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Whispering gallery mode (WGM) lasing in CsPbI3 quantum dots (QDs) coated on TiO2 spherical microcavities is demonstrated. The photoluminescence emission from a CsPbI3-QDs gain medium strongly couples with a TiO2 microspherical resonating optical cavity. Spontaneous emission in these microcavities switches to a stimulated emission above a distinct threshold point of 708.7 W/cm2. Lasing intensity increases three to four times as the power density increases by one order of magnitude beyond the threshold point when the microcavities are excited with a 632-nm laser. WGM microlasing with quality factors as high as Qâ¼1195 is demonstrated at room temperature. Quality factors are found to be higher for smaller TiO2 microcavities (â¼2â µm). CsPbI3-QDs/TiO2 microcavities are also found to be photostable even after continuous laser excitation for 75 minutes. The CsPbI3-QDs/TiO2 microspheres are promising as WGM-based tunable microlasers.
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Reported data suggest that 99% of transfemoral, transcatheter aortic valve implantations in the UK are performed under general anaesthesia. This before-and-after study is the first UK comparison of conscious sedation vs. general anaesthesia for this procedure. Patients who underwent general anaesthesia received tracheal intubation, positive pressure ventilation, radial arterial and central venous access and urinary catheterisation. Anaesthesia was maintained with propofol or sevoflurane. Patients who received conscious sedation had a fascia iliaca and ilioinguinal nerve block and low-dose remifentanil infusion, without invasive monitoring or urinary catheterisation. Recruitment took place between August 2012 and July 2015, with a 6-month crossover period between November 2013 and June 2014. A total of 88 patients were analysed, evenly divided between the two groups. Patients receiving conscious sedation had a shorter anaesthetic time (mean (SD) 121 (28) min vs. 145 (41) min; p < 0.001) and recovery room time (110 (50) min vs. 155 (48) min; p = 0.001), lower requirement for inotropes (4.6% vs 81.8%; OR (95% CI) 0.1 (0.002-0.050); p < 0.001) and a lower incidence of malignant dysrhythmia (0% vs 11.4%; p = 0.020). Conscious sedation appears a feasible alternative to general anaesthesia for this procedure and is associated with a reduced requirement for inotropic support and improved efficiency.
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Anestesia Geral , Sedação Consciente , Substituição da Valva Aórtica Transcateter/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/epidemiologia , Substituição da Valva Aórtica Transcateter/efeitos adversosRESUMO
INTRODUCTION: Irrigating solutions are used for cleaning and removing dentinal debris, and the other remains from pulpal space during biomechanical preparation. Therefore, we evaluated the impact of various irrigating agents on root fracture at 5-minute time exposure. MATERIALS AND METHODS: We sectioned 60 permanent maxillary premolars with fully formed root structures transversely maintaining the root length of approximately 14 mm. Five study groups were made comprising ethylenediaminetetraacetic acid (EDTA), cetrimide, citric acid, and so on as various irrigating agents. A universal force test machine was used to calculate the force which was enough to fracture each root. Analysis of variance (ANOVA) test was used to access the level of significance. RESULTS: About 10% citric acid solution as an irrigating agent showed minimal fracture opposing results, whereas 10% EDTA solution showed the maximum fracture resistance of root portion. CLINICAL SIGNIFICANCE: Selection of suitable EDTA concentration that has minimal adverse effect on the mechanical properties of the tooth is very important for the successful management of tooth fracture. CONCLUSION: About 10% EDTA provided the highest fracture resistance, necessitating the use of irrigating solution in root canal therapy (RCT). Further research with higher and different study groups is required to search for more efficient irrigating solution to improve the outcome of RCT.
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Irrigantes do Canal Radicular , Fraturas dos Dentes/prevenção & controle , Raiz Dentária/lesões , Cetrimônio , Compostos de Cetrimônio , Ácido Cítrico , Análise do Estresse Dentário , Doxiciclina , Ácido Edético , Humanos , Teste de Materiais , Preparo de Canal RadicularRESUMO
BACKGROUND: Various agents are used these days for increasing the esthetics. One such procedure is bleaching that offers various advantages, as it is minimal invasive and cheap option to color the teeth and remove stain. The altered enamel after the bleaching process shows surface demineralization and porosities. The present study aimed to evaluate the effect of different bleaching agents on the microhardness of enamel. MATERIALS AND METHODS: A total of 100 freshly human extracted maxillary premolar teeth were selected for the study. Teeth with sound tooth structure were included for the study. All the specimens were randomly divided into four groups with 25 specimens in each group depending upon the type of bleaching agent used: Group A, artificial saliva (Control group); Group B, 35% hydrogen peroxide (HP); Group C, 25% HP; Group D, 10% carbamide peroxide (CP). Knoop Hardness Number (KHN) was calculated at 24, 48-hour, and 7-week interval. RESULTS: Results showed no statistical significant differences between the microhardness of enamel of different groups (p < 0.005). A slight fall in the value of KHN was seen in all the groups, except for the control group, although the results were statistically nonsignificant (p > 0.005). CONCLUSION: Although nonsignificantly, all the bleaching solutions produced some amount of alterations in the microstructure of enamel. More studies with higher study groups and more advanced estimation technologies are required to minimize microstructure alterations and promote for better outcome of bleaching procedures.
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Esmalte Dentário/efeitos dos fármacos , Clareadores Dentários/farmacologia , Dureza/efeitos dos fármacos , Humanos , Técnicas In VitroRESUMO
BACKGROUND: Consumption of certain beverages may affect the esthetic and physical properties of the resin composite, thereby undermining the quality of restorations. AIM: To analyze the effect of three beverages (cola, coffee, tea) on color stability and surface roughness of three different types of resin composites at various time intervals in vitro. MATERIALS AND METHODS: Nano, microhybrid and hybrid resin composites were used. Each material was randomly divided into four equal subgroups of 10 samples each according to the beverages used (cola, coffee, tea, distilled water). The samples were immersed in each beverage for 1, 15 and 30 days. Surface roughness and color changes measurements were noted at the baseline-the first, fifteenth and thirteenth day. RESULTS: It was found that nanoresin composite followed by microhybrid and hybrid showed least surface roughness and color change. The Coke beverage subgroup showed more surface roughness and the subgroup coffee has shown more color changes with respect to other subgroups. CONCLUSION: All specimens showed discoloration after completion of the test period which was visually perceptible and clinically unacceptable. At the end of 30th day, among the materials, nanofilled composite resin showed comparatively less surface roughness and color change than microhybrid and hybrid composite resins.
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Bebidas , Resinas Compostas/química , Materiais Dentários/química , Nanocompostos/química , Bebidas Gaseificadas , Café , Cor , Polimento Dentário/métodos , Humanos , Teste de Materiais , Polimerização , Dióxido de Silício/química , Espectrofotometria , Propriedades de Superfície , Chá , Fatores de Tempo , Água/química , Zircônio/químicaRESUMO
Proteolysis by the ubiquitin-proteasome pathway (UPP) is now widely recognized as a molecular mechanism controlling myriad normal functions in the nervous system. Also, this pathway is intimately linked to many diseases and disorders of the brain. Among the diseases connected to the UPP are neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases. Perturbation in the UPP is also believed to play a causative role in mental disorders such as Angelman syndrome. The pathology of neurodegenerative diseases is characterized by abnormal deposition of insoluble protein aggregates or inclusion bodies within neurons. The ubiquitinated protein aggregates are believed to result from dysfunction of the UPP or from structural changes in the protein substrates which prevent their recognition and degradation by the UPP. An early effect of abnormal UPP in diseases of the nervous system is likely to be impairment of synaptic function. Here we discuss the UPP and its physiological roles in the nervous system and how alterations in the UPP relate to development of nervous system diseases. This article is part of a Special Issue entitled The 26S Proteasome: When degradation is just not enough!
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Doenças do Sistema Nervoso/enzimologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Processamento de Proteína Pós-Traducional , Ubiquitina/metabolismo , Animais , Humanos , Modelos Biológicos , Doenças do Sistema Nervoso/patologia , Doenças do Sistema Nervoso/terapia , Transdução de SinaisRESUMO
Introduction Non-utilization of public health care facilities by women in India is one of the crucial concerns when ensuring universal health coverage. However, contrary to the fact that women need more health care assistance throughout their lifespan, there is a considerable lack of awareness among them, and this is a major contributor to their unwillingness to use these services. Methods A community-based descriptive cross-sectional study was conducted among women of the reproductive age group (15-49 years) in an urban field practice area of a tertiary health care center in central India. Data were collected for two months by interview technique using a semi-structured questionnaire. Data were analyzed using Epi Info version 7.2.2.6 (Centers for Disease Control and Prevention, Atlanta, Georgia) software. Results Of the total 132 women, 77 (58.33%) respondents were aware of the availability of public health care facilities in their area of residence. Despite this, only 59 (44.69%) were utilizing the services. Non-utilization of public health care facilities was significantly more in those belonging to upper socioeconomic status (chi-square = 14.36, p < 0.05 at a degree of freedom [df] = 2). The common reasons being lack of personal attention, cleanliness, and overcrowding at these facilities. Conclusion Even though a substantial population in central India cannot afford private or corporate health care services, the utilization of public health care facilities has not been up to the mark. Overall, most of the subjects were aware of the facilities available to them. This awareness, however, did not match with the utilization of such facilities. Less than half of the women were utilizing the public health care facilities.
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In recent years, proteolysis by the ubiquitin-proteasome pathway has attained prominence as a new molecular mechanism that regulates many vital functions of the nervous system, including development of synaptic connections and synaptic plasticity. Here, we review the latest findings on the role of proteolysis in sculpting the nervous system through control of axonal growth, axonal and dendritic pruning, and regulation of synaptic size and number. We also discuss how protein degradation functions in synaptic plasticity and the roles of local proteolysis in neuronal compartments. In addition, we describe how proteolysis is associated with Alzheimer's disease and ataxia. Furthermore, we highlight the recent approaches that exploit components of the ubiquitin-proteasome pathway for amelioration of these diseases in animal models.
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Complexo de Endopeptidases do Proteassoma/fisiologia , Ubiquitina/fisiologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Ataxia/metabolismo , Ataxia/patologia , Modelos Animais de Doenças , Humanos , Sistema Nervoso/metabolismo , Sistema Nervoso/patologiaRESUMO
Eight derivatives of general formula 2-(2-(4-(3-((5-substituted methylene)-4-oxo-2-(phenylimino)thiazolidin-3-yl)-2-hydroxypropylamino)benzoyl)hydrazinyl)-2-oxoethyl nitrate were synthesized and tested for electrocardiographic, antiarrhythmic, vasorelaxing and antihypertensive activity as well as for in-vitro nitric oxide (NO) releasing ability. Compound 8b 2-(2-(4-(3-(5-benzyliden-4-oxo-2-(phenylimino)thiazolidin-3-yl)-2-hydroxypropylamino)benzoyl)hydrazinyl)-2-oxoethyl nitrate, was the most potent in this series. The pharmacological results suggested that the antiarrhythmic effects of these compounds were related to their adrenolytic properties which are believed to be due to the presence of the 5-(substituted)methylen-2-(phenylimino)thiazolidin-4-one moiety with less bulky, electron donating substituent on the phenyl ring at 5th position of the thiazolidin-4-one. In conclusion, most of the synthesized compounds were significantly potent as antiarrhythmic and antihypertensive; this might be due to the presence of different pharmacopores which might act at different locations with different mode of action. Further insights of the same can be obtained by doing investigation at receptor level. The potency of compounds 8a-8h were promising enough to continue further experiments.
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Anti-Hipertensivos/síntese química , Antagonistas Adrenérgicos/síntese química , Animais , Antiarrítmicos/síntese química , Antiarrítmicos/farmacologia , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/farmacologia , Aorta , Pressão Sanguínea/efeitos dos fármacos , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Frequência Cardíaca/efeitos dos fármacos , Ratos , Ratos Wistar , Relação Estrutura-AtividadeRESUMO
Transcatheter aortic valve insertion is a new development that potentially offers a number of advantages to patients and healthcare providers. These include the avoidance of sternotomy and cardiopulmonary bypass, and much faster discharge from hospital and return to functional status. The procedure itself however is quite complex, and presents significant demands in planning and implementation to the multidisciplinary team. Anaesthetic input is essential, and patient care in the perioperative period can be challenging. Early results have shown a significant mortality and morbidity rate, but the majority of procedures to date have been carried out in elderly patients with multiple comorbidities, making comparison with surgical aortic valve replacement inappropriate. Long-term outcomes are not yet known, but randomized controlled trials should allow this procedure and its application to be properly assessed.
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Estenose da Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca/métodos , Anestesia/métodos , Próteses Valvulares Cardíacas , Implante de Prótese de Valva Cardíaca/tendências , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/tendências , Seleção de Pacientes , Assistência Perioperatória/métodosRESUMO
Protein degradation by the ubiquitin-proteasome pathway plays important roles in synaptic plasticity, but the molecular mechanisms by which proteolysis regulates synaptic strength are not well understood. We investigated the role of the proteasome in hippocampal late-phase long-term potentiation (L-LTP), a model for enduring synaptic plasticity. We show here that inhibition of the proteasome enhances the induction of L-LTP, but inhibits its maintenance. Proteasome inhibitor-mediated enhancement of the early part of L-LTP requires activation of NMDA receptors and the cAMP-dependent protein kinase. Augmentation of L-LTP induction by proteasome inhibition is blocked by a protein synthesis inhibitor anisomycin and is sensitive to the drug rapamycin. Our findings indicate that proteasome inhibition increases the induction of L-LTP by stabilizing locally translated proteins in dendrites. In addition, our data show that inhibition of the proteasome blocks transcription of brain-derived neurotrophic factor (BDNF), which is a cAMP-responsive element-binding protein (CREB)-inducible gene. Furthermore, our results demonstrate that the proteasome inhibitors block degradation of ATF4, a CREB repressor. Thus, proteasome inhibition appears to hinder CREB-mediated transcription. Our results indicate that blockade of proteasome activity obstructs the maintenance of L-LTP by interfering with transcription as well as translation required to sustain L-LTP. Thus, proteasome-mediated proteolysis has different roles during the induction and the maintenance of L-LTP.
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Anisomicina/farmacologia , Potenciação de Longa Duração/efeitos dos fármacos , Inibidores de Proteassoma , Inibidores da Síntese de Proteínas/farmacologia , Ubiquitina/efeitos dos fármacos , Animais , Anisomicina/administração & dosagem , Fator Neurotrófico Derivado do Encéfalo/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Dendritos/metabolismo , Hipocampo/efeitos dos fármacos , Camundongos , Plasticidade Neuronal/efeitos dos fármacos , Peptídeo Hidrolases/farmacologia , Biossíntese de Proteínas/efeitos dos fármacos , Biossíntese de Proteínas/genética , Inibidores da Síntese de Proteínas/administração & dosagem , RNA Mensageiro/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Sinapses/efeitos dos fármacos , Ativação Transcricional/efeitos dos fármacos , Ativação Transcricional/genéticaRESUMO
Parkin and other unrelated proteins contain a ubiquitin-like domain (UbLD). This article describes a motif that might be important in the interaction of UbLD-containing proteins (UbLPs) with the proteasome. The proteasome-interacting motif, which is conserved in a subset of UbLPs, such as parkin, Rad23 and several transcription factors, is likely to enable the UbLPs to form a complex with the proteasome for proteolysis or the recently discovered non-proteolytic functions of the proteasome.
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Cisteína Endopeptidases/metabolismo , Reparo do DNA , Ligases/metabolismo , Complexos Multienzimáticos/metabolismo , Ubiquitina-Proteína Ligases , Ubiquitinas/metabolismo , Motivos de Aminoácidos , Sequência de Aminoácidos , Enzimas Reparadoras do DNA , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Humanos , Dados de Sequência Molecular , Doença de Parkinson/metabolismo , Peptídeo Hidrolases/metabolismo , Filogenia , Complexo de Endopeptidases do Proteassoma , Homologia de Sequência de AminoácidosRESUMO
Though Alzheimer's disease (AD) is a syndrome with well-defined clinical and neuropathological manifestations, an array of molecular defects underlies its pathology. A role for the ubiquitin proteasome system (UPS) was suspected in the pathogenesis of AD since the presence of ubiquitin immunoreactivity in AD-related neuronal inclusions, such as neurofibrillary tangles, is seen in all AD cases. Recent studies have indicated that components of the UPS could be linked to the early phase of AD, which is marked by synaptic dysfunction, as well as to the late stages of the disease, characterized by neurodegeneration. Insoluble protein aggregates in the brain of AD patients could result from malfunction or overload of the UPS, or from structural changes in the protein substrates, which prevent their recognition and degradation by the UPS. Defective proteolysis could cause the synaptic dysfunction observed early in AD since the UPS is known to play a role in the normal functioning of synapses. In this review, we discuss recent observations on possible links between the UPS and AD, and the potential for utilizing UPS components as targets for treatment of this disease. Publication history: Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com).
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Doença de Alzheimer/enzimologia , Complexo de Endopeptidases do Proteassoma/fisiologia , Complexos Ubiquitina-Proteína Ligase/fisiologia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Animais , Sistemas de Liberação de Medicamentos/métodos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Humanos , Inibidores de Proteassoma , Complexos Ubiquitina-Proteína Ligase/antagonistas & inibidoresRESUMO
BACKGROUND: Compliance or noncompliance with treatment significantly influences course and outcome of psychiatric disorders. While noncompliance has been extensively researched, compliance has received less attention. The current study was conducted to elicit reasons for compliance and noncompliance in patients having psychoses attending psychiatric clinics. MATERIALS AND METHODS: A total of 196 compliant and 150 noncompliant patients were interviewed using self-designed tools to elicit sociodemographic data, details of illness, and treatment. Factors contributing to compliance and noncompliance were grouped under illness-related, clinician-related, medication-related, family-related, and economic-related domains and compared. RESULTS: Compliance was significantly more in females and middle- and high-socioeconomic status patients. They had less substance use, high physical comorbidity, high attendance in the outpatient department, and better remission. Clinician-related, family-related, and medication-related domains were contributing more to compliance whereas illness-related and economic-related domains seemed to have more bearing on noncompliance. CONCLUSIONS: Compliance and noncompliance are determined multidimensionally. Domains related to clinician, family, and medications have to be reinforced to enhance compliance. Illness-related and economic domains have to be resolved to reduce noncompliance.
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Proteasome is a multi-subunit proteolytic complex that degrades proteins covalently linked to multiple molecules of ubiquitin. Earlier studies showed a role for the ubiquitin-proteasome pathway in several models of long-term memory and other forms of synaptic plasticity. In Aplysia, the ubiquitin-proteasome pathway has been shown to contribute to the induction of long-term facilitation. In other model systems, ubiquitin-proteasome-mediated proteolysis has also been shown to play a role in synapse development. Previous studies of synaptic plasticity focused on changes in components or the substrates of the ubiquitin-proteasome pathway in whole neurons. Modification of specific synapses would require precise spatial and temporal regulation of the components of the ubiquitin-proteasome pathway within the subcellular compartments of neurons during learning. As a first step towards testing the idea of local regulation of the ubiquitin-proteasome pathway in neurons, we investigated proteasome activity in nuclear and synaptosomal fractions. Here we show that proteasome activity in the synaptic terminals is higher compared to the activity in the nucleus in the Aplysia nervous system as well as in the mouse brain. Furthermore, the proteasome activity in the two neuronal compartments is differentially modulated by protein kinases. Differential regulation of proteasome activity in neuronal compartments such as the synaptic terminals is likely to be a key mechanism underlying synapse-specific plasticity.
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Núcleo Celular/enzimologia , Terminações Pré-Sinápticas/enzimologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Animais , Aplysia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neurônios/enzimologia , Proteínas Quinases/fisiologia , Serotonina/fisiologia , Sinaptossomos/enzimologiaRESUMO
BACKGROUND: In patients undergoing head and neck surgery for various pathologic conditions, implants are one of the best restorative options and are increasing widely used. Therefore, we evaluated the success of dental implants in the irradiated jaws of patients following treatment of oral cancer oral cancer treated patients. MATERIALS AND METHODS: Data of oral cancer treated patients was collected retrospectively from 2002 to 2008. We took 46 oral cancer treated patients in which implants were placed in irradiated jaws for rehabilitation. RESULTS: It was found that out of 162 dental implants placed, 52 failed. Furthermore, there was no variation in the implant survival rate in between both the jaws. Radiation dose of <50 Gy units also showed significantly increased amount of implant survival rate. CONCLUSIONS: Implant survival is multifactorial and depends upon a number of factors like level of radiation exposure in that area, time gap between last radiation doses etc., Further research is required in this field to improve the esthetics and quality of life of cancer treated patients.
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In the central nervous system (CNS), abnormal deposition of insoluble protein aggregates or inclusion bodies within nerve cells is commonly observed in association with several neurodegenerative diseases. The ubiquitinated protein aggregates are believed to result from malfunction or overload of the ubiquitin-proteasome pathway or from structural changes in the protein substrates which prevent their recognition and degradation by the ubiquitin-proteasome pathway. Impaired proteolysis might also contribute to the synaptic dysfunction seen early in neurodegenerative diseases because the ubiquitin-proteasome pathway is known to play a role in normal functioning of synapses. Because specificity of the ubiquitin proteasome mediated proteolysis is determined by specific ubiquitin ligases (E3s), identification of specific E3s and their allosteric modulators are likely to provide effective therapeutic targets for the treatment of several CNS disorders. Another unexplored area for the discovery of drug targets is the proteasome. Although many inhibitors of the proteasome are available, no effective drugs exist that can stimulate the proteasome. Since abnormal protein aggregation is a common feature of different neurodegenerative diseases, enhancement of proteasome activity might be an efficient way to remove the aggregates that accumulate in the brain. In this review, we discuss how the components of the ubiquitin-proteasome pathway could be potential targets for therapy of CNS diseases and disorders.
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Doenças do Sistema Nervoso Central/tratamento farmacológico , Complexo de Endopeptidases do Proteassoma/fisiologia , Transdução de Sinais/efeitos dos fármacos , Ubiquitina/fisiologia , Doenças do Sistema Nervoso Central/metabolismo , Doenças do Sistema Nervoso Central/fisiopatologia , Humanos , Complexo de Endopeptidases do Proteassoma/metabolismo , Ubiquitina/metabolismoRESUMO
Obsessive-compulsive disorder (OCD) is a very distressing disorder for both patient and caregiver. Usual onset of the disorder is in late second or early third decade of life. It is diagnosed in children but rarely before 5 years. A case of OCD in a 4-year-old girl is reported here. Diagnostic and therapeutic dilemmas in such a situation are discussed.
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A case of Sulphuric acid ingestion with an intention to commit suicide in a patient of Major Depressive Disorder which resulted in death is reported. Aspects of this mode of suicide and legal issues concerning suicide in mentally ill patient have been discussed.
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A detailed restriction map of the murine TGF-beta 1 locus (encoding transforming growth factor beta 1) was established and the precise junctional sequences of its seven exons and corresponding introns were elucidated. While the exons ranged in size from 78 to 357 bp, the introns ranged from about 1 to 6.5 kb. The promoter-proximal segment contains many putative regulatory motifs which may dictate TGF-beta 1 gene transcription in response to varied pathophysiological stimuli.