Search

The high morbimortality due to SARS-CoV-2 infection in oncohematological diseases (OHD) and hematopoietic stem cell transplant (HSCT) recipients in the pre-vaccine era has made vaccination a priority in this group. After HSCT, the immune responses against common vaccines such as tetanus, varicella, rubella, and polio may be lost. However, the loss of immunity developed by COVID-19 vaccination after HSCT has not been completely defined. In this study, both humoral and cellular immunity against SARS-CoV-2 were analyzed in 29 individuals with OHD who were vaccinated before receiving allogeneic (n = 11) or autologous (n = 18) HSCT. All participants had low but protective levels of neutralizing IgGs against SARS-CoV-2 after HSCT despite B-cell lymphopenia and immaturity. Although antibody-dependent cellular cytotoxicity was impaired, direct cellular cytotoxicity was similar to healthy donors in participants with autologous-HSCT, in contrast to individuals with allogeneic–HSCT, which severely deteriorated. No significant changes were observed in the immune response before and after HSCT. During follow-up, all reported post-HSCT SARS-CoV-2 infections were mild. This data emphasizes that COVID-19 vaccination is effective, necessary, and safe for individuals with OHD and also supports the persistence of some degree of immune protection after HSCT, at least in the short term, when patients cannot yet be revaccinated. This work was supported by projects PI21/00877 and PI22CIII/00059, funded by the Strategic Action in Health of the Instituto de Salud Carlos III (SICIII) and co-funded by European Regional Development Fund (ERDF), “A way to make Europe”; the Coordinated Research Activities at the National Center of Microbiology (CNM, Instituto de Salud Carlos III) (COV20_00679) to promote an integrated response against SARS-CoV-2 in Spain (Spanish Ministry of Science and Innovation) that is coordinated by Dr Inmaculada Casas (WHO National Influenza Center of the CNM); a generous donation provided by Chiesi España, S.A.U. (Barcelona, Spain); and the Spanish Ministry of Science and Innovation (PID2019-110275RB-I00). The work of Sara Rodríguez-Mora is financed by NIH grant R01AI143567. The work of Montserrat Torres and Guiomar Casado are financed by CIBERINFEC, co-financed by ERDF, “A way to make Europe”. The work of Clara Sánchez-Menéndez is financed by Programa Investigo, FIBio HRC-IRYCIS, co-financed by ERDF, “A way to make Europe”. Sí

The humoral immune response developed after receiving the full vaccination schedule against COVID-19 is impaired in individuals who received anti-CD20 therapy 6-9 months before vaccination. However, there is little information about the cellular immune responses elicited in these individuals. In this study, we analyzed the humoral and cellular immune responses in 18 individuals with hematological disease who received the last dose of rituximab 13.8 months (IQR 9.4-19) before the booster dose. One month after receiving the booster dose, the seroconversion rate in the rituximab-treated cohort increased from 83.3% to 88.9% and titers of specific IgGs against SARS-CoV-2 increased 1.53-fold (p = 0.0098), while the levels of neutralizing antibodies increased 3.03-fold (p = 0.0381). However, the cytotoxic activity of peripheral blood mononuclear cells (PBMCs) from rituximab-treated individuals remained unchanged, and both antibody-dependent cellular cytotoxicity (ADCC) and direct cellular cytotoxicity (CDD) were reduced 1.7-fold (p = 0.0047) and 2.0-fold (p = 0.0086), respectively, in comparison with healthy donors. Breakthrough infections rate was higher in our cohort of rituximab-treated individuals (33.33%), although most of the infected patients (83.4%) developed a mild form of COVID-19. In conclusion, our findings confirm a benefit in the humoral, but not in the cellular, immune response in rituximab-treated individuals after receiving a booster dose of an mRNA-based vaccine against COVID-19. This work was supported by the Strategic Action in Health 2017–2020 of the Instituto de Salud Carlos III (PI21/00877), by the Coordinated Research Activities at the National Center of Microbiology (CNM, Instituto de Salud Carlos III) (COV20_00679) to promote an integrated response against SARS-CoV-2 in Spain (Spanish Ministry of Science and Innovation) that is coordinated by Dr Inmaculada Casas (WHO National Influenza Center of the CNM), and by a generous donation provided by Chiesi España, S.A.U. (Barcelona, Spain). The work of Montserrat Torres is financed by the Hematology and Hemotherapy Service, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal (Madrid, Spain). The work of Sara Rodríguez-Mora is financed by NIH grant R01AI143567. The work of Guiomar Casado is financed by CIBERINFEC, co-financed by the European Regional Development Fund (FEDER) “A way to make Europe”. The work of Fernando Ramos-Martín is financed by the Spanish Ministry of Science and Innovation (PID2019-110275RB-I00). Sí

Constraints from surveys of post-common envelope binaries (PCEBs) consisting of a white dwarf plus an M-dwarf companion have led to significant progress in our understanding of the formation of close white dwarf binary stars with low-mass companions. The white dwarf binary pathways project aims at extending these previous surveys to larger secondary masses, i.e. secondary stars of spectral-type AFGK. Here, we present the discovery and observational characterization of three PCEBs with G-type secondary stars and orbital periods between 1.2 and 2.5 d. Using our own tools as well as MESA, we estimate the evolutionary history of the binary stars and predict their future. We find a large range of possible evolutionary histories for all three systems and identify no indications for differences in common envelope evolution compared to PCEBs with lower mass secondary stars. Despite their similarities in orbital period and secondary spectral type, we estimate that the future of the three systems is very different: TYC 4962-1205-1 is a progenitor of a cataclysmic variable system with an evolved donor star, TYC 4700-815-1 will run into dynamically unstable mass transfer that will cause the two stars to merge, and TYC 1380-957-1 may appear as supersoft source before becoming a rather typical cataclysmic variable star., MSH acknowledges support through a Fellowship for National PhD students from Agencia Nacional de Investigación y Desarrollo, ANID grant 21170070. MRS acknowledges financial support from FONDECYT (grant 1181404). SGP acknowledges the support of the STFC Ernest Rutherford Fellowship. BTG was supported by the UK STFC grant ST/T000406/1. FL acknowledges support from the ESO studentship program. RR has received funding from the postdoctoral fellowship program Beatriu de Pinós, funded by the Secretary of Universities and Research (Government of Catalonia) and by the Horizon 2020 program of research and innovation of the European Union under the Maria Skłodowska-Curiegrant 801370. OT was supported by a Leverhulme Trust Research Project Grant. GT acknowledges support from UNAM-DGAPA-PAPIIT project IN110619. MZ acknowledges support from CONICYT PAI (Concurso Nacional de Inserción en la Academia 2017, Folio 79170121) and CONICYT/FONDECYT (Programa de Iniciación, Folio 11170559). ARM acknowledges support from the MINECO under the Ramón y Cajal programme (RYC-2016-20254) and the AYA2017-86274-P grant, and the AGAUR grant SGR-661/2017. JJR acknowledges the support of the National Natural Science Foundation of China 11903048 and 11833006. We acknowledge the support of the staff of the XL216. This work was partially supported by the National Natural Science Foundation of China (NSFC), funding number is 11903048 and 11833006. The results presented in this paper are partly based on observations collected at the European Southern Observatory under program IDs 0102.D-0355(A) and 0101.D-0415(A).

[Objectives]: To describe the etiology of community-acquired pneumonia (CAP) in hospitalized children in Spain and analyze the predictors of the etiology., [Hypothesis]: The different etiological groups of pediatric CAP are associated with different clinical, radiographic, and analytical data., [Design]: Observational, multicenter, and prospective study., [Patient selection]: This study included children aged 1 month to 17 years with CAP, who were hospitalized between April 2012 and May 2019., [Methods]: An extensive microbiological workup was performed. The clinical, radiographic, and analytical parameters were analyzed for three etiological groups., [Results]: Among the 495 children included, at least one causative pathogen was identified in 262 (52.9%): pathogenic viruses in 155/262 (59.2%); atypical bacteria (AB), mainly Mycoplasma pneumonia, in 84/262 (32.1%); and typical bacteria (TyB) in 40/262 (15.3%). Consolidation was observed in 89/138 (64.5%) patients with viral CAP, 74/84 (88.1%) with CAP caused by AB, and 40/40 (100%) with CAP caused by TyB. Para-pneumonic pleural effusion (PPE) was observed in 112/495 (22.6%) patients, of which 61/112 (54.5%) presented a likely causative pathogen: viruses in 12/61 (19.7%); AB in 23/61 (37.7%); and TyB in 26/61 (42.6%). Viral etiology was significantly frequent in young patients and in those with low oxygen saturation, wheezing, no consolidation, and high lymphocyte counts. CAP patients with AB as the etiological agent had a significantly longer and less serious course as compared to those with other causative pathogens., [Conclusions]: Viruses and M. pneumoniae are the main causes of pediatric CAP in Spain. Wheezing, young age, and no consolidation on radiographs are indicative of viral etiology. Viruses and AB can also cause PPE. Since only a few cases can be directly attributed to TyB, the indications for antibiotics must be carefully considered in each patient., Instituto de Investigación Hospital 12 de Octubre (i+12), Grant/Award Number: AY191212‐1; Instituto de Salud Carlos III (Ministry of Economy, Industry and Competitiveness) and co‐funded by the European Regional Development Funds, Grant/Award Number: Project PI17/01458; Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Grant/Award Number: PCAPE 2011_0025 Register 320/11; Research Project of Universidad Europea de Madrid, Grant/Award Number: 2017/UEM03

De novo protein synthesis is required for synapse modifications underlying stable memory encoding. Yet neurons are highly compartmentalized cells and how protein synthesis can be regulated at the synapse level is unknown. Here, we characterize neuronal signaling complexes formed by the postsynaptic scaffold GIT1, the mechanistic target of rapamycin (mTOR) kinase, and Raptor that couple synaptic stimuli to mTOR-dependent protein synthesis; and identify NMDA receptors containing GluN3A subunits as key negative regulators of GIT1 binding to mTOR. Disruption of GIT1/mTOR complexes by enhancing GluN3A expression or silencing GIT1 inhibits synaptic mTOR activation and restricts the mTOR-dependent translation of specific activity-regulated mRNAs. Conversely, GluN3A removal enables complex formation, potentiates mTOR-dependent protein synthesis, and facilitates the consolidation of associative and spatial memories in mice. The memory enhancement becomes evident with light or spaced training, can be achieved by selectively deleting GluN3A from excitatory neurons during adulthood, and does not compromise other aspects of cognition such as memory flexibility or extinction. Our findings provide mechanistic insight into synaptic translational control and reveal a potentially selective target for cognitive enhancement, Ramon y Cajal program RYC2014-15784, RETOS-MINECO SAF2016-76565-R, ERANET-Neuron JTC 2019 ISCIII AC19/00077 FEDER funds (to R.A.); RETOS-MINECO SAF2017-87928-R (to A.B.); an NIH grant (NS76637) and UTHSC College of Medicine funds (to S.J.T.); and NARSAD Independent Investigator Award and grants from the MINECO (CSD2008-00005, SAF2013-48983R, SAF2016-80895-R), Generalitat Valenciana (PROMETEO 2019/020)(to I.P.O.) and Severo-Ochoa Excellence Awards (SEV-2013-0317, SEV-2017-0723)

Epidemics caused by microbial organisms are part of the natural phenomena of increasing biological complexity. The heterogeneity and constant variability of hosts, in terms of age, immunological status, family structure, lifestyle, work activities, social and leisure habits, daily division of time and other demographic characteristics make it extremely difficult to predict the evolution of epidemics. Such prediction is, however, critical for implementing intervention measures in due time and with appropriate intensity. General conclusions should be precluded, given that local parameters dominate the flow of local epidemics. Membrane computing models allows us to reproduce the objects (viruses and hosts) and their interactions (stochastic but also with defined probabilities) with an unprecedented level of detail. Our LOIMOS model helps reproduce the demographics and social aspects of a hypothetical town of 10 320 inhabitants in an average European country where COVID-19 is imported from the outside. The above-mentioned characteristics of hosts and their lifestyle are minutely considered. For the data in the Hospital and the ICU we took advantage of the observations at the Nursery Intensive Care Unit of the Consortium University General Hospital, Valencia, Spain (included as author). The dynamics of the epidemics are reproduced and include the effects on viral transmission of innate and acquired immunity at various ages. The model predicts the consequences of delaying the adoption of non-pharmaceutical interventions (between 15 and 45 days after the first reported cases) and the effect of those interventions on infection and mortality rates (reducing transmission by 20, 50 and 80%) in immunological response groups. The lockdown for the elderly population as a single intervention appears to be effective. This modeling exercise exemplifies the application of membrane computing for designing appropriate multilateral interventions in epidemic situations., MC and FB were sponsored by the Projects COV20_00067 of the Program SARS-COV-2 and COVID-19 infection of the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación of Spain, CB06/02/0053 of the Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), and the Regional Government of Madrid (InGeMICS-B2017/BMD-3691). For JCG, this study was partially founded by the Autonomous Community of Madrid, Spain (COVID-19 Grant, 2020) and the Ramón y Cajal Institute for Health Research (IRYCIS), Madrid, Spain. For AM, this study was supported by grants from the Spanish Ministry of Science and Innovation (PID2019-105969GB-I00), the government of Valencia (project Prometeo/2018/A/133) and co-financed by the European Regional Development Fund (ERDF).

The conformational stability of ribonuclease Sa (RNase Sa) has been measured at the per-residue level by NMR-monitored hydrogen exchange at pH* 5.5 and 30 °C. In these conditions, the exchange mechanism was found to be EXII. The conformational stability calculated from the slowest exchanging amide groups was found to be 8.8 kcal/mol, in close agreement with values determined by spectroscopic methods. RNase Sa is curiously rich in acidic residues (pI = 3.5) with most basic residues being concentrated in the active-site cleft. The effects of dissolved salts on the stability of RNase Sa was studied by thermal denaturation experiments in NaCl and GdmCl and by comparing hydrogen exchange rates in 0.25 M NaCl to water. The protein was found to be stabilized by salt, with the magnitude of the stabilization being influenced by the solvent exposure and local charge environment at individual amide groups. Amide hydrogen exchange was also measured in 0.25, 0.50, 0.75, and 1.00 M GdmCl to characterize the unfolding events that permit exchange. In contrast to other microbial ribonucleases studied to date, the most protected, globally exchanging amides in RNase Sa lie not chiefly in the central β strands but in the 3/10 helix and an exterior β strand. These structural elements are near the Cys7−Cys96 disulfide bond., This work was supported by the Dirección General de Investigación Científica y Técnica (Spain) (PB-93-0189 to M.R.), by the NIH (GM 37039 to C.N.P. and GM 52483 to J.M.S.), and the Robert A. Welch Foundation (BE-1060 to C.N.P. and BE-1281 to J.M.S.). D.V.L. was supported by fellowships from the Leukemia and Lymphoma Society and the Ramón y Cajal program (Spain).