RESUMEN
Virtual memory T (TVM) cells are a T cell subtype with a memory phenotype but no prior exposure to foreign antigen. Although TVM cells have antiviral and antibacterial functions, whether these cells can be pathogenic effectors of inflammatory disease is unclear. Here we identified a TVM cell-originated CD44super-high(s-hi)CD49dlo CD8+ T cell subset with features of tissue residency. These cells are transcriptionally, phenotypically and functionally distinct from conventional CD8+ TVM cells and can cause alopecia areata. Mechanistically, CD44s-hiCD49dlo CD8+ T cells could be induced from conventional TVM cells by interleukin (IL)-12, IL-15 and IL-18 stimulation. Pathogenic activity of CD44s-hiCD49dlo CD8+ T cells was mediated by NKG2D-dependent innate-like cytotoxicity, which was further augmented by IL-15 stimulation and triggered disease onset. Collectively, these data suggest an immunological mechanism through which TVM cells can cause chronic inflammatory disease by innate-like cytotoxicity.
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Alopecia Areata , Linfocitos T CD8-positivos , Humanos , Interleucina-15 , Memoria Inmunológica , Subgrupos de Linfocitos TRESUMEN
Visual detection of stromata (brown-black, elevated fungal fruiting bodies) is a primary method for quantifying tar spot early in the season, as these structures are definitive signs of the disease and essential for effective disease monitoring and management. Here, we present Stromata Contour Detection Algorithm version 2 (SCDA v2), which addresses the limitations of the previously developed SCDA version 1 (SCDA v1) without the need for empirical search of the optimal Decision Making Input Parameters (DMIPs), while achieving higher and consistent accuracy in tar spot stromata detection. SCDA v2 operates in two components: (i) SCDA v1 producing tar-spot-like region proposals for a given input corn leaf Red-Green-Blue (RGB) image, and (ii) a pre-trained Convolutional Neural Network (CNN) classifier identifying true tar spot stromata from the region proposals. To demonstrate the enhanced performance of the SCDA v2, we utilized datasets of RGB images of corn leaves from field (low, middle, and upper canopies) and glasshouse conditions under variable environments, exhibiting different tar spot severities at various corn developmental stages. Various accuracy analyses (F1-score, linear regression, and Lin's concordance correlation), showed that SCDA v2 had a greater agreement with the reference data (human visual annotation) than SCDA v1. SCDA v2 achievd 73.7% mean Dice values (overall accuracy), compared to 30.8% for SCDA v1. The enhanced F1-score primarily resulted from eliminating overestimation cases using the CNN classifier. Our findings indicate the promising potential of SCDA v2 for glasshouse and field-scale applications, including tar spot phenotyping and surveillance projects.
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Aminoacyl tRNA synthetases (ARSs) are a group of proteins, acting as transporters to transfer and attach the appropriate amino acids onto their cognate tRNAs for translation. So far, 18 out of 20 cytoplasmic ARSs are reported to be connected to different neuropathy disorders with multi-organ defects that are often accompanied with developmental delays. Thus, it is important to understand functions and impacts of ARSs at the whole organism level. Here, we systematically analyzed the spatiotemporal expression of 14 ars and 2 aimp genes during development in zebrafish that have not be previously reported. Not only in the brain, their dynamic expression patterns in several tissues such as in the muscles, liver and intestine suggest diverse roles in a wide range of development processes in addition to neuronal function, which is consistent with potential involvement in multiple syndrome diseases associated with ARS mutations. In particular, hinted by its robust expression pattern in the brain, we confirmed that aimp1 is required for the formation of cerebrovasculature by a loss-of-function approach. Overall, our systematic profiling data provides a useful basis for studying roles of ARSs during development and understanding their potential functions in the etiology of related diseases.
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Aminoacil-ARNt Sintetasas/genética , Regulación del Desarrollo de la Expresión Génica , Proteínas del Tejido Nervioso/genética , ARN Mensajero/genética , ARN de Transferencia/genética , Proteínas de Pez Cebra/genética , Pez Cebra/genética , Aminoacil-ARNt Sintetasas/clasificación , Aminoacil-ARNt Sintetasas/metabolismo , Animales , Encéfalo/crecimiento & desarrollo , Encéfalo/metabolismo , Embrión no Mamífero , Perfilación de la Expresión Génica , Ontología de Genes , Humanos , Intestinos/crecimiento & desarrollo , Intestinos/metabolismo , Hígado/crecimiento & desarrollo , Hígado/metabolismo , Anotación de Secuencia Molecular , Morfolinos/administración & dosificación , Morfolinos/genética , Morfolinos/metabolismo , Músculos/metabolismo , Proteínas del Tejido Nervioso/clasificación , Proteínas del Tejido Nervioso/metabolismo , Trastornos del Neurodesarrollo/genética , Trastornos del Neurodesarrollo/metabolismo , Trastornos del Neurodesarrollo/patología , ARN Mensajero/metabolismo , ARN de Transferencia/metabolismo , Pez Cebra/crecimiento & desarrollo , Pez Cebra/metabolismo , Proteínas de Pez Cebra/clasificación , Proteínas de Pez Cebra/metabolismoRESUMEN
BACKGROUND: The temporal changes in the Staphylococcus aureus genotypes causing S. aureus bacteremia (SAB) and the corresponding clinical changes over the last decade in South Korea are rarely investigated. METHODS: A longitudinal study of adult SAB patients was conducted in a large referral hospital in Seoul, South Korea. Adult monomicrobial SAB patients were enrolled between August 2008 and December 2018. Genotyping was performed by multilocus sequence typing (MLST) and staphylococcal protein A (spa) typing. Trends in changes were identified by linear regression analysis. RESULTS: Of 1782 adult SAB patients, the blood isolates of 1,778 (99.8%) and 1,634 (91.7%) were determined to be MLST and spa type, respectively. ST5 (-2.626%/year) and ST239 (-0.354%/year) decreased during the study period (P < 0.001 for both), but ST72 (2.009%/yr)-and ST8 (0.567%/yr) increased (P < 0.001 for both). The most common genotype was changed from ST5 in 2008 (44.9%) to ST72 in 2018 (36.3%). Panton-Valentine leukocidin-positive spa-t008-MRSA (USA300) was found in 28.6%. Central venous catheter (CVC)-related SAB (-2.440%/yr) and persistent SAB (-1.016%/yr) decreased, but mortality and recurrence rates were unchanged. CONCLUSION: Over the last decade, the hospital clones ST5 and ST239 have been replaced by community genotype ST72. This was associated with decreased CVC-related and persistent SAB. Increased USA300 was observed in community and hospital settings. Further research is required to identify the reasons for the ST72 epidemic and predict the impending epidemic of ST8 strains, including USA300.
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Antibacterianos/uso terapéutico , Bacteriemia/epidemiología , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/aislamiento & purificación , Anciano , Antígenos Bacterianos , Bacteriemia/microbiología , Femenino , Genotipo , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Tipificación de Secuencias Multilocus , República de Corea/epidemiología , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/epidemiología , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/genéticaRESUMEN
Tauopathy refers to a group of progressive neurodegenerative diseases, including frontotemporal lobar degeneration and Alzheimer's disease, which correlate with the malfunction of microtubule-associated protein Tau (MAPT) due to abnormal hyperphosphorylation, leading to the formation of intracellular aggregates in the brain. Despite extensive efforts to understand tauopathy and develop an efficient therapy, our knowledge is still far from complete. To find a solution for this group of devastating diseases, several animal models that mimic diverse disease phenotypes of tauopathy have been developed. Rodents are the dominating tauopathy models because of their similarity to humans and established disease lines, as well as experimental approaches. However, powerful genetic animal models using Drosophila, zebrafish, and C. elegans have also been developed for modeling tauopathy and have contributed to understanding the pathophysiology of tauopathy. The success of these models stems from the short lifespans, versatile genetic tools, real-time in-vivo imaging, low maintenance costs, and the capability for high-throughput screening. In this review, we summarize the main findings on mechanisms of tauopathy and discuss the current tauopathy models of these non-rodent genetic animals, highlighting their key advantages and limitations in tauopathy research.
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Modelos Animales de Enfermedad , Tauopatías/genética , Animales , Caenorhabditis elegans/genética , Caenorhabditis elegans/fisiología , Drosophila/genética , Drosophila/fisiología , Humanos , Tauopatías/fisiopatología , Pez Cebra/genética , Pez Cebra/fisiología , Proteínas tau/genéticaRESUMEN
Olfaction is an important neural system for survival and fundamental behaviors such as predator avoidance, food finding, memory formation, reproduction, and social communication. However, the neural circuits and pathways associated with the olfactory system in various behaviors are not fully understood. Recent advances in optogenetics, high-resolution in vivo imaging, and reconstructions of neuronal circuits have created new opportunities to understand such neural circuits. Here, we generated a transgenic zebrafish to manipulate olfactory signal optically, expressing the Channelrhodopsin (ChR2) under the control of the olfactory specific promoter, omp. We observed light-induced neuronal activity of olfactory system in the transgenic fish by examining c-fos expression, and a calcium indicator suggesting that blue light stimulation caused activation of olfactory neurons in a non-invasive manner. To examine whether the photo-activation of olfactory sensory neurons affect behavior of zebrafish larvae, we devised a behavioral choice paradigm and tested how zebrafish larvae choose between two conflicting sensory cues, an aversive odor or the naturally preferred phototaxis. We found that when the conflicting cues (the preferred light and aversive odor) were presented together simultaneously, zebrafish larvae swam away from the aversive odor. However, the transgenic fish with photo-activation were insensitive to the aversive odor and exhibited olfactory desensitization upon optical stimulation of ChR2. These results show that an aversive olfactory stimulus can override phototaxis, and that olfaction is important in decision making in zebrafish. This new transgenic model will be useful for the analysis of olfaction related behaviors and for the dissection of underlying neural circuits.
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Channelrhodopsins/metabolismo , Percepción Olfatoria/genética , Olfato/genética , Animales , Animales Modificados Genéticamente/genética , Channelrhodopsins/genética , Señales (Psicología) , Larva/fisiología , Luz , Red Nerviosa/metabolismo , Neuronas/metabolismo , Odorantes , Optogenética/métodos , Estimulación Luminosa , Regiones Promotoras Genéticas/genética , Natación , Pez Cebra/metabolismo , Proteínas de Pez Cebra/metabolismoRESUMEN
The failure of amyloid beta (Aß) clearance is a major cause of Alzheimer's disease, and the brain lymphatic systems play a crucial role in clearing toxic proteins. Recently, brain lymphatic endothelial cells (BLECs), a non-lumenized lymphatic cell in the vertebrate brain, was identified, but Aß clearance via this novel cell is not fully understood. We established an in vivo zebrafish model using fluorescently labeled Aß42 to investigate the role of BLECs in Aß clearance. We discovered the efficient clearance of monomeric Aß42 (mAß42) compared to oligomeric Aß42 (oAß42), which was illustrated by the selective uptake of mAß42 by BLECs and peripheral transport. The genetic depletion, pharmacological inhibition via the blocking of the mannose receptor, or the laser ablation of BLECs resulted in the defective clearance of mAß42. The treatment with an Aß disaggregating agent facilitated the internalization of oAß42 into BLECs and improved the peripheral transport. Our findings reveal a new role of BLECs in the differential clearance of mAß42 from the brain and provide a novel therapeutic strategy based on promoting Aß clearance.
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Péptidos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Células Endoteliales/metabolismo , Pez Cebra/metabolismo , Animales , Transporte Biológico , Células CultivadasRESUMEN
Parainfluenza virus (PIV) infection is a significant cause of morbidity and mortality, especially in hematologic malignancy patients including hematopoietic stem cell transplantation (HCT) recipients. However, limited information is available for risk stratification in PIV-infected patients with hematologic malignancy with or without HCT. Patients with hematologic malignancy diagnosed with PIV from January 2009 to December 2018 were retrospectively included in a tertiary care hospital in Seoul, South Korea. Upper respiratory tract infection (URTI) was defined as the detection of PIV in a nasopharyngeal sample with URTI symptoms without new pulmonary infiltrates. Lower respiratory tract infection (LRTI) was defined as detection of PIV in either upper or lower respiratory tract samples with new pulmonary infiltrates, with or without hypoxia. PIV-associated mortality was defined as death with respiratory failure and persistent LRTI within 90 days after diagnosis. The study included 143 adult patients. Of these, 55 (38%) progressed to or initially presented with LRTI. Among these, 22 (40%) died from PIV-associated mortality. An immunodeficiency risk score was developed from associated risk factors using a multivariable Cox regression model. Patients were stratified into low (0-2), moderate (3-5), and high risk (6-8) groups with PIV-associated mortalities of 0%, 9%, and 67%, respectively (p < 0.005, Harrell's C-index = 0.84). PIV infection can result in substantial mortality in patients with hematologic malignancy if it progresses to LRTI. The immunodeficiency risk score presented here may be useful for distinguishing moderate and high risk groups that might benefit from antiviral therapy.
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Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/mortalidad , Síndromes de Inmunodeficiencia/diagnóstico , Síndromes de Inmunodeficiencia/mortalidad , Infecciones por Paramyxoviridae/diagnóstico , Infecciones por Paramyxoviridae/mortalidad , Adulto , Estudios de Cohortes , Femenino , Neoplasias Hematológicas/inmunología , Humanos , Síndromes de Inmunodeficiencia/inmunología , Masculino , Persona de Mediana Edad , Mortalidad/tendencias , Infecciones por Paramyxoviridae/inmunología , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Staphylococcus aureus is a virulent gram-positive organism, which rarely involves the biliary tract. This study aimed to analyze the clinical characteristics and outcomes of S. aureus bacteremia (SAB) originating from the biliary tract by comparing them with those of catheter-related SAB and biliary Klebsiella pneumoniae bacteremia. A matched case-control study within a prospective observational cohort of patients with SAB was conducted. Biliary SAB was defined as the isolation of S. aureus from blood cultures with symptoms and signs of biliary infection. Biliary SAB patients were matched (1:3) with the control groups: patients with catheter-related SAB and biliary Klebsiella pneumoniae bacteremia. Out of 1818 patients with SAB enrolled in the cohort, 42 (2%) had biliary SAB. Majority of these patients had solid tumors involving the pancreaticobiliary tract or liver, biliary drainage stent, and/or recent broad-spectrum antibiotic exposure. Patients with biliary SAB were more likely to have community-onset SAB, solid tumors, and lower APACHE II score than those with catheter-related SAB. They were less likely to have community-acquired infection and solid tumors and more likely to have lower Charlson comorbidity index and higher APACHE II score as compared with biliary K. pneumoniae bacteremia. The 12-week mortality in the biliary SAB group was higher than those in other control groups (60% vs. 20% and 14%). After adjusting for confounding factors, biliary SAB was independently associated with higher mortality. Biliary SAB is relatively rare. When it is clinically suspected, early aggressive treatment should be considered due to high mortality.
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Bacteriemia/epidemiología , Infecciones Estafilocócicas/epidemiología , Staphylococcus aureus/aislamiento & purificación , Anciano , Bacteriemia/microbiología , Sistema Biliar/microbiología , Estudios de Casos y Controles , Cateterismo/efectos adversos , Estudios de Cohortes , Infección Hospitalaria/epidemiología , Infección Hospitalaria/etiología , Infección Hospitalaria/microbiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , República de Corea/epidemiología , Infecciones Estafilocócicas/etiología , Infecciones Estafilocócicas/microbiologíaRESUMEN
Streptococcus parauberis is the major infectious agent of streptococcosis in the olive flounder (Paralichthys olivaceus), causing serious economic damage. In this study, we identified potential vaccine candidates against S. parauberis by reverse vaccinology. In total, the 2 out of 21 proteins were identified as vaccine candidates from two available S. parauberis genomes. The membrane-anchored protein SEC10/PgrA and the metal ABC transporter substrate-binding lipoprotein mtsA were potent antigenic proteins based on western blotting with mouse-derived antiserum against whole bacteria of S. parauberis serotypes I and II. In particular, metal ABC transporter substrate-binding lipoprotein (mtsA) showed similar protective immunity to that of whole-cell bacterins against S. parauberis in a zebrafish model. These results suggest that mtsA may be considered as a novel candidate in the development of vaccines against S. parauberis.
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Antígenos Bacterianos/inmunología , Proteínas Bacterianas/inmunología , Infecciones Estreptocócicas/prevención & control , Streptococcus/inmunología , Vacunología/métodos , Animales , Vacunas Bacterianas/administración & dosificación , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/aislamiento & purificación , Modelos Animales de Enfermedad , Infecciones Estreptocócicas/inmunología , Infecciones Estreptocócicas/microbiología , Análisis de Supervivencia , Pez CebraRESUMEN
Increasing the thermogenic activity of adipocytes holds promise as an approach to combating human obesity and related metabolic diseases. We identified induction of mouse PR domain containing 4 (Prdm4) by the small molecule butein as a means to induce expression of uncoupling protein 1 (Ucp1), increase energy expenditure, and stimulate the generation of thermogenic adipocytes. This study highlights a Prdm4-dependent pathway, modulated by small molecules, that stimulates browning of white adipose tissue.
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Tejido Adiposo Pardo/efectos de los fármacos , Tejido Adiposo Blanco/efectos de los fármacos , Chalconas/farmacología , Proteínas de Unión al ADN/antagonistas & inhibidores , Factores de Transcripción/antagonistas & inhibidores , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/metabolismo , Animales , Chalconas/química , Proteínas de Unión al ADN/metabolismo , Dieta Alta en Grasa/efectos adversos , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Factores de Transcripción/metabolismoRESUMEN
The analog figure-of-merits (FOMs) of conventional inversion-mode (IM) and junctionless (JL) NanoWire Field Effect Transistor (NWFET) have been investigated, considering the gate Work-Function Variability (WFV) and Random Discrete Dopant (RDD) using 3-dimensional (3D) TCAD simulation. While the JL-NWFET shows higher immune to WFV on analog FOMs, it can be easily affected by RDD due to higher channel doping level. On the other hand, the IM-NWFET shows stronger correlation between transconductance (gm) and gate capacitance (Cgg), leading to similar variation in cut-off frequency (ft) even though it shows larger gm and Cgg variation compared to JL-NWFET.
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We report the electrical characteristics and pH responses of a Si-nanonet ion-sensitive field-effect transistor with ultra-thin parylene-H as a gate sensing membrane. The fabricated device shows excellent DC characteristics: a low subthreshold swing of 85 mV/dec, a high current on/off ratio of ~107 and a low gate leakage current of ~10-10 A. The low interface trap density of 1.04 × 1012 cm-2 and high field-effect mobility of 510 cm²V-1s-1 were obtained. The pH responses of the devices were evaluated in various pH buffer solutions. A high pH sensitivity of 48.1 ± 0.5 mV/pH with a device-to-device variation of ~6.1% was achieved. From the low-frequency noise characterization, the signal-to-noise ratio was extracted as high as ~3400 A/A with the lowest noise equivalent pH value of ~0.002 pH. These excellent intrinsic electrical and pH sensing performances suggest that parylene-H can be promising as a sensing membrane in an ISFET-based biosensor platform.
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To elucidate the contribution of CRL3-ABA-mediated responses, we attempted to find CRL3 substrate receptors involved in ABA signaling. One gene named ABA-HYPERSENSITIVE BTB/POZ PROTEIN 1 (AHT1) was upregulated more than 2.5 times by ABA, and its coding region possessed a BTB/POZ domain, which is the common feature of CRL3 substrate receptors. Loss of AHT1 led to retardation of the germination process, not inhibition of root growth. AHT1 transcripts also increased in response to mannitol, NaCl and drought treatments at the seedling stage and in dry seeds. High expression of AHT1 in dry seeds was inhibited by the defect of ABA signaling components such as ABI1, ABI3 and SRKs indicating that the expression of AHT1 is dependent on ABA signaling. Among bZIP transcription factors participating in ABA signaling, the losses of ABI5/DPBF1, AREB1/ABF2, EEL/DPBF4 and DPBF2/bZIP67 resulted in reduced AHT1 expression, showing that these transcription factors play a positive role in ABA-induced AHT1 expression. While loss of AHT1 did not affect the expression pattern of NCED3, ABI2, SRKs and AREB/ABF genes, it led to hyperinduction of ABI5/DPBF genes such as ABI5/DPBF1, EEL/DPBF4 and AREB3/DPBF3, which are mainly involved in seed development and germination, as well as ABA-inducible genes transactivated by ABI5. Overall, these findings indicate that AHT1 negatively regulates ABA-mediated inhibition of germination, possibly by repressing the expression of a subset of ABI5/DPBF subfamily genes, and that AHT1 may be regulated by a negative feedback process through its linkage with a part of ABI5/DPBF proteins.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Semillas/metabolismo , Ácido Abscísico/farmacología , Arabidopsis/efectos de los fármacos , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Dioxigenasas/genética , Dioxigenasas/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Regulación de la Expresión Génica de las Plantas/genética , Germinación/efectos de los fármacos , Germinación/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Semillas/efectos de los fármacos , Semillas/genéticaRESUMEN
We investigate the effect of adding graphene oxide (GO) sheets at the polymer-polymer interface on the dewetting dynamics and compatibility of immiscible polymer bilayer films. GO monolayers are deposited at the poly(methyl methacrylate) (PMMA)-polystyrene (PS) interface by the Langmuir-Schaefer technique. GO monolayers are found to significantly inhibit the dewetting behavior of both PMMA films (on PS substrates) and PS films (on PMMA substrates). This can be interpreted in terms of an interfacial interaction between the GO sheets and these polymers, which is evidenced by the reduced contact angle of the dewet droplets. The favorable interaction of GO with both PS and PMMA facilitates compatibilization of the immiscible polymer bilayer films, thereby stabilizing their bilayer films against dewetting. This compatibilization effect is verified by neutron reflectivity measurements, which reveal that the addition of GO monolayers broadens the interface between PS and the deuterated PMMA films by 2.2 times over that of the bilayer in the absence of GO.
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BACKGROUND: The honey bee is an important model system for increasing understanding of molecular and neural mechanisms underlying social behaviors relevant to the agricultural industry and basic science. The western honey bee, Apis mellifera, has served as a model species, and its genome sequence has been published. In contrast, the genome of the Asian honey bee, Apis cerana, has not yet been sequenced. A. cerana has been raised in Asian countries for thousands of years and has brought considerable economic benefits to the apicultural industry. A cerana has divergent biological traits compared to A. mellifera and it has played a key role in maintaining biodiversity in eastern and southern Asia. Here we report the first whole genome sequence of A. cerana. RESULTS: Using de novo assembly methods, we produced a 238 Mbp draft of the A. cerana genome and generated 10,651 genes. A.cerana-specific genes were analyzed to better understand the novel characteristics of this honey bee species. Seventy-two percent of the A. cerana-specific genes had more than one GO term, and 1,696 enzymes were categorized into 125 pathways. Genes involved in chemoreception and immunity were carefully identified and compared to those from other sequenced insect models. These included 10 gustatory receptors, 119 odorant receptors, 10 ionotropic receptors, and 160 immune-related genes. CONCLUSIONS: This first report of the whole genome sequence of A. cerana provides resources for comparative sociogenomics, especially in the field of social insect communication. These important tools will contribute to a better understanding of the complex behaviors and natural biology of the Asian honey bee and to anticipate its future evolutionary trajectory.
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Abejas/genética , Genoma de los Insectos , Análisis de Secuencia de ADN , Transcriptoma , Animales , Asia , Secuenciación de Nucleótidos de Alto Rendimiento , Sistema Inmunológico/fisiología , Filogenia , Receptores Ionotrópicos de Glutamato/genética , Receptores Odorantes/genética , Transcriptoma/fisiologíaRESUMEN
The identification and examination of potential determinants controlling the progression of cell fate toward osteoblasts can be intriguing subjects. In this study, the effects of sulfuretin, a major compound isolated from Rhus verniciflua Stokes, on osteoblast differentiation were investigated. Treatments of sulfuretin induced alkaline phosphatase (ALP) activity in mesenchymal C3H10T1/2 cells and mineralization in preosteoblast MC3T3-E1 cells. Pro-osteogenic effects of sulfuretin were consistently observed in freshly isolated primary bone marrow cells. In mechanical studies, sulfuretin specifically induced expression of TGF-ß target genes, such as SMAD7 and PAI-1, but not other signaling pathway-related genes. Similar to the results of gene expression analysis, reporter assays further demonstrated TGF-ß-specific induction by sulfuretin. Furthermore, disruption of TGF-ß signaling using treatment with TGF-ß-specific inhibitor, SB-431542, and introduction of SMAD2/3 small interfering RNA impaired the effects of sulfuretin in inducing ALP activity and expression of ALP mRNA. Together, these data indicate that the pro-osteogenic effects of sulfuretin are mediated through activation of TGF-ß signaling, further supporting the potential of sulfuretin in the prevention of bone-related diseases such as bone fracture and osteoporosis.
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Benzofuranos/farmacología , Conservadores de la Densidad Ósea/farmacología , Diferenciación Celular/efectos de los fármacos , Osteoblastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Factor de Crecimiento Transformador beta/metabolismo , Células 3T3 , Fosfatasa Alcalina/genética , Fosfatasa Alcalina/metabolismo , Animales , Benzamidas/farmacología , Dioxoles/farmacología , Relación Dosis-Respuesta a Droga , Fémur/efectos de los fármacos , Fémur/metabolismo , Flavonoides/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Osteoblastos/metabolismo , Inhibidor 1 de Activador Plasminogénico/genética , Inhibidor 1 de Activador Plasminogénico/metabolismo , Interferencia de ARN , Proteína Smad2/genética , Proteína Smad2/metabolismo , Proteína smad3/genética , Proteína smad3/metabolismo , Proteína smad7/genética , Proteína smad7/metabolismo , Factores de Tiempo , Transfección , Factor de Crecimiento Transformador beta/antagonistas & inhibidoresRESUMEN
The photoresponse characteristics of In2Se3 nanowire photodetectors with the κ-phase and α-phase structures are investigated. The as-grown κ-phase In2Se3 nanowires by the vapor-liquid-solid technique are phase-transformed to the α-phase nanowires by thermal annealing. The photoresponse performances of the κ-phase and α-phase In2Se3 nanowire photodetectors are characterized over a wide range of wavelengths (300-900 nm). The phase of the nanowires is analyzed using a high-resolution transmission microscopy equipped with energy dispersive X-ray spectroscopy and X-ray diffraction. The electrical conductivity and photoresponse characteristics are significantly enhanced in the α-phase due to smaller bandgap structure compared to the κ-phase nanowires. The spectral responsivities of the α-phase devices are 200 times larger than those of the κ-phase devices. The superior performance of the thermally phase-transformed In2Se3 nanowire devices offers an avenue to develop highly sensitive photodetector applications.
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Control of a two-dimensional (2D) structure of assembled graphene oxide (GO) sheets is highly desirable for fundamental research and potential applications of graphene devices. We show that an alkylamine surfactant, i.e., octadecylamine (ODA), Langmuir monolayer can be utilized as a template for adsorbing highly hydrophilic GO sheets in an aqueous subphase at the liquid-gas interface. The densely packed 2-D monolayer of such complex films was obtained on arbitrary substrates by applying Langmuir-Schaefer or Langmuir-Blodgett technique. Morphology control of GO sheets was also achieved upon compression by tuning the amount of spread ODA molecules. We found that ODA surfactant monolayers prevent GO sheets from sliding, resulting in formation of wrinkling rather than overlapping at the liquid-gas interface during the compression. The morphology structures did not change after a graphitization procedure of chemical hydrazine reduction and thermal annealing treatments. Since morphologies of graphene films are closely correlated to the performance of graphene-based materials, the technique employed in this study can provide a route for applications requiring wrinkled graphenes, ranging from nanoelectronic devices to energy storage materials, such as supercapacitors and fuel cell electrodes.
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Phase change random access memory (PCRAM) devices are usually constructed using tellurium based compounds, but efforts to seek other materials providing desirable memory characteristics have continued. We have fabricated PCRAM devices using Ga-doped In2O3 nanowires with three different Ga compositions (Ga/(In+Ga) atomic ratio: 2.1%, 11.5% and 13.0%), and investigated their phase switching properties. The nanowires (â¼40 nm in diameter) can be repeatedly switched between crystalline and amorphous phases, and Ga concentration-dependent memory switching behavior in the nanowires was observed with ultra-fast set/reset rates of 80 ns/20 ns, which are faster than for other competitive phase change materials. The observations of fast set/reset rates and two distinct states with a difference in resistance of two to three orders of magnitude appear promising for nonvolatile information storage. Moreover, we found that increasing the Ga concentration can reduce the power consumption and resistance drift; however, too high a level of Ga doping may cause difficulty in achieving the phase transition.