Resveratrol given intraperitoneally does not inhibit the growth of high-risk t(4;11) acute lymphoblastic leukemia cells in a NOD/SCID mouse model.

The efficacy of resveratrol as a preventive agent against the growth of t(4;11) acute lymphoblastic leukemia (ALL) was evaluated in NOD.CB17-Prkdcscid/J mice engrafted with the human t(4;11) ALL SEM cell line. SEM cells were injected into the tail vein and engraftment was monitored by flow cytometry. Once engraftment was observed, mice were injected intraperitoneally with resveratrol (10 mg/kg body weight) dissolved in dimethylsulfoxide (DMSO) or DMSO alone (control) every other day, or vincristine (0.5 mg/kg body weight) 3 times per week for 4 weeks (n=16 per group). Comparisons of the percent of human leukemia cells in blood and survival curves showed resveratrol did not inhibit progression of the disease. Liquid chromatography-tandem mass spectrometry analyses of mouse sera showed resveratrol was rapidly metabolized to glucuronidated and sulfated forms 1 h post-injection, with low to no resveratrol or metabolites observed in sera by 24-48 h. These data indicate that in contrast to findings in in vitro models, parenterally administered resveratrol does not have potential as a preventive agent against high risk t(4;11) ALL

A Comprehensive Framework for the Security Risk Management of Cyber-Physical Systems

Cyber Physical Systems are facing huge and diverse set of security risks, especially cyber-attacks that can cause disruption to physical services or create a national disaster. Information and communication technology (ICT) has made a remarkable impact on the society. A Cyber Physical System (CPS) relies basically on information and communication technology, which puts the system\u2019s assets under certain risks especially cyber ones, and hence they must be kept under control by means of security countermeasures that generate confidence in the use of these assets. And so there is a critical need to give a great attention on the cybersecurity of these systems, which consequently leads to the safety of the physical world. This goal is achieved by adopting a solution that applies processes, plans and actions to prevent or reduce the effects of threats. Traditional IT risk assessment methods can do the job, however, and because of the characteristics of a CPS, it is more efficient to adopt a solution that is wider than a method, and addresses the type, functionalities and complexity of a CPS. This chapter proposes a framework that breaks the restriction to a traditional risk assessment method and encompasses wider set of procedures to achieve a high level strategy that could be adopted in the risk management process, in particular the cybersecurity of cyber-physical systems

Determining the driving forces to environmental change processes of La Araucanía, Chile. The "cultural landscape" as a framework

Indexación: Scopus; Scielo.El artículo propone el concepto de paisaje cultural como una perspectiva holística de análisis de procesos de transformación del paisaje. Para ello se utilizó como caso de estudio el proceso de degradación ambiental de la región de La Araucanía (Chile). Se esclarecieron las motivaciones de las actuaciones en el territorio y sus fuerzas conductoras. Estas fuerzas se relacionan a objetivos económicos externos a la población local y generaron una transformación del paisaje impactando la forma de vida de sus habitantes, quebrando el acoplamiento estructural entre población y paisaje, resultando en un paisaje cultural degradado ambientalmente.The notion of cultural landscape was deployed to analyze transformation processes of rural landscapes. As a case study, environmental degradation processes in La Araucania (Chile) region were analyzed. The goals of actions over the territory and their driving forces were determined. These actions were related to economic motives external to local inhabitants and produced deep transformations of the landscape and impacted the way of life of its inhabitants, breaking down the structural coupling between population and landscape, resulting in an environmentally degraded cultural landscape.https://scielo.conicyt.cl/scielo.php?script=sci_arttext&pid=S0719-26812017000300051&lng=en&nrm=iso&tlng=e

Variability of the transport of anthropogenic CO2 at the Greenland-Portugal OVIDE section:Controlling mechanisms

The interannual to decadal variability in the transport of anthropogenic CO2 (Cant) across the subpolar North Atlantic (SPNA) is investigated, using summer data of the FOUREX and OVIDE high-resolution transoceanic sections, from Greenland to Portugal, occupied six times from 1997 to 2010. The transport of Cant across this section, Tcant hereafter, is northward, with a mean value of 254 ± 29 kmol s-1 over the 1997-2010 period. We find that Tcant undergoes interannual variability, masking any trend different from 0 for this period. In order to understand the mechanisms controlling the variability of Tcant across the SPNA, we propose a new method that quantifies the transport of Cant caused by the diapycnal and isopycnal circulation. The diapycnal component yields a large northward transport of Cant (400 ± 29 kmol s-1) that is partially compensated by a southward transport of Cant caused by the isopycnal component (-171 ± 11 kmol s-1), mainly localized in the Irminger Sea. Most importantly, the diapycnal component is found to be the main driver of the variability of Tcant across the SPNA. Both the Meridional Overturning Circulation (computed in density coordinates, MOCσ) and the Cant increase in the water column have an important effect on the variability of the diapycnal component and of Tcant itself. Based on this analysis, we propose a simplified estimator for the variability of T cant based on the intensity of the MOCσ and on the difference of Cant between the upper and lower limb of the MOCσ (ΔCant). This estimator shows a good consistency with the diapycnal component of T cant, and help to disentangle the effect of the variability of both the circulation and the Cant increase on the Tcant variability. We find that ΔCant keeps increasing over the past decade, and it is very likely that the continuous Cant increase in the water masses will cause an increase in Tcant across the SPNA at long timescale. Nevertheless, at the timescale analyzed here (1997-2010), the MOCσ controls the T cant variability, blurring any Tcant trend. Extrapolating the observed ΔCant increase rate and considering the predicted slow-down of 25% of the MOCσ, Tcant across the SPNA is expected to increase by 430 kmol s-1 during the 21st century. Consequently, an increase in the storage rate of Cant in the SPNA could be envisaged

MaxEnt and dynamical information

The MaxEnt solutions are shown to display a variety of behaviors (beyond the traditional and customary exponential one) if adequate dynamical information is inserted into the concomitant entropic-variational principle. In particular, we show both theoretically and numerically that power laws and power laws with exponential cut-offs emerge as equilibrium densities in proportional and other dynamics

Water mass distributions and transports for the 2014 GEOVIDE cruise in the North Atlantic

We present the distribution of water masses along the GEOTRACES-GA01 section during the GEOVIDE cruise, which crossed the subpolar North Atlantic Ocean and the Labrador Sea in the summer of 2014. The water mass structure resulting from an extended optimum multiparameter (eOMP) analysis provides the framework for interpreting the observed distributions of trace elements and their isotopes. Central Waters and Subpolar Mode Waters (SPMW) dominated the upper part of the GEOTRACES-GA01 section. At intermediate depths, the dominant water mass was Labrador Sea Water, while the deep parts of the section were filled by Iceland-Scotland Overflow Water (ISOW) and North-East Atlantic Deep Water. We also evaluate the water mass volume transports across the 2014 OVIDE line (Portugal to Greenland section) by combining the water mass fractions resulting from the eOMP analysis with the absolute geostrophic velocity field estimated through a box inverse model. This allowed us to assess the relative contribution of each water mass to the transport across the section. Finally, we discuss the changes in the distribution and transport of water masses between the 2014 OVIDE line and the 2002-2010 mean state. At the upper and intermediate water levels, colder end-members of the water masses replaced the warmer ones in 2014 with respect to 2002-2010, in agreement with the long-term cooling of the North Atlantic Subpolar Gyre that started in the mid-2000s. Below 2000 dbar, ISOW increased its contribution in 2014 with respect to 2002-2010, with the increase being consistent with other estimates of ISOW transports along 58-59° N. We also observed an increase in SPMW in the East Greenland Irminger Current in 2014 with respect to 2002-2010, which supports the recent deep convection events in the Irminger Sea. From the assessment of the relative water mass contribution to the Atlantic Meridional Overturning Circulation (AMOC) across the OVIDE line, we conclude that the larger AMOC intensity in 2014 compared to the 2002-2010 mean was related to both the increase in the northward transport of Central Waters in the AMOC upper limb and to the increase in the southward flow of Irminger Basin SPMW and ISOW in the AMOC lower limb

Tissue multifractality and Born approximation in analysis of light scattering: a novel approach for precancers detection

Multifractal, a special class of complex self-affine processes, are under recent intensive investigations because of their fundamental nature and potential applications in diverse physical systems. Here, we report on a novel light scattering-based inverse method for extraction/quantification of multifractality in the spatial distribution of refractive index of biological tissues. The method is based on Fourier domain pre-processing via the Born approximation, followed by the Multifractal Detrended Fluctuation Analysis. The approach is experimentally validated in synthetic multifractal scattering phantoms, and tested on biopsy tissue slices. The derived multifractal properties appear sensitive in detecting cervical precancerous alterations through an increase of multifractality with pathology progression, demonstrating the potential of the developed methodology for novel precancer biomarker identification and tissue diagnostic tool. The novel ability to delineate the multifractal optical properties from light scattering signals may also prove useful for characterizing a wide variety of complex scattering media of non-biological origin

Impact of Nutritional Stress on Honeybee Gut Microbiota, Immunity, and Nosema ceranae Infection

Honeybees are important pollinators, having an essential role in the ecology of natural and agricultural environments. Honeybee colony losses episodes reported worldwide and have been associated with different pests and pathogens, pesticide exposure, and nutritional stress. This nutritional stress is related to the increase in monoculture areas which leads to a reduction of pollen availability and diversity. In this study, we examined whether nutritional stress affects honeybee gut microbiota, bee immunity, and infection by Nosema ceranae, under laboratory conditions. Consumption of Eucalyptus grandis pollen was used as a nutritionally poor-quality diet to study nutritional stress, in contraposition to the consumption of polyfloral pollen. Honeybees feed with Eucalyptus grandis pollen showed a lower abundance of Lactobacillus mellifer and Lactobacillus apis (Firm-4 and Firm-5, respectively) and Bifidobacterium spp. and a higher abundance of Bartonella apis, than honeybees fed with polyfloral pollen. Besides the impact of nutritional stress on honeybee microbiota, it also decreased the expression levels of vitellogenin and genes associated to immunity (glucose oxidase, hymenoptaecin and lysozyme). Finally, Eucalyptus grandis pollen favored the multiplication of Nosema ceranae. These results show that nutritional stress impacts the honeybee gut microbiota, having consequences on honeybee immunity and pathogen development. Those results may be useful to understand the influence of modern agriculture on honeybee health.Fil: Castelli, L.. Instituto de Investigaciones Biológicas "Clemente Estable"; UruguayFil: Branchiccela, B.. Instituto de Investigaciones Biológicas "Clemente Estable"; UruguayFil: Garrido, Paula Melisa. Universidad Nacional de Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente; ArgentinaFil: Invernizzi, Ciro. No especifíca;Fil: Porrini, Martín Pablo. Universidad Nacional de Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente; ArgentinaFil: Romero, H.. No especifíca;Fil: Santos, E.. No especifíca;Fil: Zunino, P.. Instituto de Investigaciones Biológicas "Clemente Estable"; UruguayFil: Antúnez, Karina. Instituto de Investigaciones Biológicas "Clemente Estable"; Urugua

Learning high-order interactions for polygenic risk prediction

Within the framework of precision medicine, the stratification of individual genetic susceptibility based on inherited DNA variation has paramount relevance. However, one of the most relevant pitfalls of traditional Polygenic Risk Scores (PRS) approaches is their inability to model complex high-order non-linear SNP-SNP interactions and their effect on the phenotype (e.g. epistasis). Indeed, they incur in a computational challenge as the number of possible interactions grows exponentially with the number of SNPs considered, affecting the statistical reliability of the model parameters as well. In this work, we address this issue by proposing a novel PRS approach, called High-order Interactions-aware Polygenic Risk Score (hiPRS), that incorporates high-order interactions in modeling polygenic risk. The latter combines an interaction search routine based on frequent itemsets mining and a novel interaction selection algorithm based on Mutual Information, to construct a simple and interpretable weighted model of user-specified dimensionality that can predict a given binary phenotype. Compared to traditional PRSs methods, hiPRS does not rely on GWAS summary statistics nor any external information. Moreover, hiPRS differs from Machine Learning-based approaches that can include complex interactions in that it provides a readable and interpretable model and it is able to control overfitting, even on small samples. In the present work we demonstrate through a comprehensive simulation study the superior performance of hiPRS w.r.t. state of the art methods, both in terms of scoring performance and interpretability of the resulting model. We also test hiPRS against small sample size, class imbalance and the presence of noise, showcasing its robustness to extreme experimental settings. Finally, we apply hiPRS to a case study on real data from DACHS cohort, defining an interaction-aware scoring model to predict mortality of stage II-III Colon-Rectal Cancer patients treated with oxaliplatin

Golgi derived PI(4)P-containing vesicle drives late steps of mitochondrial division

Mitochondrial plasticity is a key regulator of cell fate decisions. Mitochondrial division involves Dynamin-related protein-1 (Drp1) oligomerization, which constricts membranes at endoplasmic reticulum (ER) contact sites. The mechanisms driving the final steps of mitochondrial division are still unclear. Here, we found that microdomains of phosphatidylinositol 4-phosphate (PI(4)P) on Trans-Golgi network (TGN) vesicles were recruited to mitochondria-ER contact sites and could drive mitochondrial division downstream of Drp1. The loss of the small GTPase ADP-ribosylation factor 1 (Arf1) or its effector, phosphatidylinositol 4-kinase IIIβ (PI(4)KIIIβ) in different mammalian cell lines, prevented PI(4)P generation and led to a hyperfused and branched mitochondrial network, marked with extended mitochondrial constriction sites. Thus, recruitment of TGN-PI(4)P-containing vesicles at mitochondria-ER contact sites may trigger final events leading to mitochondrial scission.This work was supported by the Canadian Institutes of Health Research Operating Grants Program (CIHR grant 68833 to H.M.M.), the Medical Research Council (MRC grants MC_UU_00015/7 and RG89175 to J.P.), the Isaac Newton Trust (grant RG89529 to J.P.), and the Wellcome Trust Institutional Strategic Support Fund (grant RG89305 to J.P.). H.M.M. is a Canada Research Chair. S.N. and L.-C.T. are recipients of Daiichi Sankyo Foundation of Life Science and Ramon Areces postdoctoral fellowships, respectively. L.T. was supported by an MRC-funded graduate student fellowship. V.P was supported by the European Union’s Horizon 2020 research and innovation program (MITODYN-749926)