Visualizing cellular heterogeneity by quantifying the dynamics of MAPK activity in live mammalian cells with synthetic fluorescent biosensors.

Mitogen-Activated Protein Kinases (MAPKs) control a wide array of cellular functions by transducing extracellular information into defined biological responses. In order to understand how these pathways are regulated, dynamic single cell measurements are highly needed. Fluorescence microscopy is well suited to perform these measurements. However, more dynamic and sensitive biosensors that allow the quantification of signaling activity in living mammalian cells are required. We have engineered a synthetic fluorescent substrate for human MAPKs (ERK, JNK and p38) that relocates from the nucleus to the cytoplasm when phosphorylated by the kinases. We demonstrate that this reporter displays an improved response compared to other relocation biosensors. This assay allows to monitor the heterogeneity in the MAPK response in a population of isogenic cells, revealing pulses of ERK activity upon a physiological EGFR stimulation. We show applicability of this approach to the analysis of multiple cancer cell lines and primary cells as well as its application in vivo to developing tumors. Using this ERK biosensor, dynamic single cell measurements with high temporal resolution can be obtained. These MAPK reporters can be widely applied to the analysis of molecular mechanisms of MAPK signaling in healthy and diseased state, in cell culture assays or in vivo

Assessment of the fiscal stance appropriate for the euro area in 2019

On 18 June 2018, the European Fiscal Board (EFB) has published its assessment of the general orientation of fiscal policy in the euro area. The report concludes that the favourable economic outlook offers a prime opportunity to rebuild fiscal buffers. Especially euro area Member States with a high government debt-to-GDP ratio need to do more than simply accrue the budgetary benefits of the economic expansion. Lest we repeat the mistakes of the past and rob ourselves of room to manoeuvre when the next crisis hits, this is the time to move towards a somewhat restrictive orientation of fiscal policy in the euro area. It is also the time to upgrade the EU's fiscal framework and prepare a capacity for joint stabilisation for the euro area

Role of magnetic dopants in the phase diagram of Sm1111 pnictides: The Mn case

The deliberate insertion of magnetic Mn dopants in the Fe sites of the optimally-doped SmFeAsO0.88-F0.12 iron-based superconductor can modify in a controlled way its electronic properties. The resulting phase diagram was investigated across a wide range of manganese contents (x) by means of muon-spin spectroscopy (muSR), both in zero- and in transverse fields, respectively, to probe the magnetic and the superconducting order. The pure superconducting phase (at x < 0.03) is replaced by a crossover region at intermediate Mn values (0.03 =< x < 0.08), where superconductivity coexists with static magnetic order. After completely suppressing superconductivity for x = 0.08, a further increase in Mn content reinforces the natural tendency towards antiferromagnetic correlations among the magnetic Mn ions. The sharp drop of Tc and the induced magnetic order in the presence of magnetic disorder/dopants, such as Mn, are both consistent with a recent theoretical model of unconventional superconductors [M. Gastiasoro et al., ArXiv 1606.09495], which includes correlation-enhanced RKKY-couplings between the impurity moments.Comment: 10 pages, 13 figures. Accepted on Physical Review

Primary Subcutaneous B-cell Lymphoma : Case Report and Literature Review

Primary cutaneous B-cell lymphomas are defined as malignant B-cell proliferations presenting with cutaneous involvement alone and no evidence of extracutaneous manifestations when complete staging has been performed. It has been shown that the infiltrate in some cases could involve the underlying subcutaneous tissues, but primary localization in this compartment has been rarely reported. We describe here the case of a 53-year-old woman who noticed a nodular lesion on the left shoulder that rapidly enlarged in a few months. The histological and immunophenotypical features were compatible with a subcutaneous B-cell lymphoma. The tumoural mass was confined predominantly to the subcutaneous compartment, as confirmed by computed tomography. No other tumour localizations were found. Thus, primary B-cell lymphoma of the subcutis was diagnosed. We report a review of the literature indicating that B-cell lymphomas that are primarily localized to the subcutaneous tissue represent a very rare modality of presentation with a biological behaviour different from conventional cutaneous B-cell lymphoma

primary cutaneous cd30 anaplastic large cell lymphoma in a heart transplant patient case report and literature review

Solid organ transplant recipients are at risk of develop ing a wide range of viral-associated malignancies, in cluding skin tumours and lymphoproliferative disorders. The risk of a post-transplant lymphoproliferative disorder is 28–49 times the risk of a lymphoproliferative disorder in the normal population. Most cases are of B-cell phenotype and are associated with Epstein-Barr virus infection. Post-transplant lymphoproliferative disorders presenting clinically in the skin are rare and usually of B-cell phenotype. Only rare cases of cutaneous T-cell post-transplant lymphoproliferative disorder have been reported previously, mostly mycosis fungoides type. We describe here a rare primary cutaneous T-cell lymphoma CD30+ arising in a heart transplant patient who had a nodule on the right leg, several years after heart transplantation. The morphology and immunohistochemical findings were consistent with a CD30+ anaplastic large cell lymphoma with a T-cell phenotype. Excisional biopsy and radiotherapy of the affected area were performed. In this patient, the presence of a solitary lesion and th

Experimental and numerical analysis of a CO2 dual-source heat pump with PVT evaporators for residential heating applications

Multi-source energy systems are a promising solution to lower the environmental impact of the heating and cooling sector and enhance the exploitation of renewable energy sources. In this context, dual-source solar-assisted heat pumps exploit solar energy and air as the low-temperature heat sources. However, the efficiency of solar-based systems is strictly related to weather conditions, location, and time. Therefore, there is a need for accurate models to be used in dynamic simulations of these systems and perform detailed performance analyses and study the involved energy flows. This paper presents an experimental and numerical investigation of a direct-expansion solar-assisted heat pump (DX-SAHP) operating with CO2 as the refrigerant. The heat pump prototype can work with an air-finned coil heat exchanger or photovoltaic-thermal (PVT) solar collectors as the evaporator. The solar-mode configuration allows the exploitation of the heat from solar radiation to evaporate the refrigerant and to improve the photovoltaic electricity production due to the cooling of the cells up to 8%. A numerical heat pump model, integrated with novel gas-cooler and PVT collectors models, has been developed and implemented as a TRNSYS type for dynamic simulations of the system. The model has been validated with continuous measurements during the heat pump operation in solar and air modes. The proposed model can be used for performing seasonal simulations of a heat pump operating with a transcritical CO2 cycle. Moreover, the outcomes of the analysis show how the configuration of a CO2 heat pump with a direct-expansion air-finned coil heat exchanger or PVT can be used to enhance the performance of the heat pump and increase the electrical efficiency of the photovoltaic cells