Antagonistic and cooperative AGO2-PUM interactions in regulating mRNAs.

Approximately 1500 RNA-binding proteins (RBPs) profoundly impact mammalian cellular function by controlling distinct sets of transcripts, often using sequence-specific binding to 3' untranslated regions (UTRs) to regulate mRNA stability and translation. Aside from their individual effects, higher-order combinatorial interactions between RBPs on specific mRNAs have been proposed to underpin the regulatory network. To assess the extent of such co-regulatory control, we took a global experimental approach followed by targeted validation to examine interactions between two well-characterized and highly conserved RBPs, Argonaute2 (AGO2) and Pumilio (PUM1 and PUM2). Transcriptome-wide changes in AGO2-mRNA binding upon PUM knockdown were quantified by CLIP-seq, and the presence of PUM binding on the same 3'UTR corresponded with cooperative and antagonistic effects on AGO2 occupancy. In addition, PUM binding sites that overlap with AGO2 showed differential, weakened binding profiles upon abrogation of AGO2 association, indicative of cooperative interactions. In luciferase reporter validation of candidate 3'UTR sites where AGO2 and PUM colocalized, three sites were identified to host antagonistic interactions, where PUM counteracts miRNA-guided repression. Interestingly, the binding sites for the two proteins are too far for potential antagonism due to steric hindrance, suggesting an alternate mechanism. Our data experimentally confirms the combinatorial regulatory model and indicates that the mostly repressive PUM proteins can change their behavior in a context-dependent manner. Overall, the approach underscores the importance of further elucidation of complex interactions between RBPs and their transcriptome-wide extent

Galerkin and Runge–Kutta methods: unified formulation, a posteriori error estimates and nodal superconvergence

Abstract. We unify the formulation and analysis of Galerkin and Runge–Kutta methods for the time discretization of parabolic equations. This, together with the concept of reconstruction of the approximate solutions, allows us to establish a posteriori superconvergence estimates for the error at the nodes for all methods. 1

Multiadaptive Galerkin Methods for ODEs III: A Priori Error Estimates

The multiadaptive continuous/discontinuous Galerkin methods mcG(q) and mdG(q) for the numerical solution of initial value problems for ordinary differential equations are based on piecewise polynomial approximation of degree q on partitions in time with time steps which may vary for different components of the computed solution. In this paper, we prove general order a priori error estimates for the mcG(q) and mdG(q) methods. To prove the error estimates, we represent the error in terms of a discrete dual solution and the residual of an interpolant of the exact solution. The estimates then follow from interpolation estimates, together with stability estimates for the discrete dual solution

Measuring subaqueous progradation of the Wax Lake Delta with a model of flow direction divergence

Remotely sensed flow patterns can reveal the location of the subaqueous distal tip of a distributary channel on a prograding river delta. Morphodynamic feedbacks produce distributary channels that become shallower over their final reaches before the unchannelized foreset slopes basinward. The flow direction field over this morphology tends to diverge and then converge, providing a diagnostic signature that can be captured in flow or remote sensing data. A total of 21 measurements from the Wax Lake Delta (WLD) in coastal Louisiana and 317 measurements from numerically simulated deltas show that the transition from divergence to convergence occurs in a distribution that is centered just downstream of the channel tip, on average 132&thinsp;m in the case of the WLD. These data validate an inverse model for remotely estimating subaqueous channel tip location. We apply this model to 33 images of the WLD between its initiation in 1974 and 2016. We find that six of the primary channels grew at rates of 60–80&thinsp;m&thinsp;yr−1, while the remaining channel grew at 116&thinsp;m&thinsp;yr−1. We also show that the subaqueous delta planform grew at a constant rate (1.72&thinsp;km2&thinsp;yr−1). Subaerial land area initially grew at the same rate but slowed after about 1999. We explain this behavior as a gradual decoupling of channel tip progradation and island aggradation that may be common in maturing deltas.</p

The Cytotoxicity and Insecticidal Activity of Extracts from Delphinium formosum Boiss. & Huet

Delphinium species are well-known toxic plants with diterpenoid alkaloid contents. There has been no previous investigation on the cytotoxicity of Delphinium formosum. The extracts of the different parts of D. formosum, an endemic species in Turkey, were investigated for their cytotoxic activity against the human liver carcinoma cell line (HepG2) and primary human umbilical vein endothelial cells (HUVEC). The cytotoxic effects of twelve extracts and subfractions were determined against HepG2 cells using the MTT assay. The only active extract was applied to the HUVEC as a model for healthy cells. Only one of the alkaloidcontaining extracts from the aerial parts was toxic (IC50=244,9 µg/mL against HepG2 and 144,4 µg/mL against HUVEC), while the root extracts were inactive. The results were improbable although it is predicted secondary metabolites, such as diterpene alkaloids (methyllycaconitine, browniine, lycoctonine, avardharidine, antranoyllycoctonine, delsemine A/B and lycoctonine). Based on previous studies in the literature, the cytotoxic plants were also expected to exhibit insecticidal activity. Therefore, the cytotoxic extract of D. formosum was examined for its adulticidal and larvicidal activity against the yellow fever, dengue fever and the Zika virus vector Aedes aegypti L

Lump correction and identification in the combined thermal/epithermal neutron (CTEN) method

The authors present a model for self shielding in lumps of fissile material in active-neutron assays. The model combines the formula for self-attenuation of gamma-ray in lumpy sources with the multi-group analysis techniques used in neutron transport calculations. Models for thin foils and for spheres are examined in terms of error multiplication in determining lump corrections and the basic accuracy of the model

Assessment of selected Saudi and Yemeni plants for mosquitocidal activities against the yellow fever mosquito Aedes aegypti

© 2019 by the authors. Marine organisms are recognized as a source of compounds with interesting biological activities. Vibrio neocaledonicus has been reported on for its high effectiveness against corrosion in metals but it has been little studied for its chemical and biological activities. In this study, four compounds were isolated from V. neocaledonicus: indole (1); 1H-indole-3-carboxaldehyde (2); 4-hydroxybenzaldehyde (3) and Cyclo (-Pro-Tyr) (4); using a bioassay-guided method, since in a previous study it was found that the ethyl acetate extract was active on the enzymes acetylcholinesterase (AChE), alpha-glucosidase (AG) and xanthine oxidase (XO). The inhibitory activities of the three compounds against AChE, AG and XO was also evaluated. In addition, the enzymatic inhibitory activity of indole to the toxins from the venom of Bothrops asper was tested. Results showed that indole exhibited strong inhibitory activity to AG (IC50 = 18.65 ± 1.1 µM), to AChE, and XO (51.3% and 44.3% at 50 µg/mL, respectively). 1H-indole-3-carboxaldehyde displayed strong activity to XO (IC50 = 13.36 ± 0.39 µM). 4-hydroxybenzaldehyde showed moderate activity to XO (50.75% at 50 µg/mL) and weak activity to AChE (25.7% at 50 µg/mL). Furthermore, indole showed a significant in vitro inhibition to the coagulant effect induced by 1.0 µg of venom. The findings were supported by molecular docking. This is the first comprehensive report on the chemistry of V. neocaledonicus and the bioactivity of its metabolites

Developing GIS-based eastern equine encephalitis vector-host models in Tuskegee, Alabama

<p>Abstract</p> <p>Background</p> <p>A site near Tuskegee, Alabama was examined for vector-host activities of eastern equine encephalomyelitis virus (EEEV). Land cover maps of the study site were created in ArcInfo 9.2^®from QuickBird data encompassing visible and near-infrared (NIR) band information (0.45 to 0.72 μm) acquired July 15, 2008. Georeferenced mosquito and bird sampling sites, and their associated land cover attributes from the study site, were overlaid onto the satellite data. SAS 9.1.4^®was used to explore univariate statistics and to generate regression models using the field and remote-sampled mosquito and bird data. Regression models indicated that <it>Culex erracticus </it>and Northern Cardinals were the most abundant mosquito and bird species, respectively. Spatial linear prediction models were then generated in Geostatistical Analyst Extension of ArcGIS 9.2^®. Additionally, a model of the study site was generated, based on a Digital Elevation Model (DEM), using ArcScene extension of ArcGIS 9.2^®.</p> <p>Results</p> <p>For total mosquito count data, a first-order trend ordinary kriging process was fitted to the semivariogram at a partial sill of 5.041 km, nugget of 6.325 km, lag size of 7.076 km, and range of 31.43 km, using 12 lags. For total adult <it>Cx. erracticus </it>count, a first-order trend ordinary kriging process was fitted to the semivariogram at a partial sill of 5.764 km, nugget of 6.114 km, lag size of 7.472 km, and range of 32.62 km, using 12 lags. For the total bird count data, a first-order trend ordinary kriging process was fitted to the semivariogram at a partial sill of 4.998 km, nugget of 5.413 km, lag size of 7.549 km and range of 35.27 km, using 12 lags. For the Northern Cardinal count data, a first-order trend ordinary kriging process was fitted to the semivariogram at a partial sill of 6.387 km, nugget of 5.935 km, lag size of 8.549 km and a range of 41.38 km, using 12 lags. Results of the DEM analyses indicated a statistically significant inverse linear relationship between total sampled mosquito data and elevation (R²= -.4262; p < .0001), with a standard deviation (SD) of 10.46, and total sampled bird data and elevation (R²= -.5111; p < .0001), with a SD of 22.97. DEM statistics also indicated a significant inverse linear relationship between total sampled <it>Cx. erracticus </it>data and elevation (R²= -.4711; p < .0001), with a SD of 11.16, and the total sampled Northern Cardinal data and elevation (R²= -.5831; p < .0001), SD of 11.42.</p> <p>Conclusion</p> <p>These data demonstrate that GIS/remote sensing models and spatial statistics can capture space-varying functional relationships between field-sampled mosquito and bird parameters for determining risk for EEEV transmission.</p

Health in times of uncertainty in the eastern Mediterranean region, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Background: The eastern Mediterranean region is comprised of 22 countries: Afghanistan, Bahrain, Djibouti, Egypt, Iran, Iraq, Jordan, Kuwait, Lebanon, Libya, Morocco, Oman, Pakistan, Palestine, Qatar, Saudi Arabia, Somalia, Sudan, Syria, Tunisia, the United Arab Emirates, and Yemen. Since our Global Burden of Disease Study 2010 (GBD 2010), the region has faced unrest as a result of revolutions, wars, and the so-called Arab uprisings. The objective of this study was to present the burden of diseases, injuries, and risk factors in the eastern Mediterranean region as of 2013. Methods: GBD 2013 includes an annual assessment covering 188 countries from 1990 to 2013. The study covers 306 diseases and injuries, 1233 sequelae, and 79 risk factors. Our GBD 2013 analyses included the addition of new data through updated systematic reviews and through the contribution of unpublished data sources from collaborators, an updated version of modelling software, and several improvements in our methods. In this systematic analysis, we use data from GBD 2013 to analyse the burden of disease and injuries in the eastern Mediterranean region specifically. Findings: The leading cause of death in the region in 2013 was ischaemic heart disease (90·3 deaths per 100 000 people), which increased by 17·2% since 1990. However, diarrhoeal diseases were the leading cause of death in Somalia (186·7 deaths per 100 000 people) in 2013, which decreased by 26·9% since 1990. The leading cause of disability-adjusted life-years (DALYs) was ischaemic heart disease for males and lower respiratory infection for females. High blood pressure was the leading risk factor for DALYs in 2013, with an increase of 83·3% since 1990. Risk factors for DALYs varied by country. In low-income countries, childhood wasting was the leading cause of DALYs in Afghanistan, Somalia, and Yemen, whereas unsafe sex was the leading cause in Djibouti. Non-communicable risk factors were the leading cause of DALYs in high-income and middle-income countries in the region. DALY risk factors varied by age, with child and maternal malnutrition affecting the younger age groups (aged 28 days to 4 years), whereas high bodyweight and systolic blood pressure affected older people (aged 60–80 years). The proportion of DALYs attributed to high body-mass index increased from 3·7% to 7·5% between 1990 and 2013. Burden of mental health problems and drug use increased. Most increases in DALYs, especially from non-communicable diseases, were due to population growth. The crises in Egypt, Yemen, Libya, and Syria have resulted in a reduction in life expectancy; life expectancy in Syria would have been 5 years higher than that recorded for females and 6 years higher for males had the crisis not occurred. Interpretation: Our study shows that the eastern Mediterranean region is going through a crucial health phase. The Arab uprisings and the wars that followed, coupled with ageing and population growth, will have a major impact on the region's health and resources. The region has historically seen improvements in life expectancy and other health indicators, even under stress. However, the current situation will cause deteriorating health conditions for many countries and for many years and will have an impact on the region and the rest of the world. Based on our findings, we call for increased investment in health in the region in addition to reducing the conflicts.Ali H Mokdad ... Azmeraw T Amare ... et al