Structural basis for inhibition of the histone chaperone activity of SET/TAF-Iß by cytochrome c

Chromatin is pivotal for regulation of the DNA damage process insofar as it influences access to DNA and serves as a DNA repair docking site. Recent works identify histone chaperones as key re- gulators of damaged chromatin’s transcriptional activity. However, understanding how chaperones are modulated during DNA damage response is still challenging. This study reveals that the histone chap- erone SET/TAF-Iß interacts with cytochrome c following DNA damage. Specifically, cytochrome c is shown to be translocated into cell nuclei upon induction of DNA damage, but not upon stimulation of the death receptor or stress-induced pathways. Cytochrome c was found to competitively hinder binding of SET/TAF-Iß to core histones, thereby locking its histone-binding domains and inhibiting its nucle- osome assembly activity. In addition, we have used NMR spectros- copy, calorimetry, mutagenesis, and molecular docking to provide an insight into the structural features of the formation of the complex between cytochrome c and SET/TAF-Iß. Overall, these findings estab- lish a framework for understanding the molecular basis of cyto- chrome c-mediated blocking of SET/TAF-Iß, which subsequently may facilitate the development of new drugs to silence the oncogenic effect of SET/TAF-Iß’s histone chaperone activity

Motives for exercising among young adults with a moderately positive body image

Background: People engage in exercise and sports due to several reasons, depending on factors such as age, sex and health or fitness status. These motives include enhancing health and fitness status, improving appearance and body image or enjoying in leisure time. Aims & Methods: Grounded in Self-Determination Theory (SDT), this study explored motives for exercising in healthy men and women 18 to 40 years old who were regular exercisers and held a moderately positive body image. They voluntarily completed an online survey on their exercise practice, body image and motives for exercising. Results: Contrary to previous SDT-based empirical findings, appearance improvement emerged as an important motive for exercising, and it was more frequently mentioned than health&fun-related motives by the whole sample and by subsamples of men and women and younger young and older young adults. Conclusions: Given that appearance management-related motives may have both positive and undesired outcomes on exercise behaviour and personal well-being, they should be carefully reviewed with women and men in their young adulthood who are exercise intenders, beginners or regular exercisers

Using radioastronomy techniques and cold plasmas to study transient and stable molecular species of astrophysical interest: a proof of concept.

45th EPS Conference on Plasma Physics. European Physical Society Conference on Plasma Physics. 2-6 July. Prague, Czech Republic(2018. --. https://eps2018.eli-beams.eu/en

Broad-band high-resolution rotational spectroscopy for laboratory astrophysics

We present a new experimental set-up devoted to the study of gas phase molecules and processes using broad-band high spectral resolution rotational spectroscopy. A reactor chamber is equipped with radio receivers similar to those used by radio astronomers to search for molecular emission in space. The whole range of the Q (31.5-50 GHz) and W bands (72-116.5 GHz) is available for rotational spectroscopy observations. The receivers are equipped with 16 × 2.5 GHz fast Fourier transform spectrometers with a spectral resolution of 38.14 kHz allowing the simultaneous observation of the complete Q band and one-third of the W band. The whole W band can be observed in three settings in which the Q band is always observed. Species such as CH3CN, OCS, and SO2 are detected, together with many of their isotopologues and vibrationally excited states, in very short observing times. The system permits automatic overnight observations, and integration times as long as 2.4 × 105 s have been reached. The chamber is equipped with a radiofrequency source to produce cold plasmas, and with four ultraviolet lamps to study photochemical processes. Plasmas of CH4, N2, CH3CN, NH3, O2, and H2, among other species, have been generated and the molecular products easily identified by the rotational spectrum, and via mass spectrometry and optical spectroscopy. Finally, the rotational spectrum of the lowest energy conformer of CH3CH2NHCHO (N-ethylformamide), a molecule previously characterized in microwave rotational spectroscopy, has been measured up to 116.5 GHz, allowing the accurate determination of its rotational and distortion constants and its search in space.We thank the European Research Council for funding support under Synergy Grant ERC-2013-SyG, G.A. 610256 (NANOCOSMOS). IT, VJH, and JLD acknowledge additional partial support from the Spanish State Research Agency (AEI) through grant FIS2016-77726-C3-1-P. JAMG, LM, and GS acknowledge additional partial support from the Spanish State Research Agency (AEI) through grant MAT2017-85089-C2-1R. We thank David López Romero for his help during the process of installation, commissioning, and cleaning of the chamber. We would like to thank Kremena Makasheva for the useful comments and suggestions during the experiments with Hexamethyldisiloxane. We would also like to thank Rosa Lebrón, Jesús Quintanilla, and Cristina Soria for providing us with the sample of N-ethylformamide. Sandra I. Ramírez acknowledges support from the FONCICYT under grant number 291842. Celina Bermúdez thanks the Spanish Ministerio de Ciencia Innovación y Universidades for the Juan de la Cierva grant FJCI-2016-27983

Colorectal adenomas contain multiple somatic mutations that do not coincide with synchronous adenocarcinoma specimens

We have performed a comparative ultrasequencing study of multiple colorectal lesions obtained simultaneously from four patients. Our data show that benign lesions (adenomatous or hyperplastic polyps) contain a high mutational load. Additionally multiple synchronous colorectal lesions show non overlapping mutational signatures highlighting the degree of heterogeneity between multiple specimens in the same patient. Observations in these cases imply that considering not only the number of mutations but an effective oncogenic combination of mutations can determine the malignant progression of colorectal lesions

Competitive Asymmetries in the Use of Supplementary Food by the Endangered Iberian Lynx (Lynx pardinus)

Background: As a conservation tool, supplementary feeding programs may be directed to specific individuals or sectors of the target population whose productivity or survival is thought to be limited by food scarcity. However, the use of supplemental food by different sex and age classes has received little attention. We studied individual variation in the access of the endangered Iberian lynx (Lynx pardinus) to supplementary food. Methodology/Principal Findings: From 5349 pictures taken with automatic cameras placed in 25 feeding stations, we identified 28 individuals whose sex and age were known. All individuals known to live in areas subjected to supplementation regularly visited feeding stations. Food consumption was not proportional to expected variations in energy demand within sex and age classes. Food consumption by males was higher than by females, and increased with age, in agreement with a despotic distribution. Food consumption also increased with lynx body mass, and this pattern held for individuals sharing the same breeding territories. The access of inferior competitors increased with the number of feeding stations available within lynx territories. Conclusions/Significance: All lynx exposed to food supplementation made a regular use of extra food but individuals predicted to be competitively dominant visited stations more frequently than subordinates of the same breeding territory. Our results suggest that insufficient provision of supplementary food could restrict the access of juveniles, or even adult females, to feeding stations. Limited consumption by these target individuals may compromise the efficiency of the supplementary feeding programme at the population level, in endangered species that, as the Iberian lynx, exhibit marked sexual dimorphism in body size.Peer reviewe

Oral Anticoagulation and Risk of Symptomatic Hemorrhagic Transformation in Stroke Patients Treated With Mechanical Thrombectomy: Data From the Nordictus Registry

Introduction: We aimed to evaluate if prior oral anticoagulation (OAC) and its type determines a greater risk of symptomatic hemorrhagic transformation in patients with acute ischemic stroke (AIS) subjected to mechanical thrombectomy. Materials and Methods: Consecutive patients with AIS included in the prospective reperfusion registry NORDICTUS, a network of tertiary stroke centers in Northern Spain, from January 2017 to December 2019 were included. Prior use of oral anticoagulants, baseline variables, and international normalized ratio (INR) on admission were recorded. Symptomatic intracranial hemorrhage (sICH) was the primary outcome measure. Secondary outcome was the relation between INR and sICH, and we evaluated mortality and functional outcome at 3 months by modified Rankin scale. We compared patients with and without previous OAC and also considered the type of oral anticoagulants. Results: About 1.455 AIS patients were included, of whom 274 (19%) were on OAC, 193 (70%) on vitamin K antagonists (VKA), and 81 (30%) on direct oral anticoagulants (DOACs). Anticoagulated patients were older and had more comorbidities. Eighty-one (5.6%) developed sICH, which was more frequent in the VKA group, but not in DOAC group. OAC with VKA emerged as a predictor of sICH in a multivariate regression model (OR, 1.89 [95% CI, 1.01–3.51], p = 0.04) and was not related to INR level on admission. Prior VKA use was not associated with worse outcome in the multivariate regression model nor with mortality at 3 months. Conclusions: OAC with VKA, but not with DOACs, was an independent predictor of sICH after mechanical thrombectomy. This excess risk was associated neither with INR value by the time thrombectomy was performed, nor with a worse functional outcome or mortality at 3 months

Parámetros de detección precoz de infección fúngica por aspergillus en el paciente hematológico

PO-267 Introducción: La infección fúngica invasiva (IFI) por Aspergillus es una de las principales micosis invasivas en el paciente hematológico y una importante causa de morbimortalidad. Es más frecuente en pacientes con leucemia aguda mieloide, trasplante de progenitores hematopoyéticos alogénico, enfermedad injerto contra receptor activa o neutropenia prolongada. Supone un reto diagnóstico, siendo preciso el empleo de múltiples técnicas microbiológicas y radiológicas. Avances recientes en el diagnóstico, en la profilaxos y en el tratamiento antifúngico precoz, han reducido considerablemente la mortalidad asociada a esta infección. Objetivos: Determinar si los marcadores diagnósticos empleados en la práctica clínica habitual permiten un diagnóstico precoz de IFI, si la determinación de bismetilgliotoxina (bmGT) en suero permite un diagnóstico precoz en pacientes con antígeno de galactomanano (AGA) en suero negativo y la exactitud diagnóstica de estos marcadores. ..

Zipf's Law in Short-Time Timbral Codings of Speech, Music, and Environmental Sound Signals

Timbre is a key perceptual feature that allows discrimination between different sounds. Timbral sensations are highly dependent on the temporal evolution of the power spectrum of an audio signal. In order to quantitatively characterize such sensations, the shape of the power spectrum has to be encoded in a way that preserves certain physical and perceptual properties. Therefore, it is common practice to encode short-time power spectra using psychoacoustical frequency scales. In this paper, we study and characterize the statistical properties of such encodings, here called timbral code-words. In particular, we report on rank-frequency distributions of timbral code-words extracted from 740 hours of audio coming from disparate sources such as speech, music, and environmental sounds. Analogously to text corpora, we find a heavy-tailed Zipfian distribution with exponent close to one. Importantly, this distribution is found independently of different encoding decisions and regardless of the audio source. Further analysis on the intrinsic characteristics of most and least frequent code-words reveals that the most frequent code-words tend to have a more homogeneous structure. We also find that speech and music databases have specific, distinctive code-words while, in the case of the environmental sounds, this database-specific code-words are not present. Finally, we find that a Yule-Simon process with memory provides a reasonable quantitative approximation for our data, suggesting the existence of a common simple generative mechanism for all considered sound sources

Heart Rate Variability Dynamics for the Prognosis of Cardiovascular Risk

Statistical, spectral, multi-resolution and non-linear methods were applied to heart rate variability (HRV) series linked with classification schemes for the prognosis of cardiovascular risk. A total of 90 HRV records were analyzed: 45 from healthy subjects and 45 from cardiovascular risk patients. A total of 52 features from all the analysis methods were evaluated using standard two-sample Kolmogorov-Smirnov test (KS-test). The results of the statistical procedure provided input to multi-layer perceptron (MLP) neural networks, radial basis function (RBF) neural networks and support vector machines (SVM) for data classification. These schemes showed high performances with both training and test sets and many combinations of features (with a maximum accuracy of 96.67%). Additionally, there was a strong consideration for breathing frequency as a relevant feature in the HRV analysis