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1.
Proc Natl Acad Sci U S A ; 121(10): e2313681121, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38408238

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron strain has evolved into highly divergent variants with several sub-lineages. These newly emerging variants threaten the efficacy of available COVID-19 vaccines. To mitigate the occurrence of breakthrough infections and re-infections, and more importantly, to reduce the disease burden, it is essential to develop a strategy for producing updated multivalent vaccines that can provide broad neutralization against both currently circulating and emerging variants. We developed bivalent vaccine AdCLD-CoV19-1 BA.5/BA.2.75 and trivalent vaccines AdCLD-CoV19-1 XBB/BN.1/BQ.1.1 and AdCLD-CoV19-1 XBB.1.5/BN.1/BQ.1.1 using an Ad5/35 platform-based non-replicating recombinant adenoviral vector. We compared immune responses elicited by the monovalent and multivalent vaccines in mice and macaques. We found that the BA.5/BA.2.75 bivalent and the XBB/BN.1/BQ.1.1 and XBB.1.5/BN.1/BQ.1.1 trivalent vaccines exhibited improved cross-neutralization ability compared to their respective monovalent vaccines. These data suggest that the developed multivalent vaccines enhance immunity against circulating Omicron subvariants and effectively elicit neutralizing antibodies across a broad spectrum of SARS-CoV-2 variants.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Animais , Humanos , Camundongos , Vacinas contra COVID-19/genética , COVID-19/prevenção & controle , SARS-CoV-2/genética , Anticorpos Neutralizantes , Macaca , Vacinas Combinadas , Anticorpos Antivirais
2.
Proc Natl Acad Sci U S A ; 119(35): e2204735119, 2022 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-35994638

RESUMO

Considerable electric fields are present within living cells, and the role of bioelectricity has been well established at the organismal level. Yet much remains to be learned about electric-field effects on protein function. Here, we use phototriggered charge injection from a site-specifically attached ruthenium photosensitizer to directly demonstrate the effect of dynamic charge redistribution within a protein. We find that binding of an antibody to phosphoglycerate kinase (PGK) is increased twofold under illumination. Remarkably, illumination is found to suppress the enzymatic activity of PGK by a factor as large as three. These responses are sensitive to the photosensitizer position on the protein. Surprisingly, left (but not right) circularly polarized light elicits these responses, indicating that the electrons involved in the observed dynamics are spin polarized, due to spin filtration by protein chiral structures. Our results directly establish the contribution of electrical polarization as an allosteric signal within proteins. Future experiments with phototriggered charge injection will allow delineation of charge rearrangement pathways within proteins and will further depict their effects on protein function.


Assuntos
Campos Eletromagnéticos , Proteínas , Regulação Alostérica , Elétrons , Iluminação , Fármacos Fotossensibilizantes/farmacologia , Ligação Proteica , Proteínas/efeitos dos fármacos , Proteínas/metabolismo , Proteínas/efeitos da radiação , Rutênio/farmacologia
3.
J Surg Res ; 285: 51-58, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36640610

RESUMO

INTRODUCTION: Oxidative stress contributes to tissue injury through reactive oxygen species-dependent signaling pathways during sepsis. We studied therapeutic benefits of the combination therapy of niacin, which increased reduced glutathione levels, and apocynin, which suppressed reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) activity, in septic rats. MATERIALS AND METHODS: Polymicrobial sepsis was induced through cecal ligation and puncture (CLP) with antibiotics in male Sprague-Dawley rats (n = 189). The rats were randomly divided into sham, CLP, CLP + niacin, CLP + apocynin, and CLP + niacin + apocynin groups. Six hours after CLP, vehicle, niacin (360 mg/kg through the orogastric tube), and/or apocynin (20 mg/kg through intraperitoneal injection) were administered. The occurrence of mortality for 72 h after CLP was observed. Next, a separate set of animals was euthanized at 24 h post-CLP for lung tissue analyses. RESULTS: Combination therapy with niacin and apocynin significantly improved survival in rats with sepsis (75.0% versus 28.8%, P = 0.006) but monotherapy with niacin or apocynin did not. Monotherapy with niacin and apocynin appeared to increase NADPH levels and decrease Nox levels and activity, respectively, but failed to show statistical significances. However, combination therapy significantly decreased Nox levels and activity, increased NADPH and glutathione levels, decreased intranuclear nuclear factor-κB (NF-κB) p65 levels, reduced inflammatory cytokine expression and malondialdehyde levels, and attenuated histological lung injuries. CONCLUSIONS: Combination therapy with niacin and apocynin synergistically attenuated lung injuries and improved survival in rats with sepsis through niacin-induced glutathione redox cycle activation and apocynin-induced Nox suppression.


Assuntos
Acetofenonas , Lesão Pulmonar , Niacina , Sepse , Animais , Masculino , Ratos , Glutationa/uso terapêutico , Pulmão/patologia , Lesão Pulmonar/tratamento farmacológico , NADP/metabolismo , NADPH Oxidases/metabolismo , NF-kappa B/metabolismo , Niacina/farmacologia , Ratos Sprague-Dawley , Sepse/metabolismo , Acetofenonas/farmacologia
4.
BMC Public Health ; 23(1): 282, 2023 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-36864419

RESUMO

BACKGROUND: This study aimed to look at emotions perceived about the attributes, prevention, diagnosis, and treatment of infectious diseases related to coronavirus disease (COVID-19) that were widespread across the world and identify their relevance to knowledge about infectious diseases and preventative behaviors. METHODS: Texts to measure emotional cognition were selected through a pre-test, and 282 people were chosen as participants based on the survey conducted for 20 days from August 19 to August 29, 2020, created with Google Forms. IBM SPSS Statistics 25.0 was used for the primary analysis, and the SNA package in R (version 4.0.2) was utilized to conduct the network analysis. RESULTS: It was found that universal negative emotions such as feeling "anxious" (65.5%), "afraid" (46.1%), and "scared" (32.7%) commonly appeared among most people. Also, they were found to be feeling both positive ("caring" [42.3%] and "strict" [28.2%]) and negative ("frustrating" [39.1%] and "isolated" [31.0%]) emotions about efforts to prevent and curb the spread of COVID-19. In terms of emotional cognition for the diagnosis and treatment of such diseases, "reliable" (43.3%) took the biggest ratio among the replies. The level of understanding about infectious diseases showed differences in emotional cognition, thereby affecting people's emotions. However, no differences were found in the practice of preventative behaviors. CONCLUSIONS: Emotions associated with cognition in the context of pandemic infectious diseases have been found to be mixed. Furthermore, it can be seen that feelings vary depending on the degree of understanding of the infectious disease.


Assuntos
COVID-19 , Pandemias , Humanos , Pandemias/prevenção & controle , COVID-19/epidemiologia , COVID-19/prevenção & controle , Cognição , Emoções , Mineração de Dados
5.
BMC Emerg Med ; 23(1): 47, 2023 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-37173654

RESUMO

BACKGROUND: We hypothesized that an emergency short-stay ward (ESSW) mainly operated by emergency medicine physicians may reduce the length of patient stay in emergency department without expense of clinical outcomes. METHODS: We retrospectively analysed adult patients who visited the emergency department of the study hospital and were subsequently admitted to wards from 2017 to 2019. We divided study participants into three groups: patients admitted to ESSW and treated by the department of emergency medicine (ESSW-EM), patients admitted to ESSW and treated by other departments (ESSW-Other) and patients admitted to general wards (GW). The co-primary outcomes were ED length of stay and 28-day hospital mortality. RESULTS: In total, 29,596 patients were included in the study, and 8,328 (31.3%), 2,356 (8.9%), and 15,912 (59.8%) of them were classified as ESSW-EM, ESSW-Other and GW groups, respectively. The ED length of stay of the ESSW-EM (7.1 h ± 5.4) was shorter than those of the ESSW-Other (8.0 ± 6.2, P < 0.001) and the GW (10.2 ± 9.8, P < 0.001 for both). Hospital mortality of ESSW-EM (1.9%) was lower than that of GW (4.1%, P < 0.001). In the multivariable linear regression analysis, the ESSW-EM was independently associated with shorter ED length of stay compared with the both ESSW-Other (coefficient, 1.08; 95% confidence interval, 0.70-1.46; P < 0.001) and GW (coefficient, 3.35; 95% confidence interval, 3.12-3.57; P < 0.001). In the multivariable logistic regression analyses, the ESSW-EM was independently associated with lower hospital mortality compared with both the ESSW-Other group (adjusted P = 0.030) and the GW group (adjusted P < 0.001). CONCLUSIONS: In conclusion, the ESSW-EM was independently associated with shorter ED length of stay compared with both the ESSW-Other and the GW in the adult ED patients. Independent association was found between the ESSW-EM and lower hospital mortality compared with the GW.


Assuntos
Serviço Hospitalar de Emergência , Hospitalização , Adulto , Humanos , Tempo de Internação , Estudos de Casos e Controles , Estudos Retrospectivos
6.
Molecules ; 27(16)2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-36014487

RESUMO

Fluorescent protein-DNA-binding peptides or proteins (FP-DBP) are a powerful means to stain and visualize large DNA molecules on a fluorescence microscope. Here, we constructed 21 kinds of FP-DBPs using various colors of fluorescent proteins and two DNA-binding motifs. From the database of fluorescent proteins (FPbase.org), we chose bright FPs, such as RRvT, tdTomato, mNeonGreen, mClover3, YPet, and mScarlet, which are four to eight times brighter than original wild-type GFP. Additionally, we chose other FPs, such as mOrange2, Emerald, mTurquoise2, mStrawberry, and mCherry, for variations in emitting wavelengths. For DNA-binding motifs, we used HMG (high mobility group) as an 11-mer peptide or a 36 kDa tTALE (truncated transcription activator-like effector). Using 21 FP-DBPs, we attempted to stain DNA molecules and then analyzed fluorescence intensities. Most FP-DBPs successfully visualized DNA molecules. Even with the same DNA-binding motif, the order of FP and DBP affected DNA staining in terms of brightness and DNA stretching. The DNA staining pattern by FP-DBPs was also affected by the FP types. The data from 21 FP-DBPs provided a guideline to develop novel DNA-binding fluorescent proteins.


Assuntos
DNA , Corantes Fluorescentes , DNA/metabolismo , Proteínas de Ligação a DNA/metabolismo , Corantes Fluorescentes/química , Proteínas Luminescentes/metabolismo , Microscopia de Fluorescência , Coloração e Rotulagem
7.
Small ; 17(31): e2101262, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34160907

RESUMO

Synthetic strategies of web-above-a-ring (WAR) and web-above-a-lens (WAL) nanostructures are reported. The WAR has a controllable gap between the nanoring core and a nanoweb with nanopores for the effective confinement of electromagnetic field in the nanogap and subsequent surface-enhanced Raman scattering (SERS) of Raman dyes inside the gap with high signal reproducibility, which are attributed to the generation of circular 3D hot zones along the rim of Pt@Au nanorings with wrapping nanoweb architecture. More specifically, Pt@Au nanorings are adopted as a plasmonic core for structural rigidity and built porous nanowebs above them through a controlled combination of galvanic exchange and the Kirkendall effect. Both nanoweb and nanolens structures are also formed on Pt@Au nanoring, which is WAL. structure. Remarkably, plasmonic hot zone, nanopores, and hot lens are formed inside a single WAL nanostructure, and these structural components are orchestrated to generate stronger SERS signals.


Assuntos
Nanopartículas Metálicas , Nanoestruturas , Ouro , Reprodutibilidade dos Testes , Análise Espectral Raman
8.
Sensors (Basel) ; 22(1)2021 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-35009717

RESUMO

Studies on deep-learning-based behavioral pattern recognition have recently received considerable attention. However, if there are insufficient data and the activity to be identified is changed, a robust deep learning model cannot be created. This work contributes a generalized deep learning model that is robust to noise not dependent on input signals by extracting features through a deep learning model for each heterogeneous input signal that can maintain performance while minimizing preprocessing of the input signal. We propose a hybrid deep learning model that takes heterogeneous sensor data, an acceleration sensor, and an image as inputs. For accelerometer data, we use a convolutional neural network (CNN) and convolutional block attention module models (CBAM), and apply bidirectional long short-term memory and a residual neural network. The overall accuracy was 94.8% with a skeleton image and accelerometer data, and 93.1% with a skeleton image, coordinates, and accelerometer data after evaluating nine behaviors using the Berkeley Multimodal Human Action Database (MHAD). Furthermore, the accuracy of the investigation was revealed to be 93.4% with inverted images and 93.2% with white noise added to the accelerometer data. Testing with data that included inversion and noise data indicated that the suggested model was robust, with a performance deterioration of approximately 1%.


Assuntos
Atividades Humanas , Redes Neurais de Computação , Acelerometria , Bases de Dados Factuais , Humanos
9.
J Biol Inorg Chem ; 25(2): 233-238, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31970489

RESUMO

We report the temperature dependence of the formal potential of type 1 copper (CuT1) in Thermusthermophilus HB27 laccase. Employing [Ru(NH3)4(bpy)](PF6)2 (0.505 vs. NHE) as the redox titrant, we found that the CuT12+/+ potential decreased from approximately 480 to 420 mV (vs. NHE) as the temperature was raised from 20 to 65 °C. Of importance is that the ΔSrc° of - 120 J mol-1 K-1 is substantially more negative than those for other blue copper proteins. We suggest that the highly unfavorable reduction entropy is attributable to CuT1 inaccessibility to the aqueous medium. Although the active site residues are buried, which is critical for maintaining thermostability, the flexibility around CuT1 is maintained, allowing enzyme activity at ambient temperature.


Assuntos
Lacase/química , Thermus thermophilus/enzimologia , Cobre/química , Cobre/metabolismo , Estabilidade Enzimática , Lacase/metabolismo , Oxirredução , Temperatura
10.
J Health Commun ; 25(5): 394-401, 2020 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-32536257

RESUMO

This study examines how vaccine-related books appear on Amazon, focusing on search and recommendation algorithms. We collected vaccine related books that appeared on the first 10 search result pages by Amazon for seven consecutive days and content coded each book. We also collected Amazon's recommendations for each vaccine book and mapped the network of recommendation among these books. First, we found that the number of vaccine-hesitant books outnumbered vaccine-supportive books two to one. Of these vaccine-hesitant books, 21% were written by physicians and medical experts. Second, although we did not find evidence that their search algorithm systematically favored any particular type of book, the three top ranked books across the seven days were all vaccine-hesitant ones. Lastly, using a network model, we found that books sharing similar views of vaccines were recommended together such that when a user views a vaccine-hesitant book, many other vaccine-hesitant books are further recommended for the user. The three most frequently recommended books were vaccine-hesitant ones. The potential consequences of blindly applying commercial algorithms to a complicated health messages such as vaccines are discussed.


Assuntos
Algoritmos , Comunicação , Informação de Saúde ao Consumidor/normas , Vacinas , Livros , Comércio , Humanos , Internet
11.
Cogn Emot ; 33(8): 1702-1708, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30870075

RESUMO

What three words come to your mind in response to "happiness"? Using a free-association task [cf. Nelson, D. L., McEvoy, C. L., & Dennis, S. (2000). What is free association and what does it measure? Memory and Cognition, 28, 887-899], this research finds that the number of social words (e.g. family, love) provided in link to happiness predicts people's actual life satisfaction level. However, this association was significantly moderated by the person's self-perceived financial state. The contingency between holding a socially-oriented belief about happiness and experienced life satisfaction was significant among members of low socioeconomic status (SES), but not among the high SES group. This pattern was replicated across two divergent samples (Asian college students, Study 1; American adults, Study 2), regardless of one's extraversion level (Studies 1, 2) and availability of social support (number of friends, Study 2). Given the overlapping function of money and social relationships (instrumental in promoting survival), believing in the social nature of happiness seems to be more central in the life satisfaction of those with less financial resource.


Assuntos
Amigos/psicologia , Felicidade , Satisfação Pessoal , Pobreza/psicologia , Comportamento Social , Apoio Social , Adulto , Idoso , Feminino , Humanos , Coreia (Geográfico) , Masculino , Pessoa de Meia-Idade , Autoimagem , Fatores Socioeconômicos , Estados Unidos , Adulto Jovem
12.
BMC Vet Res ; 14(1): 160, 2018 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-29769138

RESUMO

BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) causes devastating disease characterized by reproductive failure and respiratory problems in the swine industry. To understand the recent prevalence and genetic diversity of field PRRSVs in the Republic of Korea, open reading frames (ORFs) 5 and 7 of PRRSV field isolates from 631 PRRS-affected swine farms nationwide in 2013-2016 were analyzed along with 200 Korean field viruses isolated in 2003-2010, and 113 foreign field and vaccine strains. RESULTS: Korean swine farms were widely infected with PRRSVs of a single type (38.4 and 37.4% for Type 1 and Type 2 PRRSV, respectively) or both types (24.2%) with up to approximately 83% nucleotide sequence similarity to prototype PRRSVs (Lelystad or VR2332). Phylogenetic analysis based on the ORF5 nucleotide sequence revealed that Korean Type 1 field isolates were classified as subgroups A, B, and C under subtype 1, while Korean Type 2 field isolates were classified as lineages 1 and 5 as well as three Korean lineages (kor A, B, and C) with the highest infection prevalence in subgroup A (50.5%) and lineage 5 (15.3%) for Type 1 and Type 2 PRRSV, respectively, among ORF5-positive farms. In particular, the lineages kor B and C were identified as novel lineages in this study, and lineage kor B comprised only the field viruses isolated from Gyeongnam Province in 2014-2015, establishing regionally unique genetic characteristics. It has also recently been confirmed that commercialized vaccine-like viruses (subgroup C) of Type 1 PRRSV and NADC30-like viruses of Type 2 PRRSV (lineage 1) are spreading rapidly in Korean swine farms. The Korean field viruses were also expected to be antigenically variable as shown in the high diversity of neutralizing epitopes and N-glycosylation sites. CONCLUSIONS: This up-to-date information regarding recent field PRRSVs should be taken into consideration when creating strategies for the application of PRRS control measures, including vaccination in the field.


Assuntos
Síndrome Respiratória e Reprodutiva Suína/epidemiologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , Sequência de Aminoácidos , Animais , Epitopos , Fazendas , Variação Genética , Tipagem Molecular/veterinária , Fases de Leitura Aberta , Filogenia , Síndrome Respiratória e Reprodutiva Suína/virologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/classificação , Prevalência , República da Coreia/epidemiologia , Suínos
13.
Plant Cell Environ ; 40(7): 997-1008, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28054361

RESUMO

Plants generate rhythmic metabolism during the repetitive day/night cycle. The circadian clock produces internal biological rhythms to synchronize numerous metabolic processes such that they occur at the required time of day. Metabolism conversely influences clock function by controlling circadian period and phase and the expression of core-clock genes. Here, we show that AKIN10, a catalytic subunit of the evolutionarily conserved key energy sensor sucrose non-fermenting 1 (Snf1)-related kinase 1 (SnRK1) complex, plays an important role in the circadian clock. Elevated AKIN10 expression led to delayed peak expression of the circadian clock evening-element GIGANTEA (GI) under diurnal conditions. Moreover, it lengthened clock period specifically under light conditions. Genetic analysis showed that the clock regulator TIME FOR COFFEE (TIC) is required for this effect of AKIN10. Taken together, we propose that AKIN10 conditionally works in a circadian clock input pathway to the circadian oscillator.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Relógios Circadianos/fisiologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas de Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Luz , Mutação , Proteínas Nucleares/genética , Plantas Geneticamente Modificadas , Proteínas Serina-Treonina Quinases/genética
14.
Int J Mol Sci ; 18(3)2017 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-28327532

RESUMO

Soybean-derived isoflavones have been investigated for their preventative effects against UV-induced symptoms of skin damage including wrinkle formation and inflammation. Haematococcus pluvialis is a freshwater species of Chlorophyta that contains high concentrations of the natural carotenoid pigment astaxanthin. Astaxanthin is known to be involved in retinoic acid receptor (RAR) signaling and previously been associated with the inhibition of activator protein (AP)-1 dependent transcription. Based on previous studies, we hypothesized that a combination of soy extract (SE) and Haematococcus extract (HE) may prevent UVB-induced photoaging through specific signaling pathways, as measured by UVB-induced wrinkling on hairless mice skin and expression changes in human dermal fibroblasts (HDFs). The 1:2 ratio of SE and HE mixture (SHM) showed the optimal benefit in vivo. SHM was found to inhibit wrinkle formation via the downregulation of matrix metalloproteinase (MMP)-1 mRNA and protein expression. SHM also inhibited mitogen-activated protein kinase (MAPK) phosphorylation and the transactivation of AP-1 which plays an important role in regulating MMP expression. These results highlight the potential for SHM to be developed as a therapeutic agent to prevent UVB-induced skin wrinkling.


Assuntos
Clorófitas/química , Glycine max/química , Extratos Vegetais/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Envelhecimento da Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Administração Oral , Animais , Senescência Celular/efeitos dos fármacos , Senescência Celular/efeitos da radiação , Colágeno/metabolismo , Epiderme/efeitos dos fármacos , Epiderme/metabolismo , Epiderme/patologia , Epiderme/efeitos da radiação , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 1 da Matriz/metabolismo , Camundongos , Camundongos Nus , Extratos Vegetais/administração & dosagem , Proteólise , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação , Fatores de Tempo , Inibidor Tecidual de Metaloproteinase-1/metabolismo
15.
Environ Sci Technol ; 50(16): 8780-7, 2016 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-27402194

RESUMO

Multilayer heterojunction SbSn/CoTi/Ir anodes, which consist of Ir0.7Ta0.3O2 bottom layers coated onto a titanium base, Co-TiO2 interlayers, and overcoated discrete Sb-SnO2 islands, were prepared by spray pyrolysis. The Ir0.7Ta0.3O2 bottom layer serves as an Ohmic contact to facilitate electron transfer from semiconductor layers to the Ti base. The Co-TiO2 interlayer and overcoated Sb-SnO2 islands enhance the evolution of reactive chlorine. The surficial Sb-SnO2 islands also serve as the reactive sites for free radical generation. Experiments coupled with computational kinetic simulations show that while ·OH and Cl· are initially produced on the SbSn/CoTi/Ir anode surface, the dominant radical formed in solution is the dichlorine radical anion, Cl2·(-). The steady-state concentration of reactive radicals is 10 orders of magnitude lower than that of reactive chlorine. The SbSn/CoTi/Ir anode was applied to electrochemically treat human wastewater. These test results show that COD and NH4(+) can be removed after 2 h of electrolysis with minimal energy consumption (370 kWh/kg COD and 383 kWh/kg NH4(+)). Although free radical species contribute to COD removal, anodes designed to enhance reactive chlorine production are more effective than those designed to enhance free radical production.


Assuntos
Oxirredução , Águas Residuárias/química , Eletrodos , Eletrólise , Titânio/química
16.
J Immunol ; 193(3): 1383-91, 2014 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-24958900

RESUMO

The glycoprotein milk fat globule-epidermal growth factor factor 8 (MFG-E8) is expressed in several tissues and mediates diverse homeostatic functions. However, whether it plays a role in bone homeostasis has not been established. In this study, we show for the first time, to our knowledge, that osteoclasts express and are regulated by MFG-E8. Bone marrow-derived osteoclast precursors from MFG-E8-deficient (Mfge8(-/-)) mice underwent increased receptor activator of NF-κB ligand-induced osteoclastogenesis, leading to enhanced resorption pit formation compared with wild-type controls. Consistently, exogenously added MFG-E8 inhibited receptor activator of NF-κB ligand-induced osteoclastogenesis from mouse or human osteoclast precursors. Upon induction of experimental periodontitis, an oral inflammatory disease characterized by loss of bone support of the dentition, Mfge8(-/-) mice exhibited higher numbers of osteoclasts and more bone loss than did wild-type controls. Accordingly, local microinjection of anti-MFG-E8 mAb exacerbated periodontal bone loss in wild-type mice. Conversely, microinjection of MFG-E8 inhibited bone loss in experimental mouse periodontitis. In comparison with wild-type controls, Mfge8(-/-) mice also experienced >60% more naturally occurring chronic periodontal bone loss. In conclusion, MFG-E8 is a novel homeostatic regulator of osteoclasts that could be exploited therapeutically to treat periodontitis and perhaps other immunological disorders associated with inflammatory bone loss.


Assuntos
Antígenos de Superfície/fisiologia , Reabsorção Óssea/imunologia , Homeostase/imunologia , Mediadores da Inflamação/fisiologia , Osteoclastos/imunologia , Osteoclastos/patologia , Animais , Antígenos de Superfície/biossíntese , Antígenos de Superfície/genética , Reabsorção Óssea/genética , Reabsorção Óssea/patologia , Linhagem Celular , Homeostase/genética , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas do Leite/biossíntese , Proteínas do Leite/genética , Periodontite/genética , Periodontite/imunologia , Periodontite/patologia , Ligante RANK/administração & dosagem , Ligante RANK/efeitos adversos , Células-Tronco/imunologia , Células-Tronco/metabolismo , Células-Tronco/patologia
17.
Plant Cell ; 24(6): 2470-82, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22693280

RESUMO

Plants are confronted with predictable daily biotic and abiotic stresses that result from the day-night cycle. The circadian clock provides an anticipation mechanism to respond to these daily stress signals to increase fitness. Jasmonate (JA) is a phytohormone that mediates various growth and stress responses. Here, we found that the circadian-clock component TIME FOR COFFEE (TIC) acts as a negative factor in the JA-signaling pathway. We showed that the tic mutant is hypersensitive to growth-repressive effects of JA and displays altered JA-regulated gene expression. TIC was found to interact with MYC2, a key transcription factor of JA signaling. From this, we discovered that the circadian clock rhythmically regulates JA signaling. TIC is a key determinant in this circadian-gated process, and as a result, the tic mutant is defective in rhythmic JA responses to pathogen infection. TIC acts here by inhibiting MYC2 protein accumulation and by controlling the transcriptional repression of CORONATINE INSENSITIVE1 in an evening-phase-specific manner. Taken together, we propose that TIC acts as an output component of the circadian oscillator to influence JA signaling directly.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Relógios Circadianos/fisiologia , Ciclopentanos/metabolismo , Proteínas Nucleares/metabolismo , Oxilipinas/metabolismo , Arabidopsis/genética , Arabidopsis/microbiologia , Proteínas de Arabidopsis/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Núcleo Celular/metabolismo , Relógios Circadianos/genética , Regulação da Expressão Gênica de Plantas , Mutação , Proteínas Nucleares/genética , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Raízes de Plantas/crescimento & desenvolvimento , Pseudomonas syringae/patogenicidade , Transdução de Sinais/genética
18.
Plant J ; 76(2): 188-200, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23869666

RESUMO

Plants often respond to environmental changes by reprogramming metabolic and stress-associated pathways. Homeostatic integration of signaling is a central requirement for ensuring metabolic stability in living organisms. Under diurnal conditions, properly timed rhythmic metabolism provides fitness benefits to plants. TIME FOR COFFEE (TIC) is a circadian regulator known to be involved in clock resetting at dawn. Here we explored the mechanism of influence of TIC in plant growth and development, as initiated by a microarray analysis. This global profiling showed that a loss of TIC function causes a major reprogramming of gene expression that predicts numerous developmental, metabolic, and stress-related phenotypes. This led us to demonstrate that this mutant exhibits late flowering, a plastochron defect, and diverse anatomical phenotypes. We further observed a starch-excess phenotype and altered soluble carbohydrate levels. tic exhibited hypersensitivity to oxidative stress and abscisic acid, and this was associated with a striking resistance to drought. These phenotypes were connected to an increase in total glutathione levels that correlated with a readjustment of amino acids and polyamine pools. By comparatively analyzing our transcriptomic and metabolomic data, we concluded that TIC is a central element in plant homeostasis that integrates and coordinates developmental, metabolic, and environmental signals.


Assuntos
Proteínas de Arabidopsis/fisiologia , Arabidopsis/fisiologia , Regulação da Expressão Gênica de Plantas , Proteínas Nucleares/fisiologia , Ácido Abscísico/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Metabolismo dos Carboidratos , Ritmo Circadiano/genética , Glutationa/metabolismo , Homeostase , Metaboloma , Proteínas Nucleares/genética , Estresse Oxidativo , Fenótipo , Estresse Fisiológico , Transcriptoma
19.
Proc Natl Acad Sci U S A ; 108(4): 1729-34, 2011 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-21220341

RESUMO

Phytochromes are red and far-red light photoreceptors that regulate various aspects of plant development. One of the less-understood roles of phytochromes is the inhibition of hypocotyl negative gravitropism, which refers to the loss of hypocotyl gravitropism and resulting random growth direction in red or far-red light. This light response allows seedlings to curve toward blue light after emergence from the soil and enhances seedling establishment in the presence of mulch. Phytochromes inhibit hypocotyl negative gravitropism by inhibiting four phytochrome-interacting factors (PIF1, PIF3, PIF4, PIF5), as shown by hypocotyl agravitropism of dark-grown pif1 pif3 pif4 pif5 quadruple mutants. We show that phytochromes inhibit negative gravitropism by converting starch-filled gravity-sensing endodermal amyloplasts to other plastids with chloroplastic or etioplastic features in red or far-red light, whereas PIFs promote negative gravitropism by inhibiting the conversion of endodermal amyloplasts to etioplasts in the dark. By analyzing transgenic plants expressing PIF1 with an endodermis-specific SCARECROW promoter, we further show that endodermal PIF1 is sufficient to inhibit the conversion of endodermal amyloplasts to etioplasts and hypocotyl negative gravitropism of the pif quadruple mutant in the dark. Although the functions of phytochromes in gravitropism and chloroplast development are normally considered distinct, our results indicate that these two functions are closely related.


Assuntos
Proteínas de Arabidopsis/fisiologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/fisiologia , Gravitropismo/fisiologia , Hipocótilo/crescimento & desenvolvimento , Fitocromo A/fisiologia , Fitocromo B/fisiologia , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/efeitos da radiação , Proteínas de Arabidopsis/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Cloroplastos/metabolismo , Cloroplastos/ultraestrutura , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento/efeitos da radiação , Regulação da Expressão Gênica de Plantas/efeitos da radiação , Gravitropismo/efeitos da radiação , Hipocótilo/genética , Hipocótilo/efeitos da radiação , Microscopia Eletrônica de Transmissão , Mutação , Fitocromo A/genética , Fitocromo B/genética , Plantas Geneticamente Modificadas , Plastídeos/metabolismo , Plastídeos/ultraestrutura , Plântula/genética , Plântula/crescimento & desenvolvimento , Plântula/efeitos da radiação
20.
Risk Manag Healthc Policy ; 17: 715-725, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38559872

RESUMO

Purpose: This study attempted to assess the perceived importance and performance of patient-safety nursing among operating room (OR) nurses and to identify the "concentrate here" level using importance-performance analysis (IPA). The goal was to identify the educational priorities of patient-safety nursing and to use it as foundational data to develop educational programs. Methods: The IPA of patient-safety nursing (infection control, patient identification, specimen management, surgical coefficient, medical equipment and supplies, high-alert medicines, and damage prevention) was surveyed online for nurses in general hospitals in Korea, and the data of 47 participants were analyzed. Differences in the importance and performance of patient-safety nursing were analyzed using Wilcoxon signed rank test, and IPA was conducted to identify areas on which improvement efforts should be focused. Results: Within the six areas of OR patient-safety nursing, notable differences in importance and performance were observed in infection control and surgical count areas. The IPA revealed specific items that require "concentrate here", including handwashing, checking the cleanliness and sterility of medical equipment, and conducting 5-Rights checks before administering high-alert medications. Conclusion: Regular training for OR nurses should encompass preoperative, intraoperative, and postoperative infection control, as well as appropriate surgical counts. In particular, training, monitoring, feedback, and intervention should be provided on hand hygiene, sterilization maintenance, and accurate administration of high-alert medications, which are items included in "concentrate here".

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