The novel missense mutation Met48Lys in FKBP22 changes its structure and functions.

Mutations in the FKBP14 gene encoding FKBP22 (FK506 Binding Protein 22 kDa) cause kyphoscoliotic Ehlers-Danlos Syndrome (kEDS). The first clinical report showed that a lack of FKBP22 protein due to mutations causing nonsense-mediated decay of the mRNA leads to a wide spectrum of clinical phenotypes including progressive kyphoscoliosis, joint hypermobility, hypotonia, hyperelastic skin, hearing loss and aortic rupture. Our previous work showed that these phenotypic features could be correlated with the functions of FKBP22, which preferentially binds to type III, VI and X collagens, but not to type I, II or V collagens. We also showed that FKBP22 catalyzed the folding of type III collagen through its prolyl isomerase activity and acted as a molecular chaperone for type III collagen. Recently, a novel missense mutation Met48Lys in FKBP22 was identified in a patient with kEDS. In this report, we expand the list of substrates of FKBP22 and also demonstrate that the Met48Lys mutation diminishes the activities of FKBP22, indicating that pathology can arise from absence of FKBP22, or partial loss of its function

Xenon Upregulates Hypoxia Inducible Factor 1 Alpha in Neonatal Rat Brain under Normoxic Conditions

Xenon can induce cell and organ protection through different molecular mechanisms related to oxygen level. We explored the effect of xenon on oxygen-related signalling in the central nervous system via hypoxia inducible factor 1 alpha (HIF-1α) and mammalian target of rapamycin (mTOR). Methods. Postnatal day 7 (P7) Sprague Dawley rats were exposed to 25% oxygen/75% nitrogen (air group) or 25% oxygen/75% xenon (treatment group) for 120 min. Brains were collected immediately (transcript analysis—relative real-time polymerase chain reaction) or 24 hours (protein analysis—immunohistochemistry) after the 120-minute exposure period; peak anesthetic preconditioning has been previously identified at 24 hours post-exposure. Results. HIF-1α transcript and protein levels were found to be increased in xenon-exposed compared to air-exposed brains. Sustained nuclear translocation of the protein, accounting for an increased activity of HIF-1α, was also noted. mTOR transcript analysis revealed no significant difference between xenon-exposed and air-exposed brains immediately after the 120-minute exposure. Conclusion. Our data suggest that xenon induces the upregulation of HIF-1α transcription and translation, which may contribute to xenon's neuroprotective preconditioning effect. However, given that xenon exposure did not affect mTOR transcription, further investigation into other signalling cascades mediating xenon's effects on HIF-1α in developing brain is warranted

UN NUEVO HORIZONTE PARA MEDICIONES BIOLÓGICAS PRECISAS Y DE ALTA EXACTITUD

Thinking of metrology as part of biotechnology can be unimaginable. However, in the last 25 years a group of scientists have been working on it and a new concept is gaining popularity among the scientific community: biometrology. For this reason, this publication aims to bring the reader closer to the scientific background on the science of measurement applied to biotechnology. A brief introduction to the topic will be made, addressing it with examples of its different applications to end with the presentation of a definition focused on the life sciences

Xenon Upregulates Hypoxia Inducible Factor 1 Alpha in Neonatal Rat Brain under Normoxic Conditions

Xenon can induce cell and organ protection through different molecular mechanisms related to oxygen level. We explored the effect of xenon on oxygen-related signalling in the central nervous system via hypoxia inducible factor 1 alpha (HIF-1α) and mammalian target of rapamycin (mTOR). Methods. Postnatal day 7 (P7) Sprague Dawley rats were exposed to 25% oxygen/75% nitrogen (air group) or 25% oxygen/75% xenon (treatment group) for 120 min. Brains were collected immediately (transcript analysis—relative real-time polymerase chain reaction) or 24 hours (protein analysis—immunohistochemistry) after the 120-minute exposure period; peak anesthetic preconditioning has been previously identified at 24 hours post-exposure. Results. HIF-1α transcript and protein levels were found to be increased in xenon-exposed compared to air-exposed brains. Sustained nuclear translocation of the protein, accounting for an increased activity of HIF-1α, was also noted. mTOR transcript analysis revealed no significant difference between xenon-exposed and air-exposed brains immediately after the 120-minute exposure. Conclusion. Our data suggest that xenon induces the upregulation of HIF-1α transcription and translation, which may contribute to xenon's neuroprotective preconditioning effect. However, given that xenon exposure did not affect mTOR transcription, further investigation into other signalling cascades mediating xenon's effects on HIF-1α in developing brain is warranted

Adjuvant Treatment in Pancreatic Cancer: Shaping the Future of the Curative Setting

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease even in the early stages, despite progresses in surgical and pharmacological treatment in recent years. High potential for metastases is the main cause of therapeutic failure in localized disease, highlighting the current limited knowledge of underlying pathological processes. However, nowadays research is focusing on the search for personalized approaches also in the adjuvant setting for PDAC, by implementing the use of biomarkers and investigating new therapeutic targets. In this context, the aim of this narrative review is to summarize the current treatment scenario and new potential therapeutic approaches in early stage PDAC, from both a preclinical and clinical point of view. Additionally, the review examines the role of target therapies in localized PDAC and the influence of neoadjuvant treatments on survival outcomes

Sensibilidade de parâmetros de um modelo de cálculo para a simulação do ambiente acústico urbano

The applicability of the French model NMPB Routes 2008 for the simulation of the urban environmental noise in a Brazilian city is brought up in this paper, considering an analysis of the model sensitivity to the input parameters. For this purpose the calculation model is applied in an urban zone of the city of São Carlos - SP, by means of the software Cadna-A. The analysis compared field data and simulated data. Additionally simulations were processed, changing some input data configuration. The parameters verified with the sensitivity analysis were the meteorological conditions, the duration of the period of vehicular flow collection, the percentage of motorcycles in fields of light vehicles and heavy vehicles, the vehicular speed, the pavement type, the road declivity and direction of vehicular flow, the heights of the buildings and of receptors, the sound source type, and the quantity of sound sources per road. But for the meteorological conditions, the results proved that the model is sensible to the most part of the analyzed parameters. There is, however, an indication that some input fields could be adjusted to precisely fit to real data.A aplicabilidade do modelo de cálculo francês NMPB Routes 2008 para simulação do ruído ambiental urbano em uma cidade brasileira é abordada nesse artigo, considerando-se uma análise da sua sensibilidade aos parâmetros de entrada. Para isso o modelo de cálculo é aplicado em uma fração urbana da cidade de São Carlos - SP, através do programa computacional Cadna-A. A análise comparou dados de campo e dados simulados, além de serem realizadas simulações promovendo-se alterações nas configurações dos dados de entrada. Os parâmetros verificados com a análise de sensibilidade foram as condições meteorológicas, a duração do tempo de amostra do fluxo de veículos, a porcentagem de motocicletas em campos destinados ao número de veículos leves ou de veículos pesados, a velocidade dos veículos, o tipo de pavimentação, a declividade da via e a direção de fluxo de veículos, as alturas dos edifícios e as alturas de receptores, o tipo de fonte sonora e a quantidade de fontes sonoras inseridas por vias. Com exceção das condições meteorológicas, os resultados apontaram que o modelo, de uma forma geral, é sensível à maioria dos parâmetros analisados. Observou-se, no entanto, que alguns campos podem ser ajustados para que a simulação seja mais fidedigna aos dados reais.Palavras-Chave: simulação acústica, mapeamento de ruído, parâmetros acústicos, conforto acústico

The Diagnostic Potential of Transition Region Lines under-going Transient Ionization in Dynamic Events

We discuss the diagnostic potential of high cadence ultraviolet spectral data when transient ionization is considered. For this we use high cadence UV spectra taken during the impulsive phase of a solar flares (observed with instruments on-board the Solar Maximum Mission) which showed excellent correspondence with hard X-ray pulses. The ionization fraction of the transition region ion O V and in particular the contribution function for the O V 1371A line are computed within the Atomic Data and Analysis Structure, which is a collection of fundamental and derived atomic data and codes which manipulate them. Due to transient ionization, the O V 1371A line is enhanced in the first fraction of a second with the peak in the line contribution function occurring initially at a higher electron temperature than in ionization equilibrium. The rise time and enhancement factor depend mostly on the electron density. The fractional increase in the O V 1371A emissivity due to transient ionization can reach a factor of 2--4 and can explain the fast response in the line flux of transition regions ions during the impulsive phase of flares solely as a result of transient ionization. This technique can be used to diagnostic the electron temperature and density of solar flares observed with the forth-coming Interface Region Imaging Spectrograph.Comment: 18 pages, 6 figure

The Productivity of Italian Industrial Suppliers (1998-2006). Does Participation in Global Value Chains Matter?

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Ferromagnetism in Oriented Graphite Samples

We have studied the magnetization of various, well characterized samples of highly oriented pyrolitic graphite (HOPG), Kish graphite and natural graphite to investigate the recently reported ferromagnetic-like signal and its possible relation to ferromagnetic impurities. The magnetization results obtained for HOPG samples for applied fields parallel to the graphene layers - to minimize the diamagnetic background - show no correlation with the magnetic impurity concentration. Our overall results suggest an intrinsic origin for the ferromagnetism found in graphite. We discuss possible origins of the ferromagnetic signal.Comment: 11 figure