Notre Dame de París: consternación y esperanza

[EN] The dramatic blaze of the roof of Notre-Dame de Paris gave way to intense imaginative proposals for the monument repairs, far from realist and respectful considerations. In the other hand, the methodical approach, coming from the monument’s analyse and understanding, its symbolic and architectural sense, seems to be the only way for its faithful recovery. If the works for repairs are easy to adopt, the roof and the spire are in an open debate, which claims to more clever considerations: the roof cannot be studied out of its major structural assessment on the vaults; and the spire, both one of the 19th c. major masterpiece of architecture, and a legendary skyline, calls for it’s rebuilt. Back to the world famous gothic icon seems to be the only correct architectural answer.[ES] El incendio dramático de la cubierta de Notre Dame de París ha dado lugar a numerosas propuestas imaginativas para la reconstitución del monumento, más allá de una reflexión real y respetuosa. Por otro lado, la única vía para una recuperación fidedigna parece ser un enfoque  metódico que parta del análisis y comprensión del monumento y de su carácter simbólico y arquitectónico. Las reparaciones puntuales a realizar son fáciles pero la cubierta y la aguja han abierto un debate que reclama una deliberación más profunda: el estudio de la cubierta no puede desvincularse de su rol en la estabilización de las bóvedas; y la aguja, una obra maestra de la arquitectura decimonónica parte de un skyline legendario, exige su reconstrucción. El retorno al icono gótico mundialmente famoso se antoja como la única respuesta arquitectónica correcta.Mouton, B. (2019). Notre-Dame de Paris: dismay and hope. Loggia, Arquitectura & Restauración. 0(32):34-45. https://doi.org/10.4995/loggia.2019.12045OJS344503

r-Fredholm theory in Banach algebras

Harte (Mathematische Zeitschrift, 1982) initiated the study of Fredholm theory relative to a unital homomorphism T: A→B between unital Banach algebras A and B based on the following notions: an element a∈A is called Fredholm if 0 is not in the spectrum of Ta, while a is Weyl (Browder) if there exist (commuting) elements b and c in A with a = b+c such that 0 is not in the spectrum of b and c is in the null space of T. We introduce and investigate the concepts of r-Fredholm, r-Weyl and r-Browder elements, where 0 in these definitions is replaced by the spectral radii of a and b, respectively

Myomegalin is a novel A-kinase anchoring protein involved in the phosphorylation of cardiac myosin binding protein C

<p>Abstract</p> <p>Background</p> <p>Cardiac contractility is regulated by dynamic phosphorylation of sarcomeric proteins by kinases such as cAMP-activated protein kinase A (PKA). Efficient phosphorylation requires that PKA be anchored close to its targets by A-kinase anchoring proteins (AKAPs). Cardiac Myosin Binding Protein-C (cMyBPC) and cardiac troponin I (cTNI) are hypertrophic cardiomyopathy (HCM)-causing sarcomeric proteins which regulate contractility in response to PKA phosphorylation.</p> <p>Results</p> <p>During a yeast 2-hybrid (Y2H) library screen using a trisphosphorylation mimic of the C1-C2 region of cMyBPC, we identified isoform 4 of myomegalin (MMGL) as an interactor of this N-terminal cMyBPC region. As MMGL has previously been shown to interact with phosphodiesterase 4D, we speculated that it may be a PKA-anchoring protein (AKAP).</p> <p>To investigate this possibility, we assessed the ability of MMGL isoform 4 to interact with PKA regulatory subunits R1A and R2A using Y2H-based direct protein-protein interaction assays. Additionally, to further elucidate the function of MMGL, we used it as bait to screen a cardiac cDNA library. Other PKA targets, viz. CARP, COMMD4, ENO1, ENO3 and cTNI were identified as putative interactors, with cTNI being the most frequent interactor.</p> <p>We further assessed and confirmed these interactions by fluorescent 3D-co-localization in differentiated H9C2 cells as well as by <it>in vivo </it>co-immunoprecipitation. We also showed that quantitatively more interaction occurs between MMGL and cTNI under β-adrenergic stress. Moreover, siRNA-mediated knockdown of MMGL leads to reduction of cMyBPC levels under conditions of adrenergic stress, indicating that MMGL-assisted phosphorylation is requisite for protection of cMyBPC against proteolytic cleavage.</p> <p>Conclusions</p> <p>This study ascribes a novel function to MMGL isoform 4: it meets all criteria for classification as an AKAP, and we show that is involved in the phosphorylation of cMyBPC as well as cTNI, hence MMGL is an important regulator of cardiac contractility. This has further implications for understanding the patho-aetiology of HCM-causing mutations in the genes encoding cMyBPC and cTNI, and raises the question of whether MMGL might itself be considered a candidate HCM-causing or modifying factor.</p

A New Model and Method for Understanding Wolbachia-Induced Cytoplasmic Incompatibility

Wolbachia are intracellular bacteria transmitted almost exclusively vertically through eggs. In response to this mode of transmission, Wolbachia strategically manipulate their insect hosts' reproduction. In the most common manipulation type, cytoplasmic incompatibility, infected males can only mate with infected females, but infected females can mate with all males. The mechanism of cytoplasmic incompatibility is unknown; theoretical and empirical findings need to converge to broaden our understanding of this phenomenon. For this purpose, two prominent models have been proposed: the mistiming-model and the lock-key-model. The former states that Wolbachia manipulate sperm of infected males to induce a fatal delay of the male pronucleus during the first embryonic division, but that the bacteria can compensate the delay by slowing down mitosis in fertilized eggs. The latter states that Wolbachia deposit damaging “locks” on sperm DNA of infected males, but can also provide matching “keys” in infected eggs to undo the damage. The lock-key-model, however, needs to assume a large number of locks and keys to explain all existing incompatibility patterns. The mistiming-model requires fewer assumptions but has been contradicted by empirical results. We therefore expand the mistiming-model by one quantitative dimension to create the new, so-called goalkeeper-model. Using a method based on formal logic, we show that both lock-key- and goalkeeper-model are consistent with existing data. Compared to the lock-key-model, however, the goalkeeper-model assumes only two factors and provides an idea of the evolutionary emergence of cytoplasmic incompatibility. Available cytological evidence suggests that the hypothesized second factor of the goalkeeper-model may indeed exist. Finally, we suggest empirical tests that would allow to distinguish between the models. Generalizing our results might prove interesting for the study of the mechanism and evolution of other host-parasite interactions

Trying to choose the less bad route: Individual migratory behaviour of Atlantic salmon smolts (Salmo salar L.) approaching a bifurcation between a hydropower station and a navigation canal

Contrary to small- and medium-sized rivers, little attention has been paid to the downstream migration of Atlantic salmon smolts in large-sized rivers and the size-related impact of hydropower stations. From 2014 to 2016, we investigated the downstream migration of n=72 acoustic-tagged smolts in the Meuse river at a bifurcation zone between a hydropower station equipped with three Kaplan turbines and a navigation canal. A hydrodynamic model that solves the depth-integrated shallow water equations on a Cartesian grid using a finite volume technique was used to infer the influence of water discharge and flow velocity on the smolts’ behaviour upstream of the hydroelectric complex. Of the migrating smolts, 41.5 % performed back and forth movements before approaching the complex for the first time, sometimes over long distances and at a slow pace, leading to significant delays (3‒298 h). Beyond about 250 m3 s-1, the water flow direction changes towards the hydropower station with a gradual acceleration. A median water discharge of 161 m3 s-1 and associated median flow velocity of 0.14 m s-1 tended to favour a more direct and downstream movement towards the hydropower station. On the other hand, the navigation canal was mainly approached at low water discharge (median 132 m3 s-1), due to a higher flow velocity (median 0.11 m s-1) at the entrance. Of the released smolts, only 38.6 % passed through the complex, of which 36.4 % migrated by the navigation canal and 63.6 % by the hydropower station, with a median research time of 04:44. Among all the released individuals, the escapement rate at the end of the study site was 2.9 % by the canal and 8.3 % by the Meuse river. This site, which offers two non-optimal, unattractive and unsafe migration routes, turns out to be problematic for successful downstream smolt migration

Targeted proteomics links virulence factor expression with clinical severity in staphylococcal pneumonia

IntroductionThe bacterial pathogen Staphylococcus aureus harbors numerous virulence factors that impact infection severity. Beyond virulence gene presence or absence, the expression level of virulence proteins is known to vary across S. aureus lineages and isolates. However, the impact of expression level on severity is poorly understood due to the lack of high-throughput quantification methods of virulence proteins.MethodsWe present a targeted proteomic approach able to monitor 42 staphylococcal proteins in a single experiment. Using this approach, we compared the quantitative virulomes of 136 S. aureus isolates from a nationwide cohort of French patients with severe community-acquired staphylococcal pneumonia, all requiring intensive care. We used multivariable regression models adjusted for patient baseline health (Charlson comorbidity score) to identify the virulence factors whose in vitro expression level predicted pneumonia severity markers, namely leukopenia and hemoptysis, as well as patient survival.ResultsWe found that leukopenia was predicted by higher expression of HlgB, Nuc, and Tsst-1 and lower expression of BlaI and HlgC, while hemoptysis was predicted by higher expression of BlaZ and HlgB and lower expression of HlgC. Strikingly, mortality was independently predicted in a dose-dependent fashion by a single phage-encoded virulence factor, the Panton-Valentine leucocidin (PVL), both in logistic (OR 1.28; 95%CI[1.02;1.60]) and survival (HR 1.15; 95%CI[1.02;1.30]) regression models.DiscussionThese findings demonstrate that the in vitro expression level of virulence factors can be correlated with infection severity using targeted proteomics, a method that may be adapted to other bacterial pathogens

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

The European Reference Genome Atlas: piloting a decentralised approach to equitable biodiversity genomics.

ABSTRACT: A global genome database of all of Earth’s species diversity could be a treasure trove of scientific discoveries. However, regardless of the major advances in genome sequencing technologies, only a tiny fraction of species have genomic information available. To contribute to a more complete planetary genomic database, scientists and institutions across the world have united under the Earth BioGenome Project (EBP), which plans to sequence and assemble high-quality reference genomes for all ∼1.5 million recognized eukaryotic species through a stepwise phased approach. As the initiative transitions into Phase II, where 150,000 species are to be sequenced in just four years, worldwide participation in the project will be fundamental to success. As the European node of the EBP, the European Reference Genome Atlas (ERGA) seeks to implement a new decentralised, accessible, equitable and inclusive model for producing high-quality reference genomes, which will inform EBP as it scales. To embark on this mission, ERGA launched a Pilot Project to establish a network across Europe to develop and test the first infrastructure of its kind for the coordinated and distributed reference genome production on 98 European eukaryotic species from sample providers across 33 European countries. Here we outline the process and challenges faced during the development of a pilot infrastructure for the production of reference genome resources, and explore the effectiveness of this approach in terms of high-quality reference genome production, considering also equity and inclusion. The outcomes and lessons learned during this pilot provide a solid foundation for ERGA while offering key learnings to other transnational and national genomic resource projects.info:eu-repo/semantics/publishedVersio

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men