Nuclear-localized human respiratory syncytial virus NS1 protein modulates host gene transcription

Human respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in the pediatric, elderly, and immunocompromised individuals. RSV non-structural protein NS1 is a known cytosolic immune antagonist, but how NS1 modulates host responses remains poorly defined. Here, we observe NS1 partitioning into the nucleus of RSV-infected cells, including the human airway epithelium. Nuclear NS1 coimmunoprecipitates with Mediator complex and is chromatin associated. Chromatin-immunoprecipitation demonstrates enrichment of NS1 that overlaps Mediator and transcription factor binding within the promoters and enhancers of differentially expressed genes during RSV infection. Mutation of the NS1 C-terminal helix reduces NS1 impact on host gene expression. These data suggest that nuclear NS1 alters host responses to RSV infection by binding at regulatory elements of immune response genes and modulating host gene transcription. Our study identifies another layer of regulation by virally encoded proteins that shapes host response and impacts immunity to RSV

Accurate ab initio spin densities

We present an approach for the calculation of spin density distributions for molecules that require very large active spaces for a qualitatively correct description of their electronic structure. Our approach is based on the density-matrix renormalization group (DMRG) algorithm to calculate the spin density matrix elements as basic quantity for the spatially resolved spin density distribution. The spin density matrix elements are directly determined from the second-quantized elementary operators optimized by the DMRG algorithm. As an analytic convergence criterion for the spin density distribution, we employ our recently developed sampling-reconstruction scheme [J. Chem. Phys. 2011, 134, 224101] to build an accurate complete-active-space configuration-interaction (CASCI) wave function from the optimized matrix product states. The spin density matrix elements can then also be determined as an expectation value employing the reconstructed wave function expansion. Furthermore, the explicit reconstruction of a CASCI-type wave function provides insights into chemically interesting features of the molecule under study such as the distribution of $\alpha$- and $\beta$-electrons in terms of Slater determinants, CI coefficients, and natural orbitals. The methodology is applied to an iron nitrosyl complex which we have identified as a challenging system for standard approaches [J. Chem. Theory Comput. 2011, 7, 2740].Comment: 37 pages, 13 figure

Methodological challenges for living systematic reviews conducted during the COVID-19 pandemic: A concept paper

Background A living systematic review (LSR) is an emerging review type that makes use of continual updating. In the COVID-19 pandemic, we were confronted with a shifting epidemiological landscape, clinical uncertainties and evolving evidence. These unexpected challenges compelled us to amend standard LSR methodology. Objective and outline Our primary objective is to discuss some challenges faced when conducting LSRs in the context of the COVID-19 pandemic, and to provide methodological guidance for others doing similar work. Based on our experience and lessons learned from two Cochrane LSRs and challenges identified in several non-Cochrane LSRs, we highlight methodological considerations, particularly with regards to the study design, interventions and comparators, changes in outcome measure, and the search strategy. We discuss when to update, or rather when not to update the review, and the importance of transparency when reporting changes. Lessons learned and conclusion We learned that a LSR is a very suitable review type for the pandemic context, even in the face of new methodological and clinical challenges. Our experience showed that the decision for updating a LSR depends not only on the evolving disease or emerging evidence, but also on the individual review question and the review teams’ resources

Éticas convergentes en la encrucijada de la postmodernidad

Compendio de 17 trabajos de reconocidos filósofos y estudiosos que han ayudado a constituir parte del rico panorama de las investigaciones éticas en América Latina y en tres países europeos. Podemos destacar cuatro principales rasgos que hacen de este texto, una contribución a la investigación y a la formación universitaria en ética. En primer lugar, este texto colectivo integra importantes estudios éticos redactados para ayudar a pensar algunos de los principales planteamientos de la ética discursiva en la actualidad; en ellos se encuentran tanto cuestiones teóricas de la ética filosófica, como una serie de cuestiones disputadas acerca de la cultura, la sociedad, la política, la educación, etc. En segundo lugar, este texto reconocer a partir de una pluralidad presente en la investigación internacional el aporte decisivo de filósofos, que como el argentino Ricardo Maliandi, han permitido profundizar principios teóricos éticos convergentes y abiertos a las más complejas problemáticas relativas a la conflictividad. En tercer lugar, este volumen es una clara invitación para que otros investigadores, profesores y estudiantes universitarios lean y profundicen estos avances acerca de estas materias, y apropiándose de ellas, puedan reflexionar otras que no aparecen tan explícitamente trabajadas en este libro. En cuarto y último lugar, ésta es una publicación de intelectuales que homenajean a un notable filósofo argentino que nos ha legado, en más de 40 años, una investigación original y sistemática acerca de la ética, inspirada en las obras de N. Hartmann y K.O. Ape