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1.
Nature ; 616(7958): 724-730, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36796426

RESUMO

Controlling the crystallinity and surface morphology of perovskite layers by methods such as solvent engineering1,2 and methylammonium chloride addition3-7 is an effective strategy for achieving high-efficiency perovskite solar cells. In particular, it is essential to deposit α-formamidinium lead iodide (FAPbI3) perovskite thin films with few defects due to their excellent crystallinity and large grain size. Here we report the controlled crystallization of perovskite thin films with the combination of alkylammonium chlorides (RACl) added to FAPbI3. The δ-phase to α-phase transition of FAPbI3 and the crystallization process and surface morphology of the perovskite thin films coated with RACl under various conditions were investigated through in situ grazing-incidence wide-angle X-ray diffraction and scanning electron microscopy. RACl added to the precursor solution was believed to be easily volatilized during coating and annealing owing to dissociation into RA0 and HCl with deprotonation of RA+ induced by RA⋯H+-Cl- binding to PbI2 in FAPbI3. Thus, the type and amount of RACl determined the δ-phase to α-phase transition rate, crystallinity, preferred orientation and surface morphology of the final α-FAPbI3. The resulting perovskite thin layers facilitated the fabrication of perovskite solar cells with a power-conversion efficiency of 26.08% (certified 25.73%) under standard illumination.

2.
Biochem Biophys Res Commun ; 695: 149495, 2024 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-38211532

RESUMO

Piwi and its partner, Piwi-interacting RNA (piRNA), are pivotal in suppressing the harmful effects of transposable elements (TEs) linked to genomic insertional mutagenesis. While primarily active in Drosophila's adult gonadal tissues, causing sterility in its absence, Piwi's role in post-embryonic development remains unclear. Our study reveals Piwi's functional presence in the larval fat body, where it governs developmental growth through systemic insulin/insulin-like growth factor (IGF) signaling (IIS). Piwi knockdown in the fat body resulted in dysregulated TE expression, reduced developmental rate and body growth, and diminished systemic IIS activity. Notably, Piwi knockdown increased Imaginal Morphogenic Protein Late 2 (Imp-L2) expression, akin to insulin-like growth factor-binding protein 7 (IGFBP7), reducing systemic IIS and inhibiting body growth. This unveils a novel role for Piwi in larval adipose tissues, emphasizing its importance in regulating systemic IIS and overall organismal growth.


Assuntos
Proteínas de Drosophila , Drosophila , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina , Animais , Tecido Adiposo/metabolismo , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , Elementos de DNA Transponíveis , Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Peptídeos Semelhantes à Insulina , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo
3.
Microb Ecol ; 87(1): 95, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39017940

RESUMO

The study of microalgal communities is critical for understanding aquatic ecosystems. These communities primarily comprise diatoms (Heterokontophyta), with two methods commonly used to study them: Microscopy and metabarcoding. However, these two methods often deliver different results; thus, their suitability for analyzing diatom communities is frequently debated and evaluated. This study used these two methods to analyze the diatom communities in identical water samples and compare the results. The taxonomy of the species constituting the diatom communities was confirmed, and both methods showed that species belonging to the orders Bacillariales and Naviculales (class Bacillariophyceae) are the most diverse. In the lower taxonomic levels (family, genus, and species), microscopy tended to show a bias toward detecting diatom species (Nitzschia frustulum, Nitzschia inconspicua, Nitzschia intermedia, Navicula gregaria, Navicula perminuta, Navicula recens, Navicula sp.) belonging to the Bacillariaceae and Naviculaceae families. The results of the two methods differed in identifying diatom species in the communities and analyzing their structural characteristics. These results are consistent with the fact that diatoms belonging to the genera Nitzschia and Navicula are abundant in the communities; furthermore, only the Illumina MiSeq data showed the abundance of the Melosira and Entomoneis genera. The results obtained from microscopy were superior to those of Illumina MiSeq regarding species-level identification. Based on the results obtained via microscopy and Illumina MiSeq, it was revealed that neither method is perfect and that each has clear strengths and weaknesses. Therefore, to analyze diatom communities effectively and accurately, these two methods should be combined.


Assuntos
Código de Barras de DNA Taxonômico , Diatomáceas , Estuários , Microscopia , Diatomáceas/classificação , Diatomáceas/crescimento & desenvolvimento , Microscopia/métodos , República da Coreia , Biodiversidade , Filogenia , Ecossistema
4.
Appl Microbiol Biotechnol ; 108(1): 2, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38153552

RESUMO

Staphylococcus aureus is a major pathogen that causes infections and life-threatening diseases. Although antibiotics, such as methicillin, have been used, methicillin-resistant S. aureus (MRSA) causes high morbidity and mortality rates, and conventional detection methods are difficult to be used because of time-consuming process. To control the spread of S. aureus, a development of a rapid and simple detection method is required. In this study, we generated a fluorescent anti-S. aureus antibody, and established a novel fluorescence-linked immunosorbent assay (FLISA)-based S. aureus detection method. The method showed high sensitivity and low limit of detection toward MRSA detection. The assay time for FLISA was 5 h, which was faster than that of conventional enzyme-linked immunosorbent assay (ELISA) or rapid ELISA. Moreover, the FLISA-based detection method was applied to diagnose clinically isolated MRSA samples that required only 5.3 h of preincubation. The FLISA method developed in this study can be widely applied as a useful tool for convenient S. aureus detection. KEY POINTS: • A fluorescence-linked immunosorbent assay-based S. aureus detection method • Simultaneous quantification of a maximum of 96 samples within 5 h • Application of the novel system to diagnosis clinical isolates.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Imunoadsorventes , Staphylococcus aureus , Ensaio de Imunoadsorção Enzimática , Infecções Estafilocócicas/diagnóstico , Anticorpos
5.
Mar Drugs ; 22(3)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38535449

RESUMO

The anti-inflammatory effect of the ethanol extract of Sargassum yezoense and its fractions were investigated in this study. The ethanol extract exhibited a strong anti-inflammatory effect on lipopolysaccharide-stimulated RAW 264.7 macrophages and effectively suppressed the M1 polarization of murine bone-marrow-derived macrophages stimulated by lipopolysaccharides and IFN-γ (interferon-gamma). Through a liquid-liquid extraction process, five fractions (n-hexane, chloroform, ethyl acetate, butanol, and aqueous) were acquired. Among these fractions, the chloroform fraction (SYCF) was found to contain the highest concentration of phenolic compounds, along with two primary meroterpenoids, sargahydroquinoic acid (SHQA) and sargachromenol (SCM), and exhibit significant antioxidant capacity. It also demonstrated a robust anti-inflammatory effect. A direct comparison was conducted to assess the relative contribution of SHQA and SCM to the anti-inflammatory properties of SYCF. The concentrations of SHQA and SCM tested were determined based on their relative abundance in SYCF. SHQA contributed to a significant portion of the anti-inflammatory property of SYCF, while SCM played a limited role. These findings not only highlight the potential of the chloroform-ethanol fractionation approach for concentrating meroterpenoids in S. yezoense but also demonstrate that SHQA and other bioactive compounds work additively or synergistically to produce the potent anti-inflammatory effect of SYCF.


Assuntos
Alcenos , Benzopiranos , Benzoquinonas , Sargassum , Animais , Camundongos , Clorofórmio , Etanol , Lipopolissacarídeos
6.
Br J Clin Pharmacol ; 89(3): 1207-1210, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36367379

RESUMO

The goal of this study was to use a model kidney function clearance-dependent drug (vancomycin) to understand the gain or loss of precision in dosing with use of serum creatinine (Scr ), serum cystatin C (Scys ) and race and nonrace-based equations of the estimated glomerular filtration rate (eGFR). In this study of hospitalized patients, we compared Scr , Scys and their combination to estimate kidney function and vancomycin clearance. The nonrace-based Scys eGFR model outperformed other clearance models and improved the probability of target attainment by 15%. When Scys is not available, we show that the new 2021 CKD-EPI eGFRcr equation (no race factor) performs as well as the current conventional approach. This improvement in model performance does not negate the need for individualized dosing but exemplifies the need to remove race as a factor of kidney-function dose adjustment.


Assuntos
Insuficiência Renal Crônica , Vancomicina , Humanos , Taxa de Filtração Glomerular , Creatinina , Cistatina C
7.
Mol Biol Rep ; 50(5): 4715-4721, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36899277

RESUMO

BACKGROUND: Bursaphelenchus xylophilus is a pathogenic nematode that causes pine wilt disease (PWD). To prevent the rapid spread of this pathogen, developing a method for rapid and accurate detection of B. xylophilus is required. METHODS AND RESULTS: In this study, we produced a B. xylophilus peroxiredoxin (BxPrx), which is a protein that is overexpressed in B. xylophilus. Using recombinant BxPrx as an antigen, we generated and selected a novel antibody that binds to BxPrx via phage display and biopanning. We subcloned the anti-BxPrx single-chain variable fragment-encoding phagemid DNA to mammalian expression vector. We transfected the plasmid into mammalian cells and produced a highly sensitive recombinant antibody that enabled nanogram order detection of BxPrx. CONCLUSION: The sequence of anti-BxPrx antibody as well as the rapid immunoassay system described here can be applied for rapid and accurate diagnosis of PWD.


Assuntos
Nematoides , Pinus , Anticorpos de Cadeia Única , Animais , Xylophilus , Peroxirredoxinas/genética , Peroxirredoxinas/metabolismo , Nematoides/metabolismo , Proteínas Recombinantes/genética , Mamíferos/metabolismo
8.
BMC Biol ; 20(1): 258, 2022 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-36397042

RESUMO

BACKGROUND: Commensal microorganisms have a significant impact on the physiology of host animals, including Drosophila. Lactobacillus and Acetobacter, the two most common commensal bacteria in Drosophila, stimulate fly development and growth, but the mechanisms underlying their functional interactions remain elusive. RESULTS: We found that imaginal morphogenesis protein-Late 2 (Imp-L2), a Drosophila homolog of insulin-like growth factor binding protein 7, is expressed in gut enterocytes in a bacteria-dependent manner, determining host dependence on specific bacteria for host development. Imp-L2 mutation abolished the stimulatory effects of Lactobacillus, but not of Acetobacter, on fly larval development. The lethality of the Imp-L2 mutant markedly increased under axenic conditions, which was reversed by Acetobacter, but not Lactobacillus, re-association. The host dependence on specific bacteria was determined by Imp-L2 expressed in enterocytes, which was repressed by Acetobacter, but not Lactobacillus. Mechanistically, Lactobacillus and Acetobacter differentially affected steroid hormone-mediated Imp-L2 expression and Imp-L2-specific FOXO regulation. CONCLUSIONS: Our finding may provide a way how host switches dependence between different bacterial species when benefiting from varying microbiota.


Assuntos
Drosophila melanogaster , Animais , Bactérias/genética , Drosophila , Peptídeos
9.
Int J Mol Sci ; 24(16)2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37628724

RESUMO

Chemotherapy-induced peripheral neuropathy (CIPN) is a major comorbidity of cancer. Multiple clinical interventions have been studied to effectively treat CIPN, but the results have been disappointing, with no or little efficacy. Hence, understanding the pathophysiology of CIPN is critical to improving the quality of life and clinical outcomes of cancer patients. Although various mechanisms of CIPN have been described in neuropathic anti-cancer agents, the neuroinflammatory process involving cytotoxic/proinflammatory immune cells remains underexamined. While mast cells (MCs) and natural killer (NK) cells are the key innate immune compartments implicated in the pathogenesis of peripheral neuropathy, their role in CIPN has remained under-appreciated. Moreover, the biology of proinflammatory cytokines associated with MCs and NK cells in CIPN is particularly under-evaluated. In this review, we will focus on the interactions between MCs, NK cells, and neuronal structure and their communications via proinflammatory cytokines, including TNFα, IL-1ß, and IL-6, in peripheral neuropathy in association with tumor immunology. This review will help lay the foundation to investigate MCs, NK cells, and cytokines to advance future therapeutic strategies for CIPN.


Assuntos
Mastócitos , Doenças do Sistema Nervoso Periférico , Humanos , Qualidade de Vida , Células Matadoras Naturais , Neurônios , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Citocinas
10.
BMC Surg ; 22(1): 234, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35718764

RESUMO

BACKGROUND: Several studies have discussed various methods of prepectoral direct-to-implant (DTI) breast reconstruction using an acellular dermal matrix (ADM) prosthesis to achieve full coverage. However, methods for anterior coverage have rarely been reported. In this study, prepectoral DTI breast reconstruction with complete anterior implant coverage was performed using a square piece of ADM. This study aimed to introduce our prepectoral DTI technique and determine its functional and cosmetic outcomes as well as compare them with those of existing subpectoral DTI techniques. METHODS: This prospective comparative study focused on 29 patients (35 breasts) and 34 patients (35 breasts) who underwent breast reconstruction via subpectoral implant insertion (control group) and anterior coverage prepectoral implant insertion (anterior coverage group), respectively. Postoperative complications were noted, and breast symmetry was evaluated using the Vectra H2 three-dimensional scanner. The modified Kyungpook National University Hospital Breast-Q (KNUH Breast-Q) scale was used to assess the patient's subjective satisfaction with the reconstruction and postoperative quality of life. RESULTS: No remarkable differences in terms of complications (seroma, skin necrosis, nipple-areola complex necrosis, hematoma, capsular contracture, and infection) were noted in both groups. Compared with controls, considerably better results were observed among those in the anterior coverage group in terms of the mean drain removal period. Furthermore, those in the anterior coverage group showed greater symmetry on three-dimensional scans than the controls; however, this was not statistically significant. Subjective satisfaction and postoperative quality of life measured using the KNUH Breast-Q scale were not significantly different between both groups. CONCLUSIONS: Considering its stability, faster recovery time, and cosmetic benefit, prepectoral breast reconstruction with anterior implant coverage using a single, large ADM is a good choice to perform breast reconstruction with implant insertion in patients who have undergone mastectomy. LEVEL OF EVIDENCE: II.


Assuntos
Derme Acelular , Implante Mamário , Implantes de Mama , Neoplasias da Mama , Mamoplastia , Implante Mamário/métodos , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mamoplastia/métodos , Mastectomia/métodos , Necrose , Mamilos , Estudos Prospectivos , Qualidade de Vida , Estudos Retrospectivos
11.
Mol Med ; 27(1): 31, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33789563

RESUMO

BACKGROUND: Vascular endothelial cells (ECs) are subject to continuous shear stress due to blood circulation. Mechanical stress due to high shear flow can also cause arteriovenous malformation (AVM) when ECs respond hyper-sensitively to shear flow. This study was conducted to test the hypothesis that angiogenesis could be promoted in response to mechanical stress via regulation of pro-angiogenic factors in AVM cells. METHODS: ECs were extracted from the tissue samples from six AVM patients and six normal patients. Shear stress at 7 dynes/cm2 were applied for 24 h. Before and after application of shear stress to each group, RT-PCR was performed to access the expression levels of angiopoietin2(AGP2), aquaporin1(AQP1) and TGFßR1. Immunofluorescences was also performed to evaluate the level of protein expressions. RESULTS: In both normal and AVM tissues, AGP2 and TGFßR1 under the shear stress showed increased expression in the ECs compared to the non-sheared samples. When AVMs and normal arterial vasculature were compared, the expression levels of both AGP2 and TGFßR1 in AVMs were higher when compared to normal arterial vasculature with or without shear stress. Immunofluorescence-based protein analysis also confirmed shear-induced AGP2 and TGFßR1 in both samples of normal and AVM patients. CONCLUSIONS: AVMs exhibited higher sensitivity to shear stress by producing higher expressions of some marked genes and proteins that regulate the endothelial functions upon exposure to shear stress. While the physiological mechanism for AVMs remain elusive, our study shows the plausibility of physical stress imposed by the shearing flow can cause the occurrence of AVMs.


Assuntos
Malformações Arteriovenosas , Neovascularização Patológica , Estresse Mecânico , Adolescente , Adulto , Angiopoietina-2/genética , Angiopoietina-2/metabolismo , Aquaporina 1/genética , Aquaporina 1/metabolismo , Artérias/anormalidades , Artérias/metabolismo , Artérias/patologia , Malformações Arteriovenosas/genética , Malformações Arteriovenosas/metabolismo , Malformações Arteriovenosas/patologia , Criança , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Feminino , Expressão Gênica , Humanos , Masculino , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I/genética , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Adulto Jovem
12.
Proc Natl Acad Sci U S A ; 115(23): 5992-5997, 2018 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-29784791

RESUMO

Nutritional condition during the juvenile growth period considerably affects final adult size. The insulin/insulin-like growth factor signaling (IIS)/target of rapamycin (TOR) nutrient-sensing pathway is known to regulate growth and metabolism in response to nutritional conditions. However, there is limited information on how endocrine pathways communicate nutritional information to different metabolic organs to regulate organismal growth. Here, we show that Imaginal morphogenesis protein-Late 2 (Imp-L2), a Drosophila homolog of insulin-like growth factor-binding protein 7 (IGFBP7), plays a key role in the nutritional control of organismal growth. Nutritional restriction during the larval growth period causes undersized adults, which is largely diminished by Imp-L2 mutation. We delineate a pathway in which nutritional restriction increases levels of the steroid hormone ecdysone, which, in turn, triggers ecdysone signaling-dependent Imp-L2 production from the fat body, a fly adipose organ, thereby attenuating peripheral IIS and body growth. Surprisingly, this endocrine pathway operates independent of the fat-body-TOR internal nutrient sensor, long believed to be the control center for nutrition-dependent growth. Our study reveals a previously unrecognized endocrine circuit mediating nutrition-dependent juvenile growth, which could also potentially be related to the insulin resistance frequently observed in puberty.


Assuntos
Drosophila , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Fenômenos Fisiológicos da Nutrição/fisiologia , Transdução de Sinais/fisiologia , Esteroides/metabolismo , Animais , Drosophila/crescimento & desenvolvimento , Drosophila/metabolismo , Drosophila/fisiologia , Feminino , Larva/crescimento & desenvolvimento , Larva/metabolismo , Larva/fisiologia , Masculino
13.
J Cell Physiol ; 235(5): 4494-4507, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31637720

RESUMO

Cancer-associated fibroblasts (CAFs) in the tumor microenvironment play major roles in supporting cancer progression. A previous report showed that SPIN90 downregulation is correlated with CAF activation and that SPIN90-deficient CAFs promote breast cancer progression. However, the mechanisms that mediate cancer-stroma interaction and how such interactions regulate cancer progression are not well understood. Here, we show that extra domain A (EDA)-containing fibronectin (FN), FN(+)EDA, produced by mouse embryonic fibroblasts (MEFs) derived from Spin90-knockout (KO) mice increases their own myofibroblast differentiation, which facilitates breast cancer progression. Increased FN(+)EDA in Spin90-KO MEFs promoted fibril formation in the extracellular matrix (ECM) and specifically interacted with integrin α4ß1 as the mediating receptor. Moreover, FN(+)EDA expression by Spin90-KO MEFs increased proliferation, migration, and invasion of breast cancer cells. Irigenin, a specific inhibitor of the interaction between integrin α4ß1 and FN(+)EDA, significantly blocked the effects of FN(+)EDA, such as fibril formation by Spin90-KO MEFs and proliferation, migration, and invasion of breast cancer cells. In orthotopic breast cancer mouse models, irigenin injection remarkably reduced tumor growth and lung metastases. It was supported by that FN(+)EDA in assembled fibrils was accumulated in cancer stroma of human breast cancer patients in which SPIN90 expression was downregulated. Our data suggest that SPIN90 downregulation increases FN(+)EDA and promotes ECM stiffening in breast cancer stroma through an assembly of long FN(+)EDA-rich fibrils; moreover, engagement of the Integrin α4ß1 receptor facilitates breast cancer progression. Inhibitory effects of irigenin on tumor growth and metastasis suggest the potential of this agent as an anticancer therapeutic.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias da Mama/metabolismo , Fibronectinas/metabolismo , Proteínas Musculares/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Células Cultivadas , Feminino , Fibronectinas/genética , Deleção de Genes , Humanos , Neoplasias Mamárias Animais , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Musculares/genética , Neoplasias Experimentais , Proteínas do Tecido Nervoso/genética , Regulação para Cima
14.
J Craniofac Surg ; 31(1): 79-84, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31725500

RESUMO

BACKGROUND: Because the traditional technique is known to cause visible scarring, it is challenging to yield optimal outcomes while treating a severe type of microform and minor-form cleft lip. The authors present a new refined technique with minimal skin incision and philtrum formation through an intraoral incision. METHODS: The surgical technique involves single Z-plasty or double or triple unilimb Z-plasty to restore an elevated cupid's bow peak and overlapping of an orbicularis oris muscle flap to create the philtrum through an intraoral incision. Cleft lip nasal deformity was corrected with reverse-U incision and V-Y plasty. RESULTS: Eighteen patients were operated between September 2008 and June 2017. Patient age at the time of surgery ranged from 3 to 12 months. The duration of follow-up ranged from 12 months to 7 years (mean, 36 months). The elevated cupid's bow was corrected by performing single Z-plasty in 6 patients, double unilimb Z-plasty in 7 patients, and triple unilimb Z-plasty in 5 patients. In all cases, the notch or elevated cupid's bow was corrected, the surgical scar was minimal, and philtrum reconstruction was satisfactory. Minor scar revision was performed in 4 patients. Cleft lip nasal deformity was corrected in fifteen patients. CONCLUSIONS: The technique adopted here causes minimal scarring, facilitates the formation of an anatomical philtrum, preserves the continuity and function of the muscle, and presents sufficient elevation of the philtral column.


Assuntos
Fenda Labial/cirurgia , Microfilmagem , Cicatriz , Procedimentos Cirúrgicos Dermatológicos , Feminino , Humanos , Lactente , Lábio/cirurgia , Masculino , Procedimentos de Cirurgia Plástica , Reoperação , Retalhos Cirúrgicos/cirurgia , Fatores de Tempo , Resultado do Tratamento
15.
J Cell Physiol ; 234(6): 9216-9224, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30341913

RESUMO

Alterations in mechanical properties in the extracellular matrix are modulated by myofibroblasts and are required for progressive fibrotic diseases. Recently, we reported that fibroblasts depleted of SPIN90 showed enhanced differentiation into myofibroblasts via increased acetylation of microtubules in the soft matrix; the mechanisms of the underlying signaling network, however, remain unclear. In this study, we determine the effect of depletion of SPIN90 on FAK/ROCK signaling modules. Transcriptome analysis of Spin90 KO mouse embryonic fibroblasts (MEF) and fibroblasts activated by TGF-ß revealed that Postn is the most significantly upregulated gene. Knockdown of Postn by small interfering RNA suppressed cell adhesion and myofibroblastic differentiation and downregulated FAK activity in Spin90 KO MEF. Our results indicate that SPIN90 depletion activates FAK/ROCK signaling, induced by Postn expression, which is critical for myofibroblastic differentiation on soft matrices mimicking the mechanical environment of a normal tissue.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Moléculas de Adesão Celular/metabolismo , Regulação para Baixo/genética , Fibroblastos/metabolismo , Quinase 1 de Adesão Focal/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Transdução de Sinais , Quinases Associadas a rho/metabolismo , Animais , Diferenciação Celular , Adesões Focais/metabolismo , Camundongos Knockout , Miofibroblastos/metabolismo
16.
Proc Natl Acad Sci U S A ; 112(43): 13144-9, 2015 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-26460035

RESUMO

Interactions between polypeptide chains containing amino acid residues with opposite absolute configurations have long been a source of interest and speculation, but there is very little structural information for such heterochiral associations. The need to address this lacuna has grown in recent years because of increasing interest in the use of peptides generated from d amino acids (d peptides) as specific ligands for natural proteins, e.g., to inhibit deleterious protein-protein interactions. Coiled-coil interactions, between or among α-helices, represent the most common tertiary and quaternary packing motif in proteins. Heterochiral coiled-coil interactions were predicted over 50 years ago by Crick, and limited experimental data obtained in solution suggest that such interactions can indeed occur. To address the dearth of atomic-level structural characterization of heterochiral helix pairings, we report two independent crystal structures that elucidate coiled-coil packing between l- and d-peptide helices. Both structures resulted from racemic crystallization of a peptide corresponding to the transmembrane segment of the influenza M2 protein. Networks of canonical knobs-into-holes side-chain packing interactions are observed at each helical interface. However, the underlying patterns for these heterochiral coiled coils seem to deviate from the heptad sequence repeat that is characteristic of most homochiral analogs, with an apparent preference for a hendecad repeat pattern.


Assuntos
Conformação Proteica , Proteínas/química , Sequência de Aminoácidos , Modelos Moleculares , Dados de Sequência Molecular , Homologia de Sequência de Aminoácidos
17.
PLoS Biol ; 12(6): e1001881, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24914685

RESUMO

Rheumatoid arthritis (RA) is a systemic autoimmune disorder that manifests as chronic inflammation and joint tissue destruction. However, the etiology and pathogenesis of RA have not been fully elucidated. Here, we explored the role of the hypoxia-inducible factors (HIFs), HIF-1α (encoded by HIF1A) and HIF-2α (encoded by EPAS1). HIF-2α was markedly up-regulated in the intimal lining of RA synovium, whereas HIF-1α was detected in a few cells in the sublining and deep layer of RA synovium. Overexpression of HIF-2α in joint tissues caused an RA-like phenotype, whereas HIF-1α did not affect joint architecture. Moreover, a HIF-2α deficiency in mice blunted the development of experimental RA. HIF-2α was expressed mainly in fibroblast-like synoviocytes (FLS) of RA synovium and regulated their proliferation, expression of RANKL (receptor activator of nuclear factor-κB ligand) and various catabolic factors, and osteoclastogenic potential. Moreover, HIF-2α-dependent up-regulation of interleukin (IL)-6 in FLS stimulated differentiation of TH17 cells-crucial effectors of RA pathogenesis. Additionally, in the absence of IL-6 (Il6-/- mice), overexpression of HIF-2α in joint tissues did not cause an RA phenotype. Thus, our results collectively suggest that HIF-2α plays a pivotal role in the pathogenesis of RA by regulating FLS functions, independent of HIF-1α.


Assuntos
Artrite Experimental/etiologia , Artrite Reumatoide/etiologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Animais , Artrite Experimental/metabolismo , Artrite Reumatoide/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/imunologia , Diferenciação Celular , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Fenótipo , Membrana Sinovial/metabolismo , Células Th17/citologia , Regulação para Cima
18.
NMR Biomed ; 29(4): 507-18, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26871685

RESUMO

Excess exposure to ionizing radiation generates reactive oxygen species and increases the cellular inflammatory response by modifying various metabolic pathways. However, an investigation of metabolic perturbations and organ-specific responses based on the amount of radiation during the acute phase has not been conducted. In this study, high-resolution magic-angle-spinning (HR-MAS) NMR and solution NMR-based metabolic profiling were used to investigate dose-dependent metabolic changes in multiple organs and tissues--including the jejunum, spleen, liver, and plasma--of rats exposed to X-ray radiation. The organs, tissues, and blood samples were obtained 24, 48, and 72 h after exposure to low-dose (2 Gy) and high-dose (6 Gy) X-ray radiation and subjected to metabolite profiling and multivariate analyses. The results showed the time course of the metabolic responses, and many significant changes were detected in the high-dose compared with the low-dose group. Metabolites with antioxidant properties showed acute responses in the jejunum and spleen after radiation exposure. The levels of metabolites related to lipid and protein metabolism were decreased in the jejunum. In addition, amino acid levels increased consistently at all post-irradiation time points as a consequence of activated protein breakdown. Consistent with these changes, plasma levels of tricarboxylic acid cycle intermediate metabolites decreased. The liver did not appear to undergo remarkable metabolic changes after radiation exposure. These results may provide insight into the major metabolic perturbations and mechanisms of the biological systems in response to pathophysiological damage caused by X-ray radiation.


Assuntos
Especificidade de Órgãos/efeitos da radiação , Plasma/metabolismo , Espectroscopia de Prótons por Ressonância Magnética/métodos , Amilases/sangue , Animais , Peso Corporal/efeitos da radiação , Análise Discriminante , Jejuno/metabolismo , Jejuno/efeitos da radiação , Análise dos Mínimos Quadrados , Redes e Vias Metabólicas/efeitos da radiação , Análise Multivariada , Tamanho do Órgão/efeitos da radiação , Ratos Endogâmicos F344 , Baço/metabolismo , Baço/efeitos da radiação , Fatores de Tempo , Raios X
19.
Appl Nurs Res ; 31: 111-6, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27397827

RESUMO

AIM: This study examined the influence of teachers, mothers, and children themselves on weight misperceptions of preschool children. BACKGROUND: Preschool children should have correct perceptions of their weight and develop a positive body image and healthy weight-control behaviors throughout childhood. METHODS: This study used a descriptive cross-sectional design based on the biopsychosocial model. We analyzed 388 triads of Korean children aged 3-6 years, their mothers, and teachers. RESULTS: Children's body mass index (BMI) and weight satisfaction, mothers' BMI; teachers' education level, BMI, perception of and satisfaction with children's weight, body image, and attitude toward obesity were predictors of children underestimating their weight. Mothers' education level and BMI; teachers' BMI, satisfaction with children's weight, and body image were predictors of children overestimating their weight. CONCLUSIONS: Teachers influence weight misperceptions of preschool children. Intervention programs for teachers should incorporate more accurate perceptions of children's weight and promote healthy body image.


Assuntos
Peso Corporal , Ensino , Adulto , Índice de Massa Corporal , Criança , Pré-Escolar , Feminino , Humanos , Masculino , República da Coreia , Recursos Humanos
20.
Appl Environ Microbiol ; 81(6): 2075-81, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25576612

RESUMO

Millions of people suffer from foodborne diseases throughout the world every year, and the importance of food safety has grown worldwide in recent years. The aim of this study was to investigate the survival of hepatitis A virus (HAV) and viral surrogates of human norovirus (HuNoV) (bacteriophage MS2 and murine norovirus [MNV]) in food over time. HAV, MNV, and MS2 were inoculated onto either the digestive gland of oysters or the surface of fresh peppers, and their survival on these food matrices was measured under various temperature (4°C, 15°C, 25°C, and 40°C) and relative humidity (RH) (50% and 70%) conditions. Inoculated viruses were recovered from food samples and quantified by a plaque assay at predetermined time points over 2 weeks (0, 1, 3, 7, 10, and 14 days). Virus survival was influenced primarily by temperature. On peppers at 40°C and at 50% RH, >4- and 6-log reductions of MNV and HAV, respectively, occurred within 1 day. All three viruses survived better on oysters. In addition, HAV survived better at 70% RH than at 50% RH. The survival data for HAV, MS2, and MNV were fit to three different mathematical models (linear, Weibull, and biphasic models). Among them, the biphasic model was optimum in terms of goodness of fit. The results of this study suggest that major foodborne viruses such as HAV and HuNoV can survive over prolonged periods of time with a limited reduction in numbers. Because a persistence of foodborne virus on contaminated foods was observed, precautionary preventive measures should be performed.


Assuntos
Microbiologia de Alimentos , Armazenamento de Alimentos/métodos , Viabilidade Microbiana , Vírus/isolamento & purificação , Animais , Capsicum/virologia , Umidade , Modelos Teóricos , Ostreidae/virologia , Temperatura , Fatores de Tempo , Ensaio de Placa Viral
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