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Somatic cells acclimate to changes in the environment by temporary reprogramming. Much has been learned about transcription factors that induce these cell-state switches in both plants and animals, but how cells rapidly modulate their proteome remains elusive. Here, we show rapid induction of autophagy during temporary reprogramming in plants triggered by phytohormones, immune, and danger signals. Quantitative proteomics following sequential reprogramming revealed that autophagy is required for timely decay of previous cellular states and for tweaking the proteome to acclimate to the new conditions. Signatures of previous cellular programs thus persist in autophagy-deficient cells, affecting cellular decision-making. Concordantly, autophagy-deficient cells fail to acclimatize to dynamic climate changes. Similarly, they have defects in dedifferentiating into pluripotent stem cells, and redifferentiation during organogenesis. These observations indicate that autophagy mediates cell-state switches that underlie somatic cell reprogramming in plants and possibly other organisms, and thereby promotes phenotypic plasticity.
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Arabidopsis/fisiología , Autofagia , Reprogramación Celular , Proteoma , Transducción de Señal , Aclimatación , Arabidopsis/citología , Arabidopsis/inmunología , Fenotipo , Reguladores del Crecimiento de las Plantas/metabolismo , ProteómicaRESUMEN
We explore the emergence and active control of optical bistability in a two-level atom near a graphene sheet. Our theory incorporates self-interaction of the optically driven atom and its coupling to electromagnetic vacuum modes, both of which are sensitive to the electrically tunable interband transition threshold in graphene. We show that electro-optical bistability and hysteresis can manifest in the intensity, spectrum, and quantum statistics of the light emitted by the atom, which undergoes critical slow-down to steady state. The optically driven atom-graphene interaction constitutes a platform for active control of driven atomic systems in coherent quantum control and atomic physics.
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BACKGROUND: Livestock-acquired methicillin-resistant Staphylococcus aureus (LA-MRSA) is a concern in healthcare and a political priority in some countries. OBJECTIVE: This study investigates the net societal costs of 2 alternative strategies for controlling LA-MRSA in Denmark: (1) eradicating LA-MRSA in all pig housing units, and (2) containing LA-MRSA within the units. METHODS: Benefits and costs are considered for affected economic sectors: healthcare, pig production, pig-related industries, and public administration. RESULTS: The cost to society of eradication is estimated at 2.3 to 2.5 billion (present value). Containment will cost 55 to 93 million. For both strategies, the main cost lies in primary pig production-for containment this is mainly due to establishing and operating anterooms and shower rooms, and for eradication it is due to production losses, loss of genetic resources, and costs of cleaning and disinfection. CONCLUSION: Compared with these costs, health economic benefits are moderate for both strategies. Containment is superior to eradication when measured by a benefit-cost ratio.
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Contención de Riesgos Biológicos/veterinaria , Erradicación de la Enfermedad/economía , Costos de la Atención en Salud , Vivienda para Animales , Control de Infecciones/economía , Staphylococcus aureus Resistente a Meticilina/patogenicidad , Infecciones Estafilocócicas/veterinaria , Enfermedades de los Porcinos , Porcinos/microbiología , Zoonosis , Animales , Contención de Riesgos Biológicos/economía , Análisis Costo-Beneficio , Dinamarca , Humanos , Exposición Profesional/economía , Exposición Profesional/prevención & control , Medición de Riesgo , Factores de Riesgo , Infecciones Estafilocócicas/economía , Infecciones Estafilocócicas/prevención & control , Infecciones Estafilocócicas/transmisión , Enfermedades de los Porcinos/economía , Enfermedades de los Porcinos/prevención & control , Enfermedades de los Porcinos/transmisión , Zoonosis/economía , Zoonosis/microbiología , Zoonosis/prevención & controlRESUMEN
Background and purpose - It is well recognized that some knee arthroplasty (KA) patients present with prolonged postoperative inflammation and some develop persistent pain. It can reasonably be speculated that some of these problems develop because of low-grade infections with low virulence bacteria caused by intraoperative contamination. This prospective study was performed to investigate whether intraoperative contamination results in lower patient-reported outcomes (PRO) for patients who were clinically uninfected in the first year after surgery. Patients and methods - We combined data from 2 major prospective studies on patients undergoing primary KA at 2 Danish hospitals between September 2016 and January 2018. Pre- and postoperative (1.5, 3, 6, and 12 months) PROs and intraoperative microbiological cultures were obtained on a total of 714 patients who were included in the study. Based on the microbiological cultures, the patients were divided into 2 groups, contaminated and non-contaminated, and differences in PROs between the 2 groups were analyzed. Results - 84 of 714 (12%) patients were intraoperatively contaminated; none of the 714 patients developed clinical infection. The preoperative Oxford Knee Score was 24 and 23 for contaminated and non-contaminated patients, respectively, improving to 40 and 39 at 1 year (p = 0.8). 1-year AUC for Oxford Knee Score and absolute improvement at each postoperative time point for Forgotten Joint Score and EQ-5D-5L also were similar between contaminated and non-contaminated patients. Interpretation - Patient-reported outcomes from 714 patients do not indicate that intraoperative contamination affects the knee-specific or general health-related quality of life in primary KA patients who are clinically uninfected 1 year after surgery.
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Artroplastia de Reemplazo de Rodilla , Cuidados Intraoperatorios/métodos , Osteoartritis de la Rodilla , Dolor Postoperatorio , Infección de la Herida Quirúrgica/microbiología , Anciano , Artroplastia de Reemplazo de Rodilla/efectos adversos , Artroplastia de Reemplazo de Rodilla/métodos , Bacterias/clasificación , Bacterias/aislamiento & purificación , Estudios de Cohortes , Dinamarca/epidemiología , Femenino , Humanos , Masculino , Técnicas Microbiológicas/métodos , Osteoartritis de la Rodilla/epidemiología , Osteoartritis de la Rodilla/cirugía , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/epidemiología , Dolor Postoperatorio/etiología , Medición de Resultados Informados por el PacienteRESUMEN
MAP kinase (MPK) cascades in Arabidopsis thaliana and other vascular plants are activated by developmental cues, abiotic stress, and pathogen infection. Much less is known of MPK functions in nonvascular land plants such as the moss Physcomitrella patens Here, we provide evidence for a signaling pathway in P. patens required for immunity triggered by pathogen associated molecular patterns (PAMPs). This pathway induces rapid growth inhibition, a novel fluorescence burst, cell wall depositions, and accumulation of defense-related transcripts. Two P. patens MPKs (MPK4a and MPK4b) are phosphorylated and activated in response to PAMPs. This activation in response to the fungal PAMP chitin requires a chitin receptor and one or more MAP kinase kinase kinases and MAP kinase kinases. Knockout lines of MPK4a appear wild type but have increased susceptibility to the pathogenic fungi Botrytis cinerea and Alternaria brassisicola Both PAMPs and osmotic stress activate some of the same MPKs in Arabidopsis. In contrast, abscisic acid treatment or osmotic stress of P. patens does not activate MPK4a or any other MPK, but activates at least one SnRK2 kinase. Signaling via MPK4a may therefore be specific to immunity, and the moss relies on other pathways to respond to osmotic stress.
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Bryopsida/inmunología , Bryopsida/metabolismo , Regulación de la Expresión Génica de las Plantas/fisiología , Inmunidad Innata/fisiología , Alternaria/inmunología , Alternaria/patogenicidad , Arabidopsis/efectos de los fármacos , Arabidopsis/inmunología , Arabidopsis/metabolismo , Arabidopsis/microbiología , Botrytis/inmunología , Botrytis/patogenicidad , Bryopsida/efectos de los fármacos , Bryopsida/microbiología , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Regulación de la Expresión Génica de las Plantas/genética , Inmunidad Innata/genética , Presión Osmótica/efectos de los fármacos , Moléculas de Patrón Molecular Asociado a Patógenos/farmacología , Fosforilación/efectos de los fármacos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMEN
A novel nanoparticulate catalyst of copper (Cu) and ruthenium (Ru) was designed for low-temperature ammonia oxidation at near-stoichiometric mixtures using a bottom-up approach. A synergistic effect of the two metals was found. An optimum CuRu catalyst presents a reaction rate threefold higher than that for Ru and forty-fold higher than that for Cu. X-ray absorption spectroscopy suggests that in the most active catalyst Cu forms one or two monolayer thick patches on Ru and the catalysts are less active once 3D Cu islands form. The good performance of the tuned Cu/Ru catalyst is attributed to changes in the electronic structure, and thus the altered adsorption properties of the surface Cu sites.
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Caries is caused by acid production in biofilms on dental surfaces. Preventing caries therefore involves control of microorganisms and/or the acid produced. Here, calcium-phosphate-osteopontin particles are presented as a new approach to caries control. The particles are made by co-precipitation and designed to bind to bacteria in biofilms, impede biofilm build-up without killing the microflora, and release phosphate ions to buffer bacterial acid production if the pH decreases below 6. Analysis of biofilm formation and pH in a five-species biofilm model for dental caries showed that treatment with particles or pure osteopontin led to less biofilm formation compared to untreated controls or biofilms treated with osteopontin-free particles. The anti-biofilm effect can thus be ascribed to osteopontin. The particles also led to a slower acidification of the biofilm after exposure to glucose, and the pH always remained above 5.5. Hence, calcium-phosphate-osteopontin particles show potential for applications in caries control.
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Fenómenos Fisiológicos Bacterianos/efectos de los fármacos , Biopelículas , Fosfatos de Calcio/farmacología , Caries Dental/prevención & control , Osteopontina/farmacología , Desequilibrio Ácido-Base/metabolismo , Desequilibrio Ácido-Base/prevención & control , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Caries Dental/metabolismo , Caries Dental/microbiología , Combinación de Medicamentos , Humanos , Concentración de Iones de Hidrógeno/efectos de los fármacosRESUMEN
Strontium ranelate (SrR) is a new agent used in the treatment of osteoporosis and is suggested to reduce bone resorption and increase bone formation. We investigated whether SrR influences the macro- and nanomechnical properties of healing fractures in rats. A closed tibia fracture model was used to study fracture healing in rats after 3 and 8 weeks of healing. Two groups of rats were treated with SrR (900 mg/kg/day) mixed into the food, while two groups served as control animals. The healing fractures were investigated by three-point bending, dual energy X-ray absorptiometry, energy-dispersive X-ray spectroscopy (EDX), and nanoindentation. There was a 100-fold increase (P < 0.001) in serum Sr after 3 and 8 weeks of SrR treatment. The callus volume was significantly higher in the SrR-treated group than in control animals (P < 0.01) after 3 weeks of healing. This was accompanied by a significant increase in callus bone mineral content (P < 0.05). However, after 8 weeks of healing, no difference was found in either callus volume or bone mineral content. SrR did not influence maximum load or stiffness of the fractures after either 3 or 8 weeks of healing. EDX showed that Sr was incorporated into the callus; however, this did not influence the nanomechanical properties. In conclusion, SrR stimulates callus formation but has no effect on callus remodeling. Sr is incorporated into the newly formed callus tissue, but this has no deteriorating effect on the mechanical properties of rat tibial fractures at either the macroscopic or nanoscopic level after 3 or 8 weeks of healing.
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Conservadores de la Densidad Ósea/uso terapéutico , Callo Óseo/efectos de los fármacos , Curación de Fractura/efectos de los fármacos , Fracturas Óseas/tratamiento farmacológico , Compuestos Organometálicos/uso terapéutico , Tiofenos/uso terapéutico , Animales , Fenómenos Biomecánicos , Densidad Ósea , Resorción Ósea , Callo Óseo/diagnóstico por imagen , Femenino , Fracturas Óseas/diagnóstico por imagen , Radiografía , Ratas , Ratas Wistar , Tibia/diagnóstico por imagenRESUMEN
This paper investigates how perceived costs and benefits of Salmonella control among Danish pig farmers affect the farmers' choice of action toward reducing the prevalence of Salmonella in their herds. Based on data from an online questionnaire involving 163 Danish pig farmers, we find a considerable uncertainty among pig farmers about the perceived effects of the Salmonella reducing actions. The results indicate large variations in the perceived costs of implementing different types of Salmonella reducing actions (management-, hygiene- and feed-related). For some cases, farmers associate net benefits and positive productivity effects with implementation of the actions while studies by the industry indicate net costs to the farmers. Differences among farmers support the idea of an outcome-based Salmonella penalty scheme but the large uncertainties about costs and effects of actions toward Salmonella control might hamper the effectiveness of such a penalty scheme as a regulatory instrument to affect farmer behavior.
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On the basis of computational design, a focused one-bead one-compound library has been prepared on microparticle-encoded PEGA1900 beads consisting of small tripeptides with a triazole-capped N-terminal. The library was screened towards a double point-mutated version of the human FKBP12 protein, known as the destabilizing domain (DD). Inspired by the decoded library hits, unnatural peptide structures were screened in a novel on-bead assay, which was useful for a rapid structure evaluation prior to off-bead resynthesis. Subsequently, a series of 19 compounds were prepared and tested using a competitive fluorescence polarization assay, which led to the discovery of peptide ligands with low micromolar binding affinity towards the DD. The methodology represents a rapid approach for identification of a novel structure scaffold, where the screening and initial structure refinement was accomplished using small quantities of library building blocks.
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Técnicas Químicas Combinatorias , Péptidos/química , Proteína 1A de Unión a Tacrolimus/química , Sitios de Unión , Humanos , Modelos Moleculares , Estructura MolecularRESUMEN
The assays described here are pertinent to protein kinase studies in any plant. They include an immunoblot phosphorylation/activation assay and an in-gel activity assay for MAP kinases (MPKs) using the general protein kinase substrate myelin basic protein. They also include a novel in-gel peptide substrate assay for Snf1-related kinase family 2 members (SnRK2s). This kinase family-specific assay overcomes some limitations of in-gel assays and permits the identification of different types of kinase activities in total protein extracts.
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Quitina/farmacología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Proteína Básica de Mielina/metabolismo , Plantas/efectos de los fármacos , Activación Enzimática , Immunoblotting , Fosforilación , Proteínas de Plantas/metabolismo , Plantas/enzimología , Estrés Fisiológico , Especificidad por SustratoRESUMEN
Anodic bonding of silicon to glass always involves heating the glass and device to high temperatures so that cations become mobile in the electric field. We present a simple way of bonding thin silicon samples to borosilicate glass by means of heating from the glass side while locally cooling heat-sensitive areas from the silicon side. Despite the high thermal conductivity of silicon, this method allows a strong anodic bond to form just millimeters away from areas essentially at room temperature.
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A novel microfabricated chemical reactor for highly sensitive measurements of catalytic activity and surface kinetics is presented. The reactor is fabricated in a silicon chip and is intended for gas-phase reactions at pressures ranging from 0.1 to 5.0 bar. A high sensitivity is obtained by directing the entire gas flow through the catalyst bed to a mass spectrometer, thus ensuring that nearly all reaction products are present in the analyzed gas flow. Although the device can be employed for testing a wide range of catalysts, the primary aim of the design is to allow characterization of model catalysts which can only be obtained in small quantities. Such measurements are of significant fundamental interest but are challenging because of the low surface areas involved. The relationship between the reaction zone gas flow and the pressure in the reaction zone is investigated experimentally. A corresponding theoretical model is presented, and the gas flow through an on-chip flow-limiting capillary is predicted to be in the intermediate regime. The experimental data for the gas flow are found to be in good agreement with the theoretical model. At typical experimental conditions, the total gas flow through the reaction zone is around 3x10(14) molecules s(-1), corresponding to a gas residence time in the reaction zone of about 11 s. To demonstrate the operation of the microreactor, CO oxidation on low-area platinum thin film circles is employed as a test reaction. Using temperature ramping, it is found that platinum catalysts with areas as small as 15 microm(2) are conveniently characterized with the device.