Drift-induced deceleration of Solar Energetic Particles

We investigate the deceleration of Solar Energetic Particles (SEPs) during their propagation from the Sun through interplanetary space, in the presence of weak to strong scattering in a Parker spiral configuration, using relativistic full orbit test particle simulations. The calculations retain all three spatial variables describing particles’ trajectories, allowing to model any transport across the magnetic field. Large energy change is shown to occur for protons, due to the combined effect of standard adiabatic deceleration and a significant contribution from particle drift in the direction opposite to that of the solar wind electric field. The latter drift-induced deceleration is found to have a stronger effect for SEP energies than for galactic cosmic rays. The kinetic energy of protons injected at 1 MeV is found to be reduced by between 35 and 90% after four days, and for protons injected at 100 MeV by between 20 and 55%. The overall degree of deceleration is a weak function of the scattering mean free path, showing that, although adiabatic deceleration plays a role, a large contribution is due to particle drift. Current SEP transport models are found to account for drift-induced deceleration in an approximate way and their accuracy will need to be assessed in future work

Particle scattering in turbulent plasmas with amplified wave modes

High-energy particles stream during coronal mass ejections or flares through the plasma of the solar wind. This causes instabilities, which lead to wave growth at specific resonant wave numbers, especially within shock regions. These amplified wave modes influence the turbulent scattering process significantly. In this paper, results of particle transport and scattering in turbulent plasmas with excited wave modes are presented. The method used is a hybrid simulation code, which treats the heliospheric turbulence by an incompressible magnetohydrodynamic approach separately from a kinetic particle description. Furthermore, a semi-analytical model using quasilinear theory (QLT) is compared to the numerical results. This paper aims at a more fundamental understanding and interpretation of the pitch-angle scattering coefficients. Our calculations show a good agreement of particle simulations and the QLT for broad-band turbulent spectra; for higher turbulence levels and particle beam driven plasmas, the QLT approximation gets worse. Especially the resonance gap at μ = 0 poses a well-known problem for QLT for steep turbulence spectra, whereas test-particle computations show no problems for the particles to scatter across this region. The reason is that the sharp resonant wave-particle interactions in QLT are an oversimplification of the broader resonances in test-particle calculations, which result from nonlinear effects not included in the QLT. We emphasise the importance of these results for both numerical simulations and analytical particle transport approaches, especially the validity of the QLT. Appendices A-D are available in electronic form at http://www.aanda.or

Liver-specific insulin receptor isoform A expression enhances hepatic glucose uptake and ameliorates liver steatosis in a mouse model of diet-induced obesity

Among the main complications associated with obesity are insulin resistance and altered glucose and lipid metabolism within the liver. It has previously been described that insulin receptor isoform A (IRA) favors glucose uptake and glycogen storage in hepatocytes compared with isoform B (IRB), improving glucose homeostasis in mice lacking liver insulin receptor. Thus, we hypothesized that IRA could also improve glucose and lipid metabolism in a mouse model of high-fatdiet-induced obesity. We addressed the role of insulin receptor isoforms in glucose and lipid metabolism in vivo. We expressed IRA or IRB specifically in the liver by using adeno-associated viruses (AAVs) in a mouse model of diet-induced insulin resistance and obesity. IRA, but not IRB, expression induced increased glucose uptake in the liver and muscle, improving insulin tolerance. Regarding lipid metabolism, we found that AAV-mediated IRA expression also ameliorated hepatic steatosis by decreasing the expression of Fasn, Pgc1a, Acaca and Dgat2 and increasing Scd-1 expression. Taken together, our results further unravel the role of insulin receptor isoforms in hepatic glucose and lipid metabolism in an insulin-resistant scenario. Our data strongly suggest that IRA is more efficient than IRB at favoring hepatic glucose uptake, improving insulin tolerance and ameliorating hepatic steatosis. Therefore, we conclude that a gene therapy approach for hepatic IRA expression could be a safe and promising tool for the regulation of hepatic glucose consumption and lipid metabolism, two key processes in the development of non-alcoholic fatty liver disease associated with obesity

Fuzzy approach for risk assessment of brominated flame retardants in aquatic ecosystems

Brominated flame retardants (BFR) are pollutants that represent a threat to both human health and environment due to their industrial use, their persistence and their ability to bioaccumulate and biomagnify in food chains, especially in the aquatic one. For the last ten years contamination levels for this type of compounds have been reported for European, North American and Asian human tissue, sediments and biota samples [1-3]. However, monitoring efforts into the assessment of BFRs contamination levels in Latin America are scarce. In this study, a model for the evaluation of the environmental risk of BFRs in the aquatic ecosystems has been developed. It has been based on a technical application of the Fuzzy Theory [4]. In particular, three interconnected Fuzzy Inference Systems (FIS) have been created through the use of the Fuzzy Toolbox in Matlab. In order to improve and make the model scientifically robust, several international experts have been questioned about different information required to build the fuzzy system. Information from 38 questionnaires have been collected and statistically treated.Preprin

White adipose remodeling during browning in mice involves YBX1 to drive thermogenic commitment

Objective: Increasing adaptive thermogenesis by stimulating browning in white adipose tissue is a promising method of improving metabolic health. However, the molecular mechanisms underlying this transition remain elusive. Our study examined the molecular determinants driving the differentiation of precursor cells into thermogenic adipocytes. Methods: In this study, we conducted temporal high-resolution proteomic analysis of subcutaneous white adipose tissue (scWAT) after cold exposure in mice. This was followed by loss- and gain-of-function experiments using siRNA-mediated knockdown and CRISPRa-mediated induction of gene expression, respectively, to evaluate the function of the transcriptional regulator Y box-binding protein 1 (YBX1) during adipogenesis of brown pre-adipocytes and mesenchymal stem cells. Transcriptomic analysis of mesenchymal stem cells following induction of endogenous Ybx1 expression was conducted to elucidate transcriptomic events controlled by YBX1 during adipogenesis. Results: Our proteomics analysis uncovered 509 proteins differentially regulated by cold in a time-dependent manner. Overall, 44 transcriptional regulators were acutely upregulated following cold exposure, among which included the cold-shock domain containing protein YBX1, peaking after 24 h. Cold-induced upregulation of YBX1 also occurred in brown adipose tissue, but not in visceral white adipose tissue, suggesting a role of YBX1 in thermogenesis. This role was confirmed by Ybx1 knockdown in brown and brite preadipocytes, which significantly impaired their thermogenic potential. Conversely, inducing Ybx1 expression in mesenchymal stem cells during adipogenesis promoted browning concurrent with an increased expression of thermogenic markers and enhanced mitochondrial respiration. At a molecular level, our transcriptomic analysis showed that YBX1 regulates a subset of genes, including the histone H3K9 demethylase Jmjd1c, to promote thermogenic adipocyte differentiation. Conclusion: Our study mapped the dynamic proteomic changes of murine scWAT during browning and identified YBX1 as a novel factor coordinating the genomic mechanisms by which preadipocytes commit to brite/beige lineage

Periodontal disease and some adverse perinatal outcomes in a cohort of low risk pregnant women

Objective: To evaluate the association of periodontal disease (PD) in pregnancy with some adverse perinatal outcomes. Method: This cohort study included 327 pregnant women divided in groups with or without PD. Indexes of plaque and gingival bleeding on probing, probing pocket depth, clinical attachment level and gingival recession were evaluated at one periodontal examination below 32 weeks of gestation. The rates of preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA) neonates and prelabor rupture of membranes (PROM) were evaluated using Risk Ratios (95%CI) and Population Attributable Risk Fractions. Results: PD was associated with a higher risk of PTB (RRadj. 3.47 95% CI 1.62-7.43), LBW (RRadj. 2.93 95% CI 1.36-6.34) and PROM (RRadj. 2.48 95% CI 1.35-4.56), but not with SGA neonates (RR 2.38 95% CI 0.93 - 6.10). Conclusions: PD was a risk factor for PT, LBW and PROM among Brazilian low risk pregnant women

The first SEPServer event catalogue ~68-MeV solar proton events observed at 1 AU in 1996-2010

SEPServer is a three-year collaborative project funded by the seventh framework programme (FP7-SPACE) of the European Union. The objective of the project is to provide access to state-of-the-art observations and analysis tools for the scientific community on solar energetic particle (SEP) events and related electromagnetic (EM) emissions. The project will eventually lead to better understanding of the particle acceleration and transport processes at the Sun and in the inner heliosphere. These processes lead to SEP events that form one of the key elements of space weather. In this paper we present the first results from the systematic analysis work performed on the following datasets: SOHO/ERNE, SOHO/EPHIN, ACE/EPAM, Wind/WAVES and GOES X-rays. A catalogue of SEP events at 1 AU, with complete coverage over solar cycle 23, based on high-energy (~68-MeV) protons from SOHO/ERNE and electron recordings of the events by SOHO/EPHIN and ACE/EPAM are presented. A total of 115 energetic particle events have been identified and analysed using velocity dispersion analysis (VDA) for protons and time-shifting analysis (TSA) for electrons and protons in order to infer the SEP release times at the Sun. EM observations during the times of the SEP event onset have been gathered and compared to the release time estimates of particles. Data from those events that occurred during the European day-time, i.e., those that also have observations from ground-based observatories included in SEPServer, are listed and a preliminary analysis of their associations is presented. We find that VDA results for protons can be a useful tool for the analysis of proton release times, but if the derived proton path length is out of a range of 1 AU < s a 2 3 AU, the result of the analysis may be compromised, as indicated by the anti-correlation of the derived path length and release time delay from the associated X-ray flare. The average path length derived from VDA is about 1.9 times the nominal length of the spiral magnetic field line. This implies that the path length of first-arriving MeV to deka-MeV protons is affected by interplanetary scattering. TSA of near-relativistic electrons results in a release time that shows significant scatter with respect to the EM emissions but with a trend of being delayed more with increasing distance between the flare and the nominal footpoint of the Earth-connected field line

Seasonal and spatial variability in condition of age-0+ Argentine hake Merluccius hubbsi Marini, 1933, in the San Jorge Gulf (Argentina): A bottom-up perspective

In the north Patagonian region of the Argentinean Continental Shelf, the San Jorge Gulf (SJG; 45°‐47°S, 65°30ʹ‐67°30ʹW) is the main nursery ground of age‐0+ Argentine hake Merluccius hubbsi Marini, 1933, one of the most important fishery resources in Argentina. The gulf exhibits strong seasonal and spatial fluctuations in environmental features, which might affect survival of age‐0+ individuals and recruitment to the adult population. Our main goal was to evaluate the seasonal and spatial dynamics of their nutritional status within the SJG in winter 2016, spring 2016 and summer 2017. Condition indices (relative condition factor Kn, hepatosomatic index HSI and liver lipid content %L) and diet information (feeding incidence and relative importance of prey) were combined with physical (temperature and salinity) and biological (satellite chlorophyll‐a concentration; chl‐a) data. Age‐0+ condition indices and prey intake showed significant seasonal variations, with minimum values in winter, intermediate in summer and maximum in spring, strongly coupled to the mean chl‐a concentration in each season. Herbivorous euphausiids Euphausia spp. were the preferred prey along the study period. A bottom‐up effect on condition of age‐0+ hake is suggested, manifested as lower condition values in winter, the less productive season. Spatially, better conditioned individuals matched sectors of the gulf where chl‐a concentrations were higher, coupled to the presence of frontal systems. Monitoring age‐0+ hake nutritional status is relevant in the current global change scenario, which might modify phytoplankton biomass and composition and, consequently, the herbivorous zooplankton abundances.Fil: Temperoni, Brenda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Subsede Instituto Nacional de Investigación y Desarrollo Pesquero; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Massa, Agueda Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Subsede Instituto Nacional de Investigación y Desarrollo Pesquero; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Martos, Patricia. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias Marinas; ArgentinaFil: Marrari, Marina. Ministerio de Defensa. Armada Argentina. Servicio de Hidrografía Naval. Departamento Oceanografía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Safety and preliminary efficacy data of a novel Casein Kinase 2 (CK2) peptide inhibitor administered intralesionally at four dose levels in patients with cervical malignancies

<p>Abstract</p> <p>Background</p> <p>Cervical cancer is now considered the second leading cause of death among women worldwide, and its incidence has reached alarming levels, especially in developing countries. Similarly, high grade squamous intraepithelial lesion (HSIL), the precursor stage for cervical cancer, represents a growing health problem among younger women as the HSIL management regimes that have been developed are not fully effective. From the etiological point of view, the presence of Human Papillomavirus (HPV) has been demonstrated to play a crucial role for developing cervical malignancies, and viral DNA has been detected in 99.7% of cervical tumors at the later stages. CIGB-300 is a novel cyclic synthetic peptide that induces apoptosis in malignant cells and elicits antitumor activity in cancer animal models. CIGB-300 impairs the Casein Kinase (CK2) phosphorylation, by targeting the substrate's phosphoaceptor domain. Based on the perspectives of CIGB-300 to treat cancer, this "first-in-human" study investigated its safety and tolerability in patients with cervical malignancies.</p> <p>Methods</p> <p>Thirty-one women with colposcopically and histologically diagnosed microinvasive or pre-invasive cervical cancer were enrolled in a dose escalating study. CIGB-300 was administered sequentially at 14, 70, 245 and 490 mg by intralesional injections during 5 consecutive days to groups of 7 – 10 patients. Toxicity was monitored daily until fifteen days after the end of treatment, when patients underwent conization. Digital colposcopy, histology, and HPV status were also evaluated.</p> <p>Results</p> <p>No maximum-tolerated dose or dose-limiting toxicity was achieved. The most frequent local events were pain, bleeding, hematoma and erythema at the injection site. The systemic adverse events were rash, facial edema, itching, hot flashes, and localized cramps. 75% of the patients experienced a significant lesion reduction at colposcopy and 19% exhibited full histological regression. HPV DNA was negative in 48% of the previously positive patients. Long term follow-up did not reveal recurrences or adverse events.</p> <p>Conclusion</p> <p>CIGB 300 was safe and well tolerated. This is the first clinical trial where a drug has been used to target the CK2 phosphoaceptor domain providing an early proof-of-principle of a possible clinical benefit.</p

Interaction between genetic and epigenetic variation defines gene expression patterns at the asthma-associated locus 17q12-q21 in lymphoblastoid cell lines

Phenotypic variation results from variation in gene expression, which is modulated by genetic and/or epigenetic factors. To understand the molecular basis of human disease, interaction between genetic and epigenetic factors needs to be taken into account. The asthma-associated region 17q12-q21 harbors three genes, the zona pellucida binding protein 2 (ZPBP2), gasdermin B (GSDMB) and ORM1-like 3 (ORMDL3), that show allele-specific differences in expression levels in lymphoblastoid cell lines (LCLs) and CD4+ T cells. Here, we report a molecular dissection of allele-specific transcriptional regulation of the genes within the chromosomal region 17q12-q21 combining in vitro transfection, formaldehyde-assisted isolation of regulatory elements, chromatin immunoprecipitation and DNA methylation assays in LCLs. We found that a single nucleotide polymorphism rs4795397 influences the activity of ZPBP2 promoter in vitro in an allele-dependent fashion, and also leads to nucleosome repositioning on the asthma-associated allele. However, variable methylation of exon 1 of ZPBP2 masks the strong genetic effect on ZPBP2 promoter activity in LCLs. In contrast, the ORMDL3 promoter is fully unmethylated, which allows detection of genetic effects on its transcription. We conclude that the cis-regulatory effects on 17q12-q21 gene expression result from interaction between several regulatory polymorphisms and epigenetic factors within the cis-regulatory haplotype region