Knockdown of MVK does not lead to changes in NALP3 expression or activation

Mutations in the Mevalonate Kinase gene (MVK) are causes of a rare autoinflammatory disease: Mevalonate Kinase Deficiency and its more acute manifestation, Mevalonic Aciduria. The latter is characterized, among other features, by neuroinflammation, developmental delay and ataxia, due to failed cerebellar development or neuronal death through chronic inflammation. Pathogenesis of neuroinflammation in Mevalonate Kinase Deficiency and Mevalonic Aciduria has not yet been completely clarified, however different research groups have been suggesting the inflammasome complex as the key factor in the disease development. A strategy to mimic this disease is blocking the mevalonate pathway, using HMG-CoA reductase inhibitors (Statins), while knock-out mice for Mevalonate Kinase are non-vital and their hemyzygous (i.e only one copy of gene preserved) littermate display almost no pathological features

Advanced OoA and automated technologies for the manufacturing of a composite outer wing box

International audienceThis work resumes the results achieved until today in the European project AirGreen 2 of Clean Sky 2 programme, deriving from the application of two different dry preforming processes for the manufacturing of a composite outer wing box of the next generation turboprop aircrafts. Liquid Resin Infusion and Out of Autoclave techniques, by Hand-Layup and Automated Fiber Placement, are considered. The optimisation and validation of the manufacturing processes have been done according to key performance indexes: weight and cost reduction, lower energy consumption, high productivity and minimal reworking time, less intensive labour, minimal scrap and less waste of materials. The work has been performed through manufacturing tests and optimisation of the process parameters, implementation of several bagging techniques, numerical simulations of the infusion process and material characterization tests in operative conditions, from coupons level up to details and elements level (flat stiffened panels). Pro and cons, suggestions and technical considerations useful for the next step of the project (final manufacturing of large parts and components) are assessed

An alarming deterioration of neurological status

This clinical case should make us reflect on the potential dangers of lithium, often too readily prescribed by non expert physicians to elderly, and often poorly compliant, patients. There also needs to be very close monitoring of plasma lithium levels, in addition to paying attention to clinical signs, such as a persistent polyuria or hyperosmolarity, because these could be important early warning signs. It is therefore useful to reiterate that, in case of lithium intoxication with altered neurological status despite improvement blood tests, it is necessary to consider pontine or extra-pontine myelinolysis as a rare but possible complicatio

Structural Batteries for Aeronautic Applications—State of the Art, Research Gaps and Technology Development Needs

Radical innovations for all aircraft systems and subsystems are needed for realizing future carbon-neutral aircraft, with hybrid-electric aircraft due to be delivered after 2035, initially in the regional aircraft segment of the industry. Electrical energy storage is one key element here, demanding safe, energy-dense, lightweight technologies. Combining load-bearing with energy storage capabilities to create multifunctional structural batteries is a promising way to minimize the detrimental impact of battery weight on the aircraft. However, despite the various concepts developed in recent years, their viability has been demonstrated mostly at the material or coupon level, leaving many open questions concerning their applicability to structural elements of a relevant size for implementation into the airframe. This review aims at providing an overview of recent approaches for structural batteries, assessing their multifunctional performance, and identifying gaps in technology development toward their introduction for commercial aeronautic applications. The main areas where substantial progress needs to be achieved are materials, for better energy storage capabilities; structural integration and aircraft design, for optimizing the mechanical-electrical performance and lifetime; aeronautically compatible manufacturing techniques; and the testing and monitoring of multifunctional structures. Finally, structural batteries will introduce novel aspects to the certification framework

Experimental quantification of genuine four-photon indistinguishability

Photon indistinguishability plays a fundamental role in information processing, with applications such as linear-optical quantum computation and metrology. It is then necessary to develop appropriate tools to quantify the amount of this resource in a multiparticle scenario. Here we report a four-photon experiment in a linear-optical interferometer designed to simultaneously estimate the degree of indistinguishability between three pairs of photons. The interferometer design dispenses with the need of heralding for parametric down-conversion sources, resulting in an efficient and reliable optical scheme. We then use a recently proposed theoretical framework to quantify genuine four-photon indistinguishability, as well as to obtain bounds on three unmeasured two-photon overlaps. Our findings are in high agreement with the theory, and represent a new resource-effective technique for the characterization of multiphoton interference.Comment: 8+8 pages, 5+5 figure

Mast Cells in Peritoneal Fluid From Women With Endometriosis and Their Possible Role in Modulating Sperm Function

Endometriosis is a local pelvic inflammatory process, frequently associated with infertility, with altered function of immune-related cells in the peritoneal environment. Mast cells are known to be key players of the immune system and have been recently involved in endometriosis and in infertility, with their mediators directly suppressing sperm motility. In this study, we evaluated the mast cell population and their mediators in the peritoneal fluid of infertile patients with endometriosis and their impact on human sperm motility. Peritoneal fluids, collected by laparoscopy from 11 infertile patients with endometriosis and 9 fertile controls were evaluated for the presence of mast cells, tryptase levels and their effect on sperm motility. Furthermore, an in vitro model of mast cells-sperm interaction in peritoneal fluid was set up, using LAD2 cell line as a mast cell model, and analyzed from a functional as well as a morphological point of view. Mast cell peritoneal fluid population and its main mediator, tryptase, is more represented in endometriosis confirming an involvement of these cells in this disease. Anyway it appears unlikely that tryptase enriched peritoneal fluid, which fails to inhibit sperm motility, could contribute to endometriosis associated infertility. Despite of this, sperm interaction with the mast cell surface (LAD2) induced a significantly mast cell-degranulation response in the peritoneal fluid from endometriosis which could directly modulate sperm function other than motility. This evidence lead us to suppose that there is, between these elements, an interrelationship which deserves further studies

Statin-induced myotoxicity is exacerbated by aging: A biophysical and molecular biology study in rats treated with atorvastatin

Statin-induced skeletal muscle damage in rats is associated to the reduction of the resting sarcolemmal chloride conductance (gCl) and ClC-1 chloride channel expression. These drugs also affect the ClC-1 regulation by increasing protein kinase C (PKC) activity, which phosphorylate and close the channel. Also the intracellular resting calcium (restCa) level is increased. Similar alterations are observed in skeletal muscles of aged rats, suggesting a higher risk of statin myotoxicity. To verify this hypothesis, we performed a 4–5-weeks atorvastatin treatment of 24-months-old rats to evaluate the ClC-1 channel function by the two-intracellular microelectrodes technique as well as transcript and protein expression of different genes sensitive to statins by quantitative real-time-PCR and western blot analysis. The restCa was measured using FURA-2 imaging, and histological analysis of muscle sections was performed. The results show a marked reduction of resting gCl, in agreement with the reduced ClC-1 mRNA and protein expression in atorvastatin-treated aged rats, with respect to treated adult animals. The observed changes in myocyte-enhancer factor-2 (MEF2) expression may be involved in ClC-1 expression changes. The activity of PKC was also increased and further modulate the gCl in treated aged rats. In parallel, a marked reduction of the expression of glycolytic and mitochondrial enzymes demonstrates an impairment of muscle metabolism. No worsening of restCa or histological features was found in statin-treated aged animals. These findings suggest that a strong reduction of gCl and alteration of muscle metabolism coupled to muscle atrophy may contribute to the increased risk of statin-induced myopathy in the elderly

Refugiados en movimiento : retos políticos, legales y sociales en tiempos de inestabilidad

La conferencia internacional «Refugees on the move: thinking beyong the Euro-Mediterranean crisis» (21 y 22 de abril 2016) que inspira esta publicación, fue organizada gracias a la subvención de la Generalitat de Catalunya, AGAUR, a través el proyecto GRC-SGR 2014 (1524).En el marco del CER-M (UAB-UB), hemos organizado la conferencia internacional «Refugees on the move: thinking beyong the Euro-Mediterranean crisis» celebrada el 21 y 22 de abril 2016 en el CCCB y Espai Contrabandos. Esta conferencia tuvo como objetivo crear un espacio de debate y reflexión en torno a las implicaciones teóricas, político-legales y sociales que estos desplazamientos están conllevando. En el evento participaron académicos de ámbito nacional e internacional, así como personas expertas y profesionales que trabajan sobre el terreno. Fruto de estas jornadas, y a partir de las aportaciones de sus participantes, el equipo del CER-M (UAB-UB) presentamos este monográfico bilingüe.The CER-M (UAB-UB) organised the international conference "Refugees on the move: thinking beyond the Euro-Mediterranean crisis" on the 21st and 22nd of April 2016 at the CCCB and Espai Contrabandos. The conference aimed at creating a space of debate and reflection around the theoretical, political, legal and social implications of these displacements are causing. International and national academics, as well as experts and professionals working in the field participated in the event. As a result of the conference, and based on the contributions of the participants, the CER-M team presents this bilingual monographic

Recurrent, founder and hypomorphic variants contribute to the genetic landscape of Joubert syndrome

Background Joubert syndrome (JS) is a neurodevelopmental ciliopathy characterised by a distinctive mid-hindbrain malformation, the 'molar tooth sign'. Over 40 JS-associated genes are known, accounting for two-thirds of cases.Methods While most variants are novel or extremely rare, we report on 11 recurring variants in seven genes, including three known 'founder variants' in the Ashkenazi Jewish, Hutterite and Finnish populations. We evaluated variant frequencies in similar to 550 European patients with JS and compared them with controls (>15 000 Italian plus gnomAD), and with an independent cohort of similar to 600 JS probands from the USA.Results All variants were markedly enriched in the European JS cohort compared with controls. When comparing allele frequencies in the two JS cohorts, the Ashkenazim founder variant (TMEM216 c.218G>T) was significantly enriched in American compared with European patients with JS, while MKS1 c.1476T>G was about 10 times more frequent among European JS. Frequencies of other variants were comparable in the two cohorts. Genotyping of several markers identified four novel European founder haplotypes. Two recurrent variants (MKS1 c.1476T>G and KIAA0586 c.428delG), have been detected in homozygosity in unaffected individuals, suggesting they could act as hypomorphic variants. However, while fibroblasts from a MKS1 c.1476T>G healthy homozygote showed impaired ability to form primary cilia and mildly reduced ciliary length, ciliary parameters were normal in cells from a KIAA0586 c.428delG healthy homozygote.Conclusion This study contributes to understand the complex genetic landscape of JS, explain its variable prevalence in distinct geographical areas and characterise two recurrent hypomorphic variants

Differentiation of COVID-19 signs and symptoms from allergic rhinitis and common cold : An ARIA-EAACI-GA(2)LEN consensus

Background Although there are many asymptomatic patients, one of the problems of COVID-19 is early recognition of the disease. COVID-19 symptoms are polymorphic and may include upper respiratory symptoms. However, COVID-19 symptoms may be mistaken with the common cold or allergic rhinitis. An ARIA-EAACI study group attempted to differentiate upper respiratory symptoms between the three diseases. Methods A modified Delphi process was used. The ARIA members who were seeing COVID-19 patients were asked to fill in a questionnaire on the upper airway symptoms of COVID-19, common cold and allergic rhinitis. Results Among the 192 ARIA members who were invited to respond to the questionnaire, 89 responded and 87 questionnaires were analysed. The consensus was then reported. A two-way ANOVA revealed significant differences in the symptom intensity between the three diseases (p < .001). Conclusions This modified Delphi approach enabled the differentiation of upper respiratory symptoms between COVID-19, the common cold and allergic rhinitis. An electronic algorithm will be devised using the questionnaire.Peer reviewe