Imaging the complexity, plasticity, and dynamics of caveolae

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Caveolae: Mechanosensing and mechanotransduction devices linking membrane trafficking to mechanoadaptation.

Mechanical forces (extracellular matrix stiffness, vascular shear stress, and muscle stretching) reaching the plasma membrane (PM) determine cell behavior. Caveolae are PM-invaginated nanodomains with specific lipid and protein composition. Being highly abundant in mechanically challenged tissues (muscles, lungs, vessels, and adipose tissues), they protect cells from mechanical stress damage. Caveolae flatten upon increased PM tension, enabling both force sensing and accommodation, critical for cell mechanoprotection and homeostasis. Thus, caveolae are highly plastic, ranging in complexity from flattened membranes to vacuolar invaginations surrounded by caveolae-rosettes-which also contribute to mechanoprotection. Caveolar components crosstalk with mechanotransduction pathways and recent studies show that they translocate from the PM to the nucleus to convey stress information. Furthermore, caveolae components can regulate membrane traffic from/to the PM to adapt to environmental mechanical forces. The interdependence between lipids and caveolae starts to be understood, and the relevance of caveolae-dependent membrane trafficking linked to mechanoadaption to different physiopathological processes is emerging.This study was supported by grants from the Spanish Ministry of Science and Innovation(MICIIN)/Agencia Estatal de Investigación (AEI)/European Regional Development Fund (ERDF/FEDER) “A way to make Europe” – (SAF2014-51876-R, SAF2017-83130-R, IGP-SO grant MINSEV1512-07-2016, CSD2009-0016 and BFU2016-81912-REDC), Comunidad Autónoma de Madrid (Tec4Bio-CM, S2018/NMT¬4443), Fundació La Marató de TV3 (385/C/2019) and the Worldwide Cancer Research Foundation (15-0404), all to M.A.d.P. We received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 641639. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MICIIN) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

Generalized erythematous scaly rash after glucocorticoids

A 65-years-old woman with a medical history of idiopathic throm- bocytopenic purpura and psoriasis in treatment with topical glucocor- ticoids presented with a three-month history of burning, generalized erythematous, scaly rash, and chills. A few weeks before the rash, the patient presented petechiae on her thighs due to a low platelet count (28.000 platelets per microliter), for which she started treatment with prednisone 25 mg/week. The rash was initially treated with topical ointments including clobetasol, urea, salicylic acid, ammonium lactate, and propylene glycol without improvement. The physical examination showed generalized erythroderma (Fig. 1A) from neck to feet (Fig. 1B), with thick silvery desquamation respecting the face and back of the legs (Fig. 1C), involving more than 90% of the patient’s body surface area and erythematous scaly plaques on the scalp. Laboratory test results were normal. A punch biopsy specimen obtained from an arm area showed increased keratinization at the level of the corneal layer with compact parakeratosis with abundant polymorphonuclear cells. The epidermis presented psoriasiform hyperplasia with significant spongio- sis. What is the diagnosis

Mediciones de transitorios durante las maniobras de seccionadores en estaciones transformadoras de 500 KV

La falla o el deterioro dieléctrico de Transformadores de Intensidad (TI) en Estaciones Transformadoras (ET) de 500 kV, motivaron el estudio del tema orientado a medir uno de los tipos de solicitaciones transitorias a las que están sometidos los TI en las playas de las ET. Los transitorios medidos y presentados en el presente trabajo son los que se manifiestan durante la maniobra de apertura y cierre de seccionadores. Para la medición de los transitorios de tensión generados en las barras, se emplearon sensores de campo eléctrico que no requieren ninguna vinculación galvánica con las barras de la ET. Este método de medición resulta innovador, dado que su modalidad de sensado de campo permite compatibilizar el gran ancho de banda de medición requerido, con la contaminación electromagnética existente en la playa de la ET. Además es posible la instalación de los sensores sin producir cortes de energía en la ET. Se midieron los transitorios generados en dos bahías de dos ET. Cada una de las bahías poseía distintos tipos de seccionadores. Dada la versatilidad de los casos en los que se registraron los transitorios de las maniobras de los seccionadores, es posible indicar que se cubrieron los casos usuales en arreglos de 500 kV para interruptor y medio. En los registros fue posible encontrar las características de las solicitaciones que inciden en los TI, representadas por las amplitudes de tensión, tiempos de frente, duración y cantidad de reencendidos de arcos. Conociendo las solicitaciones que se generan en las barras, será posible determinar las corrientes impulsivas que inciden en los TI asociados a la barra. La captación de los transitorios mediante la medición del campo eléctrico generado, ha sido la base que posibilitó obtener, con la apropiada respuesta, el detalle del fenómeno generado por el reencendido de arcos. Tanto los sensores de campo eléctrico, fibras ópticas, transductores y registradores resultan de un reducido tamaño y peso, factores que facilitan su transporte hasta el sitio de uso y su correspondiente instalación. La selección adecuada de los componentes en la construcción de sensores, transductores y otras partes del equipamiento de captación, ha permitido implementar un sistema que registra con 10 MHz de ancho de banda.Instituto de Investigaciones Tecnológicas para Redes y Equipos Eléctricos (IITREE

Mediciones de transitorios durante las maniobras de seccionadores en estaciones transformadoras de 500 KV

La falla o el deterioro dieléctrico de Transformadores de Intensidad (TI) en Estaciones Transformadoras (ET) de 500 kV, motivaron el estudio del tema orientado a medir uno de los tipos de solicitaciones transitorias a las que están sometidos los TI en las playas de las ET. Los transitorios medidos y presentados en el presente trabajo son los que se manifiestan durante la maniobra de apertura y cierre de seccionadores. Para la medición de los transitorios de tensión generados en las barras, se emplearon sensores de campo eléctrico que no requieren ninguna vinculación galvánica con las barras de la ET. Este método de medición resulta innovador, dado que su modalidad de sensado de campo permite compatibilizar el gran ancho de banda de medición requerido, con la contaminación electromagnética existente en la playa de la ET. Además es posible la instalación de los sensores sin producir cortes de energía en la ET. Se midieron los transitorios generados en dos bahías de dos ET. Cada una de las bahías poseía distintos tipos de seccionadores. Dada la versatilidad de los casos en los que se registraron los transitorios de las maniobras de los seccionadores, es posible indicar que se cubrieron los casos usuales en arreglos de 500 kV para interruptor y medio. En los registros fue posible encontrar las características de las solicitaciones que inciden en los TI, representadas por las amplitudes de tensión, tiempos de frente, duración y cantidad de reencendidos de arcos. Conociendo las solicitaciones que se generan en las barras, será posible determinar las corrientes impulsivas que inciden en los TI asociados a la barra. La captación de los transitorios mediante la medición del campo eléctrico generado, ha sido la base que posibilitó obtener, con la apropiada respuesta, el detalle del fenómeno generado por el reencendido de arcos. Tanto los sensores de campo eléctrico, fibras ópticas, transductores y registradores resultan de un reducido tamaño y peso, factores que facilitan su transporte hasta el sitio de uso y su correspondiente instalación. La selección adecuada de los componentes en la construcción de sensores, transductores y otras partes del equipamiento de captación, ha permitido implementar un sistema que registra con 10 MHz de ancho de banda.Instituto de Investigaciones Tecnológicas para Redes y Equipos Eléctricos (IITREE

Regulation of NR4A by nutritional status, gender, postnatal development and hormonal deficiency

The NR4A is a subfamily of the orphan nuclear receptors (NR) superfamily constituted by three well characterized members: Nur77 (NR4A1), Nurr1 (NR4A2) and Nor 1 (NR4A3). They are implicated in numerous biological processes as DNA repair, arteriosclerosis, cell apoptosis, carcinogenesis and metabolism. Several studies have demonstrated the role of this subfamily on glucose metabolism, insulin sensitivity and energy balance. These studies have focused mainly in liver and skeletal muscle. However, its potential role in white adipose tissue (WAT), one of the most important tissues involved in the regulation of energy homeostasis, is not well-studied. The aim of this work was to elucidate the regulation of NR4A in WAT under different physiological and pathophysiological settings involved in energy balance such as fasting, postnatal development, gender, hormonal deficiency and pregnancy. We compared NR4A mRNA expression of Nur77, Nurr1 and Nor 1 and found a clear regulation by nutritional status, since the expression of the 3 isoforms is increased after fasting in a leptin-independent manner and sex steroid hormones also modulate NR4A expression in males and females. Our findings indicate that NR4A are regulated by different physiological and pathophysiological settings known to be associated with marked alterations in glucose metabolism and energy status.This work has been supported by grants from Fondo Investigaciones Sanitarias (ST: PI12/02842), Ministerio de Economia y Competitividad (RN: RYC-2008-02219 and BFU2012-35255; MMM: BFU2010-17116), Xunta de Galicia (ML: 10PXIB208164PR and 2012-CP070; RN: EM 2012/039 and 2012-CP069), Centro de Investigación Biomédica en Red (CIBER) de Fisiopatología de la Obesidad y Nutrición. CIBERobn is an initiative of the Instituto de Salud Carlos III (ISCIII) of Spain which is supported by FEDER funds. The research leading to these results has also received funding from the European Community's Seventh Framework Programme under the following grant: ML and RN: FP7/2007-2013: n° 245009: NeuroFASTS

RGNNV and SJNNV reassortants produce mortality and replicate in gilthead seabream larvae

Nervous Necrosis Virus (NNV) is one of the most challenging pathogens for aquaculture development nowadays, mainly affecting marine teleost fish of major interest to the aquaculture industry and causing great economic losses. NNV consist in four genotypes, which seem to have a tropism for certain teleost fish species. Among them, gilthead seabream (Sparus aurata) has been considered as a non-susceptible species to the disease produced by traditional NNV genotypes. However, there are some evidences that indicate seabream is able to develop the disease in the presence of certain reassortant strains of NNV, called RGNNV/SJNNV, which possesses the RNA1 segment of the RGNNV genotype and the RNA2 segment of the SJNNV genotype, which may cause a new threat to aquaculture. Therefore, the main objective of this study was to evaluate the susceptibility of gilthead seabream larvae to the reassortant strains RGNNV/SJNNV and SJNNV/RGNNV. For this purpose, larvae were exposed to 104 TCDI50/mL in triplicate tanks with the reassortant strains. Samples of 5 individual larvae were collected at different days post-infection and used for gene expression and infective NNV isolation. Our data show that both reassortants produced mortalities, although the RGNNV/SJNNV was the one which produced the highest mortality and viral gene transcription, which significantly increased from 1 to 7 days post-infection. In conclusion, our study demonstrate that seabream larvae are susceptible to both RGNNV/SJNNV and SJNNV/RGNNV reassortants under laboratory conditions. Further studies should be performed to understand the pathogenicity of the NNV reassortant strains to prevent and control future outbreaks in aquaculture farms

Field measurements and modelling of high frequency transients during disconnect switch operations in EHV Substations : Assessment of their effects on Current Transformers

The article describes the complete procedure carried out in order to determine the cause of high levels of gases detected in chromatographic determinations performed in Current Transformers (CT) oil. These analyses of gases are normally included in routine maintenance work. The obtained results could evidence some possible damage in the machine insulation. According to the electrical stresses that Current Transformers are typically subjected to, it was presumed that the cause of the possible damaged could be the high-frequency transients that take place during air disconnect switch operations. Therefore, with the aim of determining the presence of such electrical stress, field measurements were performed. A specially designed measuring system was utilized to accomplish this goal. Taking into account the difficulties normally encountered when measuring currents flowing through Current Transformers to ground, especially in terms of accuracy, it was decided to perform voltage measurements. Then, by determining the real frequency response of the CT in the range of interest, it was possible to achieve such currents by computer simulations. In order to achieve accurate results in the simulations, it was necessary to develop an appropriate electrical model of this type of transformers in the analyzed frequency range. Once the model was carefully adjusted, computer simulations were performed. As a result, both shape and magnitude of such currents were also achieved. Finally, one of the Current Transformers with high levels of gases was taken out of service. Then, it was completely disassembled so as to confirm the suspected damage in the insulation. The results yielded in the inspection of the insulation are commented at the end of this work.Instituto de Investigaciones Tecnológicas para Redes y Equipos Eléctricos (IITREE

Simultaneous multi-frequency observation of the unknown redshift blazar PG1553+113 in March-April 2008

5 páginas, 2 figuras, 3 tablas.-- El Pdf del artículo es la versión pre-print: arXiv: arXiv:0911.1088.-- MAGIC Collaboration: et al.The blazar PG 1553+113 is a well known TeV γ-ray emitter. In this paper we determine its spectral energy distribution through simultaneous multi-frequency data to study its emission processes. An extensive campaign was carried out between March and April 2008, where optical, X-ray, high-energy (HE) γ-ray, and very-high-energy (VHE) γ-ray data were obtained with the KVA, Abastumani, REM, RossiXTE/ASM, AGILE and MAGIC telescopes, respectively. We combine the data to derive the source's spectral energy distribution and interpret its double-peaked shape within the framework of a synchrotron self-Compton model.Major support from Germany’s Bundesministerium f¨ur Bildung, Wissenschaft, Forschung und Technologie and Max-Planck-Gesellschaft, Italy’s Istituto Nazionale di Fisica Nucleare (INFN) and Istituto Nazionale di Astrofisica (INAF), and Spain’s Ministerio de Ciencia e Innovacion is gratefully acknowledged. The work was also supported by Switzerland’s ETH Research grant TH34/043, Poland’s Ministertwo Nauki i Szkolnictwa Wy˙zszego grant N N203 390834, and Germany’s Young Investigator Program of the Helmholtz Gemeinschaft. This work was also supported by Georgian National Science Foundation grant GNSF/ST07/4-180. EP acknowledges support from the Italian Space Agency through grants ASI-INAF I/023/05/0 and ASI I/088/06/0.Peer reviewe