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1.
Proc Natl Acad Sci U S A ; 113(44): E6813-E6822, 2016 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-27742790

RESUMO

Substrate rigidity affects many physiological processes through mechanochemical signals from focal adhesion (FA) complexes that subsequently modulate gene expression. We find that shuttling of the LIM domain (domain discovered in the proteins, Lin11, Isl-1, and Mec-3) protein four-and-a-half LIM domains 2 (FHL2) between FAs and the nucleus depends on matrix mechanics. In particular, on soft surfaces or after the loss of force, FHL2 moves from FAs into the nucleus and concentrates at RNA polymerase (Pol) II sites, where it acts as a transcriptional cofactor, causing an increase in p21 gene expression that will inhibit growth on soft surfaces. At the molecular level, shuttling requires a specific tyrosine in FHL2, as well as phosphorylation by active FA kinase (FAK). Thus, we suggest that FHL2 phosphorylation by FAK is a critical, mechanically dependent step in signaling from soft matrices to the nucleus to inhibit cell proliferation by increasing p21 expression.


Assuntos
Movimento Celular/fisiologia , Núcleo Celular/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Proteínas do Citoesqueleto/fisiologia , Proteínas com Homeodomínio LIM/metabolismo , Mecanotransdução Celular/fisiologia , Proteínas Musculares/metabolismo , Fatores de Transcrição/metabolismo , Animais , Adesão Celular/fisiologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p21/genética , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Adesões Focais/metabolismo , Regulação da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas com Domínio LIM/genética , Proteínas com Domínio LIM/metabolismo , Proteínas com Homeodomínio LIM/genética , Camundongos , Proteínas Musculares/genética , Miosina Tipo II/metabolismo , Fosforilação , Mutação Puntual , RNA Polimerase II , Transdução de Sinais , Fatores de Transcrição/genética , Tirosina
2.
J Cell Sci ; 129(10): 1981-8, 2016 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-27068537

RESUMO

The nuclear transport of paxillin appears to be crucial for paxillin function but the mechanism of transport remains unclear. Here, we show that the nuclear transport of paxillin is regulated by focal adhesion turnover and the presence of FAT domains. Focal adhesion turnover was controlled using triangular or circular fibronectin islands. Circular islands caused higher focal adhesion turnover and increased the nuclear transport of paxillin relative to triangular islands. Mutating several residues of paxillin had no effect on its nuclear transport, suggesting that the process is controlled by multiple domains. Knocking out FAK (also known as PTK2) and vinculin caused an increase in nuclear paxillin. This could be reversed by rescue with wild-type FAK but not by FAK with a mutated FAT domain, which inhibits paxillin binding. Expressing just the FAT domain of FAK not only brought down nuclear levels of paxillin but also caused a large immobile fraction of paxillin to be present at focal adhesions, as demonstrated by fluorescence recovery after photobleaching (FRAP) studies. Taken together, focal adhesion turnover and FAT domains regulate the nuclear localization of paxillin, suggesting a possible role for transcriptional control, through paxillin, by focal adhesions.


Assuntos
Adesão Celular/genética , Quinase 1 de Adesão Focal/genética , Adesões Focais/genética , Paxilina/metabolismo , Transporte Ativo do Núcleo Celular/genética , Fibroblastos/metabolismo , Fibronectinas/genética , Adesões Focais/metabolismo , Técnicas de Inativação de Genes , Humanos , Paxilina/genética , Ligação Proteica , Domínios Proteicos , Vinculina/genética , Vinculina/metabolismo
3.
Appl Opt ; 53(16): 3574-80, 2014 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-24922436

RESUMO

A design strategy for the development of an all-optical, temperature insensitive, nonpendulum-type tilt sensor employing fiber Bragg gratings (FBGs) is proposed and experimentally demonstrated. Being nonpendulum-type, there is no possibility of any inherent friction and the limiting effects at mechanical joints. The sensor is observed to be capable of measuring magnitude, as well as the direction of inclination from horizontal strategically more effectively and without any inherent instability. This is reflected in a relatively better resolution (better than 0.004°), a better accuracy (~±0.05°), and a lesser maximum discrepancy (~±0.001 nm) during the forward as well as the reverse tilt. Sensitivity of the proposed sensor, theoretically proportional to the half of the mass employed in the sensor design, is observed to be 0.012 nm/° with a comparatively smaller mass. Importantly, sensor response is characterized by a very high degree of reversibility and repeatability over the designed/observed dynamic range.

4.
Appl Opt ; 52(22): 5493-9, 2013 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-23913070

RESUMO

An all-optical humidity sensor based on direct and exhaustive guided-mode attenuation in an in-house developed zinc oxide (ZnO) nanoparticle-immobilized bare solgel fiber is reported. The main objective of the present work is to enhance the sensitivity considerably while realizing a throughout linear response over a wide dynamic range. The developed sensor is characterized and performance characteristics of the sensor are compared with an optical fiber humidity sensor employing an evanescent wave absorption scheme in a straight and uniform probe, with ZnO nanoparticles-immobilized solgel film as humidity sensing cladding. Sensor response is observed to be linear over a wide dynamic range of 5%-95% relative humidity (RH). The observed linear sensitivity is 0.0103/% RH, which is ~9 times higher than the sensor employing the evanescent wave absorption scheme. In addition, sensor response is observed to be very fast, highly reversible, and repeatable.

5.
Appl Opt ; 51(12): 2164-71, 2012 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-22534929

RESUMO

An optical fiber humidity sensor employing an in-house scaled TiO2-nanoparticle doped nanostructured thin film as the fiber sensing cladding and evanescent wave absorption is reported. The main objective of the present work is to achieve a throughout-linear sensor response with high sensitivity, possibly over a wide dynamic range using the simplest possible sensor geometry. In order to realize this, first, the nanostructured sensing film is synthesized over a short length of a centrally decladded straight and uniform optical fiber and then a comprehensive experimental investigation is carried out to optimize the design configuration/parameters of the nanostructured sensing film and to achieve the best possible sensor response. Much improved sensitivity of 27.1 mV/%RH is observed for the optimized sensor along with a throughout-linear sensor response over a dynamic range as wide as 24% to 95%RH with an average response time of 0.01 s for humidification and 0.06 s for desiccation. In addition, the sensor exhibits a very good degree of reversibility and repeatability.


Assuntos
Nanopartículas Metálicas/química , Nanotecnologia/métodos , Fibras Ópticas , Titânio/química , Monitoramento Ambiental/instrumentação , Monitoramento Ambiental/métodos , Desenho de Equipamento , Umidade , Microscopia Eletrônica de Transmissão/métodos , Nanoestruturas , Óptica e Fotônica , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Fatores de Tempo
6.
Appl Opt ; 50(27): 5310-4, 2011 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-21947051

RESUMO

The main objective of the present work is to develop an optical fiber relative humidity (RH) sensor having a linear response throughout over the widest possible dynamic range. We report an optical fiber RH sensor based on the evanescent wave absorption spectroscopy that fulfills this objective. The fiber sensor employs a specific nanoparticle (zinc oxide) doped sol-gel nanostructured sensing film of optimum thickness, synthesized over a short length of a centrally decladded straight and uniform optical fiber. A detailed experimental investigation is carried out to analyze the sensor response/characteristics. Fiber sensor response is observed to be linear throughout the dynamic range as wide as 4% to 96% RH. The observed linear sensitivity for the fiber sensor is 0.0012 RH(-1). The average response time of the reported sensor is observed to be as short as 0.06 s during the humidification. In addition, the sensor exhibited a very good degree of reversibility and extremely high reliability as well as repeatability.


Assuntos
Tecnologia de Fibra Óptica/instrumentação , Umidade , Nanopartículas/química , Fibras Ópticas , Monitoramento Ambiental/instrumentação , Monitoramento Ambiental/métodos , Desenho de Equipamento , Géis , Lasers , Fotometria , Sensibilidade e Especificidade , Óxido de Zinco
7.
J Ethnopharmacol ; 84(1): 99-104, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12499083

RESUMO

Traditional physicians in and around Kotagiri village near Ootacamund, use a mixture of powdered roots of Cassia occidentalis, Derris brevipes variety coriacea and Justicia simplex to control female fertility. A mixture of powdered roots of these three plants, powdered root of Derris brevipes variety coriacea and its ethanolic extract were screened for antifertility activity in proven fertile female rats at 200 and 600 mg/kg body weight, respectively and given orally on D(1-7) of pregnancy. Both doses of the root powder of Derris brevipes variety coriacea showed 50% anti-implantation activity and also a significant reduction in the number of litters born. The ethanolic extract exhibited 40% anti-implantation activity when given orally at 600 mg/kg body weight. The rats, which continued their pregnancy, did not deliver any litters after their full term. Hence, the combined antifertility (anti-implantation and abortifacient) activity of the ethanolic extract was 100%. The results suggest that the ethanolic extract possesses more abortifacient type effect than the anti-implantation activity. The ethanolic extract also exhibited weak estrogenic activity when given alone and tested in immature ovariectomised female albino rats. But, when given along with ethinyl estradiol, it exhibited slight antiestrogenic activity. Histological and biochemical estimations were carried out to confirm this.


Assuntos
Cassia/química , Anticoncepcionais/farmacologia , Derris/química , Justicia/química , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Abortivos/farmacologia , Abortivos/toxicidade , Aborto Induzido , Animais , Anticoncepcionais/toxicidade , Implantação do Embrião/efeitos dos fármacos , Moduladores de Receptor Estrogênico/farmacologia , Moduladores de Receptor Estrogênico/toxicidade , Estrogênios/farmacologia , Estrogênios/toxicidade , Etinilestradiol/farmacologia , Feminino , Índia , Extratos Vegetais/química , Extratos Vegetais/toxicidade , Plantas Medicinais , Gravidez , Ratos , Ratos Wistar , Útero/efeitos dos fármacos , Útero/metabolismo
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