S 308 and other X-ray emitting bubbles around Wolf-Rayet stars

S 308 is an X-ray emitting bubble that surrounds the Wolf-Rayet star WR6. The structure shines in the optical as well and is thus known as the Dolphin Nebula. Due to its large angular extent, it has been covered at only 90% with past XMM-Newton observations. Thanks to the unique dataset provided by the all-sky survey performed in X-rays by SRG/eROSITA, we can show for the first time the image of the bubble in its entire extent in this band, together with its spectral characterization. Moreover, we have tried to apply the same procedure for other wind-blown bubbles detected in the optical/IR and we searched for X-ray extended emission around them. We first analyzed the diffuse emission of S308, providing a detailed spectral analysis. We then considered a sample of 22 optical/IR selected wind-blown bubbles from a previous study based on WISE data, providing an estimate of the X-ray flux for the first time. We obtained the best fit for S308 with a two-temperature non-equilibrium plasma model (kT$_{1}=0.8_{-0.3}^{+0.8}$ keV and kT$_{2}=2_{-1}^{+3}$ keV) showing super-solar N abundance and low absorption. We did not detect any of the 22 optical/IR emitting bubbles in X-rays, but using our best fit model, we estimated the 3$\sigma$ flux upper limits for each bubble. We demonstrate the new possibility offered by SRG/eROSITA to study known wind-blown bubbles and look for other ones. A two-temperature plasma description seems to fit the data quite well for S308. Since all of the 22 bubbles studied still remain undetected by SRG/eROSITA, it is very likely that absorption effects and spatial compactness are responsible for the challenges standing in the way of detecting these bubbles in soft X-rays.Comment: Accepted for publication in A&

FOB1 affects DNA topoisomerase I in vivo cleavages in the enhancer region of the Saccharomyces cerevisiae ribosomal DNA locus

In Saccharomyces cerevisiae the FOB1 gene affects replication fork blocking activity at the replication fork block (RFB) sequences and promotes recombination events within the rDNA cluster. Using in vivo footprinting assays we mapped two in vivo Fob1p-binding sites, RFB1 and RFB3, located in the rDNA enhancer region and coincident with those previously reported to be in vitro binding sites. We previously provided evidences that DNA topoisomerase I is able to cleave two sites within this region. The results reported in this paper, indicate that the DNA topoisomerase I cleavage specific activity at the enhancer region is affected by the presence of Fob1p and independent of replication and transcription activities. We thus hypothesize that the binding to DNA of Fob1p itself may be the cause of the DNA topoisomerase I activity in the rDNA enhancer

Nucleosomes represent a physical barrier for cleavage activity of DNA topoisomerase I in vivo

DNA topoisomerase I together with the other cellular DNA topoisomerases releases the torsional stress from DNA caused by processes such as replication, transcription and recombination. Despite the well-defined knowledge of its mechanism of action, DNA topoisomerase I in vivo activity has been only partially characterized. In fact the basic question concerning the capability of the enzyme to cleave and rejoin DNA wrapped around a histone octamer remains still unanswered. By studying both in vivo and in vitro the cleavage activity of DNA topoisomerase I in the presence of camptothecin on a repeated trinucleotide sequence, (TTA)35, lying in chromosome XIII of Saccharomyces cerevisiae, we can conclude that nucleosomes represent a physical barrier for the enzyme activity. © The Authors

Structure and dynamics of the integrin LFA-1 I-domain in the inactive state underlie its inside-out/outside-in signaling and allosteric mechanisms.

Lymphocyte function-associated antigen 1 (LFA-1) is an integrin that transmits information in two directions across the plasma membrane of leukocytes, in so-called outside-in and inside-out signaling mechanisms. To investigate the structural basis of these mechanisms, we studied the conformational space of the apo I-domain using replica-averaged metadynamics simulations in combination with nuclear magnetic resonance chemical shifts. We thus obtained a free energy landscape that reveals the existence of three conformational substates of this domain. The three substates include conformations similar to existing crystallographic structures of the low-affinity I-domain, the inactive I-domain with an allosteric antagonist inhibitor bound underneath α helix 7, and an intermediate affinity state of the I-domain. The multiple substates were validated with residual dipolar coupling measurements. These results suggest that the presence of three substates in the apo I-domain enables the precise regulation of the binding process that is essential for the physiological function of LFA-1.This study was supported by the Wellcome Trust and the BBSRC.This is the final version of the article. It first appeared from Cell Press via http://dx.doi.org/10.1016/j.str.2014.12.02

SRG/eROSITA and XMM-Newton observations of Vela Jr

The Vela supernova remnant complex is a region containing at least three supernova remnants: Vela, Puppis A, and Vela Jr. With the launch of the spectro-imaging X-ray telescope eROSITA on board the Spectrum Roentgen Gamma (SRG) mission, it became possible to observe the one degree wide Vela Jr in its entirety. Although several previous pointed Chandra and XMM-Newton observations are available, it is only the second time after the ROSAT all-sky survey that the whole remnant was observed in X-rays with homogeneous sensitivity. Vela Jr is one of the few remnants emitting in the TeV band, making it an important object in shock acceleration studies. However, the age and distance determination using X-ray emission is largely hampered by the presence of the Vela SNR along the same line. With the eROSITA data set our aim is to characterize the emission of Vela Jr and distinguish it from Vela emission, and also to characterize the spectral emission of the inner remnant. We processed the eROSITA data dividing the whole remnant into seven different regions. In addition, images of the whole remnant were employed to pinpoint the position of the geometric center and constrain the proper motion of the CCO. We also employed archival XMM-Newton pointed observations of the NW rim to determine the cutoff energy of the electrons and the expansion velocity. We find the magnetic field can vary between 2 $\mu$G and 16 $\mu$G in the NW rim. We also find that the remnant spectrum is uniformly featureless in most regions, except for two inner regions where an extra thermal model component improves the fit. We obtain new coordinates for the geometric remnant center, resulting in a separation of only 35.2 $\pm$ 15.8" from the position of the CCO. As a result, we reinforce the association between the CCO and a proposed faint optical/IR counterpart.Comment: Accepted for publication in A&

Road traffic injuries in one local health unit in the Lazio region: results of a surveillance system integrating police and health data

<p>Abstract</p> <p>Objective</p> <p>Different sources are available for the surveillance of Road Traffic injuries (RTI), but studied individually they present several limits. In this paper we present the results of a surveillance integrating healthcare data with the data gathered by the municipal police in the southeastern area of Rome (630,000 inhabitants) during the year 2003.</p> <p>Methods</p> <p>The Municipal police RTI reports, which list the exact location, circumstances and some risk factor of the crash, were searched in the emergency visit, hospitalization and mortality databases, to integrate them with the information on health consequences.</p> <p>A multivariate analysis was conducted to evaluate risk factors (crash circumstances, age ad gender of the casualty) associated with hospital admission following a RTI.</p> <p>Mapping of RTI locations was created. The locations with higher risk of accidents with severe health consequences and at higher risk for pedestrians were identified.</p> <p>Results</p> <p>According to police records 4571 RTI occurred in 2003, 75% of which led to emergency department admissions. Sixteen percent of these emergency visits ended in hospitalization, and 44 deaths were reported within 30 days of the event, most of which occurred in young men.</p> <p>The people with the highest risk of hospitalization after an RTI were the cyclists, pedestrians and followed by people on two-wheeled vehicles. The type of crash with the highest risk of hospitalization was head-on collision.</p> <p>Geographical analyses showed four clusters with higher severity of RTI. Specific attention was paid to pedestrian injuries. Analyzing the locations of RTIs involving pedestrians permitted us to rank the most dangerous streets. The roads at high risk for pedestrians identified problems in the bus stop constructions and in the placement of the zebra pedestrian crossings.</p> <p>Conclusion</p> <p>This study proves the feasibility of an integrated surveillance system of RTI by using routinely collected local data. The high-risk locations identified with the geographic analyses method in this study highlighted infrastructural problems, suggesting immediate preventive interventions.</p

The 2023 release of Cloudy

We describe the 2023 release of the spectral synthesis code Cloudy. Since the previous major release, migrations of our online services motivated us to adopt git as our version control system. This change alone led us to adopt an annual release scheme, accompanied by a short release paper, the present being the inaugural. Significant changes to our atomic and molecular data have improved the accuracy of Cloudy predictions: we have upgraded our instance of the Chianti database from version 7 to 10; our H- and He-like collisional rates to improved theoretical values; our molecular data to the most recent LAMDA database, and several chemical reaction rates to their most recent UDfA and KiDA values. Finally, we describe our progress on upgrading Cloudy's capabilities to meet the requirements of the X-ray microcalorimeters aboard the upcoming XRISM and Athena missions, and outline future development that will make Cloudy of use to the X-ray community.Comment: 18 pages, 10 figures, accepted for publication in RMxA

Small-molecule sequestration of amyloid-β as a drug discovery strategy for Alzheimer's disease.

Disordered proteins are challenging therapeutic targets, and no drug is currently in clinical use that modifies the properties of their monomeric states. Here, we identify a small molecule (10074-G5) capable of binding and sequestering the intrinsically disordered amyloid-β (Aβ) peptide in its monomeric, soluble state. Our analysis reveals that this compound interacts with Aβ and inhibits both the primary and secondary nucleation pathways in its aggregation process. We characterize this interaction using biophysical experiments and integrative structural ensemble determination methods. We observe that this molecule increases the conformational entropy of monomeric Aβ while decreasing its hydrophobic surface area. We also show that it rescues a Caenorhabditis elegans model of Aβ-associated toxicity, consistent with the mechanism of action identified from the in silico and in vitro studies. These results illustrate the strategy of stabilizing the monomeric states of disordered proteins with small molecules to alter their behavior for therapeutic purposes

Substantial Histone Reduction Modulates Genomewide Nucleosomal Occupancy and Global Transcriptional Output

The basic unit of genome packaging is the nucleosome, and nucleosomes have long been proposed to restrict DNA accessibility both to damage and to transcription. Nucleosome number in cells was considered fixed, but recently aging yeast and mammalian cells were shown to contain fewer nucleosomes. We show here that mammalian cells lacking High Mobility Group Box 1 protein (HMGB1) contain a reduced amount of core, linker, and variant histones, and a correspondingly reduced number of nucleosomes, possibly because HMGB1 facilitates nucleosome assembly. Yeast nhp6 mutants lacking Nhp6a and -b proteins, which are related to HMGB1, also have a reduced amount of histones and fewer nucleosomes. Nucleosome limitation in both mammalian and yeast cells increases the sensitivity of DNA to damage, increases transcription globally, and affects the relative expression of about 10% of genes. In yeast nhp6 cells the loss of more than one nucleosome in four does not affect the location of nucleosomes and their spacing, but nucleosomal occupancy. The decrease in nucleosomal occupancy is non-uniform and can be modelled assuming that different nucleosomal sites compete for available histones. Sites with a high propensity to occupation are almost always packaged into nucleosomes both in wild type and nucleosome-depleted cells; nucleosomes on sites with low propensity to occupation are disproportionately lost in nucleosome-depleted cells. We suggest that variation in nucleosome number, by affecting nucleosomal occupancy both genomewide and gene-specifically, constitutes a novel layer of epigenetic regulation

MobiDB 3.0: More annotations for intrinsic disorder, conformational diversity and interactions in proteins

The MobiDB (URL: mobidb.bio.unipd.it) database of protein disorder and mobility annotations has been significantly updated and upgraded since its last major renewal in 2014. Several curated datasets for intrinsic disorder and folding upon binding have been integrated from specialized databases. The indirect evidence has also been expanded to better capture information available in the PDB, such as high temperature residues in X-ray structures and overall conformational diversity. Novel nuclear magnetic resonance chemical shift data provides an additional experimental information layer on conformational dynamics. Predictions have been expanded to provide new types of annotation on backbone rigidity, secondary structure preference and disordered binding regions. MobiDB 3.0 contains information for the complete UniProt protein set and synchronization has been improved by covering all UniParc sequences. An advanced search function allows the creation of a wide array of custom-made datasets for download and further analysis. A large amount of information and cross-links to more specialized databases are intended to make MobiDB the central resource for the scientific community working on protein intrinsic disorder and mobility.Fil: Piovesan, Damiano. Università di Padova; ItaliaFil: Tabaro, Francesco. Università di Padova; ItaliaFil: Paladin, Lisanna. Università di Padova; ItaliaFil: Necci, Marco. Università di Padova; Italia. Instituto Agrario San Michele all'Adige Fondazione Edmund Mach; ItaliaFil: Micetić, Ivan. Università di Padova; ItaliaFil: Camilloni, Carlo. Università degli Studi di Milano; ItaliaFil: Davey, Norman. Universidad de Dublin; IrlandaFil: Dosztányi, Zsuzsanna. Eötvös Loránd University; HungríaFil: Mészáros, Bálint. Eötvös Loránd University; HungríaFil: Monzón, Alexander. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Parisi, Gustavo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Schad, Eva. Hungarian Academy Of Sciences; HungríaFil: Sormanni, Pietro. University of Cambridge; Reino UnidoFil: Tompa, Peter. Vrije Unviversiteit Brussel; BélgicaFil: Vendruscolo, Michele. University of Cambridge; Reino UnidoFil: Vranken, Wim F.. Vrije Unviversiteit Brussel; BélgicaFil: Tosatto, Silvio C. E.. Università di Padova; Itali