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Clubroot is an important disease infectible to cruciferous plants and a major threat to rapeseed production in Japan. However, no clubroot resistant rapeseed cultivars have been released. We surveyed pathotype variation of six isolates collected from rapeseed fields and found they were classified as pathotype groups 2 and 4 using Japanese F1 Chinese cabbage cultivars. We produced the resynthesized clubroot resistant Brassica napus harboring two resistant loci, Crr1 and Crr2, by interspecific crossing and developed resistant rapeseed lines for southern and northern regions by marker-assisted selection and backcrossing. We improved the DNA marker for erucic acid content to remove linkage drag between Crr1 and high erucic acid content and successfully selected lines with clubroot resistance and zero erucic acid for northern regions. A novel line, 'Tohoku No. 106', suitable for southern regions showed stable resistance against all six isolates and high performance in infested fields. We conclude that Crr1 and Crr2 are important genes for CR rapeseed breeding and marker-assisted selection is effective in improving clubroot resistance.
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High-throughput experiments (HTEs) have been powerful tools to obtain many materials data. However, HTEs often require expensive equipment. Although high-throughput ab-initio calculation (HTC) has the potential to make materials big data easier to collect, HTC does not represent the actual materials data obtained by HTEs in many cases. Here we propose using a combination of simple HTEs, HTC, and machine learning to predict material properties. We demonstrate that our method enables accurate and rapid prediction of the Kerr rotation mapping of an FexCoyNi1-x-y composition spread alloy. Our method has the potential to quickly predict the properties of many materials without a difficult and expensive HTE and thereby accelerate materials development.
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Glucosinolates (GSLs) are secondary metabolites whose degradation products confer intrinsic flavors and aromas to Brassicaceae vegetables. Several structures of GSLs are known in the Brassicaceae, and the biosynthetic pathway and regulatory networks have been elucidated in Arabidopsis (Arabidopsis thaliana). GSLs are precursors of chemical defense substances against herbivorous pests. Specific GSLs can act as feeding blockers or stimulants, depending on the pest species. Natural selection has led to diversity in the GSL composition even within individual species. However, in radish (Raphanus sativus), glucoraphasatin (4-methylthio-3-butenyl glucosinolate) accounts for more than 90% of the total GSLs, and little compositional variation is observed. Because glucoraphasatin is not contained in other members of the Brassicaceae, like Arabidopsis and cabbage (Brassica oleracea), the biosynthetic pathways for glucoraphasatin remain unclear. In this report, we identified and characterized a gene encoding GLUCORAPHASATIN SYNTHASE 1 (GRS1) by genetic mapping using a mutant that genetically lacks glucoraphasatin. Transgenic Arabidopsis, which overexpressed GRS1 cDNA, accumulated glucoraphasatin in the leaves. GRS1 encodes a 2-oxoglutarate-dependent dioxygenase, and it is abundantly expressed in the leaf. To further investigate the biosynthesis and transportation of GSLs in radish, we grafted a grs1 plant onto a wild-type plant. The grafting experiment revealed a leaf-to-root long-distance glucoraphasatin transport system in radish and showed that the composition of GSLs differed among the organs. Based on these observations, we propose a characteristic biosynthesis pathway for glucoraphasatin in radish. Our results should be useful in metabolite engineering for breeding of high-value vegetables.
Assuntos
Dioxigenases/metabolismo , Glucosinolatos/biossíntese , Ácidos Cetoglutáricos/metabolismo , Raphanus/metabolismo , Sequência de Aminoácidos , Arabidopsis/genética , Arabidopsis/metabolismo , Transporte Biológico , Vias Biossintéticas/genética , Cromatografia Líquida de Alta Pressão , Dioxigenases/classificação , Dioxigenases/genética , Regulação Enzimológica da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Glucosinolatos/análise , Engenharia Metabólica/métodos , Mutação , Filogenia , Folhas de Planta/genética , Folhas de Planta/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Plantas Geneticamente Modificadas , Raphanus/enzimologia , Raphanus/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Plântula/genética , Plântula/metabolismo , Plântula/fisiologia , Homologia de Sequência de AminoácidosRESUMO
C-X-C motif chemokine 12 (CXCL12) belongs to the family of CXC chemokines. Lipopolysaccharide (LPS) induces inflammation-induced osteoclastogenesis and bone resorption, and in recent years, stimulatory effects of CXCL12 on bone resorption have also been reported. In the present study, we investigated the effects of CXCL12 on LPS-induced osteoclastogenesis and bone resorption. LPS was administered with or without CXCL12 onto mouse calvariae by daily subcutaneous injection. Numbers of osteoclasts and bone resorption were significantly elevated in mice co-administered LPS and CXCL12 compared with mice administered LPS alone. Moreover, receptor activator of NF-kB ligand (RANKL) and tumor necrosis factor-α (TNF-α) mRNA levels were higher in mice co-administered LPS and CXCL12 compared with mice administered LPS alone. These in vitro results confirmed a direct stimulatory effect of CXCL12 on RANKL- and TNF-α-induced osteoclastogenesis. Furthermore, TNF-α and RANKL mRNA levels were elevated in macrophages and osteoblasts, respectively, co-treated in vitro with CXCL12 and LPS, in comparison with cells treated with LPS alone. Our results suggest that CXCL12 enhances LPS-induced osteoclastogenesis and bone resorption in vivo through a combination of increasing LPS-induced TNF-α production by macrophages, increasing RANKL production by osteoblasts, and direct enhancement of osteoclastogenesis.
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Reabsorção Óssea/metabolismo , Quimiocina CXCL12/metabolismo , Lipopolissacarídeos/toxicidade , Osteogênese/fisiologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteogênese/efeitos dos fármacosRESUMO
KEY MESSAGE: Genetic analysis and gene mapping of the 4-methylthio-3-butenyl glucosinolate-less trait of white radish were performed and a white radish cultivar with new glucosinolate composition was developed. A spontaneous mutant having significantly low 4-methylthio-3-butenyl glucosinolate (4MTB-GSL) content was identified from a landrace of Japanese white radish (Raphanus sativus L.) through intensive evaluation of glucosinolate profiles of 632 lines including genetic resources and commercial cultivars using high-performance liquid chromatography (HPLC) analysis. A line lacking 4MTB-GSL was developed using the selected mutant as a gene source. Genetic analyses of F1, F2, and BC1F1 populations of this line suggested that the 4MTB-GSL-less trait is controlled by a single recessive allele. Using SNP and SCAR markers, 96 F2 plants were genotyped, and a linkage map having nine linkage groups with a total map distance of 808.3 cM was constructed. A gene responsible for the 4MTB-GSL-less trait was mapped between CL1753 and CL5895 at the end of linkage group 1. The genetic distance between these markers was 4.2 cM. By selfing and selection of plants lacking 4MTB-GSL, a new cultivar, 'Daikon parental line No. 5', was successfully developed. This cultivar was characterized by glucoerucin, which accounted for more than 90% of the total glucosinolates (GSLs). The total GSL content in roots was ca. 12 µmol/g DW, significantly lower than those in common white radish cultivars. Significance of this line in radish breeding is discussed.
Assuntos
Glucosinolatos/química , Raphanus/química , Raphanus/genética , Alelos , Cromatografia Líquida de Alta Pressão , Mapeamento Cromossômico , Genes de Plantas , Genes Recessivos , Ligação Genética , Genótipo , Melhoramento Vegetal , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Proanthocyanidins, which are composed of oligomeric flavan-3-ol units, are contained in various foodstuffs (e.g., fruits, vegetables, and drinks) and are strongly biologically active compounds. We investigated which element of the proanthocyanidin structure is primarily responsible for this functionality. In this study, we elucidate the importance of the upper-unit of 4-8 condensed dimeric flavan-3-ols for antimicrobial activity against Saccharomyces cerevisiae (S. cerevisiae) and cervical epithelioid carcinoma cell line HeLa S3 proliferation inhibitory activity. To clarify the important constituent unit of proanthocyanidin, we synthesized four dimeric compounds, (-)-epigallocatechin-[4,8]-(+)-catechin, (-)-epigallocatechin-[4,8]-(-)-epigallocatechin, (-)-epigallocatechin-[4,8]-(-)-epigallocatechin-3-O-gallate, and (+)-catechin-[4,8]-(-)-epigallocatechin and performed structure-activity relationship (SAR) studies. In addition to antimicrobial activity against S. cerevisiae and proliferation inhibitory activity on HeLa S3 cells, the correlation of 2,2-diphenyl-l-picrylhydrazyl radical scavenging activity with the number of phenolic hydroxyl groups was low. On the basis of the results of our SAR studies, we concluded that B-ring hydroxyl groups of the upper-unit of the dimer are crucially important for strong and effective activity.
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Flavonoides/química , Sequestradores de Radicais Livres/química , Antifúngicos/química , Antifúngicos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Compostos de Bifenilo/química , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Flavonoides/farmacologia , Sequestradores de Radicais Livres/farmacologia , Radicais Livres/química , Células HeLa , Humanos , Concentração Inibidora 50 , Testes de Sensibilidade Microbiana , Picratos/química , Saccharomyces cerevisiae/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
OBJECTIVES: Interleukin-4 (IL-4) is a recognized immunomodulatory cytokine that regulates bone homeostasis. However, the influence of IL-4 on orthodontic tooth movement (OTM) and subsequent root resorption is still unknown. Therefore, the purpose of this study was to investigate the effect of IL-4 on tooth movement and its associated root resorption in a mouse model. MATERIALS AND METHODS: The maxillary first molars of four male mice for each experimental group were subjected to mesial force by a nickel titanium coil spring for 12 days. Control mice were not given appliances and injections. Varying doses of IL-4 were injected locally, adjacent to the first molar. Two sets of experiments were designed. The first set was composed of three groups: the control, treatment with phosphate-buffered saline (PBS), or 1.5 µg/day of IL-4. The second set was composed of five groups: the control, treatment with 0 (PBS only), 0.015, 0.15, or 1.5 µg/day of IL-4. The distance of OTM was measured and tartrate-resistant acid phosphatase positive cells along the loaded alveolar bone and root surface were identified. The root resorption associated with OTM was evaluated by a scanning electron microscope. RESULTS: The amount of OTM and the number of osteoclasts were significantly decreased in the IL-4-treated mice. Moreover, IL-4 significantly suppressed force-induced odontoclasts and root resorption. CONCLUSION: IL-4 inhibits tooth movement and prevents root resorption in the mouse model. These results suggest that IL-4 could be used as a useful adjunct to regulate the extent of OTM and also to control root resorption.
Assuntos
Interleucina-4/uso terapêutico , Reabsorção da Raiz/prevenção & controle , Técnicas de Movimentação Dentária/efeitos adversos , Fosfatase Ácida/metabolismo , Processo Alveolar/efeitos dos fármacos , Processo Alveolar/metabolismo , Animais , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Interleucina-4/administração & dosagem , Isoenzimas/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Dente Molar/efeitos dos fármacos , Osteoclastos/citologia , Reabsorção da Raiz/etiologia , Reabsorção da Raiz/patologia , Fosfatase Ácida Resistente a Tartarato , Raiz Dentária/efeitos dos fármacos , Suporte de CargaRESUMO
Unique secondary metabolites, glucosinolates (S-glucopyranosyl thiohydroximates), are naturally occurring S-linked glucosides found mainly in Brassicaceae plants. They are enzymatically hydrolyzed to produce sulfate ions, D-glucose, and characteristic degradation products such as isothiocyanates. The functions of glucosinolates in the plants remain unclear, but isothiocyanates possessing a pungent or irritating taste and odor might be associated with plant defense from microbes. Isothiocyanates have been studied extensively in experimental in vitro and in vivo carcinogenesis models for their cancer chemopreventive properties. The beneficial isothiocyanates, glucosinolates that are functional for supporting human health, have received attention from many scientists studying plant breeding, plant physiology, plant genetics, and food functionality. This review presents a summary of recent topics related with glucosinolates in the Brassica family, along with a summary of the chemicals, metabolism, and genes of glucosinolates in Brassicaceae. The bioavailabilities of isothiocyanates from certain functional glucosinolates and the importance of breeding will be described with emphasis on glucosinolates.
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Mechanical force loading exerts important effects on the skeleton by controlling bone mass and strength. Several in vivo experimental models evaluating the effects of mechanical loading on bone metabolism have been reported. Orthodontic tooth movement is a useful model for understanding the mechanism of bone remodeling induced by mechanical loading. In a mouse model of orthodontic tooth movement, TNF-α was expressed and osteoclasts appeared on the compressed side of the periodontal ligament. In TNF-receptor-deficient mice, there was less tooth movement and osteoclast numbers were lower than in wild-type mice. These results suggest that osteoclast formation and bone resorption caused by loading forces on the periodontal ligament depend on TNF-α. Several cytokines are expressed in the periodontal ligament during orthodontic tooth movement. Studies have found that inflammatory cytokines such as IL-12 and IFN-γ strongly inhibit osteoclast formation and tooth movement. Blocking macrophage colony-stimulating factor by using anti-c-Fms antibody also inhibited osteoclast formation and tooth movement. In this review we describe and discuss the effect of cytokines in the periodontal ligament on osteoclast formation and bone resorption during mechanical force loading.
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Reabsorção Óssea/metabolismo , Citocinas/metabolismo , Osteoclastos/metabolismo , Periodonto/metabolismo , Estresse Mecânico , Migração de Dente/metabolismo , Animais , Remodelação Óssea/fisiologia , Reabsorção Óssea/patologia , Humanos , Osteoclastos/patologia , Ligamento Periodontal/metabolismo , Ligamento Periodontal/patologia , Periodonto/patologia , Migração de Dente/patologiaRESUMO
Energy harvesting technologies, which generate electricity from environmental energy, have been attracting great interest because of their potential to power ubiquitously deployed sensor networks and mobile electronics. Of these technologies, thermoelectric (TE) conversion is a particularly promising candidate, because it can directly generate electricity from the thermal energy that is available in various places. Here we show a novel TE concept based on the spin Seebeck effect, called 'spin-thermoelectric (STE) coating', which is characterized by a simple film structure, convenient scaling capability, and easy fabrication. The STE coating, with a 60-nm-thick bismuth-substituted yttrium iron garnet (Bi:YIG) film, is applied by means of a highly efficient process on a non-magnetic substrate. Notably, spin-current-driven TE conversion is successfully demonstrated under a temperature gradient perpendicular to such an ultrathin STE-coating layer (amounting to only 0.01% of the total sample thickness). We also show that the STE coating is applicable even on glass surfaces with amorphous structures. Such a versatile implementation of the TE function may pave the way for novel applications making full use of omnipresent heat.
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Pituitary adenylate cyclase-activating peptide (PACAP) is widely distributed throughout the nervous system. PACAP not only acts as a neurotransmitter but also elicits a broad spectrum of biological action via the PACAP-specific receptor, PAC1. However, no studies have investigated PACAP and PAC1 in the periodontal ligament (PDL), so we aimed to perform this investigation in rats after tooth luxation. In the PDL of an intact first molar, there are few osteoclasts and osteoblasts. However, at days 3 and 5 after luxation, large PAC1-positive cells, thought to be osteoclasts because of their expression of the osteoclast marker, tartrate-resistant acid phosphatase, were detected in appreciable numbers. Osteoblast numbers increased dramatically on day 7 after luxation, and PAC1-positive mononuclear small cells were increased at day 14, many of which expressed the osteoblast marker, alkaline phosphatase. PACAP-positive nerve fibers were rarely detected in the PDL of intact first molars, but were increasingly evident at this site on days 5 and 7 after luxation. Double-immunofluorescence analysis demonstrated the relationship between PACAP-positive nerve fibers and PAC1-positive osteoclasts/-blasts in the PDL. At 5 days after luxation, PACAP-positive nerve fibers appeared in close proximity to PAC1-positive osteoclasts. At 7 days after luxation, PACAP-positive nerve fibers appeared in close proximity to PAC1-positive osteoblasts. These results suggest that PACAP may have effects on osteoclasts and osteoblasts in the PDL after tooth luxation and thus regulate bone remodeling after these types of injury.
Assuntos
Ligamento Periodontal/metabolismo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Avulsão Dentária/metabolismo , Animais , Contagem de Células , Imunofluorescência , Masculino , Fibras Nervosas/metabolismo , Osteoblastos/metabolismo , Osteoblastos/patologia , Osteoclastos/metabolismo , Osteoclastos/patologia , Ligamento Periodontal/inervação , Ratos , Ratos Sprague-Dawley , Avulsão Dentária/patologiaRESUMO
Tumor necrosis factor- α (TNF- α ) is a cytokine produced by monocytes, macrophages, and T cells and is induced by pathogens, endotoxins, or related substances. TNF- α may play a key role in bone metabolism and is important in inflammatory bone diseases such as rheumatoid arthritis. Cells directly involved in osteoclastogenesis include macrophages, which are osteoclast precursor cells, osteoblasts, or stromal cells. These cells express receptor activator of NF- κ B ligand (RANKL) to induce osteoclastogenesis, and T cells, which secrete RANKL, promote osteoclastogenesis during inflammation. Elucidating the detailed effects of TNF- α on bone metabolism may enable the identification of therapeutic targets that can efficiently suppress bone destruction in inflammatory bone diseases. TNF- α is considered to act by directly increasing RANK expression in macrophages and by increasing RANKL in stromal cells. Inflammatory cytokines such as interleukin- (IL-) 12, IL-18, and interferon- γ (IFN- γ ) strongly inhibit osteoclast formation. IL-12, IL-18, and IFN- γ induce apoptosis in bone marrow cells treated with TNF- α in vitro, and osteoclastogenesis is inhibited by the interactions of TNF- α -induced Fas and Fas ligand induced by IL-12, IL-18, and IFN- γ . This review describes and discusses the role of cells concerned with osteoclast formation and immunological reactions in TNF- α -mediated osteoclastogenesis in vitro and in vivo.
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Artrite Reumatoide/imunologia , Reabsorção Óssea/imunologia , Osso e Ossos/imunologia , Osteoclastos/imunologia , Fator de Necrose Tumoral alfa/imunologia , Animais , Artrite Reumatoide/patologia , Reabsorção Óssea/patologia , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/patologia , Expressão Gênica , Humanos , Interferon gama/genética , Interferon gama/imunologia , Interleucina-12/genética , Interleucina-12/imunologia , Interleucina-18/genética , Interleucina-18/imunologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/imunologia , Osteoblastos/patologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/patologia , Ligante RANK/genética , Ligante RANK/imunologia , Células Estromais/efeitos dos fármacos , Células Estromais/imunologia , Células Estromais/patologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/patologia , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
Patients with a dentofacial skeletal deformity have not only esthetic and morphologic problems related to facial proportions and dentition, but also problems of stomatognathic functions. Therefore, in addition to morphologic analysis, functional analysis is important for the diagnosis and evaluation of treatment in these patients. However, no reports have described longitudinal simultaneous evaluations of stomatognathic functions, and the comprehensive effects of surgical orthodontics on the stomatognathic functions are unclear. A patient was diagnosed as having a skeletal Class III jaw-base relationship, mandibular asymmetry, unilateral crossbite, asymmetric stomatognathic functions, and a temporomandibular disorder. She was treated with a combination of surgery and orthodontic therapy. As a result, facial proportions and occlusion improved; in particular, asymmetric stomatognathic functions, including masticatory muscle activity, condylar movement, and occlusal force, became symmetric between the left and right sides. Moreover, after 2 years of retention, the activity of the masticatory muscles and the values of occlusal force and occlusal contact area exceeded those at pretreatment. These results suggest that improvement of asymmetric stomatognathic functions can be achieved by correction of dentofacial morphology by surgical orthodontic treatment in patients with mandibular asymmetry.
Assuntos
Assimetria Facial/etiologia , Má Oclusão Classe III de Angle/complicações , Má Oclusão Classe III de Angle/cirurgia , Procedimentos Cirúrgicos Ortognáticos , Adolescente , Força de Mordida , Cefalometria , Estética Dentária , Assimetria Facial/cirurgia , Assimetria Facial/terapia , Feminino , Humanos , Má Oclusão Classe III de Angle/terapia , Músculos da Mastigação/fisiopatologia , Disco da Articulação Temporomandibular/patologiaRESUMO
To reveal varietally differing glucosinolate (GSL) contents in radish (Raphanus sativus L.) cultivated in Japan, the total and individual GSLs of 28 cultivars were analyzed using high-performance liquid chromatography. In these cultivars, GSL types including three aliphatic GSLs (glucoraphenin, glucoerucin, and 4-methylthio-3-butenyl GSL (4MTB-GSL)) and three indolyl GSLs (4-hydroxyglucobrassicin, glucobrassicin, and 4-methoxy-glucobrassicin) were detected. No cultivar-specific type of GSL was identified. The dominant GSL was 4MTB-GSL, but its contents differed remarkably: 8.6 µmol/g in 'Koushin' to 135.7 µmol/g in 'Karami 199'. Over about 90% of all GSLs in Japanese radish type are 4MTB-GSL, a higher percentage than in Chinese or European garden radish cultivars. A simple, rapid method for estimating total GSL contents in crude extracts was established because of the small variation of glucosinolate composition in Japanese cultivars. The total GSL content can be estimated using an equation for prediction with absorbance at 425 nm in a mixture of GSL crude extract and palladium (II) chloride solution: Total GSL (µmol/g) = 305.47 × A(425) - 29.66. Its coefficient of determination (R(2)) and standard error of prediction (SEP) are 0.968 and 8.052. This method enables total GSL content estimation from more than 200 samples per person per day.
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The level of self-incompatibility (SI) is important to the purity of F1 seeds produced using the SI system of Brassica vegetables. To analyze the genetic basis of the level of SI, we generated an F2 population derived from a cross between a turnip inbred line showing a high level of SI and a Chinese cabbage inbred line showing a low level, and evaluated the level of SI under insect pollination in two years. We constructed a detailed linkage map of Brassica rapa from the F2 progeny, consisting of SSR, SNP, indel, and CAPS loci segregating into 10 linkage groups covering approximately 700 cM. Five quantitative trait loci (QTL) for high-level SI were identified. The phenotypic variation explained by the QTL ranged between 7.2% and 23.8%. Two QTL were detected in both years. Mapping of SI-related genes revealed that these QTL were co-localized with SLG on R07 and MLPK on R03. This is the first report of QTL for high-level SI evaluated under insect pollination in a Brassica vegetable. Our results could be useful for the marker-assisted selection of parental lines with a stable SI.
Assuntos
Brassica rapa/genética , Cromossomos de Plantas/genética , Polinização/genética , Locos de Características Quantitativas/genética , Animais , Brassica rapa/crescimento & desenvolvimento , Brassica rapa/parasitologia , Mapeamento Cromossômico , DNA de Plantas/genética , Ligação Genética , Marcadores Genéticos/genética , Endogamia , Insetos/fisiologia , Polinização/fisiologia , Reação em Cadeia da Polimerase , Sementes/genética , Sementes/crescimento & desenvolvimentoRESUMO
We present semi-supervised information maximizing self-argument training (IMSAT), a neural network-based classification method that works without the preparation of labeled data. Semi-supervised IMSAT can amplify specific differences and avoid undesirable misclassification in accordance with the purpose. We demonstrate that semi-supervised IMSAT has a comparable performance with existing methods for semi-supervised learning of image classification and can also classify real experimental data (X-ray diffraction patterns and thermoelectric hysteresis curves) in the same way even though their shape and dimensions are different. Our algorithm will contribute to the automation of big data processing and artificial intelligence-driven material development.
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Bone remodeling is a complex process and it involves periods of deposition and resorption. Bone resorption is a process by which bone is broken down by osteoclasts in response to different stimuli. Osteoclast precursors differentiate into multinuclear osteoclasts in response to macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor Kappa-B ligand (RANKL). Under pathologic conditions, the cytokine profile is different and involves a mixture of inflammatory cytokines. Tumor necrosis factor alpha (TNF-α) is one of the most important cytokines as it is found in large amounts in areas involved with inflammatory osteolysis. The purpose of this protocol is to provide a method by which murine bone marrow is isolated to generate osteoclasts through induction with M-CSF and either RANKL or TNF-α which will be subsequently inhibited by increasing doses of anti-c-fms antibody, the receptor for M-CSF. This experiment highlights the therapeutic value of anti-c-fms antibody in diseases of inflammatory bone resorption.
Assuntos
Anticorpos/farmacologia , Osteoclastos/citologia , Osteoclastos/metabolismo , Receptor de Fator Estimulador de Colônias de Macrófagos/imunologia , Animais , Diferenciação Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Fator Estimulador de Colônias de Macrófagos/farmacologia , Camundongos Endogâmicos C57BL , Osteoclastos/efeitos dos fármacos , Ligante RANK/farmacologia , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
Thermoelectric technologies are becoming indispensable in the quest for a sustainable future. Recently, an emerging phenomenon, the spin-driven thermoelectric effect (STE), has garnered much attention as a promising path towards low cost and versatile thermoelectric technology with easily scalable manufacturing. However, progress in development of STE devices is hindered by the lack of understanding of the fundamental physics and materials properties responsible for the effect. In such nascent scientific field, data-driven approaches relying on statistics and machine learning, instead of more traditional modeling methods, can exhibit their full potential. Here, we use machine learning modeling to establish the key physical parameters controlling STE. Guided by the models, we have carried out actual material synthesis which led to the identification of a novel STE material with a thermopower an order of magnitude larger than that of the current generation of STE devices.
RESUMO
OBJECTIVES: Dipeptidyl peptidase 4 (DPP-4) inhibition is a new therapeutic strategy for type 2 diabetic patients. DPP-4 has been reported to enhance inflammation. However, the effect of DPP-4 inhibition on inflammation remains unknown. Lipopolysaccharide (LPS) is a strong inducer of inflammation and osteoclast formation. In this study, we investigated in vivo effects of DPP-4 inhibition on LPS-induced osteoclast formation and bone resorption, as well as in vitro effects of DPP-4 inhibition on RANKL-induced osteoclastogenesis and TNF-α-induced osteoclastogenesis. METHODS: LPS with or without a DPP-4 inhibitor was subcutaneously injected into mouse calvaria for 5 days. Histological sections of calvaria were stained for tartrate-resistant acid phosphatase, and osteoclast numbers were determined. The ratio of calvaria bone resorption was evaluated via microfocal computed tomography reconstruction images. RESULTS: Osteoclast number and bone resorption were significantly lower in mice that underwent LPS and DPP-4 inhibitor co-administration than in those that underwent LPS administration alone. Moreover, RANKL, TNF-α, and M-CSF expression was reduced in the LPS and DPP-4 inhibitor co-administration group. In vitro, there were no direct effects of DPP-4 inhibitor or DPP-4 on RANKL- and TNF-α-induced osteoclastogenesis, or on LPS-induced RANKL expression in stromal cells. Nevertheless, macrophages from LPS and DPP-4 inhibitor co-administered mice exhibited lower TNF-α expression than macrophages from LPS-only mice. Notably, TNF-α expression was not reduced in LPS and DPP-4 inhibitor co-treated macrophages in vitro, compared with macrophages treated with LPS alone.
Assuntos
Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/metabolismo , Dipeptidil Peptidase 4/metabolismo , Inibidores da Dipeptidil Peptidase IV/farmacologia , Lipopolissacarídeos/toxicidade , Osteoclastos/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Técnicas de Cocultura , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Linagliptina/farmacologia , Linagliptina/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Osteoclastos/efeitos dos fármacos , Distribuição AleatóriaRESUMO
Titanium nitride (TiN) coating by ion plating has properties such as high hardness, wear resistance, corrosion resistance, and surface lubricity, therefore TiN coating is often used in various dental appliances and materials. In this study, we evaluated the corrosion behaviors and mechanical properties of TiN coated stainless steel (SS) and nickel titanium (Ni-Ti) orthodontic wires prepared by ion plating. TiN coating by ion plating improves the corrosion resistance of orthodontic wires. The corrosion pitting of the TiN coated wire surface become small. The tensile strength and stiffness of SS wire were increased after TiN coating. In contrast, its elastic force, which is a property for Ni-Ti wire, was decreased. In addition, TiN coating provided small friction forces. The low level of friction may increase tooth movement efficiently. Therefore, TiN coated SS wire could be useful for orthodontics treatment.