Protocol to desensitize human and murine mast cells after polyclonal IgE sensitization.

In this protocol, we provide detailed instructions to desensitize human and murine mast cells (MCs) after polyclonal IgE sensitization. Moreover, we specify the steps for MC degranulation assessment after desensitization, measuring CD63 and CD107a expression by flow cytometry and b-hexosaminidase activity. Desensitized MCs can be used directly for co-culture with other cell types, immunofluorescence, live imaging, and omics approaches.post-print3350 K

Local inflammation enables a basophil-neuronal circuITCH in atopic dermatitis.

post-print1573 K

El flamenco como vehículo comunicativo entre culturas: La imagen del flamenco en la prensa japonesa.

España y Japón son dos países separados por 10.642 kilómetros que poseen un sinfín de diferencias como su lenguaje, sus costumbres o su entorno. Sin embargo, la pasión de la población japonesa por uno de los bienes culturales españoles más conocidos, el flamenco, es latente desde años antes de la dictadura franquista. Este estudio trata de conocer las relaciones entre España y Japón gracias al flamenco y de estudiar cuál es la verdadera relevancia que posee este bien cultural español en el país nipón. Para ello, se va a analizar qué importancia otorga la prensa digital japonesa al flamenco a través de su contenido. <br /

Abordaje fisioterápico en una niña con síndrome de Angelman: a propósito de un caso

Introducción. El síndrome de Angelman es un trastorno del neurodesarrollo que se caracteriza por un retraso psicomotor acompañado de trastornos en el movimiento, un profundo retraso cognitivo con graves dificultades de aprendizaje, habla muy limitada, conducta hiperactiva y risa frecuente, producida por una alteración genética en el que se ve involucrado un cromosoma materno. Objetivos. Los objetivos se centran en estimular el desarrollo psicomotor tratando de conseguir la máxima independencia, evitando a su vez la aparición de deformidades, ayudándose del uso de dispositivos ortopédicos. Metodología. Se aplica un diseño AB longitudinal prospectivo. El sujeto de estudio es una niña de 4 años de edad, diagnosticado de síndrome de Angelman, que se manifiesta clínicamente con retraso psicomotor, inestabilidad en el equilibrio estático y dinámico y alteraciones ortopédicas, afectando a su autonomía. Se realiza una valoración fisioterápica inicial para la consiguiente elaboración del plan de intervención fisioterápico, utilizando distintos dispositivos ortopédicos. Desarrollo. Se aplica el tratamiento fisioterápico 3 veces por semana durante 6 meses, observándose en los resultados de la valoración final una mejoría a nivel motor y cognitivo junto con una mayor autonomía. Conclusiones. A pesar de que los resultados no son generalizables, el plan de intervención fisioterápico propuesto muestra mejoras en la evolución de la paciente, aunque sería conveniente hacer más estudios para encontrar evidencia de otras vías de tratamiento, dado que es un síndrome poco frecuente. Palabras clave: síndrome de Angelman, hiperactividad, dispositivos ortopédicos

The impact of type 2 immunity and allergic diseases in atherosclerosis.

Allergic diseases are allergen-induced immunological disorders characterized by the development of type 2 immunity and IgE responses. The prevalence of allergic diseases has been on the rise alike cardiovascular disease (CVD), which affects arteries of different organs such as the heart, the kidney and the brain. The underlying cause of CVD is often atherosclerosis, a disease distinguished by endothelial dysfunction, fibrofatty material accumulation in the intima of the artery wall, smooth muscle cell proliferation, and Th1 inflammation. The opposed T-cell identity of allergy and atherosclerosis implies an atheroprotective role for Th2 cells by counteracting Th1 responses. Yet, the clinical association between allergic disease and CVD argues against it. Within, we review different phases of allergic pathology, basic immunological mechanisms of atherosclerosis and the clinical association between allergic diseases (particularly asthma, atopic dermatitis, allergic rhinitis and food allergy) and CVD. Then, we discuss putative atherogenic mechanisms of type 2 immunity and allergic inflammation including acute allergic reactions (IgE, IgG1, mast cells, macrophages and allergic mediators such as vasoactive components, growth factors and those derived from the complement, contact and coagulation systems) and late phase inflammation (Th2 cells, eosinophils, type 2 innate-like lymphoid cells, alarmins, IL-4, IL-5, IL-9, IL-13 and IL-17).Severo Ochoa Center of Excellence, Grant/Award Number: CEX2020-001041- S; Pro CNIC Foundation; Ministerio de Ciencia e Innovación; Ministry of Science and Innovation, Grant/ Award Number: PID2019-110369RB- I00; European Commission, Grant/Award Number: ERC-CoG 819775 and H2020-HEALTH 945118; Spanish Ministry of Universities; Ayudas Margarita Salas para la Formación de Jóvenes Doctores—Universidad Autónoma de Madrid, Grant/ Award Number: CA1/RSUE/2021–00577; Formación de Profesorado Universitario, Grant/Award Number: FPU16/03953; Sociedad Española de Alergología e Inmunología Clínica (SEAIC), Grant/ Award Number: BECA20A9; New Frontiers in Research Fund, Grant/ Award Number: NFRFE-2019- 00083; The Nutricia Research Foundation, Grant/Award Number: NRF-2021- 13; Instituto de Salud Carlos III, Grant/Award Number: PI21/00158, PI21/01126, CP20/00043, PI18/01467, PI19/00044, RD16/0006/0015 and RD21/0002/0008; Severo Ochoa Program, Grant/Award Number: AEI/SEV-2017- 0712S

Amyloid β / PKC-dependent alterations in NMDA receptor composition are detected in early stages of Alzheimer´s disease

[EN] Amyloid beta (Abeta)-mediated synapse dysfunction is an early event in Alzheimer's disease (AD) pathogenesis and previous studies suggest that NMDA receptor (NMDAR) dysregulation may contribute to these pathological effects. Although Abeta peptides impair NMDAR expression and activity, the mechanisms mediating these alterations in the early stages of AD are unclear. Here, we observed that NMDAR subunit NR2B and PSD-95 levels were aberrantly upregulated and correlated with Abeta42 load in human postsynaptic fractions of the prefrontal cortex in early stages of AD patients, as well as in the hippocampus of 3xTg-AD mice. Importantly, NR2B and PSD95 dysregulation was revealed by an increased expression of both proteins in Abeta-injected mouse hippocampi. In cultured neurons, Abeta oligomers increased the NR2B-containing NMDAR density in neuronal membranes and the NMDA-induced intracellular Ca2+ increase, in addition to colocalization in dendrites of NR2B subunit and PSD95. Mechanistically, Abeta oligomers required integrin beta1 to promote synaptic location and function of NR2B-containing NMDARs and PSD95 by phosphorylation through classic PKCs. These results provide evidence that Abeta oligomers modify the contribution of NR2B to NMDAR composition and function in the early stages of AD through an integrin beta1 and PKC-dependent pathway. These data reveal a novel role of Abeta oligomers in synaptic dysfunction that may be relevant to early-stage AD pathogenesis.We thank S. Marcos, L. Escobar, A Martínez and Z. Martínez for technical assistance. This study was supported by the Basque Government (IT1203-19; PIBA_2020_1_0012; ELKARTEK KK-2020/00034; fellowship to T.Q-L, U.B. and J.Z-I), University of the Basque Country (UPV/EHU; fellowship to C.O-S) CIBERNED, MICINN (PID2019-108465RB-I00) and Fundación Tatiana Pérez de Guzmán el Bueno (fellowship to C.L)

The impact of type 2 immunity and allergic diseases in atherosclerosis.

Allergic diseases are allergen-induced immunological disorders characterized by the development of type 2 immunity and IgE responses. The prevalence of allergic diseases has been on the rise alike cardiovascular disease (CVD), which affects arteries of different organs such as the heart, the kidney and the brain. The underlying cause of CVD is often atherosclerosis, a disease distinguished by endothelial dysfunction, fibrofatty material accumulation in the intima of the artery wall, smooth muscle cell proliferation, and Th1 inflammation. The opposed T-cell identity of allergy and atherosclerosis implies an atheroprotective role for Th2 cells by counteracting Th1 responses. Yet, the clinical association between allergic disease and CVD argues against it. Within, we review different phases of allergic pathology, basic immunological mechanisms of atherosclerosis and the clinical association between allergic diseases (particularly asthma, atopic dermatitis, allergic rhinitis and food allergy) and CVD. Then, we discuss putative atherogenic mechanisms of type 2 immunity and allergic inflammation including acute allergic reactions (IgE, IgG1, mast cells, macrophages and allergic mediators such as vasoactive components, growth factors and those derived from the complement, contact and coagulation systems) and late phase inflammation (Th2 cells, eosinophils, type 2 innate-like lymphoid cells, alarmins, IL-4, IL-5, IL-9, IL-13 and IL-17).N

Counteracting Quasispecies Adaptability: Extinction of a Ribavirin-Resistant Virus Mutant by an Alternative Mutagenic Treatment

[Background] Lethal mutagenesis, or virus extinction promoted by mutagen-induced elevation of mutation rates of viruses, may meet with the problem of selection of mutagen-resistant variants, as extensively documented for standard, nonmutagenic antiviral inhibitors. Previously, we characterized a mutant of foot-and-mouth disease virus that included in its RNA-dependent RNA polymerase replacement M296I that decreased the sensitivity of the virus to the mutagenic nucleoside analogue ribavirin.[Methodology and Principal Findings] Replacement M296I in the viral polymerase impedes the extinction of the mutant foot-and-mouth disease virus by elevated concentrations of ribavirin. In contrast, wild type virus was extinguished by the same ribavirin treatment and, interestingly, no mutants resistant to ribavirin were selected from the wild type populations. Decreases of infectivity and viral load of the ribavirin-resistant M296I mutant were attained with a combination of the mutagen 5-fluorouracil and the non-mutagenic inhibitor guanidine hydrocloride. However, extinction was achieved with a sequential treatment, first with ribavirin, and then with a minimal dose of 5-fluorouracil in combination with guanidine hydrochloride. Both, wild type and ribavirin-resistant mutant M296I exhibited equal sensitivity to this combination, indicating that replacement M296I in the polymerase did not confer a significant cross-resistance to 5-fluorouracil. We discuss these results in relation to antiviral designs based on lethal mutagenesis[Conclusions] (i) When dominant in the population, a mutation that confers partial resistance to a mutagenic agent can jeopardize virus extinction by elevated doses of the same mutagen. (ii) A wild type virus, subjected to identical high mutagenic treatment, need not select a mutagen-resistant variant, and the population can be extinguished. (iii) Extinction of the mutagen-resistant variant can be achieved by a sequential treatment of a high dose of the same mutagen, followed by a combination of another mutagen with an antiviral inhibitor.Work supported by grants BFU2005-00863, BFU2008-02816/BMC, Proyecto Intramural de Frontera del CSIC 200820FO191, FIPSE 36558/06, and Fundacio´n Ramo´n Areces. CIBERehd is funded by Instituto de Salud Carlos III. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscriptPeer reviewe

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research