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Inborn errors of OAS–RNase L in SARS-CoV-2–related multisystem inflammatory syndrome in children
No full textMultisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)–sensing OAS1 and OAS2 generate 2′-5′-linked oligoadenylates (2-5A) that activate the single-stranded RNA–degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L–deficient cells. Cytokine production in RNase L–deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS–RNase L deficiencies in these patients unleash the production of SARS-CoV-2–triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C.The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364 and R21AI160576), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1TR001866), the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the Yale High-Performance Computing Center (S10OD018521), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JBP Foundation, the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the ANR GenMISC (ANR-21-COVR-039), the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003) and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the ANR-RHU program (ANR-21-RHUS-08), the European Union’s Horizon 2020 research and innovation program under grant agreement 824110 (EASI-genomics), the HORIZON-HLTH-2021-DISEASE-04 program under grant agreement 01057100 (UNDINE), the ANR-RHU Program ANR-21-RHUS-08 (COVIFERON), the Square Foundation, Grandir – Fonds de solidarité pour l’enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, the French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), and Paris Cité University. We acknowledge support from the National Institute of Allergy and Infectious Diseases (NIAID) of the NIH under award R01AI104887 to R.H.S. and S.R.W. The Laboratory of Human Evolutionary Genetics (Institut Pasteur) is supported by the Institut Pasteur, the Collège de France, the French Government’s Investissement d’Avenir program, Laboratoires d’Excellence “Integrative Biology of Emerging Infectious Diseases” (ANR-10-LABX-62-IBEID) and “Milieu Intérieur” (ANR-10-LABX-69-01), the Fondation de France (no. 00106080), the FRM (Equipe FRM DEQ20180339214 team), and the ANR COVID-19-POPCELL (ANR-21-CO14-0003-01). A.Puj. is supported by ACCI20-759 CIBERER, EasiGenomics H2020 Marató TV3 COVID 2021-31-33, the HORIZON-HLTH-2021-ID: 101057100 (UNDINE), the Horizon 2020 program under grant no. 824110 (EasiGenomics grant no. COVID-19/PID12342), and the CERCA Program/Generalitat de Catalunya. The Canarian Health System sequencing hub was funded by the Instituto de Salud Carlos III (COV20_01333 and COV20_01334), the Spanish Ministry of Science and Innovation (RTC-2017-6471-1; AEI/FEDER, UE), Fundación MAPFRE Guanarteme (OA21/131), and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). The CoV-Contact Cohort was funded by the French Ministry of Health and the European Commission (RECOVER project). Our studies are also funded by the Ministry of Health of the Czech Republic Conceptual Development of Research Organization (FNBr, 65269705) and ANID COVID0999 funding in Chile. G. Novelli and A. Novelli are supported by Regione Lazio (Research Group Projects 2020) No. A0375-2020-36663, GecoBiomark. A.M.P., M.L.D., and J.P.-T. are supported by the Inmungen-CoV2 project of CSIC. This work was supported in part by the Intramural Research Program of the NIAID, NIH. The research work of A.M.P, M.L.D., and J.P.-T. was funded by the European Commission –NextGenerationEU (Regulation EU 2020/2094), through CSIC’s Global Health Platform (PTI Salud Global). I.M. is a senior clinical investigator at FWO Vlaanderen supported by a VIB GC PID grant, by FWO grants G0B5120N (DADA2) and G0E8420N, and by the Jeffrey Modell Foundation. I.M. holds an ERC-StG MORE2ADA2 grant and is also supported by ERN-RITA. A.Y. is supported by fellowships from the European Academy of Dermatology and Venereology and the Swiss National Science Foundation and by an Early Career Award from the Thrasher Research Fund. Y.-H.C. is supported by an A*STAR International Fellowship (AIF). M.O. was supported by the David Rockefeller Graduate Program, the New York Hideyo Noguchi Memorial Society (HNMS), the Funai Foundation for Information Technology (FFIT), the Honjo International Scholarship Foundation (HISF), and the National Cancer Institute (NCI) F99 Award (F99CA274708). A.A.A. was supported by Ministerio de Ciencia Tecnología e Innovación MINCIENCIAS, Colombia (111584467551/CT 415-2020). D.L. is supported by a fellowship from the FRM for medical residents and fellows. E.H. received funding from the Bank of Montreal Chair of Pediatric Immunology, Foundation of CHU Sainte-Justine, CIHR grants PCC-466901 and MM1-181123, and a Canadian Pediatric Society IMPACT study. Q.P.-H. received funding from the European Union’s Horizon 2020 research and innovation program (ATAC, 101003650), the Swedish Research Council, and the Knut and Alice Wallenberg Foundation. Work in the Laboratory of Virology and Infectious Disease was supported by NIH grants P01AI138398-S1, 2U19AI111825, R01AI091707-10S1, and R01AI161444; a George Mason University Fast Grant; the G. Harold and Leila Y. Mathers Charitable Foundation; the Meyer Foundation; and the Bawd Foundation. R.P.L. is on the board of directors of both Roche and the Roche subsidiary Genentech. J.L.P. was supported by a Francois Wallace Monahan Postdoctoral Fellowship at the Rockefeller University and by a European Molecular Biology Organization Long-Term Fellowship (ALTF 380-2018)
The Current Mental Health of Healthcare Workers 3 Years After the Start of the Pandemic: The Relationship Between Coping Strategies and Indices of Mental Health
No full textHealthcare workers have been a vulnerable group during the pandemic. Even today, they continue to deal with the virus and its consequences. Such sustained stress over time has led to the development of mental health problems that may still be present in this population. These may be related to the coping strategies that are being implemented to manage this situation. This study aimed to examine the mental health of health professionals after the end of the acute phase of the pandemic and investigate which coping strategies predicted levels of stress, anxiety, depression, and burnout. A total of 285 healthcare workers were assessed. Descriptive and multiple regression analyses were performed. The result showed (a) levels of mild-to-moderate depressive symptomatology, moderate levels of stress and anxiety symptomatology, and a medium level of burnout; and (b) acceptance, behavioral disengagement, negation, substance use, and active coping as the strategies most implicated in this symptomatology. Interventions that help health professionals to develop adaptive coping strategies, thus avoiding or reducing the development of psychological symptoms, should be implemented
Identificación de factores que favorecen el rendimiento académico
No full textMejorar la calidad en la educación superior requiere prestar atención a las necesidades específicas.
Este trabajo pretende analizar la percepción de la población universitaria en general y de los estudiantes
con mayores dificultades, sobre los factores que influyen en el aprendizaje y definir mejoras a
realizar en el sistema universitario para reducir el abandono. Identificar las variables que interactúan
y proporcionan información, puede ayudar a incrementar los resultados académicos de los estudiantes
y la calidad de la educación superior. La Unidad de Atención a la Diversidad de la Universidad
pone en marcha en el segundo semestre un curso dirigido a grupos de 15 estudiantes. Previamente a
la formación se les aplica un cuestionario ad-hoc que recoge datos personales, académicos y de rendimiento.
El análisis descriptivo de los datos resalta que el factor más influyente en el aprendizaje,
según la percepción de los estudiantes, es el método de estudio (M=2,27; DT=,594) y el que menos
la asistencia a clase (M=1,47; DT=,743). Este análisis proporciona información sobre la necesidad
de entrenar en competencias encaminadas a mejorar la autoestima y las estrategias del alumnado que
ayuden a afrontar con éxito el esfuerzo y la dificultad. Se propone aplicar programas bien diseñados
metodológicamente que sean efectivos, en la mejora del desempeño académico y permitan alcanzar
un modelo de educación superior inclusivo de calidad
An approach to the predator-prey power law in past ecosystems and the reconstruction of early human populations in Western Europe
Get PDFPóster presentado en XXI Congress of the International Union for Quaternary Research (XXI INQUA) celebrado durante los días 13 y 20 de julio de 2023, en Roma (Italia).Knowing the characteristics of past ecosystems is of great
interest because it allows us to gain deeper insights into how
species evolved and what parameters may have conditioned
them. We developed a paleosynecological model (PSEco) that
estimates the production of meat from prey mammals and the
densities and biomasses of secondary consumers that could
sustain these resources.Funding for this research has been provided by the Spanish Ministry of Science, Innovation and University (Refs.: CGL2016-78577-P, CGL2016- 80975-P, PGC2018-093925-B-C31, PGC2018-093925-B-C33, PID2019-111185GB-I00, PID2021-122355NB-C31), the Junta de Andalucía (Refs: UMA18-FEDERJA-188, P18-FR-3193), the Generalitat de Catalunya (Ref.: GENCAT 2017SGR 859) and by the research group RNM-146 of the Junta de Andalucía. This research has been authorized by the Consejería de Cultura of the Junta de Andalucía. G. Rodríguez-Gómez is enjoying a postdoctoral contract "Atracción de Talento de la Comunidad de Madrid" (Ref. 2019-T2 / HUM-13370) co-funded by the Comunidad de Madrid and the Universidad Complutense de Madrid. This work has also been supported by the Madrid Government (Comunidad de Madrid-Spain) under the Multiannual Agreement with Universidad Complutense de Madrid in the line Research Incentive for Young PhDs, in the context of the V PRICIT (Regional Programme of Research and Technological Innovation) (Ref. PR27/21-004). AG enjoys a FPI predoctoral Grant from the Spanish Ministry of Science, Innovation and University
Mujeres, arte y patrimonio: hilos de oro en el lienzo del tiempo
Get PDFMujeres, arte y patrimonio es el fruto de la colaboración de un amplio elenco de especialistas que ofrecen, desde una perspectiva multifocal y diacrónica, su particular análisis, tan inquisitivo y sagaz como sutil y delicado, sobre las relaciones de las mujeres con el arte y la cultura, desde la Edad Media hasta la contemporaneidad. Se encadenan a lo largo de estas páginas estudios que ahondan en los intereses, anhelos y gustos de mujeres que, a través de su promoción, contribuyeron a configurar su identidad y la de sus familias; sin olvidar, entre otros aspectos, su responsabilidad al frente de talleres escultóricos o su papel en las sociedades artísticas, incluso su habilidad y determinación en la conservación de patrimonios imprescindibles, aunque casi olvidados, según sucede con las manifestaciones artísticas atesoradas por las órdenes religiosas femeninas o custodiados en las parroquias rurales. Pero, también, la diferente forma de mirar ese patrimonio de las viajeras, la configuración de sus espacios más íntimos o la utilización de su imagen en un conflicto armado son objeto de atención.
Todo ello convierte a las mujeres en un invisible hilo conductor en la gestión de la memoria, particular y colectiva, que, al ponerse de relieve, permite trazar, en torno al hecho artístico y cultural, relatos fluidos y coherentes en la Historia. Se introducen, así, matices y perspectivas que enriquecen una lectura dominada, en exceso, por los blancos y negros. Ellas son la «llave maestra» que reclamaba, en 1761, Enríquez Flórez al publicar sus Memorias de las reynas catholicas, esos hilos de oro en el lienzo del tiempo que, con extrema generosidad, nos han regalado sus respectivos autores y autoras para conformar este volumen
Electrochemical devices for cholesterol detection
Get PDFCholesterol can be considered as a biomarker of illnesses such as heart and coronary artery diseases or arteriosclerosis. Therefore, the fast determination of its
concentration in blood is interesting as a means of achieving an early diagnosis of these unhealthy conditions. Electrochemical sensors and biosensors have become a
potential tool for selective and sensitive detection of this biomolecule, combining the analytical advantages of electrochemical techniques with the selective
recognition features of modified electrodes. This review covers the different approaches carried out in the development of electrochemical sensors for cholesterol,
differentiating between enzymatic biosensors and non-enzymatic systems, highlighting lab-on-a-chip devices. A description of the different modification procedures
of the working electrode has been included and the role of the different functional materials used has been discussed
Caracterización y propiedades funcionales de hidrolizados proteicos obtenidos a partir de subproductos de la industria agroalimentaria
Get PDFEn la industria alimentaria, uno de los mayores problemas que se está intentando trabajar es
la reducción de la generación de residuos, con el fin de conseguir un desarrollo sostenible,
así como para aumentar la rentabilidad económica del proceso industrial. En casos como el
de la industria pesquera, los subproductos generados pueden representar más del 50% de la
materia prima inicial. Teniendo en cuenta el contenido proteico de estos subproductos, se ha
propuesto la obtención de hidrolizados proteicos y péptidos bioactivos dado que son una
buena fuente para la producción de nuevos ingredientes con aplicaciones tecnológicas y
funcionales en la industria alimentaria. El presente trabajo se centra en la caracterización de
hidrolizados proteicos obtenidos mediante hidrólisis con agua subcrítica (sCW) e hidrólisis
enzimática, ya que son procedimientos con un enfoque amigable con el medio ambiente.
Los resultados mostraron que se obtuvo un mayor grado de hidrolisis en el caso de los
extractos de harina de pescado y sus fracciones hidrolizados por sCW (241,80 ± 9,87 a 175,80
± 1,21 meq Leu), esto puede deberse a la mayor capacidad hidrolítica del sCW. Como se ha
observado en el análisis HPLC-SEC, estas muestras presentan moléculas de tamaño mucho
menor que en el resto de las muestras y también son las que mayor capacidad emulsionante
presentan. Por otro lado, respecto a los resultados de solubilidad, se observa que los
resultados menores se obtuvieron con las muestras de harina de pescado y fracción insoluble
hidrolizadas por sCW (71,06 % ± 18,38 y 65,18 % ± 1,34 respectivamente), lo que puede ser
debido a la alta desnaturalización de la proteína y la exposición de grupos hidrofóbicos que
como podemos observar en el caso del experimento de fluorescencia que estas muestras son
las que mayor hidrofobicidad superficial presentan (KSV = 12,138 y 12,883 respectivamente).
Finalmente, en cuanto a los resultados de tensión superficial, los mayores valores se
obtuvieron con las muestras de harina de pescado total (sCW = 52,59 ± 0,18 y Alc= 54,89 ±
0,62) que coincide con las muestras con menor estabilidad emulsionante.In the food industry, one of the major problems being addressed is the reduction of waste
generation, in order to achieve sustainable development, as well as to increase the economic
profitability of the industrial process. In cases such as the fishing industry, the by-products
generated can represent more than 50% of the initial raw material. Taking into account the
protein content of these by-products, it has been proposed to obtain protein hydrolysates and
bioactive peptides since they are a good source for the production of new ingredients with
technological and functional applications in the food industry. The present work focuses on the
characterization of protein hydrolysates obtained by subcritical water hydrolysis (sCW) and
enzymatic hydrolysis, since these are environmentally friendly procedures.
The results showed that a higher degree of hydrolysis was obtained in the case of fish meal
extracts and their fractions hydrolyzed by sCW (241.80 ± 9.87 to 175.80 ± 1.21 meq Leu), this
may be due to the higher hydrolytic capacity of sCW. As observed in the HPLC-SEC analysis,
these samples present molecules of much smaller size than in the rest of the samples and
they are also the ones with the highest emulsifying capacity. On the other hand, regarding the
solubility results, it is observed that the lowest results were obtained with the fish meal and
insoluble fraction samples hydrolyzed by sCW (71.06 % ± 18.38 and 65.18 % ± 1.34
respectively), which may be due to the high denaturation of the protein and the exposure of
hydrophobic groups that as we can observe in the case of the fluorescence experiment that
these samples are the ones with the highest surface hydrophobicity (KSV = 12.138 and 12.883
respectively). Finally, as for the surface tension results, the highest values were obtained with
the total fish meal samples (sCW = 52.59 ± 0.18 and Alc= 54.89 ± 0.62) which coincides with
the samples with the lowest emulsifying stability
Do cultural and creative entrepreneurs make affectively driven decisions? Not when they evaluate their opportunities
Get PDFOur research studies the influence of positive affect on entrepreneurs' evaluations of
opportunities (i.e. novelty assessments and entrepreneurial selection) as well as how
this influence may be different for entrepreneurs belonging to cultural and creative
industries. Drawing on arguments on the role of affect in cognition and considering
the particular situational and individual-level factors of entrepreneurship in cultural
and creative industries, we hypothesize that positive affect influences entrepreneurs'
opportunity evaluation. We also hypothesize that this effect of positive affect is
barely present for cultural and creative entrepreneurs. We test our hypotheses in a
sample of nascent entrepreneurs who took part in entrepreneurship training programmes in six incubators in Spain, who we asked to evaluate their own opportunity.
Our results show that positive affect positively impacts the perceived novelty and
entrepreneurial selection of non-creative entrepreneurs though this impact is limited
for cultural and creative entrepreneurs