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1.
J Biol Chem ; 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32241912

RESUMO

The ATPase SecA is an essential component of the bacterial Sec machinery, which transports proteins across the cytoplasmic membrane. Most SecA proteins contain a long C-terminal tail (CTT). In Escherichia coli, the CTT contains a structurally flexible linker domain and a small metal-binding domain (MBD). The MBD coordinates zinc via a conserved cysteine-containing motif and binds to SecB and ribosomes. In this study, we screened a high-density transposon library for mutants that affect the susceptibility of E. coli to sodium azide, which inhibits SecA-mediated translocation. Results from sequencing this library suggested that mutations removing the CTT make E. coli less susceptible to sodium azide at subinhibitory concentrations. Copurification experiments suggested that the MBD binds to iron and that azide disrupts iron binding. Azide also disrupted binding of SecA to membranes. Two other E. coli proteins that contain SecA-like MBDs, YecA and YchJ, also copurified with iron, and NMR spectroscopy experiments indicated that YecA binds iron via its MBD. Competition experiments and equilibrium binding measurements indicated that the SecA MBD binds preferentially to iron and that a conserved serine is required for this specificity. Finally, structural modelling suggested a plausible model for the octahedral coordination of iron. Taken together, our results suggest that SecA-like MBDs likely bind to iron in vivo.

2.
Int J Sports Physiol Perform ; : 1-8, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31672928

RESUMO

PURPOSE: To compare the effects of velocity-based training (VBT) vs percentage-based training (PBT) on strength, speed, and jump performance in academy rugby league players during a 7-wk in-season mesocycle. METHODS: A total of 27 rugby league players competing in the Super League U19s Championship were randomized to VBT (n = 12) or PBT (n = 15). Both groups completed a 7-wk resistance-training intervention (2×/wk) that involved the back squat. The PBT group used a fixed load based on a percentage of 1-repetition maximum (1-RM), whereas the VBT group used a modifiable load based on individualized velocity thresholds. Biomechanical and perceptual data were collected during each training session. Back-squat 1-RM, countermovement jump, reactive strength index, sprint times, and back-squat velocity at 40-90% 1-RM were assessed pretraining and posttraining. RESULTS: The PBT group showed likely to most likely improvements in 1-RM strength and reactive strength index, whereas the VBT group showed likely to very likely improvements in 1-RM strength, countermovement jump height, and back-squat velocity at 40% and 60% 1-RM. Sessional velocity and power were most likely greater during VBT compared with PBT (standardized mean differences = 1.8-2.4), while time under tension and perceptual training stress were likely lower (standardized mean differences = 0.49-0.66). The improvement in back-squat velocity at 60% 1-RM was likely greater following VBT compared with PBT (standardized mean difference = 0.50). CONCLUSION: VBT can be implemented during the competitive season, instead of traditional PBT, to improve training stimuli, decrease training stress, and promote velocity-specific adaptations.

3.
J Laparoendosc Adv Surg Tech A ; 29(10): 1330-1333, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31436514

RESUMO

Background: The management of neonatal short bowel syndrome can be challenging, and it is critical that these babies are managed in a multidisciplinary team setting with specialists who are experienced in the complex management of these children. One of the surgical strategies, initially published by the Bianchi team in Manchester, UK, is controlled tissue expansion program (CTE) which is done via the insertion of catheters into the proximal and distal bowel in the form of tube stomas. The clamping of the proximal tube allows for an increase in length and circumferential diameter of the proximal bowel for a period of time, whilst the distal tube stoma allows for easy refeeding of proximal bowel contents into the distal bowel. Method: CTE is associated with the risk of dislodgement and exposing patients to further surgical procedures with the risk of losing more bowel length. This article describes a new method in the management of such a complication through a less invasive approach of an image-guided procedure by interventional radiologists. Conclusion: Radiologically guided tube stoma reinsertion in a child with ultrashort bowel syndrome is a promising technique and should be considered in a CTE program in the management of short bowel syndrome.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Síndrome do Intestino Curto/cirurgia , Cirurgia Assistida por Computador/métodos , Estomas Cirúrgicos , Expansão de Tecido/métodos , Criança , Feminino , Humanos , Recém-Nascido , Intestinos/cirurgia
4.
Opt Express ; 27(7): 10221-10233, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31045166

RESUMO

We report a coherent terahertz (THz) imaging system that utilises a quantum cascade laser (QCL) operating in pulsed-mode as both the source and detector. The realisation of a short-pulsed THz QCL feedback interferometer permits both high peak powers and improved thermal efficiency, which enables the cryogen-free operation of the system. In this work, we demonstrated pulsed-mode swept-frequency laser feedback interferometry experimentally. Our interferometric detection scheme not only permits the simultaneous creation of both amplitude and phase images, but inherently suppresses unwanted background radiation. We demonstrate that the proposed system utilising microsecond pulses has the potential to achieve 0.25 mega-pixel per second acquisition rates, paving the pathway to video frame rate THz imaging.

5.
J Pediatr Surg ; 53(5): 1006-1009, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29510872

RESUMO

PURPOSE: The purpose of this study was to determine practice patterns of Canadian surgeons managing congenital pulmonary airway malformations (CPAMs) and factors influencing practice. METHODS: Pediatric surgeons in Canada were surveyed regarding their experience, evaluation, and management CPAMs, and what factors they feel qualify patients for observation vs resection. Data were summarized, and Fisher's-Exact and Kruskal-Wallis Tests applied where appropriate. RESULTS: Sixty eight percent (n=46) of surgeons responded. However, three surveys were incomplete and excluded. The median age of initial assessment by a pediatric surgeon was one month. 98% (42/43) use CXR for initial imaging, and 83% (36/43) recommend CT scan for further evaluation. Observation is offered always, almost always, or sometimes by 2%, 35% and 37%, respectively. Only 16% almost never, and 9% never offer it. Years in practice was not associated with this decision (p=0.41). Of surgeons who offer observation, 78% (28/37) use morphology to guide their decision, and 63% (21/37) use lesion size (<1cm to <5cms). 68%(23/37) consider the number of lesions, and 61%(14/23) of those only offer observation to solitary lesions. CONCLUSION: Most pediatric surgeons in Canada offer observational management to patients with asymptomatic CPAMs. While practice variations exist, detailed imaging with a CT scan early in life to determine the morphology, size, and number of lesions guides practice. LEVEL OF EVIDENCE: V.


Assuntos
Tomada de Decisão Clínica/métodos , Pneumopatias/terapia , Padrões de Prática Médica/estatística & dados numéricos , Anormalidades do Sistema Respiratório/terapia , Conduta Expectante/estatística & dados numéricos , Canadá , Humanos , Pulmão/anormalidades , Pulmão/diagnóstico por imagem , Pneumopatias/congênito , Pneumopatias/diagnóstico por imagem , Pneumonectomia/estatística & dados numéricos , Anormalidades do Sistema Respiratório/diagnóstico por imagem , Inquéritos e Questionários , Tomografia Computadorizada por Raios X/estatística & dados numéricos
6.
Pediatr Radiol ; 48(4): 471-485, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29550864

RESUMO

This paper is based on a literature review from 2011 to 2016. The paper is divided into two main sections. The first section relates to technical advances in fetal imaging techniques, including fetal motion compensation, imaging at 3.0 T, 3-D T2-weighted MRI, susceptibility-weighted imaging, computed tomography, morphometric analysis, diffusion tensor imaging, spectroscopy and fetal behavioral assessment. The second section relates to clinical updates, including cerebral lamination, migrational anomalies, midline anomalies, neural tube defects, posterior fossa anomalies, sulcation/gyration and hypoxic-ischemic insults.


Assuntos
Doenças do Sistema Nervoso Central/diagnóstico por imagem , Doenças Fetais/diagnóstico por imagem , Feto/diagnóstico por imagem , Malformações do Sistema Nervoso/diagnóstico por imagem , Neuroimagem/tendências , Feminino , Humanos , Gravidez
7.
mBio ; 9(1)2018 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-29463657

RESUMO

Transposon-directed insertion site sequencing (TraDIS) is a high-throughput method coupling transposon mutagenesis with short-fragment DNA sequencing. It is commonly used to identify essential genes. Single gene deletion libraries are considered the gold standard for identifying essential genes. Currently, the TraDIS method has not been benchmarked against such libraries, and therefore, it remains unclear whether the two methodologies are comparable. To address this, a high-density transposon library was constructed in Escherichia coli K-12. Essential genes predicted from sequencing of this library were compared to existing essential gene databases. To decrease false-positive identification of essential genes, statistical data analysis included corrections for both gene length and genome length. Through this analysis, new essential genes and genes previously incorrectly designated essential were identified. We show that manual analysis of TraDIS data reveals novel features that would not have been detected by statistical analysis alone. Examples include short essential regions within genes, orientation-dependent effects, and fine-resolution identification of genome and protein features. Recognition of these insertion profiles in transposon mutagenesis data sets will assist genome annotation of less well characterized genomes and provides new insights into bacterial physiology and biochemistry.IMPORTANCE Incentives to define lists of genes that are essential for bacterial survival include the identification of potential targets for antibacterial drug development, genes required for rapid growth for exploitation in biotechnology, and discovery of new biochemical pathways. To identify essential genes in Escherichia coli, we constructed a transposon mutant library of unprecedented density. Initial automated analysis of the resulting data revealed many discrepancies compared to the literature. We now report more extensive statistical analysis supported by both literature searches and detailed inspection of high-density TraDIS sequencing data for each putative essential gene for the E. coli model laboratory organism. This paper is important because it provides a better understanding of the essential genes of E. coli, reveals the limitations of relying on automated analysis alone, and provides a new standard for the analysis of TraDIS data.


Assuntos
Escherichia coli K12/crescimento & desenvolvimento , Escherichia coli K12/genética , Genes Essenciais , Genoma Bacteriano , Biologia Molecular/métodos , Biologia Computacional , Elementos de DNA Transponíveis , Mutagênese Insercional , Análise de Sequência de DNA
8.
Pediatr Radiol ; 47(7): 822-830, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28331936

RESUMO

Pediatric lumbar puncture can be challenging or unsuccessful for several reasons. At the same time, the excellent sonographic window into the pediatric spine provides a distinct opportunity for ultrasound-guided lumbar puncture. Minimal cerebrospinal fluid and thecal displacement by subdural or epidural hematomas are common after failed clinical attempts. Ultrasound is useful for determining a safe infraconal level for subarachnoid access. Real-time guidance increases not only the success rate but also the safety of diagnostic lumbar puncture and injections for chemotherapy and myelography. In this article, we discuss clinical and technical factors for ultrasound-guided pediatric lumbar puncture.


Assuntos
Punção Espinal/métodos , Ultrassonografia de Intervenção , Criança , Pré-Escolar , Feminino , Hematoma Epidural Craniano/etiologia , Humanos , Lactente , Recém-Nascido , Injeções Espinhais , Masculino , Posicionamento do Paciente , Fatores de Risco , Traumatismos da Medula Espinal/etiologia , Punção Espinal/efeitos adversos
9.
Elife ; 62017 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-28137359

RESUMO

Pharmacological targeting of transcription factors holds great promise for the development of new therapeutics, but strategies based on blockade of DNA binding, nuclear shuttling, or individual protein partner recruitment have yielded limited success to date. Transcription factors typically engage in complex interaction networks, likely masking the effects of specifically inhibiting single protein-protein interactions. Here, we used a combination of genomic, proteomic and biophysical methods to discover a suite of protein-protein interactions involving the SOX18 transcription factor, a known regulator of vascular development and disease. We describe a small-molecule that is able to disrupt a discrete subset of SOX18-dependent interactions. This compound selectively suppressed SOX18 transcriptional outputs in vitro and interfered with vascular development in zebrafish larvae. In a mouse pre-clinical model of breast cancer, treatment with this inhibitor significantly improved survival by reducing tumour vascular density and metastatic spread. Our studies validate an interactome-based molecular strategy to interfere with transcription factor activity, for the development of novel disease therapeutics.


Assuntos
Antineoplásicos/metabolismo , Neoplasias da Mama/prevenção & controle , Fatores de Transcrição SOXF/antagonistas & inibidores , Transcrição Genética/efeitos dos fármacos , Animais , Fenômenos Biofísicos , Vasos Sanguíneos/embriologia , Modelos Animais de Doenças , Genômica , Camundongos , Proteômica , Resultado do Tratamento , Peixe-Zebra/embriologia , Proteínas de Peixe-Zebra/antagonistas & inibidores
10.
Semin Fetal Neonatal Med ; 21(5): 312-20, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27209280

RESUMO

Ultrasound and magnetic resonance imaging are the two imaging modalities used in the assessment of the fetus. Ultrasound is the primary imaging modality, whereas magnetic resonance is used in cases of diagnostic uncertainty. Both techniques have advantages and disadvantages and therefore they are complementary. Standard axial ultrasound views of the posterior fossa are used for routine scanning for fetal anomalies, with additional orthogonal views directly and indirectly obtainable using three-dimensional ultrasound techniques. Magnetic resonance imaging allows not only direct orthogonal imaging planes, but also tissue characterization, for example to search for blood breakdown products. We review the nomenclature of several posterior fossa anomalies using standardized criteria, and we review cerebellar abnormalities based on an etiologic classification.


Assuntos
Cerebelo/anormalidades , Fossa Craniana Posterior/diagnóstico por imagem , Síndrome de Dandy-Walker/diagnóstico por imagem , Ecoencefalografia/métodos , Malformações do Sistema Nervoso/diagnóstico por imagem , Diagnóstico Pré-Natal/métodos , Cerebelo/diagnóstico por imagem , Deficiências do Desenvolvimento/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética
11.
Am J Intellect Dev Disabil ; 121(2): 111-20, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26914466

RESUMO

The present study examined the relationship between salivary cortisol and maternal responsiveness in mothers of boys with fragile X syndrome (FXS). Maternal responsivity is strongly associated with child outcomes, and children with FXS are at risk for compromised development due to intellectual disability and problem behavior. Increased understanding of the nature and underlying mechanisms of maternal responsivity in FXS is important to optimize outcomes in children with FXS and contribute to improved family cohesion. Data from 36 mother-child dyads indicated a complex age effect with elevated cortisol levels associated with high maternal responsivity scores when children are young and low responsivity scores when children are older. Implications of these findings and directions for future research are discussed.


Assuntos
Síndrome do Cromossomo X Frágil , Mães/psicologia , Poder Familiar/psicologia , Estresse Fisiológico , Estresse Psicológico/psicologia , Adulto , Pré-Escolar , Feminino , Humanos , Hidrocortisona/análise , Lactente , Masculino , Comportamento Problema , Saliva/química
13.
Neurosurg Focus ; 39(3): E2, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26323820

RESUMO

OBJECT The objective of this study was to provide a technique that could be used in the preoperative period to facilitate the surgical exploration of peripheral nerve pathology. METHODS The authors describe a technique in which 1) ultrasonography is used in the immediate preoperative period to identify target peripheral nerves, 2) an ultrasound-guided needle electrode is used to stimulate peripheral nerves to confirm their position, and then 3) a methylene blue (MB) injection is performed to mark the peripheral nerve pathology to facilitate surgical exploration. RESULTS A cohort of 13 patients with varying indications for peripheral nerve surgery is presented in which ultrasound guidance, stimulation, and MB were used to localize and create a road map for surgeries. CONCLUSIONS Preoperative ultrasound-guided MB administration is a promising technique that peripheral nerve surgeons could use to plan and execute surgery.


Assuntos
Azul de Metileno/metabolismo , Procedimentos Neurocirúrgicos/métodos , Doenças do Sistema Nervoso Periférico/diagnóstico por imagem , Doenças do Sistema Nervoso Periférico/cirurgia , Ultrassonografia de Intervenção/métodos , Adulto , Estudos de Coortes , Feminino , Humanos , Injeções Intradérmicas , Imagem por Ressonância Magnética , Masculino , Azul de Metileno/administração & dosagem , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/normas , Doenças do Sistema Nervoso Periférico/etiologia , Doenças do Sistema Nervoso Periférico/metabolismo
14.
Res Dev Disabil ; 43-44: 150-66, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26183339

RESUMO

The efficacy of function-based interventions for the treatment of severe problem behavior exhibited by individuals with intellectual and developmental disabilities (IDD) is well established. However, few studies have reported on behavioral interventions in fragile X syndrome (FXS) specifically. The present study is a consecutive case-series analysis that reports on functional analysis and treatment of problem behavior of nine children with FXS. Assessment findings were consistent with previous research indicating that among individuals with FXS, problem behavior is more commonly maintained by escape from demands and access to tangible items, relative to the broader population of individuals with IDD. Functional analysis-based behavioral interventions resulted in a mean reduction in problem behavior of 95.2% across the nine participants. Additionally, generalization of treatment effects from controlled clinical settings to home, school, and community was demonstrated. The current findings suggest that function-based behavioral interventions shown to be effective with the broader population of individuals with IDD are also effective for individuals with FXS. Our results in combination with those of previous studies describing functional analysis outcomes provide additional evidence for a unique functional behavioral phenotype for severe problem behavior in individuals with FXS. Implications of study findings for early intervention and prevention of problem behavior in children with FXS are discussed.


Assuntos
Agressão/psicologia , Terapia Comportamental , Síndrome do Cromossomo X Frágil/reabilitação , Comportamento Problema/psicologia , Comportamento Autodestrutivo/reabilitação , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtorno do Espectro Autista/psicologia , Criança , Estudos de Coortes , Síndrome do Cromossomo X Frágil/psicologia , Humanos , Masculino , Comportamento Autodestrutivo/psicologia
15.
Development ; 142(16): 2775-80, 2015 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-26160899

RESUMO

Endothelin signaling is essential for neural crest development, and dysregulated Endothelin signaling is associated with several neural crest-related disorders, including Waardenburg and other syndromes. However, despite the crucial roles of this pathway in neural crest development and disease, the transcriptional effectors directly activated by Endothelin signaling during neural crest development remain incompletely elucidated. Here, we establish that the MADS box transcription factor MEF2C is an immediate downstream transcriptional target and effector of Endothelin signaling in the neural crest. We show that Endothelin signaling activates Mef2c expression in the neural crest through a conserved enhancer in the Mef2c locus and that CRISPR-mediated deletion of this Mef2c neural crest enhancer from the mouse genome abolishes Endothelin induction of Mef2c expression. Moreover, we demonstrate that Endothelin signaling activates neural crest expression of Mef2c by de-repressing MEF2C activity through a Calmodulin-CamKII-histone deacetylase signaling cascade. Thus, these findings identify a MEF2C-dependent, positive-feedback mechanism for Endothelin induction and establish MEF2C as an immediate transcriptional effector and target of Endothelin signaling in the neural crest.


Assuntos
Endotelinas/metabolismo , Retroalimentação Fisiológica/fisiologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Crista Neural/fisiologia , Transdução de Sinais/fisiologia , Animais , Galactosídeos , Hibridização In Situ , Indóis , Fatores de Transcrição MEF2/metabolismo , Camundongos , Camundongos Transgênicos , Crista Neural/metabolismo , beta-Galactosidase
16.
Analyst ; 140(3): 779-85, 2015 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-25460852

RESUMO

The demand for methods and technologies capable of rapid, inexpensive and continuous monitoring of health status or exposure to environmental pollutants persists. In this work, the development of novel surface-enhanced Raman spectroscopy (SERS) substrates from metal-coated silk fabric, known as zari, presents the potential for SERS substrates to be incorporated into clothing and other textiles for the routine monitoring of important analytes, such as disease biomarkers or environmental pollutants. Characterization of the zari fabric was completed using scanning electron microscopy, energy dispersive X-ray analysis and Raman spectroscopy. Silver nanoparticles (AgNPs) were prepared, characterized by transmission electron microscopy and UV-vis spectroscopy, and used to treat fabric samples by incubation, drop-coating and in situ synthesis. The quality of the treated fabric was evaluated by collecting the SERS signal of 4,4'-bipyridine on these substrates. When AgNPs were drop-coated on the fabric, sensitive and reproducible substrates were obtained. Adenine was selected as a second probe molecule, because it dominates the SERS signal of DNA, which is an important class of disease biomarker, particularly for pathogens such as Plasmodium spp. and Mycobacterium tuberculosis. Excellent signal enhancement could be achieved on these affordable substrates, suggesting that the developed fabric chips have the potential for expanding the use of SERS as a diagnostic and environmental monitoring tool for application in wearable sensor technologies.


Assuntos
DNA Bacteriano/análise , Nanopartículas Metálicas/química , Seda/análise , Prata/química , Análise Espectral Raman/métodos , Têxteis/análise , Poluentes Ambientais/análise , Microscopia Eletrônica de Varredura/métodos , Microscopia Eletrônica de Transmissão/métodos , Piridinas/química , Seda/química , Seda/economia , Propriedades de Superfície
17.
Dev Biol ; 395(2): 379-389, 2014 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-25179465

RESUMO

Endothelin-converting enzyme-1 (Ece-1), a crucial component of the Endothelin signaling pathway, is required for embryonic development and is an important regulator of vascular tone, yet the transcriptional regulation of the ECE1 gene has remained largely unknown. Here, we define the activity and regulation of an enhancer from the human ECE1 locus in vivo. The enhancer identified here becomes active in endothelial progenitor cells shortly after their initial specification and is dependent on a conserved FOX:ETS motif, a composite binding site for Forkhead transcription factors and the Ets transcription factor Etv2, for activity in vivo. The ECE1 FOX:ETS motif is bound and cooperatively activated by FoxC2 and Etv2, but unlike other described FOX:ETS-dependent enhancers, ECE1 enhancer activity becomes restricted to arterial endothelium and endocardium by embryonic day 9.5 in transgenic mouse embryos. The ECE1 endothelial enhancer also contains an evolutionarily-conserved, consensus SOX binding site, which is required for activity in transgenic mouse embryos. Importantly, the ECE1 SOX site is bound and activated by Sox17, a transcription factor involved in endothelial cell differentiation and an important regulator of arterial identity. Moreover, the ECE1 enhancer is cooperatively activated by the combinatorial action of FoxC2, Etv2, and Sox17. Although Sox17 is required for arterial identity, few direct transcriptional targets have been identified in endothelial cells. Thus, this work has important implications for our understanding of endothelial specification and arterial subspecification.


Assuntos
Ácido Aspártico Endopeptidases/metabolismo , Endocárdio/embriologia , Endotélio Vascular/embriologia , Fatores de Transcrição Forkhead/metabolismo , Metaloendopeptidases/metabolismo , Fatores de Transcrição SOXF/metabolismo , Fatores de Transcrição/metabolismo , Animais , Ácido Aspártico Endopeptidases/genética , Clonagem Molecular , Primers do DNA/genética , Ensaio de Desvio de Mobilidade Eletroforética , Endocárdio/metabolismo , Enzimas Conversoras de Endotelina , Endotélio Vascular/metabolismo , Elementos Facilitadores Genéticos/genética , Imunofluorescência , Galactosídeos , Humanos , Indóis , Metaloendopeptidases/genética , Camundongos , Camundongos Transgênicos , Mutagênese , Fatores de Transcrição SOX/metabolismo
18.
Dev Biol ; 393(2): 245-254, 2014 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-25050930

RESUMO

Coordinated contraction of the heart is essential for survival and is regulated by the cardiac conduction system. Contraction of ventricular myocytes is controlled by the terminal part of the conduction system known as the Purkinje fiber network. Lineage analyses in chickens and mice have established that the Purkinje fibers of the peripheral ventricular conduction system arise from working myocytes during cardiac development. It has been proposed, based primarily on gain-of-function studies, that Endothelin signaling is responsible for myocyte-to-Purkinje fiber transdifferentiation during avian heart development. However, the role of Endothelin signaling in mammalian conduction system development is less clear, and the development of the cardiac conduction system in mice lacking Endothelin signaling has not been previously addressed. Here, we assessed the specification of the cardiac conduction system in mouse embryos lacking all Endothelin signaling. We found that mouse embryos that were homozygous null for both ednra and ednrb, the genes encoding the two Endothelin receptors in mice, were born at predicted Mendelian frequency and had normal specification of the cardiac conduction system and apparently normal electrocardiograms with normal QRS intervals. In addition, we found that ednra expression within the heart was restricted to the myocardium while ednrb expression in the heart was restricted to the endocardium and coronary endothelium. By establishing that ednra and ednrb are expressed in distinct compartments within the developing mammalian heart and that Endothelin signaling is dispensable for specification and function of the cardiac conduction system, this work has important implications for our understanding of mammalian cardiac development.


Assuntos
Endotelinas/metabolismo , Contração Miocárdica/fisiologia , Ramos Subendocárdicos/embriologia , Receptores de Endotelina/genética , Animais , Diferenciação Celular , Transdiferenciação Celular , Conexina 43/biossíntese , Conexinas/biossíntese , Endocárdio/metabolismo , Endotélio/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Camundongos , Camundongos Knockout , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Organogênese , Ramos Subendocárdicos/fisiologia , Receptores de Endotelina/biossíntese , Transdução de Sinais
20.
J Gerontol Soc Work ; 57(2-4): 349-61, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24237011

RESUMO

Previous literature has consistently discussed reoccurring issues with conducting research in the gay and lesbian community and, for the purposes of this article, particularly the older lesbian community. Issues with sampling, including gaining access, ethical considerations, and conceptual definitions are ongoing struggles repeated within the literature. This article provides the experience of a research team in conducting such research and presents the viable solutions and ongoing barriers, as well as newer considerations that future research must take into account. In addition, this article provides the viewpoint of 189 older lesbians on the future research needs within their community.


Assuntos
Homossexualidade Feminina , Pesquisa , Idoso , Grupos de Populações Continentais/psicologia , Ética em Pesquisa , Feminino , Necessidades e Demandas de Serviços de Saúde , Homossexualidade Feminina/psicologia , Humanos , Projetos de Pesquisa , Amostragem , Serviço Social , Inquéritos e Questionários
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