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In this paper, a wet-dry hybrid technique to transfer patterned reduced graphene oxide (rGO) thin film to arbitrary substrates at predetermined locations without using any chemicals is reported. The transfer process involves water-assisted delamination of rGO, followed by dry transfer to an acceptor substrate using viscoelastic stamp. Patterned reduced graphene oxide films are transferred to silicon dioxide (SiO2/Si) substrate to begin with. Subsequently, the method is deployed to transfer rGO to different polymer substrates such as poly(methyl methacrylate) (PMMA), and crosslinked poly(4-vinylphenol) (c-PVP), which are commonly used as gate dielectric in flexible electronic applications. The credibility of the transfer process with precise spatial positioning on the target substrate leads to fabrication of freely suspended reduced graphene oxide membrane towards nanoelectromechanical systems (NEMS) based devices such as nanomechanical drum resonators.
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The capacity and condition under which the lateral transfer of olfactory memory is possible in insects is still debated. Here, we present evidence in two species of honeybees, Apis mellifera and Apis dorsata, consistent with the lack of ability to transfer olfactory associative memory in a proboscis extension response (PER) associative conditioning paradigm, where the untrained antenna is blocked by an insulating coat. We show that the olfactory system on each side of the bee can learn and retrieve information independently and the retrieval using the antenna on the side contralateral to the trained one is not affected by the training. Using the setup in which the memory on the contralateral side has been reported at 3â h after training, we see that the memory is available on the contralateral side immediately after training. In the same setup, coating the antenna with an insulator on the training side does not prevent learning, pointing to a possible insufficiency of the block of odor stimuli in this setup. Moreover, the behavior of the bee as a whole can be predicted if the sides are assumed to learn and store independently, and the organism as a whole is able to retrieve the memory if either of the sides have the memory.
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Abelhas/fisiologia , Olfato/fisiologia , Animais , Aprendizagem por Associação/fisiologia , Memória/fisiologiaRESUMO
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cutaneous melanoma have been significantly revised over the past few years in response to emerging data on immune checkpoint inhibitor therapies and BRAF-targeted therapy. This article summarizes the data and rationale supporting extensive changes to the recommendations for systemic therapy as adjuvant treatment of resected disease and as treatment of unresectable or distant metastatic disease.
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Oncologia , Melanoma , Neoplasias Cutâneas , Humanos , Oncologia/normas , Melanoma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Melanoma Maligno CutâneoRESUMO
OBJECTIVES: To develop and implement a community-based programme for screening of diabetic retinopathy (DR) in urban populations of Delhi. METHODS: Known diabetics (KDs) aged 40 years and older were identified through house-to-house surveys, volunteers and publicity. All KDs were referred to DR screening camps organised locally where procedures included brief medical history, ocular examination and non-mydriatic fundus photography using portable handheld camera. Fundal images were graded on the spot by trained optometrists for DR. Patients with DR were referred to tertiary centre for management. RESULTS: A total of 11 566 KDs were identified, of whom 9435 (81.6%) visited DR screening camps and 8432 (89.4%) had DR gradable images. DR was identified in 13.5% of subjects; 351 cases were mild NPDR, 567 moderate, 92 severe. Seventy-seven had PDR, and 49 had DME, and 2.7% of participants were blind (presenting visual acuity <3/60 in better eye). Non-use of lifestyle management, presence of systemic complications, BMI <18.5 kg/m2 , disease duration of >5 years and uncontrolled diabetes were associated with increased odds of DR. All cases with DR were referred, and 420 (37%) successful referrals to base hospital were observed. CONCLUSION: The programme of creating awareness about DR, identifying KDs and optometrist-led DR screening using non-mydriatic fundus camera based in slums was successful.
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Retinopatia Diabética/diagnóstico , Fundo de Olho , Programas de Rastreamento/métodos , Fotografação , Áreas de Pobreza , Pobreza , População Urbana , Adulto , Idoso , Cegueira/epidemiologia , Cegueira/etiologia , Índice de Massa Corporal , Cidades , Diabetes Mellitus , Retinopatia Diabética/diagnóstico por imagem , Retinopatia Diabética/epidemiologia , Gerenciamento Clínico , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Midriáticos , Encaminhamento e Consulta , Retina/patologia , Fatores de Risco , Acuidade VisualRESUMO
Neuropeptide-Y (NPY) has diverse physiological functions which are extensively studied in vertebrates. However, regulatory role of NPY in relation to brain ontogeny and recrudescence with reference to reproduction is less understood in fish. Present report for the first time evaluated the significance of NPY by transient esiRNA silencing and also analyzed its expression during brain development and gonadal recrudescence in the catfish, Clarias gariepinus. As a first step, full-length cDNA of NPY was cloned from adult catfish brain, which shared high homology with its counterparts from other teleosts upon phylogenetic analysis. Tissue distribution revealed dominant expression of NPY in brain and testis. NPY expression increased during brain development wherein the levels were higher in 100 and 150days post hatch females than the respective age-matched males. Seasonal cycle analysis showed high expression of NPY in brain during pre-spawning phase in comparison with other reproductive phases. Localization studies exhibited the presence of NPY, abundantly, in the regions of preoptic area, hypothalamus and pituitary. Transient silencing of NPY-esiRNA directly into the brain significantly decreased NPY expression in both the male and female brain of catfish which further resulted in significant decrease of transcripts of tryptophan hydroxylase 2, catfish gonadotropin-releasing hormone (cfGnRH), tyrosine hydroxylase and 3ß-hydroxysteroid dehydrogenase in brain and luteinizing hormone-ß/gonadotropin-II (lh-ß/GTH-II) in pituitary exhibiting its influence on gonadal axis. In addition, significant decrease of several ovary-related transcripts was observed in NPY-esiRNA silenced female catfish, indicating the plausible role of NPY in ovary through cfGnRH-GTH axis.
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Encéfalo/embriologia , Peixes-Gato/embriologia , Peixes-Gato/genética , Regulação da Expressão Gênica no Desenvolvimento , Gônadas/embriologia , Neuropeptídeo Y/genética , Sequência de Aminoácidos , Animais , Encéfalo/metabolismo , Clonagem Molecular , DNA Complementar/genética , Feminino , Perfilação da Expressão Gênica , Inativação Gênica , Gônadas/metabolismo , Imuno-Histoquímica , Hibridização In Situ , Masculino , Neuropeptídeo Y/metabolismo , Ovário/metabolismo , Filogenia , Hipófise/metabolismo , Polietilenoimina , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Recidiva , Reprodução , Alinhamento de SequênciaRESUMO
The NCCN Guidelines for Melanoma have been significantly revised over the past few years in response to emerging data on a number of novel agents and treatment regimens. These NCCN Guidelines Insights summarize the data and rationale supporting extensive changes to the recommendations for systemic therapy in patients with metastatic or unresectable melanoma.
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Melanoma/diagnóstico , Melanoma/terapia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Humanos , Imunoterapia , Melanoma/etiologia , Terapia de Alvo Molecular , Estadiamento de Neoplasias , Retratamento , Resultado do TratamentoRESUMO
Graphene, the thinnest possible anticorrosion and gas-permeation barrier, is poised to transform the protective coatings industry for a variety of surface applications. In this work, we have studied the structural changes of graphene when the underlying copper surface undergoes oxidation upon heating. Single-layer graphene directly grown on a copper surface by chemical vapour deposition was annealed under ambient atmosphere conditions up to 400 °C. The onset temperature of the surface oxidation of copper is found to be higher for graphene-coated foils. Parallel arrays of graphene nanoripples are a ubiquitous feature of pristine graphene on copper, and we demonstrate that these form crucial sites for the onset of the oxidation of copper, particularly for â¼0.3-0.4 µm ripple widths. In these regions, the oxidation proceeds along the length of the nanoripples, resulting in the formation of parallel stripes of oxidized copper regions. We demonstrate from temperature-dependent Raman spectroscopy that the primary defect formation process in graphene involves boundary-type defects rather than vacancy or sp(3)-type defects. This observation is consistent with a mechanical tearing process that splits graphene into small polycrystalline domains. The size of these is estimated to be sub-50 nm.
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Balance between reactive oxygen species (ROS) and the antioxidant (AO) defense mechanisms is vital for organism survival. Insects serve as an ideal model to elucidate oxidative stress responses as they are prone to different kinds of stress during their life cycle. The present study demonstrates the modulation of AO enzyme gene expression in the insect pest, Achaea janata (castor semilooper), when subjected to different oxidative stress stimuli. Antioxidant enzymes' (catalase (Cat), superoxide dismutase (Sod), glutathione-S-transferase (GST) and glutathione peroxidase (Gpx)) partial coding sequences were cloned and characterized from larval whole body. Tissue expression studies reveal a unique pattern of AO genes in the larval tissues with maximum expression in the gut and fat body. Ontogeny profile depicts differential expression pattern through the larval developmental stages for each AO gene studied. Using quantitative RT-PCR, the expression pattern of these genes was monitored during sugar-induced (d-galactose feeding), infection-induced (Gram positive, Gram negative and non-pathogenic bacteria) and pesticide-induced oxidative stress (Bt Cry toxin). d-Galactose feeding differentially modulates the expression of AO genes in the larval gut and fat body. Immune challenge with Escherichia coli induces robust upregulation of AO genes when compared to Bacillus coagulans and Bacillus cereus in the larval fat body and gut. Cry toxin feeding predominantly induced GST upregulation in the gut. The current study suggests that though there are multiple ways of generation of oxidative stress in the insect, the organism tailors its response by insult- and tissue-specific recruitment of the antioxidant players and their differential regulation for each inducer.
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Mariposas/fisiologia , Estresse Oxidativo , Sequência de Aminoácidos , Animais , Antioxidantes/metabolismo , Catalase/genética , Catalase/metabolismo , Clonagem Molecular , Escherichia coli/imunologia , Regulação da Expressão Gênica , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Mariposas/genética , Mariposas/imunologia , Espécies Reativas de Oxigênio/metabolismo , Alinhamento de Sequência , Análise de Sequência de Proteína , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismoRESUMO
Recent studies of epithelial tissues have revealed the presence of tissue-specific stem cells that are able to establish multiple cell lineages within an organ. The stem cells give rise to progenitors that replicate before differentiating into specific cell lineages. The mechanism by which homeostasis is established between proliferating stem or progenitor cells and terminally differentiated cells is unclear. This study demonstrates that Agr2 expression by mucous neck cells in the stomach promotes the differentiation of multiple cell lineages while also inhibiting the proliferation of stem or progenitor cells. When Agr2 expression is absent, gastric mucous neck cells increased in number as does the number of proliferating cells. Agr2 expression loss also resulted in the decline of terminally differentiated cells, which was supplanted by cells that exhibited nuclear SOX9 labeling. Sox9 expression has been associated with progenitor and stem cells. Similar effects of the Agr2 null on cell proliferation in the intestine were also observed. Agr2 consequently serves to maintain the balance between proliferating and differentiated epithelial cells.
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Diferenciação Celular , Linhagem da Célula , Regulação da Expressão Gênica no Desenvolvimento , Mucoproteínas/biossíntese , Células-Tronco/metabolismo , Estômago/embriologia , Animais , Proliferação de Células , Hiperplasia , Camundongos , Camundongos Mutantes , Mucoproteínas/genética , Proteínas Oncogênicas , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo , Células-Tronco/patologia , Estômago/patologiaRESUMO
BACKGROUND: There is currently no definite neuroimaging test to detect amyotrophic lateral sclerosis (ALS), which leads to significant delay in diagnosis, particularly if one takes into account the rapidity of disease evolution. Hyperintensity of the corticospinal tracts (CST) on T2 or fluid-attenuated inversion recovery (FLAIR) weighted magnetic resonance imaging (MRI) has been well described, but data on sensitivity and specificity in larger series is lacking to help guide its application to clinical care. METHODS: We analyzed clinical and MRI data from 64 patients with a definite retrospective diagnosis of ALS. In this case-control study, two experienced blinded neuroradiologists systematically assessed defined rostrocaudal segments of the intracranial course of the CST. RESULTS: The overall sensitivity and specificity of conventional MRI for the diagnosis of ALS were 48% and 76% respectively. Highest specificities for CST hyperintensity were noted for the subcortical white matter (92%), centrum semiovale (88%) and medullary pyramids (92%). The lowest specificities were found for the cerebral peduncle (36%) and internal capsule (32%). We did not find a correlation with the rate of clinical progression, age of onset or the presence of upper motor neuron signs on examination. CONCLUSION: Conventional MRI was not found to be a reliable diagnostic tool for ALS and it did not help predict clinical characteristics such as speed of evolution or prominence of upper motor neuron signs. Its main role in the setting of ALS should remain to help exclude alternative diagnostic considerations. A multimodal approach relying on newer functional and structural MRI techniques still needs to be developed and validated.Précision de l'IRM conventionnelle dans la SLA.
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Esclerose Lateral Amiotrófica/diagnóstico , Encéfalo/patologia , Imageamento por Ressonância Magnética/normas , Idoso , Esclerose Lateral Amiotrófica/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVE: System-level safety measures do not exist to ensure that patients with iron deficiency anaemia (IDA) undergo proper diagnostic evaluations. We sought to determine if a set of EHR (electronic health record) tools and an expedited referral workflow increase short-term completion of bidirectional endoscopy in higher risk patients with IDA. MATERIALS AND METHODS: We conducted a pragmatic, cluster-randomised trial randomised by primary care physician (PCP) that included 16 PCPs and 316 patients with IDA. Physicians were randomised to intervention or control groups. Intervention components included a patient registry visible within the EHR, point-of-care alert and expedited diagnostic evaluation workflow for IDA. Outcomes were assessed at 120 days. The primary outcome was completion of bidirectional endoscopy. Secondary outcomes were any endoscopy completed or scheduled, gastroenterology consultation completed, and gastroenterology referral or endoscopy ordered or completed. RESULTS: There were no differences in the primary or secondary outcomes. At 120 days, the primary outcome had occurred for 7 (4%) of the intervention group and 5 (3.5%) of the control group. For the three secondary outcomes, rates were 15 (8.6%), 12 (6.9%) and 39 (22.4%) for the immediate intervention group and 10 (7.0%), 9 (6.3%) and 25 (17.6%) for the control group, respectively, p>0.2. Lack of physician time to use the registry tools was identified as a barrier. DISCUSSION AND CONCLUSION: Providing PCPs with lists of patients with IDA and a pathway for expedited evaluation did not increase rates of completing endoscopic evaluation in the short term. TRIAL REGISTRATION NUMBER: NCT05365308.
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Anemia Ferropriva , Médicos , Humanos , Anemia Ferropriva/diagnóstico , Registros Eletrônicos de Saúde , Encaminhamento e ConsultaRESUMO
Metal contamination in drinking water has drawn attention since it gravely jeopardizes human health. This study was conducted in pre- and post-monsoon season in 2021 at Dhemaji, Assam, India. It characterized metal pollutants in groundwater, their distribution, possible sources, and evaluated the potential toxicity and associated health risk assessment. The seasonal mean concentration of Fe in both seasons is observed highest followed by Mn, Zn, Cu, As, and Ni. Furthermore, the metal concentrations during pre-monsoon are comparatively higher. The geogenic processes and agricultural practices are the major sources of groundwater metal contamination as evident from the statistical analysis. The different pollution indices viz. Heavy-metal Pollution Index (HPI), Heavy-metal Evaluation Index (HEI) and Degree of Contamination (Cd) suggested that groundwater is not suitable for drinking uses. The Heavy Metal Toxicity Load (HMTL) suggesting As, Co, Mn and Hg should be removed from the groundwater to ensure safety. Water pollution indices (WPI) suggest that Fe, Mn, As and Ni are the main pollution-causing metals in the study area which may be restored under the BIS and WHO limit by diluting the water. The human health risk has been calculated by carcinogenic and non-carcinogenic risk assessment. The non-carcinogenic risk for adults and children is within the threshold limit. The carcinogenic risk shows that continuous exposure of As and Ni may give rise to cancer among adults and children in the region. Therefore, comprehensive groundwater quality monitoring with well-planned treatment should be needed to provide safe and clean drinking water in the studied area.
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Água Potável , Monitoramento Ambiental , Água Subterrânea , Metais Pesados , Poluentes Químicos da Água , Água Subterrânea/química , Metais Pesados/análise , Metais Pesados/toxicidade , Índia , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade , Medição de Risco , Humanos , Água Potável/química , Água Potável/análise , Estações do AnoRESUMO
Soluble proteins are enriched in the endoplasmic reticulum (ER) by retrograde transport from the Golgi that is mediated by the KDEL receptors. In addition to the classic carboxyl-terminal KDEL motif, a variety of sequence variants are also capable of receptor binding that result in ER localization. Although different ER localization signals that exhibit varying affinities for the KDEL receptors exist, whether there are functional implications was unknown. The present study determines whether AGR2 requires a specific ER localization signal to be functionally active. AGR2 is expressed in most human adenocarcinomas and serves a role in promoting growth and the transformed phenotype. Using two different cell lines in which AGR2 induces expression of either the EGFR ligand amphiregulin or the transcription factor CDX2, only the highly conserved wild-type carboxyl-terminal KTEL motif results in the appropriate outcome. Deletion of the KTEL motif results in AGR2 secretion and loss of AGR2 function. AGR2 function is also lost when ER residence is achieved with a carboxyl-terminal KDEL or KSEL instead of a KTEL motif. Thus variations in ER localization sequences may serve a specific functional role, and in the case of AGR2, this role is served specifically by KTEL.
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Retículo Endoplasmático/metabolismo , Sinais Direcionadores de Proteínas/fisiologia , Proteínas/metabolismo , Motivos de Aminoácidos , Anfirregulina , Animais , Linhagem Celular Tumoral , Família de Proteínas EGF , Retículo Endoplasmático/genética , Glicoproteínas/genética , Glicoproteínas/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Mucoproteínas , Proteínas Oncogênicas , Proteínas/genética , Ratos , Receptores de Peptídeos/genética , Receptores de Peptídeos/metabolismo , Deleção de SequênciaRESUMO
Cytochrome P450 aromatase (cyp19) catalyzes the conversion of androgens into estrogens. Teleosts have distinct, ovarian specific (cyp19a1a) and brain specific (cyp19a1b) cyp19 genes. Previous studies in teleosts demonstrated regulation of cyp19a1a expression by the NR5A nuclear receptor subfamily as well as a fork head transcription factor, FOXL2. In the present study, we investigated the involvement of fushi tarazu factor 1, FTZ-F1, a NR5A subfamily member, and FOXL2 in the regulation of cyp19a1b expression in brain of the air-breathing catfish, Clarias gariepinus. Based on the synchronous expression pattern of cyp19a1b, FTZ-F1 and FOXL2 in the brain, we isolated the 5' upstream region of cyp19a1b to analyse regulatory motifs. Promoter motif analysis revealed FTZ-F1/NR5A1 and FOXL2 binding nucleotide sequences. Transient transfection studies showed that FTZ-F1 and FOXL2 together enhanced the transcriptional activity of cyp19a1b gene in mammalian cell lines. Mutation in either of their putative binding sites within the cyp19a1b promoter abolished this effect. Electrophoretic gel mobility shift experiments indicated that FTZ-F1 and FOXL2 proteins bind to the synthesized radio-labelled oligomers used as probes and mobility shifted upon addition of their respective antibodies. Chromatin immunoprecipitation assay confirmed the binding of both these transcription factors to their corresponding cis-acting elements in the upstream region of cyp19a1b. To our knowledge, this study is the first report on the transcriptional regulation of cyp19a1b by FTZ-F1 and FOXL2 in a teleost fish.
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Aromatase/genética , Encéfalo/metabolismo , Peixes-Gato/genética , Fatores de Transcrição Forkhead/genética , Regiões Promotoras Genéticas/genética , Fator Esteroidogênico 1/genética , Animais , Aromatase/metabolismo , Sequência de Bases , Sítios de Ligação/genética , Peixes-Gato/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Células HEK293 , Humanos , Dados de Sequência Molecular , Motivos de Nucleotídeos , Fator Esteroidogênico 1/metabolismo , Ativação Transcricional , Regulação para CimaRESUMO
Neuroendocrine (NE) prostate tumors and neuroendocrine differentiation (NED) in prostatic adenocarcinomas have been associated with poor prognosis. In this study, we used the TRAMP mouse model that develops NE prostate tumors to identify key factors that can lead to NED. We have previously reported that NE tumors express the forkhead transcription factor, Foxa2, Mash1 (mouse achaete scute homolog-1), as well as Synaptophysin. In TRAMP, the prostatic intraepithelial neoplasia (PIN) first expresses Foxa2 and Synaptophysin, which then progresses to NE cancer. In order to determine if Foxa2 is dispensable for development or maintenance of NE cancer, a conditional knock-out of Foxa2 in TRAMP mice was generated by breeding mice with two floxed alleles of Foxa2 and one copy of Nkx3.1-Cre. Nkx3.1-Cre/Foxa2(loxP/loxP) mice showed loss of Foxa2 expression in embryonic prostatic buds. No expression of Foxa2 was seen in the adult prostate in either conditional null or control mice. Foxa2 is universally expressed in all wild type TRAMP NE tumors, but Mash1 expression is seen only in a few samples in a few cells. With the loss of Foxa2 in the NE tumors of the TRAMP/Nkx3.1-Cre/Foxa2(loxP/loxP) mice, the expression of the pro-neuronal gene Mash1 is upregulated. NE tumors from both the TRAMP control and Foxa2-deficient TRAMP prostate express Synaptophysin and SV40 Large T-antigen, and both show a loss of androgen receptor expression in NE cells. These studies suggest that the TRAMP NE tumors can form in the absence of Foxa2 by an up regulation of Mash1.
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Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fator 3-beta Nuclear de Hepatócito/genética , Tumores Neuroendócrinos/genética , Neoplasias da Próstata/genética , Animais , Biomarcadores Tumorais/genética , Carcinoma de Células Pequenas/genética , Carcinoma de Células Pequenas/patologia , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Regulação Neoplásica da Expressão Gênica/fisiologia , Masculino , Camundongos , Camundongos Transgênicos , Tumores Neuroendócrinos/patologia , Fenótipo , Prognóstico , Próstata/embriologia , Próstata/patologia , Próstata/fisiologia , Neoplasias da Próstata/patologiaRESUMO
Juvenile hormone (JH) and 20-hydroxyecdysone (20E), co-ordinately orchestrate insect growth and development. The process of silk synthesis and secretion in lepidopteran insects is known to be under hormonal control. However, the role of JH in this process has not been demonstrated hitherto. The present study is aimed to elucidate the role of JH in H-fibroin regulation in Corcyra cephalonica, a serious lepidopteran pest. Reiterated amino acid stretches and the large molecular weight of H-fibroin render its cloning and characterization cumbersome. To address this, a commercially synthesized short amino acid peptide conjugated with a carrier protein was used to generate antibodies against the N-terminal region of H-fibroin. ELISA and immunoblot experiments demonstrated the sensitivity and specificity of antibody. Further, immunohistochemical analyses revealed the antibody's cross-reactivity with H-fibroins of C. cephalonica and Bombyx mori in the silk gland lumen. Quantitative RT-PCR and Western blot analysis demonstrated the tissue-specificity and developmental expression of H-fibroin. Hormonal studies revealed that JH alone does not alter the expression of H-fibroin. However, in the presence 20E, JH reverses the declined expression caused by 20E administration to normal levels. This study provides molecular evidence for the regulation of H-fibroin by the cumulative action of JH and 20E.
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Fibroínas/metabolismo , Proteínas de Insetos/metabolismo , Hormônios Juvenis/metabolismo , Larva/crescimento & desenvolvimento , Larva/metabolismo , Lepidópteros/crescimento & desenvolvimento , Lepidópteros/metabolismo , Metoprene/metabolismo , Animais , Western Blotting , Ecdisterona/metabolismo , Fibroínas/genética , Proteínas de Insetos/genética , Hormônios Juvenis/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Polycyclic Aromatic Hydrocarbons (PAHs) compounds are ubiquitous in ambient air due to their persistence, carcinogenicity, and mutagenicity. Gangtok being one of the cleanest cities in India located in Eastern Himalayan region, witnesses high developmental activities with enhanced urbanization affecting the ambient air quality. The present study aims to measure PM2.5 and PAHs in the ambient atmosphere of the Sikkim Himalaya to understand the influence of natural and anthropogenic activities on aerosol loading and their chemical characteristics. The PM2.5 samples were collected and analysed for the duration from Jan 2020 to Feb 2021.The seasonal mean concentrations of PM2.5 and PAHs were observed to be high during autumn and low during summer season. Overall, the annual mean concentration of PM2.5 was found higher than the prescribed limit of World Health Organization and National Ambient Air Quality Standards. The concentration of the 16 individual PAHs were found to be highest during autumn season (55.26 ± 37.15 ng/m3). Among the different PAHs, the annual mean concentration of fluorene (3.29 ± 4.07 ng/m3) and naphthalene (1.15 ± 3.76 ng/m3) were found to be the highest and lowest, respectively. The Molecular Diagnostic Ratio (MDR) test reveals higher contribution from heavy traffic activities throughout the winter and autumn seasons. The other possible sources identified over the region are fossil fuel combustion, and biomass burning. The multivariate statistical analysis (Multifactor Principal Component Analysis) also indicates a strong association between PM2.5 /PAHs and meteorological variables across the region in different seasons. The precipitation and wind pattern during the study period suggests that major contribution of the PM2.5 and PAHs were from local sources, with minimal contribution from long-range transport. The findings are important for comprehending the trends of PAH accumulation over a high-altitude urban area, and for developing sustainable air quality control methods in the Himalayan region.
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Poluentes Atmosféricos , Hidrocarbonetos Policíclicos Aromáticos , Poluentes Atmosféricos/análise , Material Particulado/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Siquim , Altitude , Monitoramento Ambiental/métodos , Atmosfera/química , Estações do Ano , Vento , Aerossóis/análise , ChinaRESUMO
Anterior Gradient Homolog 2 (AGR2) is expressed by the normal intestine and by most human adenocarcinomas, including those derived from the esophagus, pancreas, lung, breast, ovary, and prostate. Xenografts of human adenocarcinoma cell lines in nude mice previously demonstrated that AGR2 supports tumor growth. In addition, AGR2 is able to induce in vitro a transformed phenotype in fibroblast and epithelial cell lines. The mechanism underlying the growth promoting effects of AGR2 is unknown. The present study shows that AGR2 induces expression of amphiregulin (AREG), a growth promoting EGFR ligand. Induced AREG expression in adenocarcinoma cells is able to rescue the transformed phenotype that is lost when AGR2 expression is reduced. Additional experiments demonstrate that AGR2 induction of AREG is mediated by activation of the Hippo signaling pathway co-activator, YAP1. Thus AGR2 promotes growth by regulating the Hippo and EGF receptor signaling pathways.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenocarcinoma/metabolismo , Regulação Neoplásica da Expressão Gênica , Glicoproteínas/biossíntese , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Proteínas de Neoplasias/metabolismo , Fosfoproteínas/metabolismo , Proteínas/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Anfirregulina , Animais , Linhagem Celular Tumoral , Família de Proteínas EGF , Receptores ErbB/genética , Receptores ErbB/metabolismo , Glicoproteínas/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Camundongos , Camundongos Nus , Mucoproteínas , Proteínas de Neoplasias/genética , Transplante de Neoplasias , Proteínas Oncogênicas , Fosfoproteínas/genética , Proteínas/genética , Transdução de Sinais , Fatores de Transcrição , Transplante Heterólogo , Proteínas de Sinalização YAPRESUMO
BACKGROUND: Accurate tests to diagnose adenocarcinoma and high-grade dysplasia among mucinous pancreatic cysts are clinically needed. This study evaluated the diagnostic utility of amphiregulin (AREG) as a pancreatic cyst fluid biomarker to differentiate non-mucinous, benign mucinous, and malignant mucinous cysts. METHODS: A single-center retrospective study to evaluate AREG levels in pancreatic cyst fluid by ELISA from 33 patients with a histological gold standard was performed. RESULTS: Among the cyst fluid samples, the median (IQR) AREG levels for non-mucinous (n = 6), benign mucinous (n = 15), and cancerous cysts (n = 15) were 85 pg/ml (47-168), 63 pg/ml (30-847), and 986 pg/ml (417-3160), respectively. A significant difference between benign mucinous and malignant mucinous cysts was observed (p = 0.025). AREG levels greater than 300 pg/ml possessed a diagnostic accuracy for cancer or high-grade dysplasia of 78% (sensitivity 83%, specificity 73%). CONCLUSION: Cyst fluid AREG levels are significantly higher in cancerous and high-grade dysplastic cysts compared to benign mucinous cysts. Thus AREG exhibits potential clinical utility in the evaluation of pancreatic cysts.
Assuntos
Adenocarcinoma/diagnóstico , Líquido Cístico/metabolismo , Glicoproteínas/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Cisto Pancreático/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Adenocarcinoma/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anfirregulina , Biomarcadores/metabolismo , Diagnóstico Diferencial , Família de Proteínas EGF , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cisto Pancreático/metabolismo , Neoplasias Pancreáticas/metabolismo , Curva ROC , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
The COVID-19 pandemic caused by the SARS-CoV-2 virus made governments across the world announce country-wide lockdowns suspending all activities and banning travels. This affected the lives of millions of people across all the continents in the world, including South America. The low-income classes were most affected by the lockdowns as many lost their only source of income. In addition, the uncertainty of the disease and its deadly nature along with lack of access to correct information led to a deterioration of the mental health of the low-income and indigenous groups in South America. The low-income population has little chance of gaining access to proper mental healthcare as many healthcare systems collapsed due to the nature of the pandemic. A good number of them faced short-term mental effects such as anxiety and panic attacks as well as long-term effects of depression. Proper steps must be taken to maintain and help the most vulnerable sections of the population. The pandemic along with the widespread poverty-stricken regions in the country have affected the population of the country. This article assesses the impact of COVID-19 on the poor and low-income population of the South American continent and the impact it has had on their mental health. It also reviews the recommended steps that can be taken to improve the situation and help the affected people.