removable caps to more-sophisticated, closed versions containing mechanical valves. We report a significant increase in catheter-related bloodstream infections after the introduction of a new needle-free positive-pressure mechanical valve intravenous access port at our institution.


Assuntos
Cateterismo Venoso Central/efeitos adversos , Cateteres de Demora/efeitos adversos , Infecção Hospitalar/epidemiologia , Sepse/epidemiologia , Sepse/microbiologia , Centros Médicos Acadêmicos , Adulto , Baltimore , Cateterismo Venoso Central/instrumentação , Criança , Contaminação de Equipamentos , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Pressão
14.
J Cell Sci ; 118(Pt 23): 5443-51, 2005 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-16278292

RESUMO

Ca2+ release from the sarcoplasmic reticulum (SR) by the IP3 receptors (IP3Rs) crucially regulates diverse cell signalling processes from reproduction to apoptosis. Release from the IP3R may be modulated by endogenous proteins associated with the receptor, such as the 12 kDa FK506-binding protein (FKBP12), either directly or indirectly by inhibition of the phosphatase calcineurin. Here, we report that, in addition to calcineurin, FKPBs modulate release through the mammalian target of rapamycin (mTOR), a kinase that potentiates Ca2+ release from the IP3R in smooth muscle. The presence of FKBP12 was confirmed in colonic myocytes and co-immunoprecipitated with the IP3R. In aortic smooth muscle, however, although present, FKBP12 did not co-immunoprecipitate with IP3R. In voltage-clamped single colonic myocytes rapamycin, which together with FKBP12 inhibits mTOR (but not calcineurin), decreased the rise in cytosolic Ca2+ concentration ([Ca2+]c) evoked by IP3R activation (by photolysis of caged IP3), without decreasing the SR luminal Ca2+ concentration ([Ca2+]l) as did the mTOR inhibitors RAD001 and LY294002. However, FK506, which with FKBP12 inhibits calcineurin (but not mTOR), potentiated the IP3-evoked [Ca2+]c increase. This potentiation was due to the inhibition of calcineurin; it was mimicked by the phosphatase inhibitors cypermethrin and okadaic acid. The latter two inhibitors also prevented the FK506-evoked increase as did a calcineurin inhibitory peptide (CiP). In aortic smooth muscle, where FKBP12 was not associated with IP3R, the IP3-mediated Ca2+ release was unaffected by FK506 or rapamycin. Together, these results suggest that FKBP12 has little direct effect on IP3-mediated Ca2+ release, even though it is associated with IP3R in colonic myocytes. However, FKBP12 might indirectly modulate Ca2+ release through two effector proteins: (1) mTOR, which potentiates and (2) calcineurin, which inhibits Ca2+ release from IP3R in smooth muscle.


Assuntos
Calcineurina/metabolismo , Canais de Cálcio/metabolismo , Cálcio/metabolismo , Músculo Liso Vascular/metabolismo , Proteínas Quinases/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Proteínas de Ligação a Tacrolimo/metabolismo , Animais , Canais de Cálcio/efeitos dos fármacos , Células Cultivadas , Cromonas/farmacologia , Everolimo , Cobaias , Receptores de Inositol 1,4,5-Trifosfato , Masculino , Morfolinas/farmacologia , Músculo Liso Vascular/citologia , Técnicas de Patch-Clamp , Proteínas Quinases/efeitos dos fármacos , Receptores Citoplasmáticos e Nucleares/efeitos dos fármacos , Sirolimo/análogos & derivados , Sirolimo/farmacologia , Serina-Treonina Quinases TOR , Proteína 1A de Ligação a Tacrolimo/metabolismo , Proteína 1A de Ligação a Tacrolimo/farmacologia
15.
New Dir Youth Dev ; (108): 57-76, 11-2, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16570878

RESUMO

The author examines the thinking and behavior of adolescents within the digital world. What does all this instant messaging and blogging outside school hours mean? Why do adolescents do it? How much time do they spend doing it? How does it shape their social, emotional, and moral development? Bradley describes the phenomenon and explores some moral development ramifications of a new context of social experience for adolescents. It proposes that the digital world creates its own social context, with a different set of social conventions from the adult-mediated "real" world that adolescents also inhabit. It is a social context that most adults are aware of but do not understand. Adolescents' experiences in the online world influence their experiences in the face-to-face world and play an important role in the development of their social and moral knowledge. This chapter places the discussion within the context of literature on youth ethics that has been developed based on more traditional settings.


Assuntos
Desenvolvimento do Adolescente , Atitude , Internet/estatística & dados numéricos , Relações Interpessoais , Desenvolvimento Moral , Psicologia do Adolescente/ética , Adolescente , Conscientização , Humanos , Conhecimento , Apoio Social , Interface Usuário-Computador
16.
News Physiol Sci ; 19: 138-47, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15143210

RESUMO

The sarcoplasmic reticulum (SR) and apposed regions of the sarcolemma passively trap Ca2+ entering the cell to limit the rise in cytoplasmic Ca2+ concentration without SR pump involvement. When "leaky," the SR facilitates Ca2+ entry to the cytoplasm. SR Ca2+ release via inositol 1,4,5-trisphosphate receptors (IP(3)Rs) propagates as calcium waves; IP(3)Rs alone account for wave propagation.


Assuntos
Cálcio/metabolismo , Músculo Liso/fisiologia , Retículo Sarcoplasmático/metabolismo , Animais , Citoplasma/metabolismo
17.
Cell Calcium ; 36(1): 29-41, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15126054

RESUMO

In smooth muscle, active Ca(2+) uptake into regions of sarcoplasmic reticulum (SR) which are closely apposed to the sarcolemma has been proposed to substantially limit the increase in the cytoplasmic Ca(2+) concentration ([Ca(2+)](c)) following Ca(2+) influx, i.e. the 'superficial buffer barrier hypothesis'. The present study has re-examined this proposal. The results suggest that the SR close to the sarcolemma acts as a passive barrier to Ca(2+) influx limiting [Ca(2+)](c) changes; for this, SR Ca(2+) pump activity is not required. In single voltage-clamped colonic myocytes, sustained opening of the ryanodine receptor (RyR) (and depletion of the SR) using ryanodine increased the amplitude of depolarisation-evoked Ca(2+) transients and accelerated the rate of [Ca(2+)](c) decline following depolarisation. These results could be explained by a reduction in the Ca(2+) buffer power of the cytosol taking place when RyR are opened (i.e. the SR is 'leaky'). Indeed, determination of the Ca(2+) buffer power confirmed it was reduced by approximately 40%. Inhibition of the SR Ca(2+) pump (with thapsigargin) also depleted the SR of Ca(2+) but did not reduce the Ca(2+) buffer power or increase depolarisation-evoked Ca(2+) transients and slowed (rather than accelerated) Ca(2+) removal. However, thapsigargin prevented the ryanodine-induced increase in [Ca(2+)](c) decline following depolarisation. Together, these results suggest that when the SR was rendered 'leaky' (a) more of the Ca(2+) entering the cell reached the bulk cytoplasm and (b) Ca(2+) was removed more quickly at the end of cell activation. Under physiological circumstances in the absence of blocking drugs, it is proposed that the SR limits the [Ca(2+)](c) increase following influx without the need for active Ca(2+) uptake. The SR and sarcolemma may form a passive physical barrier to Ca(2+) influx, a Ca(2+) trap, which limits the [Ca(2+)](c) rise occurring during depolarisation by about 50% and from which the ion only slowly escapes into the main part of the cytoplasm.


Assuntos
Cálcio/metabolismo , Colo/metabolismo , Músculo Liso/metabolismo , Sarcolema/metabolismo , Retículo Sarcoplasmático/metabolismo , Animais , Cálcio/fisiologia , Separação Celular , Cobaias , Masculino , Modelos Biológicos , Músculo Liso/citologia , Músculo Liso/efeitos dos fármacos , Técnicas de Patch-Clamp , Rianodina/farmacologia , Tapsigargina/farmacologia
18.
J Biol Chem ; 279(9): 8417-27, 2004 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-14660609

RESUMO

The cytosolic Ca(2+) concentration ([Ca(2+)](c)) controls diverse cellular events via various Ca(2+) signaling patterns; the latter are influenced by the method of cell activation. Here, in single-voltage clamped smooth muscle cells, sarcolemma depolarization generated uniform increases in [Ca(2+)](c) throughout the cell entirely by Ca(2+) influx. On the other hand, the Ca(2+) signal produced by InsP(3)-generating agonists was a propagated wave. Using localized uncaged InsP(3), the forward movement of the Ca(2+) wave arose from Ca(2+)-induced Ca(2+) release at the InsP(3) receptor (InsP(3)R) without ryanodine receptor involvement. The decline in [Ca(2+)](c) (the back of the wave) occurred from a functional compartmentalization of the store, which rendered the site of InsP(3)-mediated Ca(2+) release, and only this site, refractory to the phosphoinositide. The functional compartmentalization arose by a localized feedback deactivation of InsP(3) receptors produced by an increased [Ca(2+)](c) rather than a reduced luminal [Ca(2+)] or an increased cytoplasmic [InsP(3)]. The deactivation of the InsP(3) receptor was delayed in onset, compared with the time of the rise in [Ca(2+)](c), persisted (>30 s) even when [Ca(2+)](c) had regained resting levels, and was not prevented by kinase or phosphatase inhibitors. Thus different forms of cell activation generate distinct Ca(2+) signaling patterns in smooth muscle. Sarcolemma Ca(2+) entry increases [Ca(2+)](c) uniformly; agonists activate InsP(3)R and produce Ca(2+) waves. Waves progress by Ca(2+)-induced Ca(2+) release at InsP(3)R, and persistent Ca(2+)-dependent inhibition of InsP(3)R accounts for the decline in [Ca(2+)](c) at the back of the wave.


Assuntos
Cálcio/metabolismo , Inositol 1,4,5-Trifosfato/química , Inositol 1,4,5-Trifosfato/metabolismo , Músculo Liso/metabolismo , Fotólise , Animais , Cafeína/farmacologia , Cálcio/análise , Cálcio/farmacologia , Canais de Cálcio/efeitos dos fármacos , Canais de Cálcio/fisiologia , Carbacol/farmacologia , Membrana Celular/metabolismo , Colo , Condutividade Elétrica , Ativação Enzimática , Retroalimentação Fisiológica , Cobaias , Receptores de Inositol 1,4,5-Trifosfato , Cinética , Masculino , Proteína Quinase C/metabolismo , Receptores Citoplasmáticos e Nucleares/efeitos dos fármacos , Receptores Citoplasmáticos e Nucleares/fisiologia , Canal de Liberação de Cálcio do Receptor de Rianodina/fisiologia , Sarcolema/metabolismo , Transdução de Sinais
19.
J Biol Chem ; 279(11): 10702-9, 2004 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-14688253

RESUMO

The transcription factor NFAT (nuclear factor of activated T-cells) is implicated in cardiac hypertrophy and vasculogenesis. NFAT activation, reflecting dephosphorylation by the calcium-dependent phosphatase, calcineurin, and subsequent nuclear localization, is generally thought to require a sustained increase in intracellular calcium. However, in smooth muscle we have found that elevation of calcium by membrane depolarization fails to induce an increase in nuclear localization of the NFATc3 isoform. Here, we demonstrate that physiological intravascular pressure (100 mm Hg) induces an increase in NFATc3 nuclear localization in mouse cerebral arteries. Pressure-induced NFATc3 nuclear accumulation is abrogated by endothelial denudation and by nitric-oxide synthase, cGMP-dependent kinase (PKG), and voltage-dependent calcium channels inhibition. We further show that exogenous nitric oxide, in combination with an elevation in calcium, is an effective stimulus for NFATc3 nuclear accumulation. c-Jun terminal kinase 2 (JNK) activity, which has been shown to regulate NFATc3 nuclear export, is also reduced by pressure, an effect that is prevented by pretreatment with a PKG inhibitor. Consistent with this, pressure-induced NFATc3 nuclear accumulation is independent of PKG in arteries from JNK2(-/-) mice. Collectively, our results indicate that both activation of the NO/PKG pathway and elevation of smooth muscle calcium are required for NFATc3 nuclear accumulation and that PKG inhibits JNK2 to decrease NFAT nuclear export. Our findings suggest that at physiological intravascular pressures NFATc3 is localized to the nucleus in smooth muscle cells of intact arteries and indicate a novel and unexpected role for nitric oxide/PKG in NFAT activation.


Assuntos
Cálcio/metabolismo , Núcleo Celular/metabolismo , Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , Proteínas de Ligação a DNA/biossíntese , Endotélio Vascular/metabolismo , Óxido Nítrico/metabolismo , Fatores de Transcrição/biossíntese , Transporte Ativo do Núcleo Celular , Animais , Células Cultivadas , Proteínas Quinases Dependentes de GMP Cíclico/antagonistas & inibidores , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência , Proteína Quinase 9 Ativada por Mitógeno , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Modelos Biológicos , Músculo Liso/embriologia , Músculo Liso/metabolismo , Fatores de Transcrição NFATC , Óxido Nítrico Sintase/metabolismo , Fosforilação , Potássio/metabolismo , Pressão , Isoformas de Proteínas , Transporte Proteico , Fatores de Tempo
20.
J Cell Sci ; 116(Pt 21): 4291-306, 2003 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-12966165

RESUMO

Ca2+ release via ryanodine receptors (RyRs) is vital in cell signalling and regulates diverse activities such as gene expression and excitation-contraction coupling. Cyclic ADP ribose (cADPR), a proposed modulator of RyR activity, releases Ca2+ from the intracellular store in sea urchin eggs but its mechanism of action in other cell types is controversial. In this study, caged cADPR was used to examine the effect of cADPR on Ca2+ signalling in single voltage-clamped smooth muscle cells that have RyR but lack FKBP12.6, a proposed target for cADPR. Although cADPR released Ca2+ in sea urchin eggs (a positive control), it failed to alter global or subsarcolemma [Ca2+]c, to cause Ca2+-induced Ca2+ release or to enhance caffeine responses in colonic myocytes. By contrast, caffeine (an accepted modulator of RyR) was effective in these respects. The lack of cADPR activity on Ca2+ release was unaffected by the introduction of recombinant FKBP12.6 into the myocytes. Indeed in western blots, using brain membrane preparations as a source of FKBP12.6, cADPR did not bind to FKBPs, although FK506 was effective. However, cADPR increased and its antagonist 8-bromo-cADPR slowed the rate of Ca2+ removal from the cytoplasm. The evidence indicates that cADPR modulates [Ca2+]c but not via RyR; the mechanism may involve the sarcolemma Ca2+ pump.


Assuntos
Cálcio/metabolismo , ADP-Ribose Cíclica/metabolismo , Células Musculares/fisiologia , Óvulo/fisiologia , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Transdução de Sinais , Animais , ATPases Transportadoras de Cálcio/metabolismo , Calmodulina/metabolismo , Células Cultivadas , Colo/metabolismo , Citoplasma/fisiologia , Eletrofisiologia , Regulação da Expressão Gênica , Cobaias , Masculino , Músculo Liso/fisiologia , Proteínas Recombinantes/metabolismo , Ouriços-do-Mar , Tacrolimo/metabolismo , Proteínas de Ligação a Tacrolimo/metabolismo
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