A (3D-nuclear) space odyssey: making sense of Hi-C maps

Three-dimensional 3D)-chromatin organization is critical for proper enhancer-promoter communication and, therefore, for a precise execution of the transcriptional programs governing cellular processes. The emergence of Chromosome Conformation Capture (3C) methods, in particular Hi-C, has allowed the investigation of chromatin interactions on a genome-wide scale, revealing the existence of overlapping molecular mechanisms that we are just starting to decipher. Therefore, disentangling Hi-C signal into these individual components is essential to provide meaningful biological data interpretation. Here, we discuss emerging views on the molecular forces shaping the genome in 3D, with a focus on their respective contributions and interdependence. We discuss Hi-C data at both population and single-cell levels, thus providing criteria to interpret genomic function in the 3D-nuclear space

Effects of Gamma Irradiation on the Kinetics of the Adsorption and Desorption of Hydrogen in Carbon Microfibres

In this study, three types of carbon fibres were used, they were ex-polyacrylonitrile carbon fibres with high bulk modulus, ex-polyacrylonitrile fibres with high strength, and vapour grown carbon fibres. All the samples were subjected to a hydrogen adsorption process at room temperature in an over-pressured atmosphere of 25 bars. The adsorption process was monitored through electrical resistivity measurements. As conditioning of the fibres, a chemical activation by acid etching followed by ¿-ray irradiation with 60Co radioisotopes was performed. The surface energy was deter-mined by means of the sessile drop test. Both conditioning treatments are supplementary; the chemical activation works on the outer surface and the ¿-irradiation works in the bulk material as well. Apparently, the most significant parameter for hydrogen storage is the crystallite size. From this point of view, the mostPeer Reviewe

First evidence of paleoearthquakes along the Carboneras Fault Zone (SE Iberian Peninsula): Los Trances site

Seismogenic faults that have not produced historical large earthquakes remain unnoticed and, thus, are dangerously left out from seismic hazard analyses. The seismogenic nature of the Carboneras Fault Zone, a left-lateral strikeslip fault in the Eastern Betic Shear Zone (southeastern Spain), has not been fully explored to date in spite of having a morphological expression equivalent to the Alhama de Murcia Fault, a seismogenic fault in the same tectonic system. This study provides the first paleoseismic evidence of the seismogenic nature of the Carboneras Fault Zone, based on the analysis of 3 trenches at Los Trances site, on the northwestern edge of the La Serrata Range. Cross cutting relationships and numerical dating, based on radiocarbon, thermoluminescence and U-series, reveal a minimum of 4 paleoearthquakes: Paleoearthquake1 (the oldest) and Paleoearthquake2 took place after 133ka, Paleoearthquake3 occurred between 83-73ka and Paleoearthquake4 happened after 42.5ka (probably after 30.8ka), resulting in a maximum possible average recurrence of 33ka. This value, based on a minimum amount of paleoearthquakes, is probably overestimated, as it does not scale well with published slip-rates derived from offset channels or GPS geodetical data. The characterization of this fault as seismogenic, implies that it should be considered in the seismic hazard analyses of the SE Iberian Peninsula

Unifying inflation with dark energy in modified F(R) Horava-Lifshitz gravity

We study FRW cosmology for a non-linear modified F(R) Horava-Lifshitz gravity which has a viable convenient counterpart. A unified description of early-time inflation and late-time acceleration is possible in this theory, but the cosmological dynamic details are generically different from the ones of the convenient viable F(R) model. Remarkably, for some specific choice of parameters they do coincide. The emergence of finite-time future singularities is investigated in detail. It is shown that these singularities can be cured by adding an extra, higher-derivative term, which turns out to be qualitatively different when compared with the corresponding one of the convenient F(R) theory.Comment: LaTeX 12 pages, typos are correcte

Data sources for drug utilization research in Latin American countries—A cross-national study: DASDUR-LATAM study

Purpose: Drug utilization research (DUR) contributes to inform policymaking and to strengthen health systems. The availability of data sources is the first step for conducting DUR. However, documents that systematize these data sources in Latin American (LatAm) countries are not known. We compiled the potential data sources for DUR in the LatAm region. Methods: A network of DUR experts from nine LatAm countries was assembled and experts conducted: (i) a website search of the government, academic, and private health institutions; (ii) screening of eligible data sources, and (iii) liaising with national experts in pharmacoepidemiology (via an online survey). The data sources were characterized by accessibility, geographic granularity, setting, sector of the data, sources and type of the data. Descriptive analyses were performed. Results: We identified 125 data sources for DUR in nine LatAm countries. Thirty-eight (30%) of them were publicly and conveniently available; 89 (71%) were accessible with limitations, and 18 (14%) were not accessible or lacked clear rules for data access. From the 125 data sources, 76 (61%) were from the public sector only; 46 (37%) were from pharmacy records; 43 (34%) came from ambulatory settings and; 85 (68%) gave access to individual patient-level data. Conclusions: Although multiple sources for DUR are available in LatAm countries, the accessibility is a major challenge. The procedures for accessing DUR data should be transparent, feasible, affordable, and protocol-driven. This inventory could permit a comparison of drug utilization between countries identifying potential medication-related problems that need further exploration.Fil: Lopes, Luciane C.. University Of Sorocaba; BrasilFil: Salas, Daiana Maribel. University of Pennsylvania; Estados UnidosFil: Osorio de Castro, Claudia Garcia Serpa. Fundación Oswaldo Cruz; BrasilFil: Freitas Leal, Lisiane. McGill University; CanadáFil: Doubova, Svetlana V.. Mexican Institute of Social Security; MéxicoFil: Cañás, Martín. Universidad Nacional Arturo Jauretche; Argentina. Federación Médica de la Provincia de Buenos Aires; ArgentinaFil: Dreser, Anahi. Instituto Nacional de Salud Pública; MéxicoFil: Acosta, Angela. Universidad ICESI; ColombiaFil: Oliveira Baldoni, Andre. Federal University of São João Del-Rei; BrasilFil: de Cássia Bergamaschi, Cristiane. University of Sorocaba; BrasilFil: Marques Mota, Daniel. Brazilian Health Regulatory Agency; BrasilFil: Gómez Galicia, Diana L.. Universidad Autónoma del Estado de Morelos; MéxicoFil: Sepúlveda Viveros, Dino. Universidad de Chile; ChileFil: Narvaez Delgado, Edgard. No especifíca;Fil: da Costa Lima, Elisangela. Universidade Federal do Rio de Janeiro; BrasilFil: Chandia, Felipe Vera. Pontificia Universidad Católica de Chile; ChileFil: Ferre, Felipe. Universidade Federal de Minas Gerais; BrasilFil: Marin, Gustavo Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata; ArgentinaFil: Olmos, Ismael. State Health Services Administration; UruguayFil: Zimmermann, Ivan R.. Universidade do Brasília; BrasilFil: Fulone, Izabela. University of Sorocaba; BrasilFil: Roldán Saelzer, Juan. Instituto de Salud Pública; ChileFil: Sánchez Salgado, Juan Carlos. No especifíca;Fil: Castro Pastrana, Lucila I.. Universidad de Las Américas de Puebla; MéxicoFil: de Souza, Luiz Jupiter Carneiro. Fundación Oswaldo Cruz; BrasilFil: Machado Beltrán, Manuel. Universidad Nacional de Colombia; ColombiaFil: Tolentino Silva, Marcus. University of Sorocaba; BrasilFil: Mena, María Belén. Universidad Central del Ecuador; EcuadorFil: de França Fonteles, Marta Maria. Universidade Federal do Ceara; BrasilFil: Urtasun, Martín Alejandro. Universidad Nacional Arturo Jauretche; Argentina. Federación Médica de la Provincia de Buenos Aires; Argentin

New endoperoxides highly active in vivo and in vitro against artemisinin-resistant Plasmodium falciparum

Background: The emergence and spread of Plasmodium falciparum resistance to artemisinin-based combination therapy in Southeast Asia prompted the need to develop new endoperoxide-type drugs. Methods: A chemically diverse library of endoperoxides was designed and synthesized. The compounds were screened for in vitro and in vivo anti-malarial activity using, respectively, the SYBR Green I assay and a mouse model. Ring survival and mature stage survival assays were performed against artemisinin-resistant and artemisinin-sensitive P. falciparum strains. Cytotoxicity was evaluated against mammalian cell lines V79 and HepG2, using the MTT assay. Results: The synthesis and anti-malarial activity of 21 new endoperoxide-derived compounds is reported, where the peroxide pharmacophore is part of a trioxolane (ozonide) or a tetraoxane moiety, flanked by adamantane and a substituted cyclohexyl ring. Eight compounds exhibited sub-micromolar anti-malarial activity (IC50 0.3–71.1 nM), no cross-resistance with artemisinin or quinolone derivatives and negligible cytotoxicity towards mammalian cells. From these, six produced ring stage survival < 1% against the resistant strain IPC5202 and three of them totally suppressed Plasmodium berghei parasitaemia in mice after oral administration. Conclusion: The investigated, trioxolane–tetrazole conjugates LC131 and LC136 emerged as potential anti-malarial candidates; they show negligible toxicity towards mammalian cells, ability to kill intra-erythrocytic asexual stages of artemisinin-resistant P. falciparum and capacity to totally suppress P. berghei parasitaemia in mice.info:eu-repo/semantics/publishedVersio

Multiscale modelling for fusion and fission materials: the M4F project

The M4F project brings together the fusion and fission materials communities working on the prediction of radiation damage production and evolution and its effects on the mechanical behaviour of irradiated ferritic/martensitic (F/M) steels. It is a multidisciplinary project in which several different experimental and computational materials science tools are integrated to understand and model the complex phenomena associated with the formation and evolution of irradiation induced defects and their effects on the macroscopic behaviour of the target materials. In particular the project focuses on two specific aspects: (1) To develop physical understanding and predictive models of the origin and consequences of localised deformation under irradiation in F/M steels; (2) To develop good practices and possibly advance towards the definition of protocols for the use of ion irradiation as a tool to evaluate radiation effects on materials. Nineteen modelling codes across different scales are being used and developed and an experimental validation programme based on the examination of materials irradiated with neutrons and ions is being carried out. The project enters now its 4th year and is close to delivering high-quality results. This paper overviews the work performed so far within the project, highlighting its impact for fission and fusion materials science.This work has received funding from the Euratom research and training programme 2014-2018 under grant agreement No. 755039 (M4F project)

Genes left behind: Climate change threatens cryptic genetic diversity in the canopy-forming seaweed bifurcaria bifurcata

The global redistribution of biodiversity will intensify in the coming decades of climate change, making projections of species range shifts and of associated genetic losses important components of conservation planning. Highly-structured marine species, notably brown seaweeds, often harbor unique genetic variation at warmer low-latitude rear edges and thus are of particular concern. Here, a combination of Ecological Niche Models (ENMs) and molecular data is used to forecast the potential near-future impacts of climate change for a warm-temperate, canopy forming seaweed, Bifurcaria bifurcata. ENMs for B. bifurcata were developed using marine and terrestrial climatic variables, and its range projected for 2040-50 and 2090-2100 under two greenhouse emission scenarios. Geographical patterns of genetic diversity were assessed by screening 18 populations spawning the entire distribution for two organelle genes and 6 microsatellite markers. The southern limit of B. bifurcata was predicted to shift northwards to central Morocco by the mid-century. By 2090-2100, depending on the emission scenario, it could either retreat further north to western Iberia or be relocated back to Western Sahara. At the opposing margin, B. bifurcata was predicted to expand its range to Scotland or even Norway. Microsatellite diversity and endemism were highest in Morocco, where a unique and very restricted lineage was also identified. Our results imply that B. bifurcata will maintain a relatively broad latitudinal distribution. Although its persistence is not threatened, the predicted extirpation of a unique southern lineage or even the entire Moroccan diversity hotspot will erase a rich evolutionary legacy and shrink global diversity to current (low) European levels. NW Africa and similarly understudied southern regions should receive added attention if expected range changes and diversity loss of warm-temperate species is not to occur unnoticed.Portuguese FCT (Fundacao para a Ciencia e a Tecnologia) [PTDC/AAC-CLI/109108/2008, EXPL/BIA-BIC/1471/2012, EXCL/AAG-GLO/0661/2012]; [SFRH/BPD/88935/2012]info:eu-repo/semantics/publishedVersio

A modern network approach to revisiting the positive and negative affective schedule (PANAS) construct validity

Introduction: The factor structure of the Positive and Negative Affective Schedule (PANAS) is still a topic of debate. There are several reasons why using Exploratory Graph Analysis (EGA) for scale validation is advantageous and can help understand and resolve conflicting results in the factor analytic literature. Objective: The main objective of the present study was to advance the knowledge regarding the factor structure underlying the PANAS scores by utilizing the different functionalities of the EGA method. EGA was used to (1) estimate the dimensionality of the PANAS scores, (2) establish the stability of the dimensionality estimate and of the item assignments into the dimensions, and (3) assess the impact of potential redundancies across item pairs on the dimensionality and structure of the PANAS scores. Method: This assessment was carried out across two studies that included two large samples of participants. Results and Conclusion: In sum, the results are consistent with a two-factor oblique structure.Fil: Flores Kanter, Pablo Ezequiel. Universidad Empresarial Siglo XXI; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Garrido, Luis Eduardo. Pontificia Universidad Católica Madre y Maestra; República DominicanaFil: Moretti, Luciana Sofía. Universidad Empresarial Siglo XXI; Argentina. Pontificia Universidad Católica Madre y Maestra; República Dominicana. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Medrano, Leonardo. Universidad Empresarial Siglo XXI; Argentina. Pontificia Universidad Católica Madre y Maestra; República Dominicana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin