RESUMO
The artificial intelligence (AI) tools based on large-language models may serve as a demonstration that we are reaching a groundbreaking new paradigm in which machines themselves will generate knowledge autonomously. This statement is based on the assumption that the ability to master natural languages is the ultimate frontier for this new paradigm and perhaps an essential step to achieving the so-called general artificial intelligence. Autonomous knowledge generation implies that a machine will be able, for instance, to retrieve and understand the contents of the scientific literature and provide interpretations for existing data, allowing it to propose and address new scientific problems. While one may assume that the continued development of AI tools exploiting large-language models, with more data used for training, may lead these systems to learn autonomously, this learning can be accelerated by devising human-assisted strategies to deal with specific tasks. For example, strategies may be implemented for AI tools to emulate the analysis of multivariate data by human experts or in identifying and explaining patterns in temporal series. In addition to generic AI tools, such as Chat AIs, one may conceive personal AI agents, potentially working together, that are likely to serve end users in the near future. In this perspective paper, we discuss the development of this type of agent, focusing on its architecture and requirements. As a proof-of-concept, we exemplify how such an AI agent could work to assist researchers in materials sciences.
Assuntos
Inteligência Artificial , Ciência dos Materiais , Humanos , Idioma , Aprendizagem , PesquisadoresRESUMO
Doxorubicin (DOX) is a chemotherapeutic agent that has been used in the treatment of breast cancer. However, serious toxic effects have limited its use, mainly cardiotoxicity. To minimize the adverse effects, liposomal preparations containing DOX have been developed. These preparations can reach the target in the tumor region as well as bypass the resistance-related problems. An alternative to increased therapeutic efficacy may be the fusion of liposomes with exosomes released from tumor cells to facilitate membrane and fusion interactions, achieving greater cell uptake. Thus, the purpose of this study was the fusion of exosomes derived from breast tumor cells with long-circulating and pH-sensitive liposomes loading DOX (ExoSpHL-DOX) for the treatment of breast cancer. The mean diameter of ExoSpHL-DOX was 100.8 ± 7.8 nm, the polydispersity index was 0.122 ± 0.004, and the encapsulated DOX content was equal to 83.5 ± 2.5%. The fusion of exosomes with long-circulating and pH-sensitive liposomes was confirmed by Fourier transform infrared spectroscopy, Raman spectroscopy, and nano-flow cytometry. The physicochemical characteristics of ExoSpHL-DOX were maintained for 60 days, at 4 °C. The study of the release of DOX from ExoSpHL-DOX in dilution media with different pH values showed the pH sensitivity characteristic of the nanosystem, since 96.6 ± 0.2% of DOX was released from ExoSpHL-DOX at pH 5.0, while at pH 7.4, the release was 70.1 ± 1.7% in the medium. The cytotoxic study against the breast cancer cell line demonstrated that ExoSpHL-DOX treatment significantly reduced the cancer cell viability.
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Antineoplásicos , Neoplasias da Mama , Exossomos , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Doxorrubicina/química , Doxorrubicina/farmacologia , Exossomos/patologia , Feminino , Humanos , Concentração de Íons de Hidrogênio , Lipossomos/químicaRESUMO
Pesticides are used worldwide to control arthropod parasites in cattle herds. The indiscriminate and/or inappropriate use of pesticides without veterinary guidance is a reality in several countries of South America. Improper pesticide use increases the chances of contamination of food and the environment with chemical pesticides and their metabolites. Reduction of these contamination events is an increasing challenge for those involved in livestock production. The horn fly, Haematobia irritans (Linnaeus) (Diptera: Muscidae), is one of the most economically important parasites affecting cattle herds around the world. As such, horn fly control efforts are often required to promote the best productive performance of herds. Pesticide susceptibility bioassays revealed that pyrethroid resistance was widespread and reached high levels in horn fly populations in the Brazilian state of Rondônia. The knockdown resistance (kdr) sodium channel gene mutation was detected in all horn fly populations studied (n = 48), and the super kdr sodium channel gene mutation was found in all homozygous resistant kdr individuals (n = 204). Organophosphate resistance was not identified in any of the fly populations evaluated.
Assuntos
Resistência a Inseticidas/genética , Inseticidas/farmacologia , Muscidae/efeitos dos fármacos , Organofosfatos/farmacologia , Piretrinas/farmacologia , Animais , Brasil , Muscidae/genéticaRESUMO
The Maytenus genus is a member of the Celastraceae family. Numerous medicinal uses were assigned to species of this genus, with the use of roots, bark, and leaves for the treatment of gastric ulcers, as anti-inflammatory, analgesic, antiallergic, antitumor, among others. Several studies have demonstrated that natural products derived from plants have an important role in the prevention and treatment of obesity. Accordingly, we evaluated the effect of Maytenus imbricata extracts in the treatment of obesity induced by diet rich in refined carbohydrate (HC). BALB/c mice were fed chow or HC diet for 8 weeks. At the beginning of the 9th week, the HC group was subdivided into three groups: (i) group of animals that continued to consume only HC diet; (ii) the group of animals fed HC diet supplemented with ethyl acetate extract of M. imbricata roots (HC + EAE); (iii) the group of animals fed HC diet supplemented with extract in hexane/ethyl ether (HC + HEE). The period of extracts supplementation was 4 weeks. It was observed that EAE and EHE when added to the HC diet modulated the metabolic and inflammatory changes, such as: reduced the adipocytes area, improved glucose intolerance, reduced the levels of triglycerides and resistin in serum, and the number of total leukocytes in blood. In the epididymal adipose tissue, the extracts reduced proinflammatory mediators' concentration. According to the results, it was concluded that the species Maytenus imbricata has the potential to be used for the treatment of obesity.
Assuntos
Celastraceae/química , Inflamação/tratamento farmacológico , Maytenus/química , Doenças Metabólicas/tratamento farmacológico , Extratos Vegetais/farmacologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Carboidratos/farmacologia , Dieta/efeitos adversos , Suplementos Nutricionais , Inflamação/metabolismo , Resistência à Insulina/fisiologia , Masculino , Doenças Metabólicas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Triglicerídeos/metabolismoRESUMO
Defective apoptosis might be involved in the pathogenesis of multiple sclerosis (MS). We evaluated apoptosis-related molecules in MS patients before and after autologous haematopoietic stem cell transplantation (AHSCT) using BCNU, Etoposide, AraC and Melphalan (BEAM) or cyclophosphamide (CY)-based conditioning regimens. Patients were followed for clinical and immunological parameters for 2 years after AHSCT. At baseline, MS patients had decreased proapoptotic BAD, BAX and FASL and increased A1 gene expression when compared with healthy counterparts. In the BEAM group, BAK, BIK, BIMEL , FAS, FASL, A1, BCL2, BCLXL , CFLIPL and CIAP2 genes were up-regulated after AHSCT. With the exception of BIK, BIMEL and A1, all genes reached levels similar to controls at day + 720 post-transplantation. Furthermore, in these patients, we observed increased CD8+ Fas+ T cell frequencies after AHSCT when compared to baseline. In the CY group, we observed increased BAX, BCLW, CFLIPL and CIAP1 and decreased BIK and BID gene expressions after transplantation. At day + 720 post-AHSCT, the expression of BAX, FAS, FASL, BCL2, BCLXL and CIAP1 was similar to that of controls. Protein analyses showed increased Bcl-2 expression before transplantation. At 1 year post-AHSCT, expression of Bak, Bim, Bcl-2, Bcl-xL and cFlip-L was decreased when compared to baseline values. In summary, our findings suggest that normalization of apoptosis-related molecules is associated with the early therapeutic effects of AHSCT in MS patients. These mechanisms may be involved in the re-establishment of immune tolerance during the first 2 years post-transplantation.
Assuntos
Apoptose/genética , Proteína 5 Relacionada à Autofagia/genética , Esclerose Múltipla/genética , Adulto , Linfócitos T CD8-Positivos/efeitos dos fármacos , Ciclofosfamida/uso terapêutico , Feminino , Expressão Gênica/genética , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/tratamento farmacológico , Condicionamento Pré-Transplante/métodos , Transplante Autólogo/métodos , Adulto JovemRESUMO
The aim of this study was to determine the isotopic-turnover rate (RIT ) and trophic-discrimination factor (FTD ) in muscle tissues of Lebranche mullet Mugil liza fed an experimental diet (δ13 C = -27·1; δ15 N = 1·0). Juvenile M. liza exhibited a relatively fast RIT , with a half-life (t50 ) of only 16 and 14 days for δ13 C and δ15 N respectively and a nearly complete isotopic turnover (t95 ) of 68 and 60 days for δ13 C and δ15 N.
Assuntos
Dieta , Músculos/química , Smegmamorpha/metabolismo , Animais , Isótopos de Carbono/análise , Isótopos de Carbono/metabolismo , Comportamento Alimentar , Cadeia Alimentar , Músculos/metabolismo , Isótopos de Nitrogênio/análise , Isótopos de Nitrogênio/metabolismo , Smegmamorpha/fisiologiaRESUMO
Klebsiella pneumoniae is considered one of the most important Gram-negative opportunistic pathogens. The contact between humans and birds poses health risks to both. The aim of this study was to investigate the resistance and virulence of K. pneumoniae isolates from psittacines and passerines, seized from illegal trade in Brazil. We analysed 32 strains isolated from birds of the orders Psittaciformes and Passeriformes by polymerase chain reaction (PCR) for virulence factor genes. Antibiotic resistance was assessed by disk diffusion assay and PCR. The results indicated that fimH (100%), uge (96.8%), kfu (81.2%) and irp-2 (68.7%) were the most common virulence genes, followed by kpn (46.8%), K2 (43.7%), mrkD (34.3%) and iroN (15.6%). The combination of virulence genes resulted in a great diversity of genotypes and the heterogeneity of the strains is also confirmed in the analysis by amplified fragment length polymorphism. The susceptibility profiles of the K. pneumoniae showed 25% of multiple antibiotic resistance strains. We identified seven strains that presented non-extended spectrum beta lactamase blaSHV variants SHV-1 and SHV-11 and one strain positive to the blaTEM-1 gene. Plasmid-mediated quinolone resistance was present in 10 strains (10/32). The data obtained in this study reveal the pathogenic potential of this pathogen and highlight the need for surveillance and monitoring.
Assuntos
Farmacorresistência Bacteriana , Klebsiella pneumoniae/patogenicidade , Passeriformes/microbiologia , Psittaciformes/microbiologia , Fatores de Virulência/genética , beta-Lactamases/genética , Animais , Anti-Infecciosos/farmacologia , Proteínas de Bactérias/genética , Brasil , Variação Genética , Genótipo , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Plasmídeos/genética , Quinolonas/farmacologia , VirulênciaRESUMO
The objective of the present study was to estimate genetic parameters for skin thickness (ST) and postweaning weight gain (PWG550) in Nellore cattle. Records were obtained from 152,392 Nellore animals born between 2001 and 2011. ST was measured in the posterior region of the animal's scapula with a millimeter caliper. The animals were assigned to different contemporary groups, formed on the basis of farm, year, sex, feeding regimen at weaning, date of weaning, feeding regimen at 450 days of age, and date of weighing at 450 days of age. The genetic parameters were estimated by Bayesian analysis using the GIBBS1F90 program. The mean ST and PWG550 observed were 7.71 ± 2.04 mm and 115.95 ± 36.17 kg, respectively. The posterior mean estimates of heritability (h2) were 0.12 ± 0.02 and 0.29 ± 0.02 for ST and PWG550, respectively. The posterior mean estimates of the phenotypic, genetic, and environmental correlations between the traits were 0.16 ± 0.0, 0.17 ± 0.02, and 0.17 ± 0.09, respectively. The traits ST and PWG550 showed sufficient additive genetic variance to be used as selection criteria in breeding programs. The low genetic correlation obtained indicates that genes favoring the expression of one trait may not influence the other. Consequently, a selection favoring ST would be less efficient in increasing PWG550.
Assuntos
Bovinos/genética , Modelos Genéticos , Característica Quantitativa Herdável , Pele/anatomia & histologia , Aumento de Peso/genética , Animais , Teorema de Bayes , Cruzamento , Bovinos/anatomia & histologia , Bovinos/fisiologia , Feminino , Interação Gene-Ambiente , MasculinoRESUMO
Quantitative real-time polymerase chain reaction (RT-qPCR) is a powerful tool used to measure gene expression. However, because of its high sensitivity, the method is strongly influenced by the quality and concentration of the template cDNA and by the amplification efficiency. Relative quantification is an effective strategy for correcting random and systematic errors by using the expression level of reference gene(s) to normalize the expression level of the genes of interest. To identify soybean reference genes for use in studies of flooding stress, we compared 5 candidate reference genes (CRGs) with the NormFinder and GeNorm programs to select the best internal control. The expression stability of the CRGs was evaluated in root tissues from soybean plants subjected to hypoxic conditions. Elongation factor 1-beta and actin-11 were identified as the most appropriate genes for RT-qPCR normalization by both the NormFinder and GeNorm analyses. The expression profiles of the genes for alcohol dehydrogenase 1, sucrose synthase 4, and ascorbate peroxidase 2 were analyzed by comparing different normalizing combinations (including no normalization) of the selected reference genes. Here, we have identified potential genes for use as references for RT-qPCR normalization in experiments with soybean roots growing in O2-depleted environments, such as flooding-stressed plants.
Assuntos
Regulação da Expressão Gênica de Plantas/genética , Glycine max/genética , Proteínas de Plantas/biossíntese , Reação em Cadeia da Polimerase em Tempo Real/métodos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/fisiologia , Hipóxia , Proteínas de Plantas/genética , Raízes de PlantasRESUMO
Abscisic acid-responsive element binding protein (AREB1) is a basic domain/leucine zipper transcription factor that binds to the abscisic acid (ABA)-responsive element motif in the promoter region of ABA-inducible genes. Because AREB1 is not sufficient to direct the expression of downstream genes under non-stress conditions, an activated form of AREB1 (AREB1ΔQT) was created. Several reports claim that plants overexpressing AREB1 or AREB1ΔQT show improved drought tolerance. In our studies, soybean plants overexpressing AREB1ΔQT were characterized molecularly, and the phenotype and drought response of three lines were accessed under greenhouse conditions. Under conditions of water deficit, the transformed plants presented a higher survival rate (100%) than those of their isoline, cultivar BR 16 (40%). Moreover, the transformed plants displayed better water use efficiency and had a higher number of leaves than their isoline. Because the transgenic plants had higher stomatal conductance than its isoline under well-watered conditions, it was suggested that the enhanced drought response of AREB1ΔQT soybean plants might not be associated with altered transpiration rates mediated by ABA-dependent stomatal closure. However, it is possible that the smaller leaf area of the transgenic plants reduced their transpiration and water use, causing delayed stress onset. The difference in the degree of wilting and percentage of survival between the 35S-AREB1ΔQT and wildtype plants may also be related to the regulation of genes that protect against dehydration because metabolic impairment of photosynthesis, deduced by an increasing internal CO2 concentration, was not observed in the transgenic plants.
Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Fatores de Transcrição de Zíper de Leucina Básica/genética , Regulação da Expressão Gênica de Plantas , Glycine max/genética , Folhas de Planta/genética , Água/metabolismo , Ácido Abscísico/metabolismo , Arabidopsis/química , Proteínas de Arabidopsis/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Secas , Folhas de Planta/metabolismo , Plantas Geneticamente Modificadas , Elementos de Resposta , Glycine max/metabolismo , TransgenesRESUMO
We investigate a hybrid device allowing a photon-phonon coupling of a transmission line radiation (TLR) and a nanoeletromechanical system (NEMS), mediated by a superconducting qubit population imbalance. We demonstrate the derivation of an effective Hamiltonian for the strongly dispersive regime for this system. The qubit works as a quantum switch, allowing a conditioned transfer of excitations between the TLR and NEMS. We show that this regime allows the system to be employed for signal processing and force estimation. Additionally, we explore the ability of the quantum switch to generate non-classical states.
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In this study, we investigated the infection by pulmonary parasites in the water snake Helicops angulatus. We found four nymphs of the pentastomide parasite Sebekia oxycephala, parasitizing two adult females H. angulatus collected in the municipality of Rio Tinto, Paraíba, Brazil. This occurrence is likely due to the nymphs of this parasite directly infecting aquatic intermediate hosts, such as fish. The result of this study represents the first record of pentastomid infecting H. angulatus.
Assuntos
Colubridae , Pentastomídeos , Animais , Feminino , Colubridae/parasitologia , Brasil/epidemiologia , Pulmão , NinfaRESUMO
Binding of ligands to DNA can be studied by measuring the change of the persistence length of the complex formed, in single-molecule assays. We propose a methodology for persistence length data analysis based on a quenched disorder statistical model and describing the binding isotherm by a Hill-type equation. We obtain an expression for the effective persistence length as a function of the total ligand concentration, which we apply to our data of the DNA-cationic ß-cyclodextrin and to the DNA-HU protein data available in the literature, determining the values of the local persistence lengths, the dissociation constant, and the degree of cooperativity for each set of data. In both cases the persistence length behaves nonmonotonically as a function of ligand concentration and based on the results obtained we discuss some physical aspects of the interplay between DNA elasticity and cooperative binding of ligands.
Assuntos
DNA/química , Modelos Químicos , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , DNA/metabolismo , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/metabolismo , Elasticidade , Ligantes , Modelos Estatísticos , Relação Estrutura-Atividade , beta-Ciclodextrinas/química , beta-Ciclodextrinas/metabolismoRESUMO
We use the classical correlation between a quantum system being measured and its measurement apparatus to analyze the amount of information being retrieved in a quantum measurement process. Accounting for decoherence of the apparatus, we show that these correlations may have a sudden transition from a decay regime to a constant level. This transition characterizes a nonasymptotic emergence of the pointer basis, while the system apparatus can still be quantum correlated. We provide a formalization of the concept of emergence of a pointer basis in an apparatus subject to decoherence. This contrast of the pointer basis emergence to the quantum to classical transition is demonstrated in an experiment with polarization entangled photon pairs.
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BACKGROUND: Citrobacter koseri has not been associated to infection caused by blood component transfusions. CASE REPORT: A 46-year-old female patient presented sudden chills, dyspnoea, and tachycardia during a transfusion from a unit of packed red blood cells. Citrobacter koseri was isolated in the two sample collected from the patient and from the content of the packed red blood cells. RESULTS: We report a case of bacteraemia due to a transfusion of contaminated red blood cells. CONCLUSION: C. koseri should be taken into account in bacteraemias caused by transfusion of blood components.
Assuntos
Bacteriemia/etiologia , Citrobacter koseri/isolamento & purificação , Infecções por Enterobacteriaceae/etiologia , Transfusão de Eritrócitos/efeitos adversos , Eritrócitos/microbiologia , Bacteriemia/sangue , Infecções por Enterobacteriaceae/sangue , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
The control of parasitic diseases in small ruminants is mainly done with the use of synthetic anthelmintics. However, incorrect and indiscriminate use of these products has caused the emergence of parasite resistance. Plants with anthelmintic activity are used in folk veterinary medicine, but it is necessary to investigate and scientifically validate low-cost phytotherapeutic alternatives for future use to control gastrointestinal nematodes in small ruminants by family farmers. Thus, the aim of this study was to evaluate the in vitro anthelmintic effect of plant extracts from Melia azedarach and Trichilia claussenii by the egg hatch test (EHT) and larval development test (LDT) against sheep gastrointestinal nematodes. The hexane extract of M. azedarach fruits was extracted through cold percolation and the methanol extract of T. claussenii leaves was obtained by extraction at room temperature in solvents in order of increasing polarity. The efficacy results were analyzed using the Probit program of SAS. The M. azedarach extract showed a LC(50) of 572.2 µg/mL and LC(99) of 1137.8 µg/mL in the EHT, and LC(50) of 0.7 µg/mL and LC(99) of 60.8 µg/mL in the LDT. In turn, the T. claussenii extract presented a LC(50) of 263.8 µg/mL and LC(99) of 522.5 µg/mL in the EHT and LC(50) of 1.1 µg/mL and LC(99) of 26.4 µg/mL in the LDT. Comparing the extracts of the species from the Meliaceae family, T. claussenii showed greater anti-parasite potential in vitro than M. azedarach. However, studies on the isolated compounds, toxicity and administration forms to animals are also needed to validate low-cost alternative herbal remedies for use to control gastrointestinal nematodes by family farmers.
Assuntos
Haemonchus/efeitos dos fármacos , Melia azedarach/química , Meliaceae/química , Extratos Vegetais/farmacologia , Trichostrongylus/efeitos dos fármacos , Animais , Anti-Helmínticos/isolamento & purificação , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Relação Dose-Resposta a Droga , Fezes/parasitologia , Haemonchus/crescimento & desenvolvimento , Enteropatias Parasitárias/tratamento farmacológico , Enteropatias Parasitárias/parasitologia , Enteropatias Parasitárias/veterinária , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Infecções por Nematoides/tratamento farmacológico , Infecções por Nematoides/parasitologia , Infecções por Nematoides/veterinária , Contagem de Ovos de Parasitas/veterinária , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Ovinos , Doenças dos Ovinos/tratamento farmacológico , Doenças dos Ovinos/parasitologia , Trichostrongylus/crescimento & desenvolvimentoRESUMO
Climate changes can affect the distribution and intensity of insect infestations through direct effects on their life cycles. Experiments were carried out during three consecutive generations to evaluate the effect of different temperatures (25°C, 28°C, 31°C, 34°C and 37±1°C) on biological traits of the velvetbean caterpillar Anticarsia gemmatalis Hübner, 1818 (Lepidoptera: Noctuidae). The insects were fed on artificial diet and reared in environmental chambers set at 14 h photophase. The developmental cycle slowed with the increase in the temperature, within the 25°C to 34°C range. Male and female longevities were reduced with an increase in temperature from 25°C to 28°C. Egg viability was highest at 25°C, and the sex ratio was not influenced by temperature, in the three generations. There was no interactive effect between development time and temperature on pupal weight. The results suggested that the increase in the temperature negatively impacted A. gemmatalis development inside the studied temperature range, indicating a possible future reduction of its occurrence on soybean crops, as a consequence of global warming, mainly considering its impact on tropical countries where this plant is cropped. A. gemmatalis was not able to adapt to higher temperatures in a three-generation interval for the studied temperature range. However, a gradual increase and a longer adaptation period may favor insect selection and consequently adaptation, and must be considered in future studies in this area. Moreover, it is important to consider that global warming might turn cold areas more suitable to A. gemmatalis outbreaks. Therefore, more than a future reduction of A. gemmatalis occurrence due to global warming, we might expect changes regarding its area of occurrence on a global perspective.
Assuntos
Glycine max/parasitologia , Longevidade , Mariposas/crescimento & desenvolvimento , Razão de Masculinidade , Temperatura , Animais , Feminino , Aquecimento Global , Larva/crescimento & desenvolvimento , Masculino , Óvulo/fisiologia , Pupa/crescimento & desenvolvimentoRESUMO
We apply estimation theory to a system formed by two interacting trapped ions. By using the Fisher matrix formalism, we introduce a simple scheme for estimation of the temperature of the longitudinal vibrational modes of the ions. We use the ions interaction to effectively infer the temperature of the individual ions, by optimising the interaction time evolution and by measuring only over one of the ions. We also investigate the effect of a non-thermal reservoir over the inference approach. The non-classicality of one of the ions vibrational modes, introduced due to a squeezed thermal reservoir, does not directly affect the inference of the individual temperatures, although allowing the modes to be entangled. To check actual experimental conditions, we analyze the temperature inference under heating due to surface-electrode noise.
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Pioglitazone, an agonist at peroxisome proliferator-activated receptor gamma, is FDA-approved for the treatment of insulin resistance in type 2 diabetes. Numerous studies in male rodents suggest that pioglitazone inhibits inflammatory and neuropathic pain, but few included female subjects. To address this gap, we compared the effects of pioglitazone in both sexes in the intraplantar methylglyoxal model (MG) model of chemical pain and painful diabetic neuropathy (PDN), the plantar incision model (PIM) of postoperative pain, the spared nerve injury (SNI) model of traumatic nerve injury, and the ZDF rat and db/db mouse models of PDN. We administered pioglitazone by one-time intrathecal or intraperitoneal injection or by adding it to chow for 6 weeks, followed by measurement of hypersensitivity to non-noxious mechanical, noxious mechanical, heat, and/or cold stimuli. In all mouse models, injection of pioglitazone decreased pain-like behaviors with greater potency and/or efficacy in females as compared to males: heat and mechanical hypersensitivity in the MG model (0.1-10 mg/kg); mechanical hypersensitivity in the PIM model (10 µg); mechanical and cold hypersensitivity in the SNI model (100 mg/kg); and heat hypersensitivity in the db/db model (100 mg/kg). Furthermore, co-administration of low doses of morphine (1 mg/kg) and pioglitazone (10 mg/kg) decreased SNI-induced mechanical and cold hypersensitivity in female but not male mice. In the ZDF rat, pioglitazone (100 mg/kg) decreased heat and mechanical hypersensitivity with no sex difference. In the db/db model, pioglitazone had no effect when given into chow for 6 weeks at 0.3, 3 or 30 mg/kg doses. We conclude that females exhibit greater anti-hyperalgesic responses to pioglitazone in mouse models of chemical-induced nociception, postsurgical pain, neuropathic pain, and PDN. These findings set the stage for clinical trials to determine whether pioglitazone has analgesic properties across a broad spectrum of chronic pain conditions, particularly in women.
Assuntos
Analgésicos/farmacologia , Hiperalgesia/tratamento farmacológico , Neuralgia/tratamento farmacológico , Dor Nociceptiva/tratamento farmacológico , PPAR gama/agonistas , Dor Pós-Operatória/tratamento farmacológico , Pioglitazona/farmacologia , Analgésicos/administração & dosagem , Animais , Neuropatias Diabéticas/complicações , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Morfina/farmacologia , Neuralgia/etiologia , Dor Nociceptiva/induzido quimicamente , Dor Pós-Operatória/etiologia , Traumatismos dos Nervos Periféricos/complicações , Pioglitazona/administração & dosagem , Aldeído Pirúvico/farmacologia , Caracteres SexuaisRESUMO
To gain insight into stress-responsive gene regulation in soybean plants, we identified consensus sequences that could categorize the transcription factors MYBJ7, BZIP50, C2H2, and NAC2 as members of the gene families myb, bzip, c2h2, and nac, respectively. We also investigated the evolutionary relationship of these transcription factors and analyzed their expression levels under drought stress. The NCBI software was used to find the predicted amino acid sequences of the transcription factors, and the Clustal X software was used to align soybean and other plant species sequences. Phylogenetic trees were built using the Mega 4.1 software by neighbor joining and the degree of confidence test by Bootstrap. Expression level studies were carried out using hydroponic culture; the experiments were designed in completely randomized blocks with three repetitions. The blocks consisted of two genotypes, MG/BR46 Conquista (drought-tolerant) and BR16 (drought-sensitive) and the treatments consisted of increasingly long dehydration periods (0, 25, 50, 75, and 100 min). The transcription factors presented domains and/or conserved regions that characterized them as belonging to the bzip, c2h2, myb, and nac families. Based on the phylogenetic trees, it was found that the myb, bzip and nac genes are closely related to myb78, bzip48 and nac2 of soybean and that c2h2 is closely related to c2h2 of Brassica napus. Expression of all genes was in general increased under drought stress in both genotypes. Major differences between genotypes were due to the lowering of the expression of the mybj7 and c2h2 genes in the drought-tolerant variety at some times. Over-expression or silencing of some of these genes has the potential to increase stress tolerance.