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1.
Nano Lett ; 18(9): 5475-5481, 2018 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-30080970

RESUMO

We report strongly nonreciprocal behavior for quantum dot exciton spins coupled to nanophotonic waveguides under resonant laser excitation. A clear dependence of the transmission spectrum on the propagation direction is found for a chirally coupled quantum dot, with spin up and spin down exciton spins coupling to the left and right propagation directions, respectively. The reflection signal shows an opposite trend to the transmission, which a numerical model indicates is due to direction-selective saturation of the quantum dot. The chiral spin-photon interface we demonstrate breaks reciprocity of the system and opens the way to spin-based quantum optical components such as optical diodes and circulators in a chip-based solid-state environment.

2.
Endocrinology ; 148(7): 3523-31, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17446180

RESUMO

In this study, we investigated the transcriptional regulation of the adrenergic induction of type II iodothyronine deiodinase (Dio2) in rat pinealocytes. Treatment of pinealocytes with norepinephrine (NE) caused an increase in the mRNA level of Dio2 that peaked around 2 h and declined over the next 5 h. Both beta- and alpha1-adrenergic receptors contributed to the NE induction of Dio2 expression through a cAMP/protein kinase A mechanism. In pinealocytes that had been stimulated by NE, inhibition of transcription by actinomycin had no discernible effect on Dio2 expression. In contrast, inhibition of protein synthesis by cycloheximide enhanced the NE induction of Dio2 expression, suggesting the involvement of a repressor protein. Transient transfection of pinealocytes with adenovirus expressing small interfering RNA against Fos-related antigen 2 (Fra2) enhanced the NE induction of Dio2 expression, whereas the effect of overexpression of the full-length transcript of Fra2 was inhibitory. Time-course study indicated that preventing the NE induction of Fra2 enhanced the NE induction of Dio2 after 3 h, and the enhancement persisted beyond 6 h after NE stimulation. In comparison, transient transfection of pinealocytes with small interfering RNA against inducible cAMP early repressor (Icer) had no effect on the NE induction of Dio2 expression, whereas overexpression of the full-length transcript of Icer caused a small reduction of the NE-stimulated Dio2 expression. Together, our results support Fra-2 as an important transcriptional repressor that helps shape the time profile of the adrenergic induction of Dio2 expression in the rat pineal gland.


Assuntos
Iodeto Peroxidase/genética , Norepinefrina/farmacologia , Glândula Pineal/efeitos dos fármacos , Proteínas Repressoras/fisiologia , Animais , Western Blotting , Células Cultivadas , Modulador de Elemento de Resposta do AMP Cíclico/genética , Modulador de Elemento de Resposta do AMP Cíclico/metabolismo , Modulador de Elemento de Resposta do AMP Cíclico/fisiologia , Antígeno 2 Relacionado a Fos/genética , Antígeno 2 Relacionado a Fos/metabolismo , Antígeno 2 Relacionado a Fos/fisiologia , Isoproterenol/farmacologia , Masculino , Fenilefrina/farmacologia , Glândula Pineal/citologia , Glândula Pineal/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Ratos , Ratos Sprague-Dawley , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Transcrição Gênica/efeitos dos fármacos , Transfecção , Iodotironina Desiodinase Tipo II
3.
Endocrinology ; 148(10): 4592-600, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17628002

RESUMO

In this study we investigated the effect of histone acetylation on the transcription of adrenergic-induced genes in rat pinealocytes. We found that treatment of pinealocytes with trichostatin A (TSA), a histone deacetylase inhibitor, caused hyperacetylation of histone H3 (H3) Lys14 at nanomolar concentrations. Hyperacetylation of H3 was also observed after treatment with scriptaid, a structurally unrelated histone deacetylase inhibitor. The effects of TSA and scriptaid were inhibitory on the adrenergic induction of arylalkylamine-n-acetyltransferase (aa-nat) mRNA, protein, and enzyme activity, and on melatonin production. TSA at higher concentrations also inhibited the adrenergic induction of mapk phosphatase-1 (mkp-1) and inducible cAMP early repressor mRNAs. In contrast, the effect of TSA on the norepinephrine induction of the c-fos mRNA was stimulatory. Moreover, the effect of TSA on adrenergic-induced gene transcription was dependent on the time of its addition; its effect was only observed during the active phase of transcription. Chromatin immunoprecipitation with antibodies against acetylated Lys14 of H3 showed an increase in DNA recovery of the promoter regions of aa-nat, mkp-1, and c-fos after treatment with TSA. Together, our results demonstrate that histone acetylation differentially influences the transcription of adrenergic-induced genes, an enhancing effect for c-fos but inhibitory for aa-nat, mkp-1, and inducible cAMP early repressor. Moreover, both inhibitory and enhancing effects appear to be mediated through specific modification of promoter-bound histones during gene transcription.


Assuntos
Adrenérgicos/farmacologia , Histonas/metabolismo , Glândula Pineal/metabolismo , Transcrição Gênica/efeitos dos fármacos , Acetilação , Agonistas alfa-Adrenérgicos/administração & dosagem , Agonistas alfa-Adrenérgicos/farmacologia , Animais , Arilalquilamina N-Acetiltransferase/antagonistas & inibidores , Arilalquilamina N-Acetiltransferase/genética , Arilalquilamina N-Acetiltransferase/metabolismo , Proteínas de Ciclo Celular/genética , Células Cultivadas , Modulador de Elemento de Resposta do AMP Cíclico/genética , Esquema de Medicação , Fosfatase 1 de Especificidade Dupla , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacologia , Inibidores de Histona Desacetilases , Ácidos Hidroxâmicos/administração & dosagem , Ácidos Hidroxâmicos/farmacologia , Hidroxilaminas/farmacologia , Proteínas Imediatamente Precoces/genética , Melatonina/biossíntese , Norepinefrina/administração & dosagem , Norepinefrina/farmacologia , Fosfoproteínas Fosfatases/genética , Glândula Pineal/citologia , Proteína Fosfatase 1 , Proteínas Tirosina Fosfatases/genética , Proteínas Proto-Oncogênicas c-fos/genética , Quinolinas/farmacologia , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/metabolismo , Ratos
4.
Endocrinology ; 148(2): 743-51, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17082254

RESUMO

In this study, we investigated the role of two inducible repressor proteins, inducible cAMP early repressor (ICER) and Fos-related antigen 2 (Fra-2) in the adrenergic induction of MAPK phosphatase-1 (MKP-1) as compared with their roles in the induction of arylalkylamine-N-acetyltransferase (AA-NAT) in rat pinealocytes. Treatment of pinealocytes with norepinephrine (NE) caused an increase in the mRNA and protein levels of MKP-1 and AA-NAT, as well as in the AA-NAT activity and melatonin production. NE stimulation also caused a simultaneous increase in the mRNA and protein levels of ICER and Fra-2. Transient knockdown of icer using adenovirus expressing small interfering RNA (siRNA) abolished the NE induction of icer expression but had little effect on the NE induction of mkp-1 or aa-nat expression. In contrast, pretreatment with adenovirus overexpressing icer was effective in reducing the NE induction of mkp-1 and aa-nat. The inhibitory effect of overexpressing icer was reversed by cotreatment with siRNA against icer. siRNA against fra-2 also abolished the NE-stimulated expression of fra-2 but had little effect on the NE induction of mkp-1 and aa-nat expression. Proteasomal inhibition, which reduced the NE-stimulated induction of aa-nat, caused a reduction of ICER and Fra-2. Together, these results indicate that whereas overexpression of ICER can suppress the NE induction of aa-nat and mkp-1, the amount of the repressors, ICER and Fra-2, present during NE induction appears insufficient to exert a significant effect in controlling the expression of these genes.


Assuntos
Agonistas alfa-Adrenérgicos/farmacologia , Arilalquilamina N-Acetiltransferase/biossíntese , Proteínas de Ciclo Celular/biossíntese , Modulador de Elemento de Resposta do AMP Cíclico/fisiologia , Antígeno 2 Relacionado a Fos/fisiologia , Proteínas Imediatamente Precoces/biossíntese , Lactonas/farmacologia , Norepinefrina/farmacologia , Fosfoproteínas Fosfatases/biossíntese , Glândula Pineal/metabolismo , Proteínas Tirosina Fosfatases/biossíntese , Animais , Células Cultivadas , Modulador de Elemento de Resposta do AMP Cíclico/antagonistas & inibidores , Modulador de Elemento de Resposta do AMP Cíclico/genética , Modulador de Elemento de Resposta do AMP Cíclico/metabolismo , Fosfatase 1 de Especificidade Dupla , Antígeno 2 Relacionado a Fos/antagonistas & inibidores , Antígeno 2 Relacionado a Fos/genética , Antígeno 2 Relacionado a Fos/metabolismo , Técnicas de Transferência de Genes , Masculino , Glândula Pineal/citologia , Glândula Pineal/enzimologia , Inibidores de Proteassoma , Proteína Fosfatase 1 , RNA Interferente Pequeno/farmacologia , Ratos , Ratos Sprague-Dawley
5.
Endocrinology ; 148(4): 1465-72, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17185373

RESUMO

In this study, we investigated phosphorylation of Ser10 in histone H3 by norepinephrine (NE) in the rat pineal gland. In whole-animal studies, we demonstrated a marked increase in histone H3 phosphorylation in the rat pineal gland during the first half of the dark period. Exposure to light during this period caused a rapid decline in histone H3 phosphorylation with an estimated t1/2 of less than 15 min, indicating a high level of dephosphorylation activity. Corresponding studies in cultured pineal cells revealed that treatment with NE produced an increase in histone H3 phosphorylation that peaked between 2 and 3 h and declined rapidly by 4 h. The NE-induced histone H3 phosphorylation was blocked by cotreatment with propranolol or KT5720, a protein kinase A inhibitor, but not by prazosin or other kinase inhibitors. Moreover, only treatment with dibutyryl cAMP but not other kinase activators mimicked the effect of NE on histone H3 phosphorylation. The NE-stimulated H3 phosphorylation was markedly increased by cotreatment with a serine/threonine phosphatase inhibitor, tautomycin or okadaic acid, supporting a high level of ongoing histone H3 dephosphorylation activity. Together, our results indicate that histone H3 phosphorylation is a naturally occurring event at night in the rat pineal gland that is driven almost exclusively by a NE-->beta-adrenergic-->cAMP/protein kinase A signaling mechanism. This transient histone H3 phosphorylation probably reflects the nocturnal activation of multiple adrenergic-regulated genes in the rat pineal gland.


Assuntos
Ritmo Circadiano , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Histonas/metabolismo , Norepinefrina/farmacologia , Glândula Pineal/metabolismo , Animais , Células Cultivadas , Luz , Masculino , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Monoéster Fosfórico Hidrolases/antagonistas & inibidores , Fosforilação , Glândula Pineal/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptores Adrenérgicos beta/metabolismo
6.
Mol Cell Endocrinol ; 263(1-2): 134-41, 2007 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-17079074

RESUMO

We have previously shown that mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) is induced at night under the control of a photoneural system in the rat pineal gland. Because of the established roles of MAPKs, glucocorticoids and proteasome activity in regulating MKP-1 expression in other cell types, their relative contributions to MKP-1 regulation were investigated in rat pinealocytes. We found that neither inhibition of MAPKs nor treatment with dexamethasone affected norepinephrine-stimulated MKP-1 expression. In contrast, treatment with proteasome inhibitors increased norepinephrine-stimulated MKP-1 protein levels and abolished the decline in norepinephrine-stimulated MKP-1 protein levels caused by inhibition of transcription or translation, or blockade of alpha-adrenergic receptors. Taken together, our results indicate that in rat pinealocytes, the continuous and rapid turnover of MKP-1 protein allows for its rapid induction but is not sufficient to generate the sustained increase in MKP-1 expression post-adrenergic stimulation.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Proteínas Imediatamente Precoces/metabolismo , Fosfoproteínas Fosfatases/metabolismo , Glândula Pineal/metabolismo , Proteínas Tirosina Fosfatases/metabolismo , Agonistas alfa-Adrenérgicos/farmacologia , Animais , Western Blotting , Proteínas de Ciclo Celular/genética , Células Cultivadas/efeitos dos fármacos , Células Cultivadas/metabolismo , Dexametasona/farmacologia , Fosfatase 1 de Especificidade Dupla , Glucocorticoides/farmacologia , Proteínas Imediatamente Precoces/genética , Masculino , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Norepinefrina/farmacologia , Fosfoproteínas Fosfatases/genética , Fosforilação/efeitos dos fármacos , Glândula Pineal/citologia , Glândula Pineal/efeitos dos fármacos , Biossíntese de Proteínas/efeitos dos fármacos , Proteína Fosfatase 1 , Proteínas Tirosina Fosfatases/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Adrenérgicos alfa/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Transcrição Gênica/efeitos dos fármacos
7.
Mol Cell Endocrinol ; 252(1-2): 34-9, 2006 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-16672173

RESUMO

Activation of members of the mitogen-activated protein kinase (MAPK) family of signaling cascades is a tightly controlled event in rat pinealocytes. Cell culture studies indicate that whereas the NE-->cGMP activation of p42/44MAPK is rapid and transient, the NE-->cAMP activation of p38MAPK is slower and more sustained. The decline in the p42/44MAPK response is in part due to the induction of MAPK phosphatase-1 by NE. In comparison, p38MAPK activation is tightly coupled to the synthesis and degradation of an upstream element in its activation cascade. Whole animal studies confirm activation of p42/44MAPK occurring during the early part of night and precedes p38MAPK activation. Studies with selective MAPK inhibitors reveal a modulating effect of MAPKs on arylalkylamine-N-acetyltransferse (AA-NAT) activity, with involvement of p42/44MAPK in the induction of AA-NAT and p38MAPK participating in the amplitude and duration of the AA-NAT response. These effects of p42/44MAPK and p38MAPK on AA-NAT activity match their timing of activation. Taken together, our studies on the timing of MAPK activation and regulation of AA-NAT by MAPKs add to the importance of MAPKs in regulating the circadian biology of the pineal gland.


Assuntos
Proteínas Quinases Ativadas por Mitógeno/metabolismo , Glândula Pineal/enzimologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Arilalquilamina N-Acetiltransferase/metabolismo , Ativação Enzimática , Cinética , Norepinefrina/farmacologia , Glândula Pineal/fisiologia , Ratos , Transdução de Sinais
8.
Chronobiol Int ; 23(1-2): 361-7, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16687309

RESUMO

In the rat pineal gland, the steady-state level of arylalkylamine N-acetyltransferase (AANAT) protein is controlled by transcriptional and translational mechanisms as well as by proteasome-mediated degradation. Studies with proteasome inhibitors, MG132 and clasto-lactacystin beta-lactone (c-lact), show two opposite effects of proteasomal inhibition on norepinephrine (NE)-induction of Aanat. Addition of MG132 or c-lact following NE stimulation causes an increase in AANAT protein level and enzyme activity without affecting the level of Aanat mRNA. In contrast, addition of inhibitors prior to NE stimulation reduces the NE-stimulated Aanat mRNA, AANAT protein, and enzyme activity. The inhibitory effect of proteasomal inhibition on adrenergic-induced Aanat transcription appears specific for Aanat because it has no effect on the adrenergic induction of mitogen-activated protein kinase phosphatase-1 (mkp-1). The effects of the proteasome inhibitors on NE-stimulated Aanat induction appear to be mediated by accumulation of a protein repressor.


Assuntos
Arilalquilamina N-Acetiltransferase/biossíntese , Glândula Pineal/citologia , Glândula Pineal/enzimologia , Inibidores de Proteases/farmacologia , Inibidores de Proteassoma , Adrenérgicos/metabolismo , Animais , Lactonas/metabolismo , Leupeptinas/farmacologia , Modelos Biológicos , Ratos , Fatores de Tempo
9.
J Anim Sci ; 94(2): 602-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27065130

RESUMO

This experiment examined the relationship between prenatal stress and subsequent calf temperament through weaning. The prenatal stressor used was repeated transportation of pregnant Brahman cows for 2 h at 60 ± 5, 80 ± 5, 100 ± 5, 120 ± 5, and 140 ± 5 d of gestation. Prenatally stressed calves ( = 41) were compared with controls ( = 44; dams did not undergo transportation during pregnancy) from 2 wk of age until weaning (average age at weaning = 174.8 ± 1.3 d). Temperament was defined by pen score (PS; 1 = calm and 5 = excitable), exit velocity (EV; m/sec), and temperament score (TS; (PS + EV)/2) and was recorded for each calf on d -168, -140, -112, -84, -56, -28, and 0 relative to weaning (d 0 = weaning). Cortisol concentrations were determined in serum samples obtained on d -168, -140, -28, and 0 relative to weaning. Birth weight and weaning weight were not different between treatment groups ( > 0.1). Pen score was greater ( = 0.03) in prenatally stressed calves (2.84 ± 0.21) relative to controls (2.31 ± 0.21). Exit velocity was greater ( < 0.01) in prenatally stressed calves (2.1 ± 0.14 m/sec) than in controls (1.61 ± 0.14 m/sec). Exit velocity was affected by a treatment × calf sex interaction ( = 0.04) and was greater in prenatally stressed females. Exit velocity was also affected by day ( < 0.0001). Temperament score was greater ( = 0.01) in prenatally stressed calves (2.45 ± 0.16) than in controls (1.95 ± 0.16). Temperament score was affected by day ( < 0.01). Basal cortisol concentrations were greater ( = 0.04) in prenatally stressed calves (15.87 ± 1.04 ng/mL) than in controls (13.42 ± 1.03 ng/mL). Basal cortisol concentrations were greater ( < 0.01) in females (16.61 ± 1.06 ng/mL) than in males (12.68 ± 1.02 ng/mL). Cortisol concentrations were positively correlated ( < 0.01) with PS ( = 0.55, < 0.01), EV ( = 0.4, < 0.01), and TS ( = 0.55, < 0.01). Overall, suckling Brahman calves that were prenatally stressed were more temperamental and had greater circulating serum concentrations of cortisol than control calves.


Assuntos
Animais Lactentes/fisiologia , Bovinos/fisiologia , Hidrocortisona/sangue , Animais , Animais Recém-Nascidos/fisiologia , Animais Recém-Nascidos/psicologia , Animais Lactentes/sangue , Animais Lactentes/psicologia , Peso ao Nascer , Bovinos/sangue , Bovinos/psicologia , Feminino , Masculino , Gravidez , Fatores Sexuais , Estresse Fisiológico , Estresse Psicológico , Temperamento , Meios de Transporte , Desmame
10.
Nat Commun ; 7: 11183, 2016 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-27029961

RESUMO

Scalable quantum technologies may be achieved by faithful conversion between matter qubits and photonic qubits in integrated circuit geometries. Within this context, quantum dots possess well-defined spin states (matter qubits), which couple efficiently to photons. By embedding them in nanophotonic waveguides, they provide a promising platform for quantum technology implementations. In this paper, we demonstrate that the naturally occurring electromagnetic field chirality that arises in nanobeam waveguides leads to unidirectional photon emission from quantum dot spin states, with resultant in-plane transfer of matter-qubit information. The chiral behaviour occurs despite the non-chiral geometry and material of the waveguides. Using dot registration techniques, we achieve a quantum emitter deterministically positioned at a chiral point and realize spin-path conversion by design. We further show that the chiral phenomena are much more tolerant to dot position than in standard photonic crystal waveguides, exhibit spin-path readout up to 95±5% and have potential to serve as the basis of spin-logic and network implementations.

11.
J Anim Sci ; 94(9): 3958-3965, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27898926

RESUMO

Vitamin D is critical for the growth and development of calves and positively contributes to immune function of cattle. Serum 25-hydroxyvitamin D (25(OH)D) concentrations above 20 ng/mL have traditionally been considered adequate for growth and development of cattle, but recent evidence has indicated that concentrations below 30 ng/mL are insufficient for immunity. Because little information is available regarding vitamin D status of beef cattle, the objective of this study was to evaluate vitamin D status of beef cow-calf herds on pasture as affected by season and location. Serum samples were collected from 43 cow-calf pairs plus an additional 54 calves in herds located in Florida, Idaho, and Minnesota in the spring calving season. Samples were collected again over the summer months from animals in the Florida and Minnesota herds. Effects of subcutaneous injection of vitamins A, D, and E also were investigated in a subset of calves from the Idaho herd. All cows sampled had serum 25(OH)D concentrations above 30 ng/mL at the time of calving in the spring. The average serum 25(OH)D concentrations of cows rose from near 60 ng/mL in the spring to 75 ng/mL in the summer ( < 0.001). Most calves, on the other hand, had serum 25(OH)D concentrations below 20 ng/mL. The calves in the Florida and Minnesota herds similarly rose from averages of 10 to 15 ng/mL at birth to near 50 ng/mL by the end of summer. Serum 25(OH)D of severely deficient calves increased from 3 ng/mL in nonsupplemented calves to 11 ng/mL at 48 h after birth if given a bolus supplementation of 40,000 IU of vitamin D via subcutaneous injection of a vitamin A, D, and E supplement at birth ( < 0.001). Vitamin D supplementation of cows late in pregnancy has been shown to increase serum 25(OH)D of calves; however, beef cattle generally receive very little supplemental vitamin D, as was the case for the cows studied here. The lower serum 25(OH)D of cows in spring compared with summer and the prevalence of vitamin D deficiency of calves observed here indicate that increased vitamin D supplementation of cows over the winter months or vitamin D supplementation of newborn calves would be beneficial.


Assuntos
Doenças dos Bovinos/sangue , Estações do Ano , Deficiência de Vitamina D/veterinária , Vitamina D/análogos & derivados , Animais , Calcifediol/administração & dosagem , Calcifediol/farmacologia , Bovinos , Doenças dos Bovinos/prevenção & controle , Suplementos Nutricionais , Feminino , Florida/epidemiologia , Idaho/epidemiologia , Minnesota/epidemiologia , Parto , Gravidez , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/prevenção & controle , Vitaminas
12.
Biochem Pharmacol ; 70(12): 1840-50, 2005 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-16236272

RESUMO

Differences in the time profiles of activation between p38MAPK and p42/44MAPK by norepinephrine (NE) in rat pinealocytes suggest involvement of mechanisms other than the phosphorylation cascades in their activation. In the present study we investigated whether protein turnover played a role in regulating p38MAPK activation in the rat pineal gland. NE stimulation caused an increase in MAPK kinase3/6 (MKK 3/6) and p38MAPK phosphorylation that occurred in the absence of changes in the mRNA or protein levels of p38MAPK or MKK3/6. The stimulatory effect of NE on phosphorylated MKK3/6 and p38MAPK, but not phosphorylated p42/44MAPK, was blocked by treatment with actinomycin or cycloheximide, indicating a requirement of transcription and translation in activation of the p38MAPK but not the p42/44MAPK pathway. Moreover, inhibition of proteasomes by clasto-lactacystin beta-lactone or Z-Leu-Leu-Leu-CHO (MG132) selectively increased basal and NE-stimulated phosphorylated MKK3/6 and p38MAPK levels without affecting the mRNA or protein levels of MKK3 or p38MAPK. In contrast, the effect of proteasomal inhibition on NE-stimulated p42/44MAPK phosphorylation was inhibitory. Treatment with MG132 also reduced the decline in the phosphorylated levels of NE-stimulated MKK3/6 and p38MAPK that normally follows beta-adrenergic blockade. Together, our results indicate that p38MAPK but not p42/44MAPK activation in the rat pineal gland is tightly coupled to protein synthesis and degradation. The synthesis of an activator upstream of MKK3/6 is required for the NE-activation of p38MAPK.


Assuntos
Glândula Pineal/enzimologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Cicloeximida/farmacologia , Dactinomicina/farmacologia , Ativação Enzimática , Leupeptinas/farmacologia , MAP Quinase Quinase 3/metabolismo , Sistema de Sinalização das MAP Quinases , Masculino , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Norepinefrina/farmacologia , Fosforilação , Glândula Pineal/citologia , Complexo de Endopeptidases do Proteassoma/fisiologia , Ratos , Ratos Sprague-Dawley
13.
J Anim Sci ; 93(2): 737-45, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26020755

RESUMO

This study characterized physiological responses to repeated transportation (TRANS) of gestating cows of differing temperaments. Cows were classified as Calm (C; = 10), Intermediate (I; = 28), or Temperamental (T; = 10). Based on artificial insemination date and pregnancy confirmation, cows were TRANS for 2 h on d 60 (TRANS1), 80 (TRANS2), 100 (TRANS3), 120 (TRANS4), and 140 (TRANS5) ± 5 d of gestation. Indwelling vaginal temperature (VT) monitoring devices were inserted 24 h before each TRANS with VT recorded from 2 h before TRANS and averaged into 5-min intervals through 30 min after TRANS. Serum samples were collected before loading and on unloading from the trailer to determine concentrations of cortisol, glucose, and nonesterified fatty acids (NEFA). Data were analyzed by repeated measures analysis in SAS. Serum cortisol concentrations were affected by temperament ( < 0.001), with T cows having the greater concentrations of cortisol before each TRANS event. All cows (100%) regardless of temperament exhibited elevations in cortisol following each TRANS event. Peak VT was greater ( < 0.001) at TRANS1 relative to all other TRANS events regardless of cow temperament. During TRANS, the T cows tended ( < 0.09) to have greater peak VT (39.86 ± 0.15°C) compared to C (39.41 ± 0.16°C) and I cows (39.55 ± 0.08°C). Area under the VT curve decreased ( = 0.002) from TRANS1 through TRANS5. Pre-TRANS serum glucose concentration at TRANS1 was greater ( < 0.03) for T (68.13 ± 4.31mg/dL) compared to I (53.42 ± 2.78 mg/dL) and C cows (52.76 ± 4.60 mg/dL). The C and I cows had greater changes in NEFA concentration between pre- and post-transport, and T cows showed the least change ( < 0.001). Cow VT and serum glucose concentration decreased in all temperaments ( < 0.01) with repeated TRANS; however, serum NEFA concentration post-TRANS did not vary ( > 0.10) with repeated TRANS events. Serum glucose concentrations were affected ( < 0.02) by a TRANS event by temperament interaction with T cows taking more TRANS events to decrease their change in glucose concentration compared to C and I cows. These results demonstrate that temperament influences physiological responses to stress in gestating Brahman cows. Although repeated transport in our study is confounded with day of gestation, seasonal changes, and learning from repeated handling and transport, repeated transport is a useful model of repeated stress in studying the effects of temperament.


Assuntos
Bovinos/fisiologia , Bovinos/psicologia , Metabolismo Energético/fisiologia , Prenhez/fisiologia , Prenhez/psicologia , Meios de Transporte , Animais , Comportamento Animal/fisiologia , Glicemia/metabolismo , Temperatura Corporal/fisiologia , Ácidos Graxos não Esterificados/sangue , Feminino , Desenvolvimento Fetal/fisiologia , Hidrocortisona/sangue , Gravidez , Estresse Psicológico/psicologia , Temperamento/fisiologia , Fatores de Tempo
14.
Endocrinology ; 145(3): 1167-74, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-14617573

RESUMO

We have previously shown that inhibition of p38(MAPK) increases adrenergic-stimulated p42/44(MAPK) activation in rat pinealocytes. In this study we investigated whether p38(MAPK) played a role in the adrenergic regulation of arylalkylamine-N-acetyltransferase (AA-NAT) induction and melatonin (MT) synthesis. Treatment of pinealocytes with norepinephrine (NE) caused a time-dependent increase in the levels of AA-NAT mRNA, AA-NAT protein, and enzymatic activity as well as MT production. Cotreatment with SB202190, a selective p38(MAPK) inhibitor, although having no effect on AA-NAT activity or protein level 3 h after NE treatment, caused a sustained increase in AA-NAT activity and protein level after 6 h of NE treatment. The increases in NE-stimulated AA-NAT activity and protein level by SB202190 occurred in the absence of an increase in AA-NAT mRNA. Similar results were obtained when AA-NAT was induced by (Bu)(2)cAMP or when SB203580 was used to inhibit p38(MAPK). In comparison, SB202474, the inactive analog, had no effect on NE or (Bu)(2)cAMP-stimulated AA-NAT activity or protein level. SB202190 also increased cumulative NE-stimulated MT production, provided that the medium was supplemented with 5-methoxytryptamine. p38(MAPK) inhibitors had no effect on hydroxyindole-O-methyltransferase activity. These results show that inhibition of p38(MAPK), although having no effect on cAMP-mediated AA-NAT transcription, appears to increase AA-NAT activity either by increasing translation or by reducing degradation of the AA-NAT protein. The lack of effect on NE-stimulated MT accumulation by p38(MAPK) inhibitors in the absence of 5-methoxytryptamine could be secondary to a lack of substrate, or alternatively, hydroxyindole-O-methyltransferase may become limiting.


Assuntos
Arilamina N-Acetiltransferase/metabolismo , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Glândula Pineal/enzimologia , Acetilserotonina O-Metiltransferasa/metabolismo , Animais , Arilamina N-Acetiltransferase/genética , Bucladesina/farmacologia , Ativação Enzimática/efeitos dos fármacos , Indução Enzimática/fisiologia , Inibidores Enzimáticos/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Imidazóis/farmacologia , Masculino , Melatonina/biossíntese , Melatonina/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Norepinefrina/farmacologia , Glândula Pineal/citologia , Piridinas/farmacologia , RNA Mensageiro/análise , Ratos , Ratos Sprague-Dawley , Simpatomiméticos/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno
15.
Am J Med Genet ; 20(2): 227-32, 1985 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-3976717

RESUMO

Approximately 1 of 500 individuals is a carrier of a balanced chromosome translocation. Since many translocations are inherited, many (but not all) relatives of carriers have a need to be informed of their potential carrier status. Presently, no data are available as to what extent individuals identified as balanced carriers inform at-risk relatives of the problem. We interviewed 12 balanced translocation carriers to learn whether such information had been transmitted to relatives. The 12 propositi had 36 surviving sibs and 21 surviving parents. Of the 36 sibs, 32 were informed of their risk. The four sibs not informed were from two families. Only 16 of the 32 informed sibs had subsequent carrier testing. Of the 21 surviving parents, 14 were told by their children of their carrier status; subsequently, three parent couples were tested. This survey provides data showing that individuals do not always disclose genetic risk information to relatives. Therefore, genetic professionals need to determine if they have a duty to transmit such information to at-risk relatives in light of the harm that may occur when information is withheld.


Assuntos
Família , Aconselhamento Genético , Heterozigoto , Translocação Genética , Confidencialidade , Ética Profissional , Feminino , Seguimentos , Humanos , Masculino , Risco
16.
Int J Pharm ; 192(1): 85-96, 1999 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-10572202

RESUMO

Micro-thermal analysis combines the imaging capabilities of atomic force microscopy with the ability to characterise, with high spatial resolution, the thermal behaviour of materials. The conventional AFM tip is replaced by a miniature heater/thermometer which enables a surface to be visualised according to its response to the input of heat (in addition to measuring its topography). Areas of interest may then be selected and localised thermal analysis (modulated temperature calorimetry and thermomechanical analysis) carried out. Localised dynamic mechanical measurements are also possible. Spatially resolved chemical analysis can be performed using the same basic apparatus by means of pyrolysis gas chromatography-mass spectrometry or high-resolution photothermal infrared spectrometry.


Assuntos
Análise Diferencial Térmica/métodos , Microscopia de Força Atômica/métodos , Acetaminofen/química , Calorimetria , Propriedades de Superfície , Comprimidos
17.
Int J Pharm ; 192(1): 97-103, 1999 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-10572203

RESUMO

The use of micro-thermal analysis (microTA) as a novel means of differentiating between components in a model tablet formulation is described. This technique involves a modification of atomic force microscopy (AFM) such that the standard AFM tip is replaced with a Wollaston wire, thereby allowing the probe to act as a thermistor and temperature probe. Consequently it is possible to map not only the topology but also the thermal conductivity of the sample. Furthermore, it is possible to apply a heating signal to the material and thereby to perform thermal analysis on highly localised regions of the sample. Compacts were prepared comprising ibuprofen, HPMC E4M prem and 1:1 mixes of the two components and analysed using a microTA micro-thermal analyser. The surface topology and conductivity images of the three systems are reported. In addition, the ability of the technique to perform thermal analysis on highly specific regions of the sample is described. The method was able to differentiate between the components of the sample on the basis of micro-thermomechanical experiments. The implications of the use of the technique for the study of pharmaceutical tablets is discussed.


Assuntos
Análise Diferencial Térmica/métodos , Lactose/análogos & derivados , Metilcelulose/análogos & derivados , Microscopia de Força Atômica/métodos , Composição de Medicamentos , Excipientes , Ibuprofeno/química , Lactose/química , Metilcelulose/química , Oxazinas , Comprimidos
18.
Heart Lung ; 20(2): 183-8, 1991 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-2004930

RESUMO

This is a descriptive study of the relative importance of needs as reported by 213 family members of 114 patients hospitalized in critical care units of a large, urban, teaching, medical center. In this study we used Molter's Critical Care Family Needs Inventory (revised), an instrument that has been used in other similar investigations, but never before in such a large sample or one with similar demographics. In general, the findings were consistent with those in previous studies using the Critical Care Family Needs Inventory. One striking difference was the relatively low ranking accorded by this sample to the need "to feel there was hope." Parents, spouses, siblings, adult children, and "significant others" ranked their needs in strikingly similar ways. Family members of critically ill patients need two things most: to have honest, intelligible, and timely information and to feel assured that their loved one is being cared for by competent and caring people. Clinical, educational, and research implications are identified and briefly discussed.


Assuntos
Centros Médicos Acadêmicos , Cuidados Críticos/psicologia , Família/psicologia , Relações Profissional-Família , Adulto , Criança , Comunicação , Feminino , Hospitais Urbanos , Humanos , Unidades de Terapia Intensiva , Masculino , Inquéritos e Questionários
19.
Heart Lung ; 21(1): 25-30, 1992 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-1735654

RESUMO

In this study we explored the relationship between the empathy of intensive care unit (ICU) nurses and their ability to assess accurately the perceived needs of family members of patients hospitalized in ICU settings. Thirty family needs were studied by using Molter's 1983 revision of the Critical Care Family Needs Inventory (CCFNI). Data consisted of 92 pairs of CCFNI responses obtained from 92 family members of ICU patients and 60 ICU nurses providing direct care for these patients. Multiple regression analysis was performed to determine the extent to which empathy and nursing experience contribute to accurate assessment of the needs of ICU family members. The more emphatic ICU nurses were, the greater their ability to assess ICU family members' needs accurately on six of the needs studied (p less than or equal to 0.05). Length of nursing experience negatively affected the nurse's ability to assess three of the ICU family members' needs accurately (p less than 0.05).


Assuntos
Cuidados Críticos , Empatia , Família/psicologia , Enfermeiras e Enfermeiros/psicologia , Adulto , Humanos , Pessoa de Meia-Idade , Análise de Regressão , Fatores de Tempo
20.
Heart Lung ; 19(6): 655-61, 1990 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-2228656

RESUMO

In this study we explored the relationship between critical care family members' perceived needs and the assessment of these needs by a confederate sample of intensive care unit (ICU) nurses. Family needs were measured by using Molter's revised Critical Care Family Needs Inventory. Data consisted of 92 confederate pairs of Critical Care Family Needs Inventory responses obtained from 92 family members of adult patients hospitalized in a variety of ICUs and 49 ICU nurses providing direct care for these patients. Paired t tests (two tailed) were calculated to detect significant differences between confederate pairs of family members' perceptions and ICU nurses' assessments of the importance of the needs studied. Family members' perceptions and ICU nurses' assessments of the most and least important critical care family needs were identified. Significant (p less than 0.001 to p less than 0.05) differences were detected between confederate pairs of family members' perceptions and ICU nurses' assessments of the importance of 15 (50%) of the critical care family needs studied. Therefore, it appears that these nurses were only moderately accurate in their assessments of critical care family needs. Implications for nursing practice, education, and research were identified and discussed.


Assuntos
Atitude Frente a Saúde , Cuidados Críticos/psicologia , Família/psicologia , Avaliação em Enfermagem/normas , Adolescente , Adulto , Idoso , Contratransferência , Humanos , Pessoa de Meia-Idade , Pesquisa em Avaliação de Enfermagem , Recursos Humanos de Enfermagem Hospitalar/psicologia , Relações Profissional-Família , Inquéritos e Questionários
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