Studying DNA Double-Strand Break Repair: An Ever-Growing Toolbox

To ward off against the catastrophic consequences of persistent DNA double-strand breaks (DSBs), eukaryotic cells have developed a set of complex signaling networks that detect these DNA lesions, orchestrate cell cycle checkpoints and ultimately lead to their repair. Collectively, these signaling networks comprise the DNA damage response (DDR). The current knowledge of the molecular determinants and mechanistic details of the DDR owes greatly to the continuous development of ground-breaking experimental tools that couple the controlled induction of DSBs at distinct genomic positions with assays and reporters to investigate DNA repair pathways, their impact on other DNA-templated processes and the specific contribution of the chromatin environment. In this review, we present these tools, discuss their pros and cons and illustrate their contribution to our current understanding of the DDR.European Research Council (ERC-2014-CoG 647344

The supporting role of the teres major muscle, an additional component in glenohumeral stability? An anatomical and radiological study

Muscle coordination plays an important role in glenohumeral stability. The rotator cuff and the long head of the biceps are considered the primary dynamic stabilizers muscles. However, the fact that a subgroup of patients with a massive tear in the rotator cuff were able to keep a normal function, should make us question this traditional view. We hypothesize that the teres major which is also a monoarticular scapulohumeral muscle, although it is not part of the conjoined tendon of the rotator cuff, can play a role in glenohumeral stability by a direct support of the humeral head generated by the particular posteroanterior location of this muscle under the humeral head and which, as far as we know, has not been written up previously. This particular effect could appear while the arm is being lifted and the humeral head could be leaning on against the teres major muscle belly underneath it. An anatomical a radiological study was carried out to substantiate our hypothesis. Two cadaver specimens were used for the anatomical study. Frist body was studied through conventional dissection. The second body was analysed through sectional anatomy. Then a radiological study was carried out using magnetic resonance imaging in a healthy male volunteer. Both anatomically and radiologically, the anteroinferior surface of the humeral head was showed firmly resting against the muscle belly of the teres major, to the point of misshaping it from 110 degrees of arm elevation with external rotation. The specific contribution of this effect to the glenohumeral stability needs to be confirmed by further studies and can help us to prevent the high incidence of glenohumeral dislocations

High-Flow Oxygen with Capping or Suctioning for Tracheostomy Decannulation

9 p.BACKGROUND When patients with a tracheostomy tube reach a stage in their care at which decannulation appears to be possible, it is common practice to cap the tracheostomy tube for 24 hours to see whether they can breathe on their own. Whether this approach to establishing patient readiness for decannulation leads to better outcomes than one based on the frequency of airway suctioning is unclear. METHODS In five intensive care units (ICUs), we enrolled conscious, critically ill adults who had a tracheostomy tube; patients were eligible after weaning from mechanical ventilation. In this unblinded trial, patients were randomly assigned either to undergo a 24-hour capping trial plus intermittent high-flow oxygen therapy (control group) or to receive continuous high-flow oxygen therapy with frequency of suctioning being the indicator of readiness for decannulation (intervention group). The primary outcome was the time to decannulation, compared by means of the log-rank test. Secondary outcomes included decannulation failure, weaning failure, respiratory infections, sepsis, multiorgan failure, durations of stay in the ICU and hospital, and deaths in the ICU and hospital. RESULTS The trial included 330 patients; the mean (±SD) age of the patients was 58.3±15.1 years, and 68.2% of the patients were men. A total of 161 patients were assigned to the control group and 169 to the intervention group. The time to decannulation was shorter in the intervention group than in the control group (median, 6 days [interquartile range, 5 to 7] vs. 13 days [interquartile range, 11 to 14]; absolute difference, 7 days [95% confidence interval, 5 to 9]). The incidence of pneumonia and tracheobronchitis was lower, and the duration of stay in the hospital shorter, in the intervention group than in the control group. Other secondary outcomes were similar in the two groups. CONCLUSIONS Basing the decision to decannulate on suctioning frequency plus continuous highflow oxygen therapy rather than on 24-hour capping trials plus intermittent highflow oxygen therapy reduced the time to decannulation, with no evidence of a between-group difference in the incidence of decannulation failure. (REDECAP ClinicalTrials.gov number, NCT02512744.

Stiff monatomic gold wires with a spinning zigzag geometry

Using first principles density functional calculations, gold monatomic wires are found to exhibit a zigzag shape which remains under tension, becoming linear just before breaking. At room temperature they are found to spin, what explains the extremely long apparent interatomic distances shown by electron microscopy.The zigzag structure is stable if the tension is relieved, the wire holding its chainlike shape even as a free-standing cluster. This unexpected metallic-wire stiffness stems from the transverse quantization in the wire, as shown in a simple free electron model.Comment: 4 pages, latex, 5 figures, submitted to PR

Micromorphological Study of Site Formation Processes at El Sidrón Cave (Asturias, Northern Spain): Encrustations over Neanderthal Bones

El Sidrón Cave is an archaeological and anthropological reference site of the Neanderthal world. It shows singular activity related to cannibalisation, and all existing processes are relevant to explain the specific behaviour of the concerned individuals. This paper presents geoarchaeological data, primarily based on mineralogical and petrographic techniques, from an investigation of the nature of the encrustations or hard coatings that affect a large part of the Neanderthal bone remains and their relationship with the depositional and post-depositional processes at the archaeological site. Crusts and patina were found to be numerous and diverse, mainly composed of calcite and siliciclastic grains, with different proportions and textures. The analysis indicated different origins and scenarios from their initial post-mortem accumulation to the final deposit recovered during the archaeological work. The presence of micromorphological features, such as clotted-peloidal micrite, needle-fibre calcite (NFC) aggregates, clay coatings, iron–manganese impregnation, and/or adhered aeolian dust may indicate that a significant proportion of the remains were affected by subaerial conditions in a relatively short period of time in a shelter, cave entrance, or shallower level of the karstic system, prior to their accumulation in the Ossuary Gallery.This work has been supported since 1999 through different research contracts between the Government of the Principality of Asturias, the University of Oviedo, the University of Alicante, the National Museum of Natural Sciences (CSIC, Madrid), and the University of Salamanca

Geoarchaeological study of the Sidrón cave (Piloña, Asturias)

El relleno sedimentario que alberga el registro arqueológico y antropológico de la Galería del Osario (cueva de El Sidrón) presenta una alta complejidad, tanto en los tipos de sedimentos como en su distribución espacial en la cavidad. Los principales factores que rigen esta complejidad son la naturaleza episódica y altamente energética de gran parte de las unidades litoestratigráficas reconocidas y la irregular geometría del propio conducto, que compartimenta significativamente las áreas de deposición. A modo de resumen puede indicarse que en la Galería del Osario quedan representados todos los tipos de materiales detríticos típicos de depósitos alóctonos en ambiente kárstico; desde materiales bien seleccionados de granulometría fina representativos de facies de encharcamiento (arcillas de la unidad O) o de desbordamiento (Unidad IV), a depósitos groseros mal seleccionados correspondientes a coladas de barro y detritos en masa (Unidad II y base de unidad III), pasando por típicas facies fluvio-kársticas o de canal compuestas por materiales arenosos con laminaciones y estructuras de flujo (unidades I y II). Los restos óseos se concentran en la unidad III. El área fuente se sitúa en cotas superiores a la Galería del Osario, es decir, en los niveles intermedio o superior del sistema kárstico, y el depósito o entrada de material óseo a la Galería del Osario se activaría en episodios de alta energía relacionado con eventos de inundación y/o tormenta.The sedimentary infill bearing the archaeological and anthropological record of the Ossuary Gallery (the Sidrón cave) shows high complexity in both sediment types and their spatial distribution in the cavity. The main factors that govern this complexity are the episodic and highly energetic nature of the recorded sedimentary infill units and the irregular geometry of the gallery itself, which significantly compartmentalized areas of deposition. Briefly, all types of typical allochthonous detrital material deposits in karst environments are represented in the Ossuary Gallery; from well-sorted fine-grained sediment facies representative of backswamp (clays of the unit O) or slackwater (Unit IV), to poorly-sorted coarse-grained deposits corresponding to mudflows and debris flows (Unit II and Unit III base), and typical channel facies composed of laminated sands and silts (units I and II). The bone and lithic remains are concentrated in unit III. The source area is above the Ossuary Gallery, at the intermediate or higher karst levels. The input of archeological material to the Ossuary Gallery was triggered in high energy episodes in association to flood events and / or storms.Este trabajo se ha financiado desde 1999 mediante diferentes contratos de investigación realizados entre el Gobierno del Principado de Asturias, la Universidad de Oviedo, la Universidad de Alicante, el Museo Nacional de Ciencias Naturales (CSIC, Madrid) y la Universidad de Salamanca

A linguistic rule-based approach to extract drug-drug interactions from pharmacological documents

<p>Abstract</p> <p>Background</p> <p>A drug-drug interaction (DDI) occurs when one drug influences the level or activity of another drug. The increasing volume of the scientific literature overwhelms health care professionals trying to be kept up-to-date with all published studies on DDI.</p> <p>Methods</p> <p>This paper describes a hybrid linguistic approach to DDI extraction that combines shallow parsing and syntactic simplification with pattern matching. Appositions and coordinate structures are interpreted based on shallow syntactic parsing provided by the UMLS MetaMap tool (MMTx). Subsequently, complex and compound sentences are broken down into clauses from which simple sentences are generated by a set of simplification rules. A pharmacist defined a set of domain-specific lexical patterns to capture the most common expressions of DDI in texts. These lexical patterns are matched with the generated sentences in order to extract DDIs.</p> <p>Results</p> <p>We have performed different experiments to analyze the performance of the different processes. The lexical patterns achieve a reasonable precision (67.30%), but very low recall (14.07%). The inclusion of appositions and coordinate structures helps to improve the recall (25.70%), however, precision is lower (48.69%). The detection of clauses does not improve the performance.</p> <p>Conclusions</p> <p>Information Extraction (IE) techniques can provide an interesting way of reducing the time spent by health care professionals on reviewing the literature. Nevertheless, no approach has been carried out to extract DDI from texts. To the best of our knowledge, this work proposes the first integral solution for the automatic extraction of DDI from biomedical texts.</p

A first-principles approach to electrical transport in atomic-scale nanostructures

We present a first-principles numerical implementation of Landauer formalism for electrical transport in nanostructures characterized down to the atomic level. The novelty and interest of our method lies essentially on two facts. First of all, it makes use of the versatile Gaussian98 code, which is widely used within the quantum chemistry community. Secondly, it incorporates the semi-infinite electrodes in a very generic and efficient way by means of Bethe lattices. We name this method the Gaussian Embedded Cluster Method (GECM). In order to make contact with other proposed implementations, we illustrate our technique by calculating the conductance in some well-studied systems such as metallic (Al and Au) nanocontacts and C-atom chains connected to metallic (Al and Au) electrodes. In the case of Al nanocontacts the conductance turns out to be quite dependent on the detailed atomic arrangement. On the contrary, the conductance in Au nanocontacts presents quite universal features. In the case of C chains, where the self-consistency guarantees the local charge transfer and the correct alignment of the molecular and electrode levels, we find that the conductance oscillates with the number of atoms in the chain regardless of the type of electrode. However, for short chains and Al electrodes the even-odd periodicity is reversed at equilibrium bond distances.Comment: 14 pages, two-column format, submitted to PR

Spectral characterization of laser-accelerated protons with CR-39 nuclear track detector

CR-39 nuclear track material is frequently used for the detection of protons accelerated in laser-plasma interactions. The measurement of track densities allows for determination of particle angular distributions, and information on the kinetic energy can be obtained by the use of passive absorbers. We present a precise method of measuring spectral distributions of laser-accelerated protons in a single etching and analysis process. We make use of a one-to-one relation between proton energy and track size and present a precise calibration based on monoenergetic particle beams. While this relation is limited to proton energies below 1 MeV, we show that the range of spectral measurements can be significantly extended by simultaneous use of absorbers of suitable thicknesses. Examples from laser-plasma interactions are presented, and quantitative results on proton energies and particle numbers are compared to those obtained from a time-of-flight detector. The spectrum end points of continuous energy distributions have been determined with both detector types and coincide within 50-100 keV