ALBERT

Beschreibung: 〈p〉Publication date: October–December 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Mutation Research/Reviews in Mutation Research, Volume 782〈/p〉 〈p〉Author(s): Yuxiao Liao, Zhao Peng, Liangkai Chen, Liegang Liu, Qinghua Wu, Wei Yang〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Mycotoxins, produced by fungi, are secondary metabolites causing adverse, toxic and pathological effects on human and animals. Studies about the association between mycotoxins and microRNAs (miRNAs) were developed since miRNAs have been demonstrated to play a critical role in many developmental processes for regulating messenger RNA (mRNA). As published studies showed, dozens of miRNAs were influenced by mycotoxins, indicating that miRNAs can play important roles in the occurrence and development of mycotoxicosis. Besides, a hypothesis called competing endogenous RNA (ceRNA) was reported to indirectly modulate the expression of mRNA 〈em〉via〈/em〉 miRNA response elements (MREs) to consequently regulate cell functions. As a result, four common miRNAs were focused to predict the corresponding ceRNAs based on their own characteristics and the effects of mycotoxins on them, in hope of providing potential ways or directions of miRNAs regulation for mycotoxicosis, and expanding the research field about mycotoxicosis from ceRNA.〈/p〉〈/div〉

Beschreibung: 〈p〉Publication date: October–December 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Mutation Research/Reviews in Mutation Research, Volume 782〈/p〉 〈p〉Author(s): Yanan Xu, Qian Zhang, Liang Tan, Xubiao Xie, Yong Zhao〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Niemann–Pick C disease (NPC) is a rare autosomal recessive disorder characterized by severe neurodegeneration of central nervous system. Linkage studies in multiplex NPC families and genetic complementation research revealed two disease genes, 〈em〉NPC1 and NPC2,〈/em〉 both of which are important transporters for cholesterol trafficking. NPC2 executes cholesterol-transport function through protein-protein interaction with NPC1 as well as through protein-membrane interaction directly with membrane of late endosome and lysosome. In addition, NPC2 may play many other roles as indicated by its widely expressing pattern in different cells and presenting in numerous secretory fluids, although it biological significance is less studied today. About 50 clinical cases have been reported documenting over twenty different mutations of 〈em〉NPC2〈/em〉 in NPC patients so far. In this review, we will mainly summarize the molecular characteristics and biological significance of NPC2, highlighting its vital roles in NPC disease.〈/p〉〈/div〉

Beschreibung: 〈p〉Publication date: 15 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Bioorganic & Medicinal Chemistry, Volume 27, Issue 16〈/p〉 〈p〉Author(s): Tao Li, Jing Li, Yang Yang, Yilin Han, Dirong Wu, Tao Xiao, Yang Wang, Ting Liu, Yonglong Zhao, Yongjun Li, Zeqin Dai, Xiaozhong Fu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The deficiency of nucleos(t)ide analogues (NAs) as anti-hepatitis B virus (HBV) drugs in clinical use is attributable to their insufficient enrichment in liver and non-target organ toxicity. We aimed to develop potent anti-HBV adefovir derivatives with hepatotrophic properties and reduced nephrotoxicity. A series of adefovir mono 〈span〉l〈/span〉-amino acids, mono cholic acid-drug conjugates were designed and synthesized, and their antiviral activity and uptake in rat primary hepatocytes and Na〈sup〉+〈/sup〉-dependent taurocholate co-transporting polypeptide (NTCP)-HEK293 cells were evaluated. We isolated compound 〈strong〉6c〈/strong〉 as the optimal molecular candidate, with the highest antiviral activity (EC〈sub〉50〈/sub〉 0.42 μmol/L, SI 1063.07) and highest cellular uptake in primary hepatocytes and NTCP-HEK293 cells. In-depth mechanistic studies demonstrated that 〈strong〉6c〈/strong〉 exhibited a lower toxicity in HK-2 cells when compared to adefovir dipivoxil (ADV). This is because 〈strong〉6c〈/strong〉 cannot be transported by the human renal organic anion transporter 1 (hOAT1). Furthermore, pharmacokinetic characterization and tissue distribution of 〈strong〉6c〈/strong〉 indicates it has favorable druggability and pharmacokinetic properties. Further docking studies suggested compounds with ursodeoxycholic acid and 〈span〉l〈/span〉-amino acid groups are better at binding to NTCP due to their hydrophilic properties, indicating that 〈strong〉6c〈/strong〉 is a potential candidate as an anti-HBV therapy and therefore merits further investigation.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0968089619309034-ga1.jpg" width="327" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: 1 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Bioorganic & Medicinal Chemistry, Volume 27, Issue 17〈/p〉 〈p〉Author(s): Bo Hou, Ze Liu, Xiao-Bei Yang, Wen-Fei Zhu, Jin-Yu Li, Liu Yang, Fu-Cai Reng, Yong-Feng Lv, Jiang-Miao Hu, Guo-Yang Liao, Jun Zhou〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The stems of 〈em〉Dryopteris crassirhizoma〈/em〉, one of the main components of Lianhua-Qingwen Formula (LQF) was traditionally used for heat-clearing and detoxifying. Dryocrassin 〈strong〉ABBA〈/strong〉 is a key antiviral component in the herbal medicine while the compound is hard to get in large amounts with the features of homologous compounds, polyphenol groups, and low contents. Therefore, the present work aims to seek influenza H7N9 virus inhibitors from natural source by synthesis of dryocrassin 〈strong〉ABBA〈/strong〉 and its analogues. As a result, total synthesis of the compound was achieved in nine steps with an over-all yield of 4.6%. Neuraminidases (NAs) inhibitory activities of the synthesized product and its analogues were evaluated afterward. Comparing with the positive control, OSV (9.6 μM), it was very exciting that dryocrassin 〈strong〉ABBA〈/strong〉 and its analogues (〈strong〉b5〈/strong〉 and 〈strong〉e2〈/strong〉) showed better NAs inhibitory activity against Anhui H7N9 with IC〈sub〉50〈/sub〉 values of 3.6 μM, 2.5 μM and 1.6 μM. For the highly resistant Shanghai N9, these compounds can also show medium inhibitory activities. Docking results indicated the direct interaction of synthesized 3 hits with the key K294 by hydrogen bonds, but no direct interaction of OSV with the key K294 was observed in Shanghai N9. This study suggested that dryocrassin 〈strong〉ABBA〈/strong〉 and its analogues especially 〈strong〉AB〈/strong〉, which consisted of polyphenol groups may have beneficial effects on treating avian influenza H7N9 virus.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉 〈p〉Total synthesis of dryocrassin ABBA and analogue structures with potential inhibitory activity against drug-resistant neuraminidases.〈/p〉 〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0968089619308879-ga1.jpg" width="278" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉 〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Volume 1867, Issue 9〈/p〉 〈p〉Author(s): 〈/p〉

Beschreibung: 〈p〉Publication date: Available online 8 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochimica et Biophysica Acta (BBA) - Biomembranes〈/p〉 〈p〉Author(s): Deo R. Singh, Christopher King, Matt Salotto, Kalina Hristova〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉EGFR is a receptor tyrosine kinase that plays a critical role in cell proliferation, differentiation, survival and migration. Its activating ligand, EGF, has long been believed to stabilize the EGFR dimer. Two research studies aimed at quantitative measurements of EGFR dimerization, however, have led to contradicting conclusions and have questioned this view. Given the controversy, here we sought to measure the dimerization of EGFR in the absence and in the presence of saturating EGF concentrations, and to tease out the effect of ligand on dimer stability, using a FRET-based quantitative method. Our measurements show that the dissociation constant is decreased ~150 times due to ligand binding, indicative of significant dimer stabilization. In addition, our measurements demonstrate that EGF binding induces a conformational change in the EGFR dimer.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0005273619301476-ga1.jpg" width="265" alt="Unlabelled Image" title="Unlabelled Image"〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: Available online 8 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics〈/p〉 〈p〉Author(s): Martina Paumann-Page, Rupert Tscheliessnig, Benjamin Sevcnikar, Romy-Sophie Katz, Irene Schwartz, Stefan Hofbauer, Vera Pfanzagl, Paul G. Furtmüller, Christian Obinger〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Human peroxidasin 1 is a multidomain peroxidase situated in the basement membrane. The iron enzyme with covalently bound heme oxidizes bromide to hypobromous acid which facilitates the formation of distinct sulfilimine cross-links in the collagen IV network and therefore contributes to its mechanical stability. Additional to the catalytically active peroxidase domain peroxidasin comprises a leucine rich repeat domain, four Ig domains and a C-terminal von Willebrand factor type C module (VWC). Peroxidasin has been shown to form homotrimers involving two redox-sensitive cysteine residues and to undergo posttranslational C-terminal proteolytic cleavage. The present study on several recombinantly produced truncated peroxidasin variants showed that the VWC is not required for trimer formation whereas the alpha-helical linker region located between the peroxidase domain and the VWC is crucial for trimerization. Our data furthermore implies that peroxidasin oligomerization occurs intracellularly before C-terminal cleavage. For the first time we present overall solution structures of monomeric and trimeric truncated peroxidasin variants which were determined by rotary shadowing combined with transmission electron microscopy and by small-angle X-ray scattering (SAXS). A triangular arrangement of the peroxidase domains to each other within the homotrimer was revealed and this structure was confirmed by a model of trimeric peroxidase domains. Our SAXS data showed that the Ig domains are highly flexible and interact with the peroxidase domain and that within the homotrimer each alpha-helical linker region interacts with the respective adjacent peroxidase domain. The implications of our findings on the structure-function relationship of peroxidasin are discussed.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S1570963919301219-ga1.jpg" width="240" alt="Unlabelled Image" title="Unlabelled Image"〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 The International Journal of Biochemistry & Cell Biology, Volume 114〈/p〉 〈p〉Author(s): Deep Pooja, Anusha Gunukula, Nitin Gupta, David J. Adams, Hitesh Kulhari〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The biggest challenge in delivering anticancer agents is the ability to direct these molecules specifically to cancer cells. With this in mind, modern research is focussing on improving the precision of cancer drug delivery by incorporating a ligand that has the ability to specifically recognize cancer cells. Peptides are emerging as a new tool in drug and gene delivery. Peptide-drug conjugates, peptide-modified drug delivery systems, and peptide-coupled imaging agents have been shown to increase on-site delivery. This has allowed better tumor mass contouring in imaging and increased therapeutic efficacy of chemotherapies, reducing adverse effects. Benefits of peptide ligands include their small size, easy and affordable production, high specificity and remarkable flexibility regarding their sequence and conjugation possibilities. Bombesin (Bn) receptors have shown great promise for tumor targeting due to their increased expression in a variety of human cancers, including prostate, breast, small cell lung, and pancreatic cells. This review discusses the overexpression of Bn receptors in different cancers and various approaches to target these receptors for therapeutic and diagnostic interventions in human malignancies.〈/p〉〈/div〉

Beschreibung: 〈p〉Publication date: Available online 8 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Journal of Computational Physics〈/p〉 〈p〉Author(s): Maxim Rakhuba, Alexander Novikov, Ivan Oseledets〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Such problems as computation of spectra of spin chains and vibrational spectra of molecules can be written as 〈em〉high-dimensional eigenvalue problems〈/em〉, i.e., when the eigenvector can be naturally represented as a multidimensional tensor. Tensor methods have proven to be an efficient tool for the approximation of solutions of high-dimensional eigenvalue problems, however, their performance deteriorates quickly when the number of eigenstates to be computed increases. We address this issue by designing a new algorithm motivated by the ideas of 〈em〉Riemannian optimization〈/em〉 (optimization on smooth manifolds) for the approximation of multiple eigenstates in the 〈em〉tensor-train format〈/em〉, which is also known as matrix product state representation. The proposed algorithm is implemented in TensorFlow, which allows for both CPU and GPU parallelization.〈/p〉〈/div〉

Beschreibung: 〈p〉Publication date: Available online 8 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Journal of Computational Physics〈/p〉 〈p〉Author(s): Chen Liu, Florian Frank, Faruk O. Alpak, Béatrice Rivière〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Permeability estimation of porous media from directly solving the Navier–Stokes equations has a wide spectrum of applications in petroleum industry. In this paper, we utilize a pressure-correction projection algorithm in conjunction with the interior penalty discontinuous Galerkin scheme for space discretization to build an incompressible Navier–Stokes simulator and to use this simulator to calculate permeability of real rock samples. The proposed method is accurate, numerically robust, and exhibits the potential for tackling realistic problems.〈/p〉〈/div〉

Beschreibung: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Journal of Contaminant Hydrology, Volume 226〈/p〉 〈p〉Author(s): Mehrdad Bastani, Thomas Harter〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈p〉Nitrate in drinking water may cause serious health problems for consumers. Agricultural activities are known to be the main source of groundwater nitrate contaminating rural domestic and urban public water supply wells in farming regions. Management practices have been proposed to reduce the amount of nitrate in groundwater, including improved nutrient management practices and “pump and fertilize” with nitrate-affected irrigation wells. Here, we evaluate the feasibility and long-term impacts of agricultural managed aquifer recharge (Ag-MAR) in the source area of public water supply wells. A numerical model of nitrate fate and transport was developed for the Modesto basin, part of California's Central Valley aquifer system. The basin is representative of semi-arid agricultural regions around the world with a diversity of crop types, overlying an unconsolidated sedimentary aquifer system. A local public supply well in an economically disadvantaged community surrounded by farmland was the focus of this study. Model scenarios implemented include business as usual, alternative low-impact crops, and Ag-MAR in the source area of the public supply well. Alternative nutrient management and recharge practices act as remediation tools in the area between farmland and the public supply well. Improved agricultural source area management practices are shown to be an effective tool to maintain or even enhance groundwater quality in the targeted supply well while remediating ambient groundwater.〈/p〉 〈p〉Best results are obtained when lowering nitrate load while also increasing recharge in the source area simultaneously. This scenario reduced nitrate in the supply well's drinking water by 80% relative to the business as usual scenario. It also remediated ambient groundwater used by domestic wells between the source area farmlands and the supply well and showed 60% more reduction of nitrate after 60 years of application. Increasing recharge led to shorter initial response time (five years) and showed the most sustainable impact. Our analysis further suggests that Ag-MAR in a highly discontinuous, wide-spread pattern leads to slow water quality response and may not yield sufficient water quality improvements.〈/p〉 〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: Available online 8 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Journal of Computational Physics〈/p〉 〈p〉Author(s): Mustapha Malek, Nouh Izem, M. Shadi Mohamed, Mohammed Seaid, Omar Laghrouche〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉An efficient partition of unity finite element method for three-dimensional transient diffusion problems is presented. A class of multiple exponential functions independent of time variable is proposed to enrich the finite element approximations. As a consequence of this procedure, the associated matrix for the linear system is evaluated once at the first time step and the solution is obtained at subsequent time step by only updating the right-hand side of the linear system. This results in an efficient numerical solver for transient diffusion equations in three space dimensions. Compared to the conventional finite element methods with 〈em〉h〈/em〉-refinement, the proposed approach is simple, more efficient and more accurate. The performance of the proposed method is assessed using several test examples for transient diffusion in three space dimensions. We present numerical results for a transient diffusion equation with known analytical solution to quantify errors for the new method. We also solve time-dependent diffusion problems in complex geometries. We compare the results obtained using the partition of unity finite element method to those obtained using the standard finite element method. It is shown that the proposed method strongly reduces the necessary number of degrees of freedom to achieve a prescribed accuracy.〈/p〉〈/div〉

Beschreibung: 〈p〉Publication date: Available online 8 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Journal of Computational Physics〈/p〉 〈p〉Author(s): Lahbib Bourhrara〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉This document presents a new numerical scheme dealing with the Boltzmann transport equation. This scheme is based on the expansion of the angular flux in a truncated spherical harmonics function and the discontinuous finite element method for the spatial variable. The advantage of this scheme lies in the fact that we can deal with unstructured, non-conformal and curved meshes. Indeed, it is possible to deal with distorted regions whose boundary is constituted by edges that can be either line segments or circular arcs or circles. In this document, we detail the derivation of the method for 2D geometries. However, the generalization to 2D extruded geometries is trivial.〈/p〉〈/div〉

Beschreibung: 〈p〉Publication date: Available online 8 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Journal of Contaminant Hydrology〈/p〉 〈p〉Author(s): Héloïse A.A. Thouement, Tomasz Kuder, Timo J. Heimovaara, Boris M. Van Breukelen〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Back-diffusion of chlorinated ethenes (CEs) from low-permeability layers (LPLs) causes contaminant persistence long after the primary spill zones have disappeared. Naturally occurring degradation in LPLs lowers remediation time frames, but its assessment through sediment sampling is prohibitive in conventional remediation projects. Scenario simulations were performed with a reactive transport model (PHT3D in FloPy) accounting for isotope effects associated with degradation, sorption, and diffusion, to evaluate the potential of CSIA data from aquifers in assessing degradation in aquitards. The model simulated a trichloroethylene (TCE) DNAPL and its pollution plume within an aquifer-aquitard-aquifer system. Sequential reductive dechlorination to ethene and sorption were uniform in the aquitard and did not occur in the aquifer. After 10 years of loading the aquitard through diffusion from the plume, subsequent source removal triggered release of TCE by back-diffusion. In the upper aquifer, during the loading phase, δ〈sup〉13〈/sup〉C-TCE was slightly enriched (up to 2‰) due to diffusion effects stimulated by degradation in the aquitard. In the upper aquifer, during the release phase, (i) source removal triggered a huge δ〈sup〉13〈/sup〉C increase especially for higher CEs, (ii) moreover, downstream decreasing isotope ratios (caused by downgradient later onset of the release phase) with temporal increasing isotope ratios reflect aquitard degradation (as opposed to downstream increasing and temporally constant isotope ratios in reactive aquifers), and (iii) the carbon isotope mass balance (CIMB) enriched up to 4‰ as lower CEs (more depleted, less sorbing) have been transported deeper into the aquitard. Thus, enriched CIMB does not indicate oxidative transformation in this system. The CIMB enrichment enhanced with more sorption and lower aquitard thickness. Thin aquitards are quicker flushed from lower CEs leading to faster CIMB enrichment over time. CIMB enrichment is smaller or nearly absent when daughter products accumulate. Aquifer CSIA patterns indicative of aquitard degradation were similar in case of linear decreasing rate constants but contrasted with previous simulations assuming a thin bioactive zone. The Rayleigh equation systematically underestimates the extent of TCE degradation in aquifer samples especially during the loading phase and for conditions leading to long remediation time frames (low groundwater flow velocity, thicker aquitards, strong sorption in the aquitard). The Rayleigh equation provides a good and useful picture on aquitard degradation during the release phase throughout the sensitivity analysis. This modelling study provides a framework on how aquifer CSIA data can inform on the occurrence of aquitard degradation and its pitfalls.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Ocean Modelling, Volume 140〈/p〉 〈p〉Author(s): Oleg Druzhinin, Yuliya Troitskaya, Wu-ting Tsai, Po-chen Chen〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The present study is concerned with direct numerical simulation (DNS) of turbulent air flow over a waved water surface. Three-dimensional, turbulent Couette flow is considered in DNS as a model of a constant-flux layer in the marine atmospheric surface layer. Two-dimensional stationary waves at the water surface are prescribed and assumed to be unaffected by the air-flow. We consider capillary-gravity water surface waves and are interested in the influence of “parasitic” capillary ripples riding on the carrier, energy-containing waves, on the properties of the air-flow. The surface waves are prescribed and considered to be stationary, the capillaries being in phase with the carrier wave. The surface elevations spectra are also prescribed and mimicking stationary capillaries riding on Stokes waves observed in a 2D numerical simulation of water-surface capillary-gravity waves by Hung & Tsai (2009). The bulk air velocity and the carrier water surface waves lengths are considered in our DNS in the range of 3 to 5 m/s and 3 to 7 cm, respectively. Under these conditions, the capillaries are found to be submerged within the viscous sublayer of the atmospheric boundary layer. Our DNS results show that although the flow fields are characterized by instantaneous separations of the boundary layer, the ensemble (wave-phase) averaged flow fields are non-separating and well predicted by a quasilinear theoretical model. We find also that capillaries mitigate the development of coherent (horse-shoe) vortex structures as compared to the no-ripples flow-case. We further use DNS results and quasilinear model formulation to parameterize the water surface roughness height in terms of critical layer thickness and the amplitude of a dominant, energy-containing harmonic of the water surface elevation spectrum.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Transportation Research Part F: Traffic Psychology and Behaviour, Volume 64〈/p〉 〈p〉Author(s): Kayla Fleskes, David S. Hurwitz〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉One proposed benefit of automated vehicles (AVs) is their potential to mitigate the occurrence of serious crashes due to human error or poor decision making while driving. However, there are still many concerns associated with the use of SAE Level 3 AVs, which require intervention by a human driver after a take-over request (TOR). These concerns intensify when vulnerable road users, such as bicyclists, are introduced to the driving environment. The objective of this research was to investigate how human drivers of AVs interact with bicyclists during a right-turn maneuver after receiving a TOR. Changes in driver performance, including visual attention and crash avoidance behavior, were measured by using a high-fidelity driving simulator, with 43 participants each completing 18 right-turn maneuvers. Three independent variables were studied: the bicyclist’s proximity to the intersection, the driver’s proximity from the intersection when the TOR was received, and the driver’s engagement in a distracting secondary task (a game on a tablet). In general, the results showed that the introduction of the secondary task led to decreased driver performance with respect to time-to-collision and the time that it took a driver to first identify the bicyclist on the roadway. When given more time to react before the intersection, drivers generally had safer interactions with the bicyclist.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S136984781830411X-ga1.jpg" width="426" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: Available online 8 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Quaternary International〈/p〉 〈p〉Author(s): Brian F. Codding, Adrian R. Whitaker, Nathan E. Stevens〈/p〉

Beschreibung: 〈p〉Publication date: 15 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Quaternary Science Reviews, Volume 218〈/p〉 〈p〉Author(s): Athanassios Athanassiou, Alexandra A.E. van der Geer, George A. Lyras〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The Eastern Mediterranean islands, most of which belong to the Aegean archipelago, have a complex biogeographic history, which puts its stamp on their fauna and flora. A now extinct but most important faunal component, in terms of geographic spread and taxonomic diversity, are the elephants. The Eastern Mediterranean islands are particularly rich in Pleistocene endemic elephant localities, which preserve samples of extinct endemic populations. These were either descendants of the European straight-tusked elephant 〈em〉Palaeoloxodon antiquus〈/em〉 or the Southern mammoth, 〈em〉Mammuthus meridionalis〈/em〉. Their presence, history and palaeobiogeography has been documented only for Cyprus, Crete, Kasos, Rhodes, Tilos, Kýthera, Naxos, and Delos. For six other islands only anecdotal references exist in the literature: Kálymnos, Astypálaia, Milos, Sériphos, Kýthnos and Paros. Here, we provide an update on previously published specimens and taxa, describe previously undescribed specimens that were relocated in museum collections, as well as recently excavated specimens, and put these in the context of island palaeobiogeography. We conclude that dwarf elephants, endemic to their palaeo-island, lived on the islands of palaeo-Cyclades, Astypálaia, Crete, Kasos–Kárpathos–Saría, Tilos, Rhodes and Cyprus, whereas the elephants from Kephallenía, Kálymnos and Kýthera are indistinguishable on the species level from mainland 〈em〉Palaeoloxodon antiquus〈/em〉. Elephant fossils of unresolved taxonomic status are reported from five present-day islands. The Eastern Mediterranean endemic elephants likely derived from separate and independent colonisation events from the mainland. No island supported more than one proboscidean species at any time. We found that isolation had no effect on the degree of dwarfism, but that there exists a threshold of about 6–10 km distance between the island and the mainland, below which no dwarfism evolved, likely as a result of genetic contact with the mainland population. We also found that although island area is correlated with the degree of dwarfism in elephants, other factors, such as the level of interspecific competition, may limit this degree.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: Available online 8 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Remote Sensing of Environment〈/p〉 〈p〉Author(s): Julie A. Fortin, Jeffrey A. Cardille, Elijah Perez〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈p〉The ongoing march toward freely available, highly pre-processed satellite imagery has given both researchers and the public unprecedented access to a vast and varied data stream teeming with potential. Among many sources, the multi-decade Landsat archive is certainly the best known, but legacy and current data from other sensors is available as well through the USGS data portals: these include CBERS, ASTER, and more. Though the particular band combinations or non-global missions have made their integration into analyses more challenging, these data, in conjunction with the entire Landsat record, are available to contribute to multi-decade surveys of land-cover change.〈/p〉 〈p〉With the goal of tracing forest change through time near the Roosevelt River in the state of Mato Grosso, Brazil, we used BULC and Google Earth Engine to fuse information from 13 space-borne imagers capturing 140 images spanning 45 years. With high accuracy, the resulting time series of classifications shows the timing and location of land-use/land-cover change—both deforestation and regrowth—at sub-annual time scales. Accuracy estimates showed that the synthesized BULC classification time series was better than nearly all of the single-day image classifications, covering the entire study area at sub-annual frequency while reducing the impact of clouds and most unwanted noise as it fused information derived from a wide array of imaging platforms. The time series improved and gradually sharpened as the density of observations increased in recent decades, when there were three or more clear, higher-resolution views of a pixel annually from any sensor combination. In addition to detailing the methodology and results of multi-source data fusion with the BULC approach, this study raises timely points about integrating information from early satellite data sources and from sensors with footprints smaller than Landsat's. There are decades of research deriving sensor-specific techniques for classifying land use and land cover from a single image in a variety of settings. The BULC approach leverages the many successes of single-sensor research and can be used as a straightforward, complementary tool for blending many good-quality mapped classifications from disparate sources into a coherent, high-quality time series.〈/p〉 〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: Available online 8 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Quaternary International〈/p〉 〈p〉Author(s): Xiaolin Ren, Duowen Mo, Michael Storozum, Ximena Lemoine, Yanyan Yu, Wanfa Gu, Xingshan Lei, Jiaqiang Zhang, Jianqing Lü, Tristram R. Kidder〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Archaeologists have focused on the social conditions surrounding the development of urbanism around the world, however the environmental impact of these ancient cities remains unclear. In this paper, we present palynological data from the early Bronze Age city of Dongzhao, Henan Province, China. Our data indicate that vegetation change and the development of early urban settlements are closely linked, with the advent of urban development significantly accelerating deforestation and altering the composition of local vegetation communities. The pollen record from Dongzhao provides new evidence to support the claim that urban expansion, coupled with a drying climate and the expansion of agriculture, dramatically reconfigured the landscapes of Bronze Age China.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Computers & Geosciences, Volume 132〈/p〉 〈p〉Author(s): T. Carlotto, P.L.B. Chaffe〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Streamflow recession analysis is crucial for understanding how catchments release water in periods of drought and therefore is important for water resources planning and management. Despite there being several theories on how to model recession curves, few studies compare the different approaches to that problem. In this work, we developed the Master Recession Curve Parameterization tool (MRCPtool), which brings together a set of automated methods for the analysis of recession periods based only on streamflow data. The methods include: (i) hydrograph separation using numerical filters; (ii) automatic extraction of recession periods; (iii) creation of the MRC with the matching strip method; (iv) creation of the MRC for different flow classes defined from the flow duration curve; (v) analysis of flow recession rates 〈math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline" altimg="si1.svg"〉〈mrow〉〈mo〉(〈/mo〉〈mo linebreak="goodbreak" linebreakstyle="after"〉−〈/mo〉〈mi〉d〈/mi〉〈mi〉Q〈/mi〉〈mo〉∕〈/mo〉〈mi〉d〈/mi〉〈mi〉t〈/mi〉〈mo〉)〈/mo〉〈/mrow〉〈/math〉 as a function of flow 〈math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline" altimg="si2.svg"〉〈mrow〉〈mo〉(〈/mo〉〈mi〉Q〈/mi〉〈mo〉)〈/mo〉〈/mrow〉〈/math〉 and (vi) creation of the MRC from simulated recession curves with different analytical approaches, including linear and nonlinear models. The MRCPtool contains a graphical user interface developed in MATLAB software that facilitates the analysis of streamflow datasets. Finally, we present an example application of the MRCPtool using a streamflow dataset of 44 years. The MRCPtool is an open source tool that can be downloaded from the site: 〈a href="http://www.labhidro.ufsc.br/static/software/MRCPtool.rar" target="_blank"〉http://www.labhidro.ufsc.br/static/software/MRCPtool.rar〈/a〉.〈/p〉〈/div〉

Beschreibung: 〈p〉Publication date: September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 141〈/p〉 〈p〉Author(s): Chao Wang, Yuan Yuan, Jie Wu, Yuanlin Zhao, Xing Gao, Yihua Chen, Chao Sun, Liming Xiao, Pengfei Zheng, Peizhen Hu, Zengshan Li, Zhe Wang, Jing Ye, Lijun Zhang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉While cardiac hypertrophy and heart failure are accompanied by significant alterations in energy metabolism, more than 50–70% of energy is obtained from fatty acid β-oxidation (FAO) in adult hearts under physiological conditions. Plin5 is involved in the metabolism of lipid droplets (LDs) and is highly abundant in oxidative tissues including heart, liver and skeletal muscle. Plin5 protects the storage of triglyceride (TG) in LDs by inhibiting lipolysis, thereby suppressing excess FAO and preventing excessive oxidative stress in the heart. In this study, we investigated the roles of Plin5 in cardiac hypertrophy and heart failure in mice treated with transverse aortic constriction (TAC). The results indicated that Plin5 deficiency aggravated myocardial hypertrophy in the TAC-treated mice and exacerbated the TAC-induced heart failure. We also found that Plin5 deficiency reduced the cardiac lipid accumulation and upregulated the levels of PPARα and PGC-1α, which stimulate mitochondrial proliferation. Moreover, Plin5 deficiency aggravated the TAC-induced oxidative stress. We consistently found that Plin5 knockdown disrupted TG storage and elevated FAO and lipolysis in H9C2 rat cardiomyocytes. In addition, Plin5 knockdown also provoked mitochondrial proliferation and lipotoxic injury in H9C2 cells. In conclusion, Plin5 deficiency increases myocardial lipolysis, elevates FAO and oxidative burden, and thereby exacerbates cardiac hypertrophy and heart failure in TAC-treated mice.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S089158491930471X-fx1.jpg" width="336" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Beschreibung: 〈p〉Publication date: Available online 7 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Experimental Cell Research〈/p〉 〈p〉Author(s): Rong Jiang, Yan Liao, Fuhuang Yang, Yusi Cheng, Xiaoniu Dai, Jie Chao〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Endothelial-mesenchymal transition (EndoMT) is a key step during lung fibrosis. Studies have shown that bone marrow mesenchymal stem cells (BMSCs) may act as therapeutic candidates for lung fibrosis. However, the effects of BMSCs on EndoMT induced by SiO〈sub〉2〈/sub〉 have not been elucidated, and means to label and track grafted cells have been lacking. The current study explored whether BMSCs prevented pulmonary fibrosis by targeting EndoMT, as well as analyzed the distribution of BMSCs labeled with superparamagnetic iron oxide (SPIO) nanoparticles during treatment. TIE2-GFP mice, human umbilical vein endothelial cells (HUVECs), and BMSCs labeled with SPIO nanoparticles were used to explore the distributions and therapeutic effects of BMSCs in vivo and in vitro. We found that BMSCs reversed lung fibrosis by targeting EndoMT in vivo. Furthermore, we show that BMSCs labeled with SPIO nanoparticles could be used to track stem cells reliably in the lungs for 14 days. Conditioned medium from BMSCs attenuated the increased functional changes and reversed the SiO〈sub〉2〈/sub〉-induced upregulation of ER stress and autophagy markers irrespective of whether they were nanoparticle labeled or not. Our findings identify novel methods to track labeled BMSCs with therapeutic potential.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1862, Issue 8〈/p〉 〈p〉Author(s): Ruifan Wu, Guanqun Guo, Zhen Bi, Youhua Liu, Yuanling Zhao, Nana Chen, Fengqin Wang, Yizhen Wang, Xinxia Wang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉〈em〉N〈/em〉〈sup〉6〈/sup〉-methyladenosine (m〈sup〉6〈/sup〉A), the most abundant internal mRNA modification in eukaryotes, plays a vital role in regulating adipogenesis. However, its underlying mechanism remains largely unknown. Here, we reveal that deletion of m〈sup〉6〈/sup〉A demethylase FTO in porcine and mouse preadipocytes inhibits adipogenesis through JAK2-STAT3-C/EBPβ signaling. Mechanistically, FTO deficiency suppresses JAK2 expression and STAT3 phosphorylation, leading to attenuated transcription of C/EBPβ, which is essential for the early stage of adipocyte differentiation. Using dual-luciferase assay, we validate that knockdown of FTO reduces expression of JAK2 in an m〈sup〉6〈/sup〉A-dependent manner. Furthermore, we find that m〈sup〉6〈/sup〉A “reader” protein YTHDF2 directly targets m〈sup〉6〈/sup〉A-modified transcripts of JAK2 and accelerates mRNA decay, which results in decreased JAK2 expression and inactivated JAK2-STAT3-C/EBPβ signaling, thereby inhibiting adipogenesis. Collectively, our results provide a novel insight into the molecular mechanism of m〈sup〉6〈/sup〉A methylation in post-transcriptional regulation of JAK2-STAT3-C/EBPβ signaling axis and highlight the crucial role of m〈sup〉6〈/sup〉A modification and its modulators in adipogenesis.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: 1 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochimica et Biophysica Acta (BBA) - Biomembranes, Volume 1861, Issue 8〈/p〉 〈p〉Author(s): 〈/p〉

Beschreibung: 〈p〉Publication date: 1 October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1865, Issue 10〈/p〉 〈p〉Author(s): Tomonaga Ichikawa, Shingo Nakahata, Masahiro Fujii, Hidekatsu Iha, Kazuya Shimoda, Kazuhiro Morishita〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉N-myc downstream-regulated gene 2 (NDRG2) is a candidate tumor suppressor that is frequently downregulated in adult T-cell leukemia/lymphoma (ATLL) and functions to negatively regulate several cellular signaling pathways as PP2A recruiter. To clarify the molecular mechanisms of suppression of NDRG2 expression, we initially determined the expression pattern of NDRG2 in various types of T-cells and ATLL cells. NDRG2 expression was significantly upregulated in HTLV-1/Tax-immortalized T-cells, which was mediated by NF-κB activation through Tax expression. On the other hand, NDRG2 expression was suppressed in HTLV-1-infected cell lines and various types of ATLL cells, which was dependent on the DNA methylation of the NDRG2 promoter. We found that the expression of enhancer of zeste homolog 2 (EZH2), a member of the polycomb family, is increased in ATLL, and that EZH2 directly binds to the NDRG2 promoter and induces DNA methylation of the NDRG2 promoter. Since the expression of EZH2 were anti-parallelly regulated with the NDRG2 expression, EZH2 might be one of the most important regulators of the downregulation of NDRG2, contributing to enhanced activation of signaling pathways during ATLL development.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: 1 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochimica et Biophysica Acta (BBA) - Biomembranes, Volume 1861, Issue 9〈/p〉 〈p〉Author(s): Mariafrancesca Scalise, Michele Galluccio, Lorena Pochini, Jessica Cosco, Miriam Trotta, Manuele Rebsamen, Giulio Superti-Furga, Cesare Indiveri〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The lysosomal amino acid transporter SLC38A9 is referred to as transceptor, i.e. a transporter with a receptor function. The protein is responsible for coupling amino acid transport across the lysosomal membrane according to the substrate availability to mTORC1 signal transduction. This process allows cells to sense amino acid level responding to growth stimuli in physiological and pathological conditions triggering mTOR regulation. The main substrates underlying this function are glutamine and arginine. The functional and kinetic characterization of glutamine and arginine transport was performed using human SLC38A9 produced in 〈em〉E. coli〈/em〉, purified by affinity chromatography and reconstituted in liposomes. A cooperative behaviour for the wild type protein was revealed for both the substrates. A novel Na〈sup〉+〈/sup〉 binding site, namely T453, was described by combined approaches of bioinformatics, site-directed mutagenesis and transport assay. Stimulation by cholesterol of glutamine and arginine transport was observed. The biological function of SLC38A9 relies on the interaction between its N-terminus and components of the mTOR complex; a deletion mutant of the N-terminus tail was produced and transport of glutamine was assayed revealing that this portion does not play any role in the intrinsic transport function of the human SLC38A9. Different features for glutamine and arginine transport were revealed: human SLC38A9 is competent for glutamine efflux, while that of arginine is negligible. In line with these results, imposed ∆pH stimulated glutamine, not arginine transport. Arginine plays, on the contrary, a modulatory function and is able to stimulate glutamine efflux. Interestingly, reciprocal inhibition experiments also supported by bioinformatics, suggested that glutamine and arginine may bind to different sites in the human SLC38A9 transporter.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉Proteoliposome reconstitution of hSLC38A9 WT and mutants.〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0005273619301567-ga1.jpg" width="301" alt="Unlabelled Image" title="Unlabelled Image"〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: Available online 8 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Computer Methods and Programs in Biomedicine〈/p〉 〈p〉Author(s): Alae Ammour, Ibtissame Aouraghe, Ghizlane Khaissidi, Mostapha Mrabti, Ghita Aboulem, Faouzi Belhacen〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Parkinson's disease (PD) is the second most common neurodegenerative disease affecting significant portion of elderly population. One of the most frequent hallmarks and the first manifestation of PD is deterioration of handwriting. Since the diagnosis of Parkinson's disease is difficult, researchers have worked to develop a support tool based on algorithms to separate healthy controls from PD patients. On-line handwriting analysis is one of the methods that can be used to diagnose PD. In this study, we aimed to analyze the Arabic Handwriting of 28 Parkinson's disease patients and 28 healthy controls (HCs) who were the same age and have the same intellectual level. We focused on copying an Arabic text task. For each participant we have calculated 1482 features. Based on the most relevant features selected by the Pearson's coefficient correlation, the Hierarchical Ascendant Classification (HAC) was applied and generated 3 clusters of writers. The characterization of these clusters was carried out by using the quantitative and qualitative parameters. The obtained results show that the combination of these two aspects can discriminate at best PD patients from HCs.〈/p〉〈/div〉

Beschreibung: 〈p〉Publication date: September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1863, Issue 9〈/p〉 〈p〉Author(s): 〈/p〉

Beschreibung: 〈p〉Publication date: 1 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochimica et Biophysica Acta (BBA) - Biomembranes, Volume 1861, Issue 9〈/p〉 〈p〉Author(s): Oumaima Et-Thakafy, Fanny Guyomarc'h, Christelle Lopez〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The biological membrane surrounding milk fat globules (MFGM) exhibits lateral phase separation of lipids, interpreted as gel or liquid-ordered phase sphingomyelin-rich (milk SM) domains dispersed in a fluid continuous lipid phase. The objective of this study was to investigate whether changes in the phase state of milk SM-rich domains induced by temperature (T 〈 Tm or T 〉 Tm) or cholesterol affected the Young modulus of the lipid membrane. Supported lipid bilayers composed of MFGM polar lipids, milk SM or milk SM/cholesterol (50:50 mol) were investigated at 20 °C and 50 °C using atomic force microscopy (AFM) and force spectroscopy. At 20 °C, gel-phase SM-rich domains and the surrounding fluid phase of the MFGM polar lipids exhibited Young modulus values of 10–20 MPa and 4–6 MPa, respectively. Upon heating at 50 °C, the milk SM-rich domains in MFGM bilayers as well as pure milk SM bilayers melted, leading to the formation of a homogeneous membrane with similar Young modulus values to that of a fluid phase (0–5 MPa). Upon addition of cholesterol to the milk SM to reach 50:50 mol%, membranes in the liquid-ordered phase exhibited Young modulus values of a few MPa, at either 20 or 50 °C. This indicated that the presence of cholesterol fluidized milk SM membranes and that the Young modulus was weakly affected by the temperature. These results open perspectives for the development of milk polar lipid based vesicles with modulated mechanical properties.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0005273619301555-ga1.jpg" width="317" alt="Unlabelled Image" title="Unlabelled Image"〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Advances in Water Resources, Volume 131〈/p〉 〈p〉Author(s): Shaokun He, Shenglian Guo, Kebing Chen, Lele Deng, Zhen Liao, Feng Xiong, Jiabo Yin〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The optimal impoundment operation of cascade reservoirs can dramatically improve the utilization of water resources. However, their complex non-convexity and computational costs pose challenges to optimal hydroelectricity output and limit further development of joint operation within larger-scale cascade reservoirs. In recent decades, parallel dynamic programming (PDP) has emerged as a means of alleviating the ‘curse of dimensionality’ in the mid-long term reservoir operation with more involved computing processors. But it still can't effectively solve the daily impoundment operation of more than three reservoirs. Here, we propose a novel method called importance sampling-PDP (IS-PDP) algorithm in which the merits of PDP are integrated with importance sampling and successive approximation strategy. Importance sampling is first used to construct the state vectors of each period by introducing ‘Manhattan distance’ in the discrete state space. Then the PDP recursive equation is used to find an improved solution during the iteration. The IS-PDP method is tested to optimize hydropower output for the joint operation of an 11-reservoir system located in the upper Yangtze River basin of China after establishing impoundment operation by advancing impoundment timings and rising water levels. We find that our methodology could effectively deal with the ‘curse of dimensionality’ for such mega reservoir systems and make better use of water resources in comparison to the Standard Operation Policy (SOP). Given its computational efficiency and robust convergence, the methodology is an attractive alternative for non-convex operation of large-scale cascade reservoirs.〈/p〉〈/div〉

Beschreibung: 〈p〉Publication date: August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 ISPRS Journal of Photogrammetry and Remote Sensing, Volume 154〈/p〉 〈p〉Author(s): 〈/p〉

Beschreibung: 〈p〉Publication date: July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Ocean Modelling, Volume 139〈/p〉 〈p〉Author(s): 〈/p〉

Beschreibung: 〈p〉Publication date: November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 World Development, Volume 123〈/p〉 〈p〉Author(s): Adriana Camacho, Emily Conover〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Small-scale farmers in developing countries often make production and sale decisions based on imprecise, informal, and out-of-date sources of information, such as family, neighbors, or tradition. Lack of timely and accurate information on climate and prices can lead to inefficiencies in the production, harvesting, and commercialization of agricultural products, which in turn can affect farmers’ revenues and well-being. We did a Randomized Controlled Trial (RCT) experiment with 500 small-scale farmers in a rural area of Colombia where there is nearly full mobile phone usage and coverage. Treated farmers received around 8 text messages per week with prices in the main markets for crops grown in the region, and customized weather forecasts. Compared to a control group, we find that treated farmers were more likely to report that text messages provide useful information for planting and selling, and more likely to always read their messages, indicating an increase in appreciation and use of this type of technology. We also found heterogeneous effects by farmer size. Smaller farmers try to make use of the intervention by planting more crops for which they have price information. Larger farmers seek new markets and increase conversations with other producers. Despite these positive effects, we do not find a significant difference in farmers reporting a price, price differential with the market price, or sale prices received. Our results indicate that farmers are amenable to learning and using new technologies, but that the introduction of these technologies do not always translate into short-run welfare improvements for them. Given the increased interest in incorporating information and communication technologies into agriculture, our findings indicate that prior to a large-scale implementation it is necessary to better understand what prevents farmers from more directly profiting from this new information.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Remote Sensing of Environment, Volume 232〈/p〉 〈p〉Author(s): Yue Ma, Nan Xu, Jinyan Sun, Xiao Hua Wang, Fanlin Yang, Song Li〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Currently, 〈em〉in-situ〈/em〉 data and the time duration of altimeter data are limitations in calculating the water level and water volume of lakes and reservoirs from remotely sensed data. A novel method is proposed to estimate the temporal change in water levels and water volumes for lakes with only remotely sensed data. First, the surface profiles, including the ground and the underwater bottom, were extracted from the MABEL (Multiple Altimeter Beam Experimental Lidar) photon-counting lidar raw data via a new surface detecting algorithm. Second, the lake boundaries between land and water in different years were identified using a thresholding method based on the annual median Landsat composite. Third, water levels were calculated by matching the lidar surface profiles with the lake boundaries based on the nearby georeferenced coordinates. Finally, the water volumes in different years were estimated via the contours (i.e., lake boundaries) with different elevations. Lake Mead was selected as the study area, which is the largest reservoir in the United States in terms of water capacity. With only one day measuring lidar points in February 2012 and over 20 years of Landsat images (from 1987 to 2007), the water levels and water volumes in different years were estimated and compared with the 〈em〉in-situ〈/em〉 data. Our results performed well in accordance with the 〈em〉in-situ〈/em〉 measurements; the R-square of the water levels and water volumes were both over 0.99; the RMSE of the interannual variations of water levels and water volumes were 0.96 m and 0.31 km〈sup〉3〈/sup〉, respectively. The MABEL was used as a technology demonstrator for the satellite photon-counting laser altimeter and had similar data to the ICESat-2 dataset. Future ICESat-2 datasets will broaden this method to estimate water volumes for remote lakes from the 1980s, where no 〈em〉in-situ〈/em〉 data are available (such as the Tibetan Plateau and polar regions with thousands of remote and wild lakes), which could not be achieved in previous studies.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Weather and Climate Extremes, Volume 25〈/p〉 〈p〉Author(s): Jeremy Diaz, Maxwell B. Joseph〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Tornadoes are the most violent of all atmospheric storms. In a typical year, the United States experiences hundreds of tornadoes with associated damages on the order of one billion dollars. Community preparation and resilience would benefit from accurate predictions of these economic losses, particularly as populations in tornado-prone areas increase in density and extent. Here, we use a zero-inflated modeling approach and artificial neural networks to predict tornado-induced property damage using publicly available data. We developed a neural network that predicts whether a tornado will cause property damage (out-of-sample accuracy = 0.821 and area under the receiver operating characteristic curve, AUROC, = 0.872). Conditional on a tornado causing damage, another neural network predicts the amount of damage (out-of-sample mean squared error = 0.0918 and 〈math xmlns:mml="http://www.w3.org/1998/Math/MathML" altimg="si1.svg"〉〈mrow〉〈msup〉〈mrow〉〈mi〉R〈/mi〉〈/mrow〉〈mrow〉〈mn〉2〈/mn〉〈/mrow〉〈/msup〉〈/mrow〉〈/math〉  = 0.432). When used together, these two models function as a zero-inflated log-normal regression with hidden layers. From the best-performing models, we provide static and interactive gridded maps of monthly predicted probabilities of damage and property damages for the year 2019. Two primary weaknesses include (1) model fitting requires log-scale data which leads to large natural-scale residuals and (2) beginning tornado coordinates were utilized rather than tornado paths. Ultimately, this is the first known study to directly model tornado-induced property damages, and all data, code, and tools are publicly available. The predictive capacity of this model along with an interactive interface may provide an opportunity for science-informed tornado disaster planning.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 92〈/p〉 〈p〉Author(s): Yang Hu, Wei-Chao Chen, Yu-Feng Shen, Bin Zhu, Gao-Xue Wang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Viral diseases in aquaculture were challenging because there are few preventative measures and/or treatments. Our previous study indicated that imidazole arctigenin derivatives possessed antiviral activities against infectious hematopoietic necrosis virus (IHNV). Based on the structure-activity relationship in that study, a new imidazole arctigenin derivative, 4-(8-(2-ethylimidazole)octyloxy)-arctigenin (EOA), was designed, synthesized and its anti-IHNV activity was evaluated. By comparing inhibitory concentration at half-maximal activity (IC〈sub〉50〈/sub〉), we found that EOA (IC〈sub〉50〈/sub〉 = 0.56 mg/L) possessed a higher antiviral activity than those imidazole arctigenin derivatives in our previous study. Besides, EOA could significantly decrease cytopathic effect (CPE) and viral titer induced by IHNV in epithelioma papulosum cyprinid (EPC) cells. In addition, EOA significantly inhibited apoptosis induced by IHNV in EPC cells. Further data verified that EOA inhibited IHNV replication in rainbow trout, with reducing 32.0% mortality of IHNV-infected fish. The results suggested that EOA was more stable with a prolonged inhibitory half-life in the early stage of virus infection (1–4 days). Consistent with above results, EOA repressed IHNV glycoprotein gene expression in virus sensitive tissues (kidney and spleen) in the early stage of virus infection. Moreover, histopathological evaluation showed that tissues from the spleen and kidney of fish infected with IHNV exhibited pathological changes. But there were no lesions in any of the tissues from the control group and EOA-treaten group. In accordance with the histopathological assay, EOA could elicited anti-inflammation response in non-viral infected rainbow trout by down-regulating the expression of cytokine genes (〈em〉IL-8〈/em〉, 〈em〉IL-12p40〈/em〉, and 〈em〉TNF-α〈/em〉). Altogether, EOA was expected to be a therapeutic agent against IHNV infection in the field of aquaculture.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Journal of Hydrology: Regional Studies, Volume 24〈/p〉 〈p〉Author(s): Johnson U. Kitheka〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Study region〈/h6〉 〈p〉This study was undertaken in the Athi-Sabaki river basin in Kenya in East Africa.〈/p〉 〈/div〉 〈div〉 〈h6〉Study focus〈/h6〉 〈p〉The study focused on the determination of the influence of streamflow variability on salt fluxes. This involved monitoring of river discharge and river salinity in the period between 2012 and 2018.〈/p〉 〈/div〉 〈div〉 〈h6〉New hydrological insights〈/h6〉 〈p〉: This study demonstrates that Athi-Sabaki river discharges significant quantity of salt to the sea. There are significant seasonal and inter-annual variations in salt fluxes that are due to variations in river discharge and rainfall in the basin. The relationship between streamflow variations and variations of salinity in the river was inverse with highest salinity concentrations and fluxes occurring during low flow conditions. The river salinity and TDS concentrations decreased with an increase in river discharge due to dilution effect and flushing of salt from the river. The highly polluted sub-basins draining through the City of Nairobi exhibited relatively higher salinity and salt fluxes as compared to non-polluted ones draining rural areas. The total salt flux in the basin ranged between 29 × 10〈sup〉3〈/sup〉 and 261 × 10〈sup〉3〈/sup〉 tons year〈sup〉−1〈/sup〉. The relatively high salinity and salt fluxes were attributed to the discharge of wastewaters, seepage of groundwater and irrigation return flows. The study calls for water pollution control, sustainable irrigation and landuse practices in the basin.〈/p〉 〈/div〉

Beschreibung: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Geoforum, Volume 105〈/p〉 〈p〉Author(s): Arnab Roy Chowdhury, Kuntala Lahiri-Dutt〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Hirashasan is the term used for governance of diamond mining and trade – with a small bureaucracy and an exclusive set of rules and regulations – by the district administration of Panna in the state of Madhya Pradesh in India. Diamond mining in Panna encompasses diverse extractive practices that range from fully mechanised large-scale mining operations owned by the state, to small-scale and semi-mechanised mining carried out by farmers and landowners in groups, to individuals carrying out seasonal and part-time mining of diamonds in an artisanal manner. Based on an ethnographic study was undertaken from September 2016 to April 2017, we argue that Hirashasan has created an “extractive assemblage” that comprises four genres of mining and production systems: large-scale, small-scale, licensed artisanal and unlicensed artisanal. This assemblage is a product of historical, cultural and geographical contingencies as much as place-specificities, and does not lend itself to a single mode of governance. Mineral resource governance in a particular place, therefore, necessitates understanding and internalising the variegated and pluri-form extractive assemblages, such as that of the diamond economy in Panna.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 92〈/p〉 〈p〉Author(s): Junjun He, Haiying Liang, Jiaping Zhu, Xiaochen Fang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Antibacterial peptides (AMPs) constitute an important part of the body's innate immune system and are responsible for a wide range of inhibitory effects against pathogens such as bacteria, fungi, and viruses. In this study, multi-step high performance liquid chromatography (HPLC), combined with Mass Spectrometry (MS), was used to isolate and identify proteins with antibacterial activity from the serum of 〈em〉Pinctada fucata martensii〈/em〉 (〈em〉P.f. Martensii〈/em〉) and obtain a component named 〈em〉P.f. Martensii〈/em〉 antimicrobial peptide-1 (PmAMP-1). 〈em〉PmAMP-1〈/em〉 cDNA was cloned and sequenced by rapid amplification of cDNA ends (RACE) and mRNA expression of was analyzed by quantitative real-time PCR (qRT-PCR). From the results of this study, full-length 〈em〉PmAMP-1 c〈/em〉DNA was shown to be 700 base pairs (bp) long with an open reading frame (ORF) of 294 bp, encoding 97 amino acids with a predicted structure that is mostly α-helices. 〈em〉PmAMP-〈/em〉1 mRNA was constitutively expressed in all tested tissues including the adductor muscle, mantle, hepatopancreas, gill, gonads and hemocytes. The highest level of 〈em〉PmAMP-〈/em〉1 transcription was observed at 8 h and 2 h after bacterial challenge in hemocytes and adductor muscle (p 〈 0.01), respectively. Furthermore, PmAMP-1 caused significant morphological alterations in 〈em〉E. coli,〈/em〉 as shown by transmission electron microscopy (TEM). The results from this study provide a valuable base for further exploration of molluscan innate immunity and immune response.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: Available online 5 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Technological Forecasting and Social Change〈/p〉 〈p〉Author(s): Sorin M.S. Krammer, Alfredo Jiménez〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉We posit that the investments in political connections made by a firm in an emerging market will impact differently its propensity to introduce radical and incremental innovations. In addition, we argue that this effect will be moderated by alternate non-market firm strategies, such as bribery. Using a dataset of more than 9000 firms in 30 emerging economies from Eastern Europe and Central Asia we find that political connections increase the probability of radical innovation but have no significant impact on incremental innovation. Moreover, larger bribing reduces the positive impact of political connections on radical innovation. Our results confirm the importance of political connections for firm activities, but also caution firms on their heterogeneous impact on various types of innovations, and their detrimental interplay with other non-market strategies.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Journal of Magnetic Resonance, Volume 305〈/p〉 〈p〉Author(s): A. Gallo, W.T. Franks, J.R. Lewandowski〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉We present a suite of two-receiver solid-state NMR experiments for backbone and side chain resonance assignment. The experiments rely on either dipolar coupling or scalar coupling for polarization transfer and are devised to acquire a 〈sup〉1〈/sup〉H–detected 3D experiment AND a nested 〈sup〉13〈/sup〉C–detected 2D from a shared excitation pulse. In order to compensate for the lower sensitivity of detection on 〈sup〉13〈/sup〉C nucleus, 2D rows are signal averaged during 3D planes. The 3D dual receiver experiments do not suffer from any appreciable signal loss compared to their single receiver versions and require no extra optimization. The resulting data is higher in information content with no additional experiment time. The approach is expected to become widespread as multiple receivers become standard for new NMR spectrometers.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S1090780719301302-ga1.jpg" width="500" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Journal of Magnetic Resonance, Volume 305〈/p〉 〈p〉Author(s): Ibrahim A. Elabyad, M. Terekhov, M.R. Stefanescu, D. Lohr, M. Fischer, L.M. Schreiber〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The design, simulation, assembly and testing of a novel dedicated antisymmetric transmit/receive (Tx/Rx) coil array to demonstrate the feasibility of cardiac magnetic resonance imaging (cMRI) in pigs at 7 T was described. The novel antisymmetric array is composed of eight elements based on mirrored and reversed loop orientations to generate varying 〈math xmlns:mml="http://www.w3.org/1998/Math/MathML" altimg="si1.svg"〉〈mrow〉〈msubsup〉〈mi〉B〈/mi〉〈mrow〉〈mn〉1〈/mn〉〈/mrow〉〈mo〉+〈/mo〉〈/msubsup〉〈/mrow〉〈/math〉 field harmonics for RF shimming. The central four loop elements formed together a pair of antisymmetric L-shaped channels to allow good decoupling between all neighboring elements of the entire array. The antisymmetric array was compared to a standard symmetric rectilinear loop array with an identical housing dimension. Both arrays were driven in the parallel transmit (pTx) mode forming an 8-channel transmit and 16-channel receive (8Tx/16Rx) coil array, where the same posterior array was combined with both anterior arrays. The hardware and imaging performance of the dedicated cardiac arrays were validated and compared by means of electromagnetic (EM) simulations, bench-top measurements, phantom, and 〈em〉ex-vivo〈/em〉 MRI experiments with 46 kg female pig. Combined signal-to-noise ratio (SNR), geometry factor (g-factor), noise correlation maps, and high resolution 〈em〉ex-vivo〈/em〉 cardiac images were acquired with an in-plane resolution of 0.3 mm × 0.3 mm using both arrays. The novel antisymmetric array enhanced the SNR within the heart by about two times and demonstrated good decoupling and improved control of the 〈math xmlns:mml="http://www.w3.org/1998/Math/MathML" altimg="si1.svg"〉〈mrow〉〈msubsup〉〈mi〉B〈/mi〉〈mrow〉〈mn〉1〈/mn〉〈/mrow〉〈mo〉+〈/mo〉〈/msubsup〉〈/mrow〉〈/math〉 field distributions for RF shimming compared to the standard coil array. Parallel imaging with acceleration factor (R) up to 4 was possible using the novel antisymmetric coil array while maintaining the mean g-factor within the heart region of 1.13.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S1090780719301284-ga1.jpg" width="356" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: Available online 5 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Transportation Research Part A: Policy and Practice〈/p〉 〈p〉Author(s): Amit Agarwal, Dominik Ziemke, Kai Nagel〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Bicycle is a sustainable low-carbon transport mode. However, insufficient or unplanned infrastructure leads to decrease in the share of bicycle in many cities of developing nations. In order to increase the bicycle share and to provide safer, faster and more direct routes, a bicycle superhighway is proposed for urban areas. This study identifies the potential of increase in the bicycle share. For maximum utilization of the new infrastructure, an algorithm is presented to identify the optimum number and locations of the connectors between proposed new infrastructure and existing network. Household income levels are incorporated into the decision making process of individual travellers for a better understanding of the modal shift. A real-world case study of Patna, India is chosen to show the application of the proposed superhighway. It is shown that for Patna, the bicycle share can escalate as high as 48% up from 32% by providing this kind of infrastructure. However, together with bicycles, allowing motorbikes on the superhighway limits the bicycle share to 44%. The increase in bicycle share is mainly a result of people switching from motorbike, public transport and walk to the bicycle. Further, to evaluate the benefits of the bicycle superhighway, this study first extends an emission modelling tool to estimate the time-dependent, vehicle-specific emissions under mixed traffic conditions. Allowing only bicyclists on the superhighway improves congested urban areas, reduces emissions, and increases accessibility. However, allowing motorbikes on the superhighway increases emissions significantly in the central part of the urban area and reduces accessibilities by bicycle mode to education facilities which are undesirable. This study elicits that a physically segregated high-quality bicycle superhighway will not only attract current non-cyclist travellers and increase the share of the bicycle mode, but will also reduce negative transport externalities significantly.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: Available online 6 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Experimental Cell Research〈/p〉 〈p〉Author(s): Yan Zhang, Hongyan Wang, Tao Yin, Yue Liu, Wenchao Zhou, Xinbin Fan, Liang Wu, Chao Song, Jin Shao, Tieyi Yang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Transmembrane protein 18 (〈em〉Tmem18〈/em〉) is an obesity-associated gene essential for adipogenesis; however, its function in the osteogenic differentiation of bone marrow–derived mesenchymal stem cells (BMSCs) is still unclear. In this study, we found that 〈em〉Tmem18〈/em〉 was significantly downregulated in rat BMSCs after osteogenic induction. TMEM18 overexpression remarkably downregulated osteo-specific genes including alkaline phosphatase (〈em〉Alp〈/em〉), Runt˗related transcription factor 2 (〈em〉Runx2〈/em〉), osteocalcin (〈em〉Ocn〈/em〉), and osteopontin (〈em〉Opn〈/em〉), and reduced the number of mineral deposits and ALP activity 〈em〉in vitro〈/em〉, whereas knockdown of 〈em〉Tmem18〈/em〉 yielded the opposite results. 〈em〉In vivo〈/em〉 assays also indicated that TMEM18 knockdown BMSCs have an increased bone formation potential in a rat model of calvarial defects. Analyses of the mechanism suggested that TMEM18 overexpression decreased β-catenin expression, whereas the TMEM18 knockdown enhanced β-catenin expression and promoted its nuclear translocation. The positive effects on osteogenic differentiation of rat BMSCs owing to the TMEM18 knockdown were attenuated by β-catenin downregulation. Taken together, these results indicate that TMEM18 plays an inhibitory role in osteogenic differentiation of BMSCs via inactivation of β-catenin.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: Available online 5 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Experimental Cell Research〈/p〉 〈p〉Author(s): Olaf Strømme, Katarzyna M. Psonka-Antonczyk, Bjørn Torger Stokke, Anders Sundan, Carl-Jørgen Arum, Gaute Brede〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Multiple myeloma is an incurable cancer of antibody-producing plasma cells. Hepatocyte growth factor (HGF), a cytokine aberrantly expressed in half of myeloma patients, is involved in myeloma pathogenesis by enhancing myeloma growth and invasiveness, and may play a role in myeloma bone disease by inhibiting osteoblastogenesis. In this study, we investigated whether extracellular vesicles (EVs) may play a role in HGF signaling between myeloma cells and osteoblast-like target cells. EVs from the HGF-positive cell line JJN-3 and the HGF-negative cell line INA-6, and from bone marrow plasma and primary human myeloma cells, were isolated using sequential centrifugation techniques and the presence of HGF on the EV-surface was investigated with ELISA. EVs from both cell lines were added to an established bioassay where HGF is known to induce interleukin-11 secretion in osteoblast-like cells. Our results show that HGF was bound to the surface of JJN-3-derived EVs, while INA-6-derived EVs were negative for HGF. Only JJN-3-derived EVs induced IL-11 secretion in osteoblast-like recipient cells. When osteoblast-like cells were preincubated with a specific HGF-receptor (c-Met) inhibitor, no induction of interleukin-11 was observed. Downstream c-Met phosphorylation was demonstrated by immunoblotting. EVs isolated from bone marrow plasma and primary myeloma cells were HGF-positive for a subset of myeloma patients. Taken together, this work shows for the first time that HGF bound on the surface of myeloma-derived EVs can effectuate HGF/c-Met signaling in osteoblast-like cells. Myeloma-derived EVs may play a role in myeloma bone disease by induction of the osteoclast-activating cytokine interleukin-11 in osteoblasts.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0014482719303313-fx1.jpg" width="280" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Beschreibung: 〈p〉Publication date: Available online 5 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Experimental Cell Research〈/p〉 〈p〉Author(s): Kepeng Ou, Sonja Mertsch, Sofia Theodoropoulou, Jiahui Wu, Jian Liu, David A. Copland, Stefan Schrader, Lei Liu, Andrew D. Dick〈/p〉

Beschreibung: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biomaterials, Volume 218〈/p〉 〈p〉Author(s): Yuwei Liu, Biao Kuang, Benjamin B. Rothrauff, Rocky S. Tuan, Hang Lin〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Mesenchymal stem cells (MSCs) embedded in their secreted extracellular matrix (mECM) constitute an exogenous scaffold-free construct capable of generating different types of tissues. Whether MSC-mECM constructs can recapitulate endochondral ossification (ECO), a developmental process during 〈em〉in vivo〈/em〉 skeletogenesis, remains unknown. In this study, MSC-mECM constructs are shown to result in robust bone formation both 〈em〉in vitro〈/em〉 and 〈em〉in vivo〈/em〉 through the process of endochondral ossification when sequentially exposed to chondrogenic and osteogenic cues. Of interest, a novel trypsin pre-treatment was introduced to change cell morphology, which allowed MSC-mECM constructs to undergo the N-cadherin-mediated developmental condensation process and subsequent chondrogenesis. Furthermore, bone formation by MSC-mECM constructs were significantly enhanced by the ECO protocol, as compared to conventional 〈em〉in vitro〈/em〉 culture in osteogenic medium alone. This was designed to promote direct bone formation as seen in intramembranous ossification (IMO). The developmentally informed method reported in this study represents a robust and efficacious approach for stem-cell based bone generation, which is superior to the conventional osteogenic induction procedure.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: Available online 5 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Bioorganic & Medicinal Chemistry Letters〈/p〉 〈p〉Author(s): Gyeong Han Jeong, Jae-Hyeon Cho, Tae Hoon Kim〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Convenient structure modification of (+)-catechin (〈strong〉1〈/strong〉) induced by nonthermal dielectric barrier discharge (DBD) plasma treatment afforded three novel methylene-linked flavan-3-ol oligomers, methylenetetracatechin (〈strong〉2〈/strong〉), methylenetricatechin (〈strong〉3〈/strong〉), and methylenedicatechin (〈strong〉4〈/strong〉), together with two known catechin dimers, 〈em〉bis〈/em〉 8,8′-catechinylmethane (〈strong〉5〈/strong〉) and 〈em〉bis〈/em〉 6,8′-catechinylmethane (〈strong〉6〈/strong〉). The structures of the three new catechin oligomers 〈strong〉2〈/strong〉–〈strong〉4〈/strong〉 with methylene bridges were elucidated by detailed 1D- and 2D-NMR analysis, and the absolute configurations were established by the observation of circular dichroism (CD). The novel products 〈strong〉2〈/strong〉 and 〈strong〉3〈/strong〉 showed significantly enhanced anti-adipogenic capacities against both pancreatic lipase and differentiation of 3T3-L1 preadipocytes compared to the parent (+)-catechin.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0960894X19304536-ga1.jpg" width="500" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: 1 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Bioorganic & Medicinal Chemistry, Volume 27, Issue 17〈/p〉 〈p〉Author(s): Miriam Rossi, Francesco Caruso, Ilaria Costanzini, Carmen Kloer, Aron Sulovari, Elena Monti, Marzia Gariboldi, Emanuela Marras, Neduri V. Balaji, Modukuri V. Ramani, Gottumukkala V. Subbaraju〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The antiproliferative action of hispolon derivatives is stronger than that of related curcumin against several tumor cell lines. Hispolon size, smaller than curcumin, fits better than curcumin into the active site of HDAC6, an enzyme involved in deacetylation of lysine residues. HDACs are considered potential targets for tumor drug discovery and hydroxamates are known inhibitors of HDACs. One of them, SAHA (Vorinostat) is used in clinical studies. Investigations into possible mechanisms for hispolon derivatives active against the HCT116 colon tumor cell line are done after examining the structural results obtained from hispolon X-ray crystal structures as well as performing associated computational docking and Density Functional Theory techniques on HDAC6. These studies show preference for the HDAC6 active site by chelating the Zn center, in contrast with other ineffective hispolon derivatives, that establish only a single bond to the metal center. Structure activity relationships make clear that hydrogenation of the hispolon bridge also leads to single bond (non chelate) hispolon-Zn binding, and consistently nullifies the antiproliferative action against HCT116 tumor.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0968089619301907-ga1.jpg" width="366" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: Available online 5 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Bioorganic & Medicinal Chemistry Letters〈/p〉 〈p〉Author(s): Yasushi Ogasawara, Yo Nakagawa, Chitose Maruyama, Yoshimitsu Hamano, Tohru Dairi〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Mitomycins, produced by several 〈em〉Streptomyces〈/em〉 strains, are potent anticancer antibiotics that comprise an aziridine ring fused to a tricyclic mitosane core. Mitomycins have remarkable ability to crosslink DNA with high efficiency. Despite long clinical history of mitomycin C, the biosynthesis of mitomycins, especially mitosane core formation, remains unknown. Here, we report 〈em〉in vitro〈/em〉 characterization of three proteins, MmcB (acyl carrier protein), MitE (acyl AMP ligase), and MitB (glycosyltransferase) involved in mitosane core formation. We show that 3-amino-5-hydroxybenzoic acid (AHBA) is first loaded onto MmcB by MitE at the expense of ATP. MitB then catalyzes glycosylation of AHBA-MmcB with uridine diphosphate-〈em〉N〈/em〉-acetylglucosamine (UDP-GlcNAc) to generate a key intermediate, GlcNAc-AHBA-MmcB, which contains all carbon and nitrogen atoms of the mitosane core. These results provide important insight into mitomycin biosynthesis.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0960894X19304548-ga1.jpg" width="490" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: 15 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Bioorganic & Medicinal Chemistry, Volume 27, Issue 16〈/p〉 〈p〉Author(s): Zahra Mojallal-Tabatabaei, Parham Foroumadi, Mahsa Toolabi, Fereshteh Goli, Setareh Moghimi, Sussan Kaboudanian-Ardestani, Alireza Foroumadi〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The development of novel leishmanicidal agents that are capable of being replaced by the available therapeutic options has become a priority. In the present study, the synthesis and leishmanicidal activity of a series of 5-(nitroheteroaryl-2-yl)-1,3,4-thiadiazole derivatives are described. All compounds appeared to be potent anti-leishmanial agents against both promastigote and amastigote forms of 〈em〉Leishmania major〈/em〉 (〈em〉L. major)〈/em〉. Amongst the synthesized compounds, 2-([1,4′-bipiperidin]-1′-yl)-5-(5-nitrofuran-2-yl)-1,3,4-thiadiazole (〈strong〉IIa〈/strong〉) and 1-(5-(1-methyl-5-nitro-1〈em〉H〈/em〉-imidazole-2-yl)-1,3,4-thiadiazol-2-yl)-4-(piperidine-1-yl) piperidine (〈strong〉IIc〈/strong〉) are the most effective. Infection index was statistically declined in the presence of all compounds. The analysis of redox-related factors revealed that exposure of 〈em〉L. major〈/em〉 cells to 〈strong〉IIa〈/strong〉 and 〈strong〉IIc〈/strong〉 led to an increase in reactive oxygen species (ROS). Furthermore, two compounds were able to increase ROS and NO levels in infected macrophages in a dose-independent manner. In addition, we showed that these compounds induced cell death in promastigotes. Altogether, our results indicated the anti-leishmanial potential of 〈strong〉IIa〈/strong〉 and 〈strong〉IIc〈/strong〉 is mediated by apoptosis through an imbalance in the redox system resulting in the elevation of ROS. This new class of compound seems to hold great promise for the development of new and useful anti-leishmanial agents.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0968089619303700-ga1.jpg" width="335" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: 15 October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Geomorphology, Volume 343〈/p〉 〈p〉Author(s): Wenmin Yao, Changdong Li, Qingjun Zuo, Hongbin Zhan, Robert E. Criss〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Variations of reservoir water level and seasonal precipitation have resulted in significant movement and destabilization of landslides in the Three Gorges Reservoir (TGR) region of China since reservoir impoundment in 2003. An example is the Baijiabao landslide, a large, actively creeping landslide located in the steep lower valley of the Xiangxi River, about 55 km upstream of the TGR dam in the Yangtze River. Twelve years of monthly monitoring at four GPS stations and routine, monthly field observations show cumulative GPS displacements as large as 〉1.5 m and widely developed ground cracks. GPS monitoring results show that most movement takes place in rapid steps that coincide with the rainy season and the period of annual reservoir drawdown, with particularly large steps in 2009, 2012 and 2015. This step-like pattern of displacement is also shown by daily data from an automatic monitoring system installed in 2017. The total period of acceleration shown by these daily data was about six weeks long, with rapid movement starting during rapid reservoir drawdown, and terminating when the reservoir began to rise again. In particular, most of the 2018 displacement occurred in only two weeks. Different subzones of the landslide move at different rates and exhibit different features of deformation. The neighborhood rough set theory is used to identify the triggering factors responsible for landslide deformation. The most important triggering factors vary between different sites, data types and the time interval used to define them. The surface deformation and ground crack widening are controlled by the combination of rainfall and variations in the reservoir water levels, whereas the deformation of the sliding zone is most sensitive to the latter. The results show that daily data are needed to capture important, short-term landslide responses. The neighborhood rough set theory for determination of triggering factors is suggested for deformation prediction, stability evaluation, and prevention and control of reservoir landslides in this and other regions.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 International Journal of Applied Earth Observation and Geoinformation, Volume 83〈/p〉 〈p〉Author(s): Sergio Sánchez-Ruiz, Álvaro Moreno-Martínez, Emma Izquierdo-Verdiguier, Marta Chiesi, Fabio Maselli, María Amparo Gilabert〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Growing stock volume (GSV) is one of the most important variables for forest management and is traditionally estimated from ground measurements. These measurements are expensive and therefore sparse and hard to maintain in time on a regular basis. Remote sensing data combined with national forest inventories constitute a helpful tool to estimate and map forest attributes. However, most studies on GSV estimation from remote sensing data focus on small forest areas with a single or only a few species. The current study aims to map GSV in peninsular Spain, a rather large and very heterogeneous area. Around 50 000 wooded land plots from the Third Spanish National Forest Inventory (NFI3) were used as reference data, whereas more than 8 000 Landsat-5 TM and Landsat-7 ETM + scenes covering both the study period (1997–2007) and area were chosen as a compromise between availability and suitable temporal and spatial resolution to estimate GSV. Google Earth Engine (GEE) was used to handle the huge amount of remotely sensed data. A total of 805 predictors were calculated from Landsat spectral reflectances. Guided regularized random forests algorithm (RF) was used to deal with the arising multicolinearity and identify the most important predictors by comparing with NFI3 plot-level GSV data. As a result, to model the relationship between spectral information and GSV, the original 805 predictors were reduced to only 29 (highlighting texture metrics, vegetation indices and band ratios involving short wave infrared reflectance) while maintaining the accuracy level (〈em〉R〈/em〉〈sup〉2〈/sup〉 ≈ 0.4 and RMSE ≈ 60 m〈sup〉3〈/sup〉 ha〈sup〉–1〈/sup〉). A 30-m spatial resolution wall-to-wall GSV map over Peninsular Spain was obtained from a standard RF with the 29 selected predictors through GEE. Its accuracy was evaluated against NFI3 province-level GSV data, resulting in 〈em〉R〈/em〉〈sup〉2〈/sup〉 ≈ 0.91 and RMSE ≈ 15 m〈sup〉3〈/sup〉 ha〈sup〉–1〈/sup〉.〈/p〉〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0303243419301898-ga1.jpg" width="298" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Beschreibung: 〈p〉Publication date: November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 World Development, Volume 123〈/p〉 〈p〉Author(s): Alwin Keil, Archisman Mitra, Amit K. Srivastava, Andrew McDonald〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Sustainable intensification (SI) approaches to agricultural development are urgently needed to meet the growing demand for crop staples while protecting ecosystem services and environmental quality. However, SI initiatives have been criticized for neglecting social welfare outcomes. A recent review found that better-off farmers benefitted disproportionately from SI and highlighted the dearth of studies assessing the equity of outcomes. In this study, we explore the social inclusiveness of zero-tillage (ZT) wheat adoption in Bihar, India. ZT is a proven SI technology for enhancing wheat productivity while boosting profitability and reducing greenhouse gas emissions from agricultural machinery in the densely populated Indo-Gangetic Plains. With an average landholding size of 0.39 ha, most farmers in Bihar depend on custom-hiring services to access the technology. While service provision models should foster inclusive growth by reducing financial barriers to technology adoption, early evidence suggested that smallholders remained at a disadvantage. Building on this previous research, we use a panel dataset from 961 wheat-growing households that spans a six-year period to analyze ZT adoption dynamics over time while accounting for the role of social networks and access to service provision. Using a heckprobit approach to correct for non-exposure bias, we compare determinants of ZT awareness and use in 2012 and 2015. We apply a multinomial logit model to identify determinants of early adoption, recent adoption, non-adoption, and dis-adoption. Furthermore, we explore the quality of ZT services as an additional dimension of socially-inclusive technology access. We find that the strong initial scale bias in ZT use declined substantially as awareness of the technology increased and the service economy expanded. Land fragmentation replaced total landholding size as a significant adoption determinant, which also affected the quality of ZT services received. Hence, farmers with small but contiguous landholdings appear to have gained a significant degree of access over time. We conclude that early-stage assessments of SI may be misleading, and that private sector-based service provision can contribute to socially inclusive development outcomes as markets mature.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 World Development, Volume 123〈/p〉 〈p〉Author(s): Chiara Ravetti, Mare Sarr, Daniel Munene, Tim Swanson〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉This paper analyses the ways in which ethnic identity and labour institutions shape favouritism and discrimination among workers. We conduct a lab experiment in the field with South African coal miners from various ethnic groups and with different trade union membership status. Our analysis suggests that union identity and ethnic identity are two social constructs that operate in a distinct and opposite fashion. Unionization acts as a factor of workers solidarity beyond the confine of union membership. Conversely, ethnicity operates as the linchpin through which discrimination among workers is infused not only between ethnic majority and minorities, but also within the majority group itself. We find that the widespread practice of subcontracting in the mining sector exacerbates ethnic discrimination among workers both between and within ethnic groupings.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 World Development, Volume 123〈/p〉 〈p〉Author(s): Vanesa Jordá, Miguel Niño-Zarazúa〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Despite the growing interest in global inequality, assessing inequality trends is a major challenge because individual data on income or consumption is not often available. Nevertheless, the periodic release of certain summary statistics of the income distribution has become increasingly common. Hence, grouped data in form of income shares have been conventionally used to construct inequality trends based on lower bound approximations of inequality measures. This approach introduces two potential sources of measurement error: first, these estimates are constructed under the assumption of equality of incomes within income shares; second, the highest income earners are not included in the household surveys from which grouped data is obtained. In this paper, we propose to deploy a flexible parametric model, which addresses these two issues in order to obtain a reliable representation of the income distribution and accurate estimates of inequality measures. This methodology is used to estimate the recent evolution of global interpersonal inequality from 1990 to 2015 and to examine the effect of survey under-coverage of top incomes on the level and direction of global inequality. Overall, we find that item non-response at the top of the distribution substantially biases global inequality estimates, but, more importantly, it might also affect the direction of the trends.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: 15 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Quaternary Science Reviews, Volume 218〈/p〉 〈p〉Author(s): Weizhe Chen, Dan Zhu, Philippe Ciais, Chunju Huang, Nicolas Viovy, Masa Kageyama〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Climate and atmospheric CO〈sub〉2〈/sub〉 strongly influence the vegetation distribution and the terrestrial carbon storage. Process-based dynamic global vegetation models (DGVM) are important tools for simulating past vegetation dynamics and carbon cycle; yet the link between spatial gradients of climate and vegetation cover in geological past has received less attention. In this study, we simulate the distribution of vegetation under three CO〈sub〉2〈/sub〉 levels for two climate states, the Last Glacial Maximum (LGM) and Pre-industrial (PI) climate with fire activated or deactivated using the ORCHIDEE-MICT DGVM. Results show that elevated CO〈sub〉2〈/sub〉 and warmer climate promote global total tree cover but the impacts are different between forest biomes. Regional tree cover is highly regulated by mean annual precipitation (MAP) especially in the tropics, and by temperature for the boreal-arctic tree line. Based on quantile nonlinear regressions, we analyze the MAP threshold at which maximum tree cover is reached. This threshold is significantly reduced with elevated CO〈sub〉2〈/sub〉 for tropical and temperate trees. With higher CO〈sub〉2〈/sub〉, increased tree cover leads to reduced fire ignition and burned area, and provides a positive feedback to tree cover, especially in Africa. Besides, in our model, increasing CO〈sub〉2〈/sub〉-induced enhancement of gross primary productivity (GPP) is more prominent for tropical trees than for temperate and boreal trees, and for dry regions than wet regions. This difference explains why CO〈sub〉2〈/sub〉 is the major factor influencing forest cover in the tropics. It also highlights that special attention should be paid to collect paleo-vegetation data across savannas-forest transition in dry regions.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 World Development, Volume 123〈/p〉 〈p〉Author(s): Ben Siegelman, Nora Haenn, Xavier Basurto〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉This paper relates how fishermen in San Evaristo on Mexico’s Baja peninsula employ fabrications to strengthen bonds of trust and navigate the complexities of common pool resource extraction. We argue this trickery complicates notions of social capital in community-based natural resource management, which emphasize communitarianism in the form of trust. Trust, defined as a mutual dependability often rooted in honesty, reliable information, or shared expectations, has long been recognized as essential to common pool resource management. Despite this, research that takes a critical approach to social capital places attention on the activities that foster social networks and their norms by arguing that social capital is a process. A critical approach illuminates San Evaristeño practices of lying and joking across social settings and contextualizes these practices within cultural values of harmony. As San Evaristeños assert somewhat paradoxically, for them “lies build trust.” Importantly, a critical approach to this case study forces consideration of gender, an overlooked topic in social capital research. San Evaristeña women are excluded from the verbal jousting through which men maintain ties supporting their primacy in fishery management. Both men’s joke-telling and San Evaristeños’ aversion to conflict have implications for conservation outcomes. As a result, we use these findings to help explain local resistance to outsiders and external management strategies including land trusts, fishing cooperatives, and marine protected areas.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: 1 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochimica et Biophysica Acta (BBA) - Biomembranes, Volume 1861, Issue 9〈/p〉 〈p〉Author(s): Anargyros Doukas, Ekaterini Karena, Maria Botou, Konstantinos Papakostas, Amalia Papadaki, Olympia Tziouvara, Evaggelia Xingi, Stathis Frillingos, Haralabia Boleti〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Recombinant expression systems for mammalian membrane transport proteins are often limited by insufficient yields to support structural studies, inadequate post-translational processing and problems related with improper membrane targeting or cytotoxicity. Use of alternative expression systems and optimization of expression/purification protocols are constantly needed. In this work, we explore the applicability of the laboratory strain LEXSY of the ancient eukaryotic microorganism 〈em〉Leishmania tarentolae〈/em〉 as a new expression system for mammalian nucleobase permeases of the NAT/NCS2 (Nucleobase-Ascorbate Transporter/Nucleobase-Cation Symporter-2) family. We achieved the heterologous expression of the purine-pyrimidine permease rSNBT1 from 〈em〉Rattus norvegicus〈/em〉 (tagged at C-terminus with a red fluorescent protein), as confirmed by confocal microscopy and biochemical analysis of the subcellular fractions enriched in membrane proteins. The cDNA of rSNBT1 has been subcloned in a pLEXSY-〈em〉sat-mrfp1〈/em〉vector and used to generate transgenic 〈em〉L〈/em〉. 〈em〉tarentolae-rsnbt1-mrfp1〈/em〉 strains carrying the pLEXSY-sat-〈em〉rsnbt1-mrfp1〈/em〉 plasmid either episomally or integrated in the chromosomal DNA. The chimeric transporter rSNBT1-mRFP1 is targeted to the ER and the plasma membrane of the 〈em〉L〈/em〉. 〈em〉tarentolae〈/em〉 promastigotes. The transgenic strains are capable of transporting nucleobases that are substrates of rSNBT1 but also of the endogenous 〈em〉L〈/em〉. 〈em〉tarentolae〈/em〉 nucleoside/nucleobase transporters. A dipyridamole-resistant Na〈sup〉+〈/sup〉-dependent fraction of uptake is attributed to the exogenously expressed rSNBT1.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0005273619301452-ga1.jpg" width="500" alt="Unlabelled Image" title="Unlabelled Image"〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical Pharmacology, Volume 168〈/p〉 〈p〉Author(s): Daniel Lavall, Nadine Jacobs, Felix Mahfoud, Peter Kolkhof, Michael Böhm, Ulrich Laufs〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Mineralocorticoid receptor (MR) overactivation promotes cardiac fibrosis. We studied the ability of the non-steroidal MR antagonist finerenone to prevent fibrotic remodeling. In neonatal rat cardiac fibroblasts, finerenone prevented aldosterone-induced nuclear MR translocation. Treatment with finerenone decreased the expression of connective tissue growth factor (CTGF) (74 ± 15% of control, p = 0.005) and prevented aldosterone-induced upregulation of CTGF and lysyl oxidase (LOX) completely. Finerenone attenuated the upregulation of transforming growth factor ß (TGF-ß), which was induced by the Rac1 GTPase activator 〈span〉l〈/span〉-buthionine sulfoximine. Transgenic mice with cardiac-specific overexpression of Rac1 (RacET) showed increased left ventricular (LV) end-diastolic (63.7 ± 8.0 vs. 93.8 ± 25.6 µl, p = 0.027) and end-systolic (28.0 ± 4.0 vs. 49.5 ± 16.7 µl, p = 0.014) volumes compared to wild-type FVBN control mice. Treatment of RacET mice with 100 ppm finerenone over 5 months prevented LV dilatation. Systolic and diastolic LV function did not differ between the three groups. RacET mice exhibited overactivation of MR and 11ß hydroxysteroid dehydrogenase type 2. Both effects were reduced by finerenone (reduction about 36%, p = 0.030, and 40%, p = 0.032, respectively). RacET mice demonstrated overexpression of TGF-ß, CTGF, LOX, osteopontin as well as collagen and myocardial fibrosis in the left ventricle. In contrast, expression of these parameters did not differ between finerenone-treated RacET and control mice. Finerenone prevented left atrial dilatation (6.4 ± 1.5 vs. 4.7 ± 1.4 mg, p = 0.004) and left atrial fibrosis (17.8 ± 3.1 vs. 12.8 ± 3.1%, p = 0.046) compared to vehicle-treated RacET mice. In summary, finerenone prevented from MR-mediated structural remodeling in cardiac fibroblasts and in RacET mice. These data demonstrate anti-fibrotic myocardial effects of finerenone.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0006295219302564-ga1.jpg" width="500" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: Available online 5 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Quaternary International〈/p〉 〈p〉Author(s): Rodrigo Loyola, Lautaro Núñez, Isabel Cartajena〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉It has often been assumed that a link exists between climate change and human dispersion during the initial peopling of the Atacama Desert. However, there is little understanding of how hunter-gatherers acquired and processed environmental information. We examine paleoenvironmental and archaeological data to propose that the early peopling of the highlands of the south-central Atacama was a gradual process modulated by landscape learning. Evidence suggests that initial occupations at the end of the Pleistocene were limited to intermediate altitude levels, where the ecological structure was more easily legible and productive. This allowed human groups to make use of general, transferrable landscape knowledge, based mainly on the hunting of wild camelids and the gathering of plant resources in azonal formations. However, the arid event of the Early Holocene led to successive episodes of abandonment and relocation to new areas, consolidating complementary land-use between the desert lowlands and the high puna. Two complementary strategies for the acquisition and transmission of information can be identified: (1) scouting as part of logistical hunting parties; and (2) information-pooling rooted in broad, flexible social networks. We conclude that in the face of uncertain conditions, hunter-gatherers invested more effort in learning the landscape and sharing environmental knowledge.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cellular Signalling, Volume 62〈/p〉 〈p〉Author(s): Vitor de Miranda Ramos, Juciano Gasparotto, Fabrício Figueiró, Amanda de Fraga Dias, Diana Carolina Rostirolla, Nauana Somensi, Helen Tais da Rosa, Lucas Kich Grun, Florencia María Barbé-Tuana, Daniel Pens Gelain, José Cláudio Fonseca Moreira〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Recent studies have investigated the use of retinoic acid (RA) molecule in combined chemotherapies to cancer cells as an attempt to increase treatment efficiency and circumvent cell resistance. Positive results were obtained in clinical trials from lung cancer patients treated with RA and cisplatin. Meanwhile, the signalling process that results from the interaction of both molecules remains unclear. One of the pathways that RA is able to modulate is the activity of NRF2 transcription factor, which is highly associated with tumour progression and resistance. Therefore, the aim of this work was to investigate molecular mechanism of RA and cisplatin co-treatment in A549 cells, focusing in NRF2 pathway. To this end, we investigated NRF2 and NRF2-target genes expression, cellular redox status, cisplatin-induced apoptosis, autophagy and DNA repair through homologous recombination. RA demonstrated to have an inhibitory effect over NRF2 activation, which regulates the expression of thiol antioxidants enzymes. Moreover, RA increased reactive species production associated with increased oxidation of thiol groups within the cells. The expression of proteins associated with DNA repair through homologous recombination was also suppressed by RA pre-treatment. All combined, these effects appear to create a more sensitive cellular environment to cisplatin treatment, increasing apoptosis frequency. Interestingly, autophagy was also increased by combination therapy, suggesting a resistance mechanism by A549 cells. In conclusion, these results provided new information about molecular mechanisms of RA and cisplatin treatment contributing to chemotherapy optimization.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0898656819301524-ga1.jpg" width="487" alt="Unlabelled Image" title="Unlabelled Image"〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: Available online 5 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Methods〈/p〉 〈p〉Author(s): Athanasia Mizi, Eduardo Gade Gusmao, Argyris Papantonis〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Genome organization is now understood to be tightly linked to all genomic functions. Thus, the high-resolution mapping of higher-order chromosomal structures via 3C-based approaches has become an integral tool for studying transcriptional and cell cycle regulation, signaling effects or disease onset. Nonetheless, 3C-based protocols are not without caveats, like dependencies on fixation conditions, restriction enzyme pervasiveness in crosslinked chromatin and ligation efficiency. To address some of these caveats, we describe here the streamlined iHi-C 2.0 protocol that allows for the genome-wide interrogation of native spatial chromatin contacts without a need for chemical fixation. This approach improves ligation efficiency and presents minimal material losses, and is thus suitable for analysing samples with limiting cell numbers. Following high throughput sequencing, iHi-C 2.0 generates high signal-to-noise and focal maps of the interactions within and between mammalian chromosomes under native conditions.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Computers & Geosciences, Volume 132〈/p〉 〈p〉Author(s): Hongxing Zhang, Mingliang Zhang, Yongpeng Ji, Yini Wang, Tianping Xu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Vegetation exerts a significant damping effect on tsunami wave run-up on coastal beaches, thus effectively mitigating the tsunami hazard. A depth-integrated two-dimensional numerical model (HydroSed2D, Liu et al., 2008; Liu et al., 2010) is developed to investigate tsunami wave run-up and land inundation on coastal beaches covered with 〈em〉Pandanus odoratissimus〈/em〉 (〈em〉P. odoratissimus〈/em〉). The present model is based on a finite volume Roe-type scheme, that solves the non-linear shallow water equations with the capacity of treating the wet or dry boundary at the wave front. The momentum equations in this model are modified by adding a drag force term, thus considering the resistance effects of vegetation on tsunami waves. The accuracy of the numerical scheme and the vegetation drag force are validated by three experimental cases of dam-break flow propagation in a dry channel, solitary wave propagation in a vegetated flume, and tsunami run-up over an uneven bed. Subsequently, a numerical model is applied to simulate tsunami run-up and land inundation on actual-scale vegetated beaches and a series of sensitive analyses are conducted by comparing numerical results. The obtained numerical results suggest that 〈em〉P. odoratissimus〈/em〉 can effectively attenuate tsunami run-up and land inundation distance on coastal beaches, and a higher attenuation rate for tsunami wave can be achieved by increasing both vegetation width and vegetation density. The tsunami wave height is also an important factor that impacts the tsunami wave run-up and land inundation on vegetated beaches.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: 15 October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Geomorphology, Volume 343〈/p〉 〈p〉Author(s): Nieves G. Valiente, Robert Jak McCarroll, Gerd Masselink, Tim Scott, Mark Wiggins〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Predicting the future behavior of beach and nearshore systems requires an accurate delineation and understanding of coastal cell boundaries, sediment transport pathways, and sediment sources and sinks. Unfortunately, there is a paucity of field datasets on beach and nearshore morphological change that extend fully from the top of the dunes to beyond the depth of closure to enable quantification of the sediment budget. Here, for the first time, we employ a total sediment budget approach, examining a sandy and embayed beach located in the north coast of SW England, to investigate inter- and multi-annual embayment scale sediment dynamics over a 10-year period that includes extreme storm erosion and post-storm recovery. We demonstrate that, despite the deeply embayed nature of the beach, the shoreline orientation roughly parallel to the dominant wave direction and the overwhelmingly cross-shore forcing of the inter-tidal beach volume, the system is neither closed, nor balanced. The very significant net changes in the recorded sediment volume from dune top to depth of closure (−14.5 m ODN), representing a loss of c. 100 m〈sup〉3〈/sup〉 m〈sup〉−1〈/sup〉 during the extreme storm period and a gain of c. 200 m〈sup〉3〈/sup〉 m〈sup〉−1〈/sup〉 during the recovery period, indicate that significant sediment transport occurs seaward of the base of the terminating headlands and beyond the morphological depth of closure. The results further indicate that the inter-tidal region is partly uncoupled from the sub-tidal region, with the former region dominated by cross-shore sediment fluxes, whereas the subtidal region is also significantly affected by longshore sediment fluxes. A conceptual model is presented that balances the observed volume changes with inferred fluxes, forced by variations in total and alongshore wave power. This study contradicts the general assumption that when sediment exits the inter-tidal, it rests undisturbed in the sub-tidal, waiting for a period of low-moderate energy to bring it onshore. The large sediment volumetric variations across the lower shoreface (depth of 5–20 m), which are of the same order of magnitude as, but uncorrelated with, those occurring in the inter-tidal region, are suggestive of an energetic longshore transport system across this deeper region. It is possible that this transport system extends along the whole north coast of SW England and this finding may lead to a shift in understanding of sediment budgets along exposed and macrotidal embayments globally.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0169555X19302739-ga1.jpg" width="439" alt="Unlabelled Image" title="Unlabelled Image"〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: July–December 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 SoftwareX, Volume 10〈/p〉 〈p〉Author(s): R.D. Martin, Q. Cai, T. Garrow, C. Kapahi〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉QExpy is an open source python-3 module that was developed in order to simplify the analysis of data in undergraduate physics laboratories. Through the use of this module, students can focus their time on understanding the science and the data from their experiments, rather than on processing their data. In particular, the module allows users to easily propagate uncertainties from measured quantities using a variety of techniques (derivatives, Monte Carlo), as well as to plot and fit functions to data. The interface is designed to be pedagogical so that students with no prior programming experience can be eased into using python in their introductory physics laboratories.〈/p〉〈/div〉

Beschreibung: 〈p〉Publication date: July–December 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 SoftwareX, Volume 10〈/p〉 〈p〉Author(s): Simon Behrendt, Thomas Dimpfl, Franziska J. Peter, David J. Zimmermann〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉This paper shows how to quantify and test for the information flow between two time series with Shannon transfer entropy and Rényi transfer entropy using the 〈math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline" altimg="si1.svg"〉〈mi〉R〈/mi〉〈/math〉 package 〈em〉RTransferEntropy〈/em〉. We discuss the methodology, the bias correction applied to calculate effective transfer entropy and outline how to conduct statistical inference. Furthermore, we describe the package in detail and demonstrate its functionality by means of several simulated processes and present an application to financial time series.〈/p〉〈/div〉

Beschreibung: 〈p〉Publication date: July–December 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 SoftwareX, Volume 10〈/p〉 〈p〉Author(s): Jacob L. Moore, Nathaniel R. Morgan, Mark F. Horstemeyer〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉We discuss the creation and implementation of a generalized library, named ELEMENTS, of mathematical functions for supporting a very broad range of element types including: linear, quadratic, and cubic serendipity elements in 2D and 3D; high-order spectral elements; and a linear 4D element. The ELEMENTS library can be used for research and development of both continuous and discontinuous finite element methods for solving a diverse range of partial differential equations. The library has functions for calculating quantities that are commonly used in finite element methods such as the gradient of a basis function, the Jacobi matrix, the inverse Jacobi matrix, the determinant of the Jacobi matrix, and a physical position inside the element, to name a few examples. The library also supports both Gauss–Legendre and Gauss–Lobatto quadrature rules up to 8 quadrature points in each coordinate direction. The examples and discussions in this paper will focus on Lagrangian solid mechanics and dynamics, but ELEMENTS can be used for many other applications.〈/p〉〈/div〉

Beschreibung: 〈p〉Publication date: September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Advances in Water Resources, Volume 131〈/p〉 〈p〉Author(s): Maria Maza, Javier L. Lara, Iñigo J. Losada〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉With the aim of better understand and parameterize the physical processes involved in flow-mangrove interaction, wave attenuation and drag forces along a 1:6 scale fringe 〈em〉Rhizophora〈/em〉 mangrove forest are studied experimentally. The 26 m long forest is composed by 135 models built reproducing mature 〈em〉Rhizophora〈/em〉 mangrove trees with 24 prop roots. Hydrodynamic conditions are scaled using Froude similarity based on values collected in nature. Regular and random waves are tested and three water depths are considered to account for the influence of variable mangroves frontal area along the vertical. Wave decay analysis highlights the importance of considering the effect of flume bottom and walls friction. Neglecting this additional damping can result in a high overestimation of the mangrove dissipation capacity. It is proven that water depth, and the associated mangroves frontal area, and wave height are the dominant variables driving wave attenuation for short waves. The slope seaward the forest induces wave shoaling leading to an increase of wave steepness. Accordingly, the exerted forces on the mangroves also increase along the first 3–4 m of the forest. Smaller forces are recorded further into the forest where wave decay formulations fit well to the recorded wave heights. In general, analytical drag forces obtained by using mangrove trees induced damping coefficients compare well to the forces measured within the forest. However, analytical drag forces can lead to overestimations of up to double in some cases. This aspect is very important when experimental results are used to feed numerical or analytical models based on the introduction of a drag force in the momentum equation. These models should be calibrated using, whenever possible, direct force measurements.〈/p〉〈/div〉

Beschreibung: 〈p〉Publication date: Available online 10 April 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Technological Forecasting and Social Change〈/p〉 〈p〉Author(s): John Rice, Nigel Martin〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Smart Information and Communications Technology (ICT) is envisaged to provide the capabilities to plan, design, construct, operate and manage Australia's key infrastructure. With over 75% of Australia's population living in cities and accessing public and private goods and services, ICT is positioned as a strategic resource for smart infrastructure developments. In this study, international and domestic stakeholder inputs on the future role of smart ICT in advancing Australia's infrastructure development and operations were crowdsourced for analysis. The study identifies several forms of smart ICT (e.g. building information modelling software) enabled infrastructure that possesses potential to deliver over A$9 billion per annum in domestic economic improvements, with commensurate advancement of communities, regions and urban environments. However, to be effective these smart ICT require enablement through open and interoperable data, sound governance and policy, and government leadership and coordination using dedicated resources. While smart infrastructure development is presently slow and lumbering, the identified smart ICT present as valuable strategic technologies for change and development in domestic communities.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: Available online 24 April 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Technological Forecasting and Social Change〈/p〉 〈p〉Author(s): Rahat Iqbal, Faiyaz Doctor, Brian More, Shahid Mahmud, Usman Yousuf〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Big Data has significant impact in developing functional smart cities and supporting modern societies. In this paper, we investigate the importance of Big Data in modern life and economy, and discuss challenges arising from Big Data utilization. Different computational intelligence techniques have been considered as tools for Big Data analytics. We also explore the powerful combination of Big Data and Computational Intelligence (CI) and identify a number of areas, where novel applications in real world smart city problems can be developed by utilizing these powerful tools and techniques. We present a case study for intelligent transportation in the context of a smart city, and a novel data modelling methodology based on a biologically inspired universal generative modelling approach called Hierarchical Spatial-Temporal State Machine (HSTSM). We further discuss various implications of policy, protection, valuation and commercialization related to Big Data, its applications and deployment.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: Available online 12 April 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Technological Forecasting and Social Change〈/p〉 〈p〉Author(s): F.W. Geels, A. McMeekin, B. Pfluger〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Social acceptance and political feasibility are important issues in low-carbon transitions. Since computer models struggle to address these issues, the paper advances socio-technical scenarios as a novel methodological tool. Contributing to recent dialogue approaches, we develop an eight-step methodological procedure that produces socio-technical scenarios through various interactions between the multi-level perspective and computer models. As a specific contribution, we propose ‘transition bottlenecks’ as a methodological aid to mediate dialogue between qualitative MLP-based analysis of 〈em〉contemporary〈/em〉 dynamics and quantitative, model-generated 〈em〉future〈/em〉 pathways. The transition bottlenecks also guide the articulation of socio-technical storylines that suggest how the social acceptance and political feasibility of particular low-carbon innovations can be improved through social interactions and endogenous changes in discourses, preferences, support coalitions and policies. Drawing on results from the 3-year PATHWAYS project, we demonstrate these contributions for the UK electricity system, developing two low-carbon transition pathways to 2050 commensurate with the 2 °C target, one based on technological substitution (enacted by incumbent actors), and one based on broader system transformation (enacted by new entrants).〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Technological Forecasting and Social Change, Volume 147〈/p〉 〈p〉Author(s): Emrah Karakilic〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The transition from industrial capitalism to cognitive capitalism and the rise of the digital revolution have brought the subject of intellectual property rights to the forefront as a controversial issue. This paper holds that the theoretical apparatus and concepts belonging to the industrial phase of capitalism largely fall short with respect to the repercussions that intellectual property rights regime yields. Embracing the methodological precept that social theory must be moulded in order to address the contours of contemporary social reality, this paper engages in an autonomist Marxist update on the concept of intellectual property rights. It ultimately challenges the “intellectual property rights are a socio-economic need” thesis and speculatively argues that the current system of intellectual property rights, directed politically towards the enclosure of commons, constitutes a structural contradiction by i) forming a basis for a social crisis in terms of the established relations of production, and ii) curtailing a part of the socio-economic opportunities for innovation, profit-making, and growth.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: Available online 9 April 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Technological Forecasting and Social Change〈/p〉 〈p〉Author(s): Daniela Maresch, Johannes Gartner〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Disruptive technological change can contribute to a more abundant world. However, potentially disruptive technologies often struggle to significantly influence practice. One prominent example is additive manufacturing (AM). Although AM is often regarded as the next great technological revolution in waiting, it has not yet established itself on a large scale in many fields of application. We investigate the reasons behind those challenges by looking at the various fields in which AM is applied and relating them to the specific challenges AM faces, as well as the opportunities it offers in those fields. Our findings rely on a multi-perspective technology foresight process that is based on a discourse analytic approach and that comprises data tomography covering the biggest German-language online magazine on AM and qualitative interview data collected from a range of AM stakeholders. The findings provide an empirically well-founded evaluation and explanation of the link between the challenges and opportunities offered by AM and the extent to which this disruptive technology is leveraged in specific fields. The findings prompt recommendations on how new potentially disruptive technologies can foster abundance in traditional, well established market economies based on the example of the well-developed but traditional market economy of Austria.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: Available online 24 April 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Technological Forecasting and Social Change〈/p〉 〈p〉Author(s): Måns Nilsson, Adis Dzebo, Georgia Savvidou, Katarina Axelsson〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Quantitative models of transitions, such as energy systems models and integrated assessment models, do not usually represent social processes, institutions and politics. Their view of societal transitions, along with the governance required to drive them, is therefore limited. Socio-technical systems approaches, in contrast, represent the social side but lack a quantitative view of the future system. This paper addresses this by bridging an energy systems model with socio-technical systems analysis and a local action study, analysing the future transition of the residential heating system in Sweden. The paper focuses on demand-side shifts that would drive a transition to a highly efficient, low-carbon heating system until 2050. A conceptual framework for bridging three approaches is introduced and applied. For example, niche-innovations identified in the socio-technical study are implemented as scenario options in the model. Landscape signals are external drivers of the scenario, and the regime study identifies barriers and governance requirements. The local action study provides insights into community attitudes affecting niches and regime change. Our results indicate that the linking of approaches is meaningful, in that it provides an enriched understanding of future systems change in many dimensions. Further research is required using a variety of models on a variety of domains or sectors to draw more generalizable lessons about bridging modelling and social science-based approaches for transition studies.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: 1 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Bioorganic & Medicinal Chemistry, Volume 27, Issue 17〈/p〉 〈p〉Author(s): Shweta Sinha, Mukesh Doble, S.L. Manju〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The most common inflammatory disease of the airways is asthma among children affecting around 235 million people worldwide. 5-Lipoxygenase (5-LOX) is a crucial enzyme which helps in the conversion of arachidonic acid (AA) to leukotrienes (LTs), the lipid mediators. It is associated with several inflammation related disorders such as asthma, allergy, and atherosclerosis. Therefore, it is considered as a promising target against inflammation and asthma. Currently, the only drug against 5-LOX which is available is Zileuton, while a few inhibitors are in clinical trial stages such as Atreleuton and Setileuton. So, there is a dire requirement in the area of progress of novel 5-LOX inhibitors which necessitates an understanding of their structure activity relationship and mode of action. In this review, novel 5-LOX inhibitors reported so far, their structural design, SAR and developmental strategies along with clinical updates are discussed over the last two decades.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0968089619306777-ga1.jpg" width="412" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: 1 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Bioorganic & Medicinal Chemistry, Volume 27, Issue 17〈/p〉 〈p〉Author(s): Fa-Qian Shen, Lu Shi, Ze-Feng Wang, Chen-Ru Wang, Jin-Jin Chen, Yi Liu, Han-Yue Qiu, Hai-Liang Zhu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉For the purpose of synthesizing drug candidates with desirable bioactivity, a class of benzoyl amide containing nitrogen heterocyclic ring derivatives targeting VEGFR-2 was designed and screened out using Discovery Studio. Eighteen target compounds were synthesized and then selected by some biological trials sequentially including inhibition of VEGFR-2, anti-proliferation in vitro, flow cytometry. Among them, compound 〈strong〉8h〈/strong〉 showed the best inhibitory activity (IC〈sub〉50〈/sub〉 = 0.34 ± 0.02 μM against VEGFR-2, IC〈sub〉50〈/sub〉 = 1.08 ± 0.06 μM and 2.44 ± 0.15 μM against MCF-7 and HepG-2, respectively, which were at the same inhibitory level with the commercially antitumor drug: vandetanib). In addition, flow cytometry demonstrated that compound 〈strong〉8h〈/strong〉 induced MCF-7 cell apoptosis through a cell membrane-mediated pathway. This research highlights the therapeutic potential of novel VEGFR-2 inhibitors in treating cancers and provides a promising strategy for drug discovery.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉 〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0968089619304043-ga1.jpg" width="353" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉 〈p〉Binding mode of compound 〈strong〉8h〈/strong〉 with VEGFR-2 (PDB code: 〈strong〉4ASD〈/strong〉). The 3D diagram of the interaction between compound 〈strong〉8h〈/strong〉 and key amino acid residues.〈/p〉 〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: 15 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Bioorganic & Medicinal Chemistry, Volume 27, Issue 16〈/p〉 〈p〉Author(s): George Amato, Robert Wiethe, Amruta Manke, Vineetha Vasukuttan, Rodney Snyder, Scott Runyon, Rangan Maitra〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Antagonists of type 1 cannabinoid receptors (CB1) may be useful in treating diabetes, hepatic disorders, and fibrosis. Otenabant (〈strong〉1〈/strong〉) is a potent and selective CB1 inverse agonist that was under investigation as an anti-obesity agent, but its development was halted once adverse effects associated with another marketed inverse agonist rimonabant (〈strong〉2〈/strong〉) became known. Non-tissue selective antagonists of CB1 that have high levels of brain penetration produce adverse effects in a small subset of patients including anxiety, depression and suicidal ideation. Currently, efforts are underway to produce compounds that have limited brain penetration. In this report, novel analogs of 〈strong〉1〈/strong〉 are explored to develop and test strategies for peripheralization. The piperidine of 〈strong〉1〈/strong〉 is studied as a linker, which is functionalized with alkyl, heteroalkyl, aryl and heteroaryl groups using a connector in the form of an amine, amide, sulfonamide, sulfamide, carbamate, oxime, amidine, or guanidine. We also report more polar replacements for the 4-chlorophenyl group in the 9-position of the purine core, which improve calculated physical properties of the molecules. These studies resulted in compounds such as 〈strong〉75〈/strong〉 that are potent inverse agonists of hCB1 with exceptional selectivity for hCB1 over hCB2. SAR studies revealed ways to adjust physical properties to limit brain exposure.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0968089619306431-ga1.jpg" width="500" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: Available online 4 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Bioorganic & Medicinal Chemistry Letters〈/p〉 〈p〉Author(s): Hiroyuki Miyachi, Tomohiro Yuzuriha, Ryotaro Tabata, Syohei Fukuda, Kazuto Nunomura, Bangzhong Lin, Tadayuki Kobayashi, Kenji Ishimoto, Takefumi Doi, Keisuke Tachibana〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉We previously reported that 1〈em〉H〈/em〉-pyrazolo-[3,4-〈em〉b〈/em〉]pyridine-4-carboxylic acid derivative 〈strong〉6〈/strong〉 is an agonist of human peroxisome proliferator-activated receptor alpha (hPPARα). Here, we prepared a series of 1〈em〉H〈/em〉-pyrazolo-[3,4-〈em〉b〈/em〉]pyridine-4-carboxylic acid derivatives in order to examine the structure-activity relationships (SAR). SAR studies clearly indicated that the steric bulkiness of the substituent on 1〈em〉H〈/em〉-pyrazolo-[3,4-〈em〉b〈/em〉]pyridine ring, the position of the distal hydrophobic tail part, and the distance between the distal hydrophobic tail part and the acidic head part are critical for hPPARα agonistic activity. These SAR results are somewhat different from those reported for fibrate-class hPPARα agonists. A representative compound (〈strong〉10f〈/strong〉) was as effective as fenofibrate in reducing the elevated plasma triglyceride levels in a high-fructose-fed rat model.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0960894X19304445-ga1.jpg" width="408" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: 1 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Bioorganic & Medicinal Chemistry, Volume 27, Issue 17〈/p〉 〈p〉Author(s): Pedro Silvino Pereira, Maria do Carmo Alves de Lima, Pedro Paulo Marcelino Neto, Cícera Datiane de Morais Oliveira-Tintino, Saulo Relison Tintino, Irwin Rose de Alencar Menezes, Jamerson Ferreira de Oliveira, Pascal Marchand, Henrique Douglas Melo Coutinho, Maria do Desterro Rodrigues, Teresinha Gonçalves da Silva〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Thiazol and thiazolidinedione derivatives are known in the literature for presenting several biological activities, such as anti-diabetic, anti-inflammatory, antiparasitic, antifungal and antimicrobial activity. With this in mind, this study reports on the synthesis and antibacterial activity of thiazole (NJ) and thiazolidinedione (NW) derivatives, as well as their effects in association with norfloxacin, against NorA efflux pumps in the 〈em〉Staphylococcus aureus〈/em〉 1199B (SA-1199B) strain. Among the 14 compounds evaluated, 9 were found to potentiate norfloxacin activity, with 4 compounds from the NJ series promoting a threefold norfloxacin MIC reduction. Molecular docking assays were used to confirm the binding mode of most active compounds. In the 〈em〉in silico〈/em〉 study, the efficiency of the interaction of NJ series compounds with the NorA pump were evaluated. Derivatives from both series did not show considerable intrinsic antibacterial activity (MIC 〉 1024 μg/mL) against any of the tested strains. However, the NJ16 and NJ17 compounds, when associated with norfloxacin, reduced the MIC of this drug threefold and inhibited NorA pumps in the 1199B strain. Moreover, some NW (05, 10, 18, 19 and 21) and NJ compounds (16, 17, 18 and 20) presented low to moderate cytotoxicity against normal cells. Molecular docking studies supported the potent 〈em〉in vitro〈/em〉 inhibitory activity of NJ16 and NJ17, which showed NJ16 and NJ17 possessed more favorable binding energies of −9.03 Kcal/mol and −9.34 Kcal/mol, respectively. In addition, NJ16 showed different types of interactions involved in complex stabilization. In conclusion, NJ16 and NJ17, in combination with norfloxacin, were able to completely restore the antibacterial activity of norfloxacin against 〈em〉S. aureus〈/em〉 SA-1199B, the norA-overexpressing strain, with low cytotoxicity in normal cells.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S096808961930481X-ga1.jpg" width="267" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: 15 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Bioorganic & Medicinal Chemistry, Volume 27, Issue 16〈/p〉 〈p〉Author(s): Tamila Galaka, Bruno N. Falcone, Catherine Li, Sergio H. Szajnman, Silvia N.J. Moreno, Roberto Docampo, Juan B. Rodriguez〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉As an extension of our project aimed at the search for new chemotherapeutic agents against Chagas disease and toxoplasmosis, several 1,1-bisphosphonates were designed, synthesized and biologically evaluated against 〈em〉Trypanosoma cruzi〈/em〉 and 〈em〉Toxoplasma gondii〈/em〉, the etiologic agents of these diseases, respectively. In particular, and based on the antiparasitic activity exhibited by 2-alkylaminoethyl-1,1-bisphosphonates targeting farnesyl diphosphate synthase, a series of linear 2-alkylaminomethyl-1,1-bisphosphonic acids (compounds 〈strong〉21〈/strong〉–〈strong〉33〈/strong〉), that is, the position of the amino group was one carbon closer to the 〈em〉gem〈/em〉-phosphonate moiety, were evaluated as growth inhibitors against the clinically more relevant dividing form (amastigotes) of 〈em〉T. cruzi〈/em〉. Although all of these compounds resulted to be devoid of antiparasitic activity, these results were valuable for a rigorous SAR study. In addition, unexpectedly, the synthetic designed 2-cycloalkylaminoethyl-1,1-bisphosphonic acids 〈strong〉47〈/strong〉–〈strong〉49〈/strong〉 were free of antiparasitic activity. Moreover, long chain sulfur-containing 1,1-bisphosphonic acids, such as compounds 〈strong〉54〈/strong〉–〈strong〉56〈/strong〉, 〈strong〉59〈/strong〉, turned out to be nanomolar growth inhibitors of tachyzoites of 〈em〉T. gondii〈/em〉. As many bisphosphonate-containing molecules are FDA-approved drugs for the treatment of bone resorption disorders, their potential nontoxicity makes them good candidates to control American trypanosomiasis and toxoplasmosis.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0968089619307400-ga1.jpg" width="413" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: Available online 5 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Trends in Neurosciences〈/p〉 〈p〉Author(s): Ruslan Rust, Lisa Grönnert, Rebecca Zoe Weber, Geertje Mulders, Martin E. Schwab〈/p〉 〈div xml:lang="en"〉〈div〉〈p〉Stroke patients have only limited therapeutic options and often remain with considerable disabilities. To promote neurological recovery, angiogenesis in the ischemic peri-infarct region has been recognized as an encouraging therapeutic target. Despite advances in mechanistic understanding of vascular growth and repair, effective and safe angiogenic treatments are currently missing. Besides the most intensively studied angiogenic growth factors, recent research has indicated that the process of vascular sprouting and migration also requires the participation of guidance molecules, many of which were initially identified as regulators of axonal growth. Here, we review the inhibitory and growth-promoting effects of guidance molecules on the vascular system and discuss their potential as novel angiogenic targets for neurovascular diseases.〈/p〉〈/div〉〈/div〉

Beschreibung: 〈p〉Publication date: November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Protein Expression and Purification, Volume 163〈/p〉 〈p〉Author(s): Derrick Afful, Liming Cai, Cory Momany〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The bacterial RNA polymerase (RNAP) is a large, complex molecular machine that is the engine of gene expression. Despite global conservation in their structures and function, RNAPs from different bacteria can have unique features in promoter and transcription factor recognition. Therefore, availability of purified RNAP from different bacteria is key to understanding these species-specific aspects and will be valuable for antibiotic drug discovery. 〈em〉Pseudomonas aeruginosa〈/em〉 is one of the leading causes of hospital and community acquired infections worldwide - making the organism an important public health pathogen. We developed a method for producing high quantities of highly pure and active recombinant 〈em〉P. aeruginosa〈/em〉 str. PAO1 RNAP core and holoenzyme complexes that employed two-vector systems for expressing the core enzyme (α, β, β’, and ω subunits) and for expressing the holoenzyme complex (core + σ〈sup〉70〈/sup〉). Unlike other RNAP expression approaches, we used a low temperature autoinduction system in 〈em〉E. coli〈/em〉 with T7 promoters that produced high cell yields and stable protein expression. The purification strategy comprised of four chromatographic separation steps (metal chelate, heparin, and ion-exchange) with yields of up to 11 mg per 500 mL culture. Purified holoenzyme and reconstituted holoenzyme from core and σ〈sup〉70〈/sup〉 were highly active at transcribing both small and large-sized DNA templates, with a determined elongation rate of ~18 nt/s for the holoenzyme. The successful purification of the 〈em〉P. aeruginosa〈/em〉 RNAP provides a gateway for studies focusing on 〈em〉in vitro〈/em〉 transcriptional regulation in this pathogen.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Journal of Magnetic Resonance, Volume 305〈/p〉 〈p〉Author(s): Michael Mullen, Alexander Gutierrez, Naoharu Kobayashi, Jarvis Haupt, Michael Garwood〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Large magnetic field inhomogeneity can be a significant cause of spatial flip-angle variation when using ordinary, limited-bandwidth RF pulses. Multidimensional RF pulses are particularly sensitive to inhomogeneity due to their extended pulse length, which decreases their bandwidth. Previously, it was shown that, by breaking a 2D pulse into multiple undersampled k-space segments, the excitation bandwidth can be increased at the expense of increased imaging time. The present study shows how this increased imaging time can be offset by undersampling acquisition k-space in a phase-encoded dimension that is in the direction of excitation segmentation. Data from each segment are viewed as originating from “virtual receive coils” rather than multiple physical coils. The undersampled data are reconstructed using parallel imaging techniques (e.g. as in GRAPPA). The method was tested in vivo with brain imaging at both 3 T and 4 T, and used in conjunction with a 32-channel head coil and conventional GRAPPA on the 3 T data. Relationships with existing techniques and future applications are discussed.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S1090780719301259-ga1.jpg" width="366" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 141〈/p〉 〈p〉Author(s): Ningning Wang, Yanan Ma, Zhuoqun Liu, Lei Liu, Keming Yang, Yaguang Wei, Yang Liu, Xin Chen, Xiance Sun, Deliang Wen〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Exposure to fine particular matter (≤2.5 μM, PM〈sub〉2.5〈/sub〉) contributes to increased risk of obesity and type 2 diabetes. Hydroxytyrosol (HT), a simple polyphenol found in virgin olive oil, is considered to be beneficial for cardiovascular and metabolic disorders. The current study determined whether HT could improve PM〈sub〉2.5〈/sub〉-induced adiposity and insulin resistance (IR), and explored the underlying mechanisms. Fifteen adult female C57BL/6j mice on a chow diet were randomly divided into three groups receiving (1) sterile PBS, (2) PM〈sub〉2.5〈/sub〉 suspended in sterile PBS (1 mg/mL) and (3) PM〈sub〉2.5〈/sub〉+HT (50 mg/kg/day). PM〈sub〉2.5〈/sub〉/PBS exposure was administered by oropharynx instillation every other day and HT supplementation was achieved by gavage every day. Four-week PM〈sub〉2.5〈/sub〉 exposure did not affect body weight, but significantly increased visceral fat mass. The abdominal adiposity coincided with adipocyte hypertrophy and proliferation in visceral white adipose tissue (WAT), as well as decreased metabolic activity in brown adipose tissue and subcutaneous WAT. PM〈sub〉2.5〈/sub〉 enhanced the oxidative stress by diminishing antioxidant enzyme activities in liver and serum, whereas contents of 4-hydroxynonenal (4-HNE), malondialdehyde (MDA) levels in liver and serum were elevated. These changes were accompanied by macrophage infiltration and activation of NF-κB pathway in the liver. Moreover, PM〈sub〉2.5〈/sub〉 exposure led to glucose intolerance and insulin insensitivity, impaired hepatic glycogenesis, and decreased insulin-stimulated Akt phosphorylation in peripheral tissues. Importantly, HT treatment prevented PM〈sub〉2.5〈/sub〉-induced visceral adipogenesis, oxidative stress, hepatic inflammation and NF-κB activation, systemic and peripheral IR. In vitro, after HepG2 cells were incubated with PM〈sub〉2.5〈/sub〉 (0, 5, 25, 50, 100 and 200 μg/mL), reduced glutathione depletion and 4-HNE, 8-hydroxy-2'-deoxyguanosine, MDA increment in a dose-dependent manner were observed; likewise, insulin-stimulated glucose uptake decreased in a dose-dependent manner. Further, with antioxidant NAC and NF-κB inhibitor PDTC, we confirmed that HT attenuated PM〈sub〉2.5〈/sub〉-induced IR through restraining NF-κB activation evoked by oxidative stress. In addition, HT could expand gut microbiota richness, reduce pathogenic bacteria and accommodate the microbial architecture in PM〈sub〉2.5〈/sub〉-exposed mice, which were correlated with parameters of adiposity, oxidative stress and glycometabolism. HT could effectively correct imbalanced oxidative stress triggered by PM〈sub〉2.5〈/sub〉, in turn ameliorated NF-κB pathway and insulin signaling. Gut microbiota may mediate the actions of HT.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉A schematic illustration of how HT interfered with PM〈sub〉2.5〈/sub〉-induced oxidative stress and metabolic disorders in vivo and in vitro. vWAT, visceral white adipose tissue; scWAT, subcutaneous WAT; BAT, brown adipose tissue; PPARγ, peroxisome proliferator-activated receptor gamma; C/EBPα, CCAAT/enhancer-binding protein alpha; UCP1, uncoupling protein 1; COX2, cyclooxygenase 2; IL-1β, interleukin 1beta; TNFα, tumor necrosis factor alpha; GSK3β, glycogen synthase kinase 3β; GS, glycogen synthase; ↑indicates increase, ↓indicates decrease.〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584919301856-fx1.jpg" width="281" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Beschreibung: 〈p〉Publication date: Available online 4 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Genomics〈/p〉 〈p〉Author(s): Filipe P. Matteoli, Hemanoel Passarelli-Araujo, Francisnei Pedrosa-Silva, Fabio L. Olivares, Thiago M. Venancio〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉〈em〉Enterobacter bugandensis〈/em〉 is a recently described species that has been largely associated with nosocomial infections. We report the genome of a non-clinical 〈em〉E. bugandensis〈/em〉 strain, which was integrated with publicly available genomes to study the pangenome and general population structure of 〈em〉E. bugandensis〈/em〉. Core- and whole-genome multilocus sequence typing allowed the detection of five 〈em〉E. bugandensis〈/em〉 phylogroups (PG-A to E), which contain important antimicrobial resistance and virulence determinants. We uncovered several extended-spectrum β-lactamases, including 〈em〉bla〈/em〉〈sub〉CTX-M-55〈/sub〉 and 〈em〉bla〈/em〉〈sub〉NDM-5〈/sub〉, present in an IncX replicon type plasmid, described here for the first time in 〈em〉E. bugandensis〈/em〉. Genetic context analysis of 〈em〉bla〈/em〉〈sub〉NDM-5〈/sub〉 revealed the resemblance of this plasmid with other IncX plasmids from other bacteria from the same country. Three distinctive siderophore producing operons were found in 〈em〉E. bugandensis〈/em〉: 〈em〉ent〈/em〉erobactin (〈em〉ent〈/em〉), aerobactin (〈em〉iuc〈/em〉/〈em〉iut〈/em〉), and salmochelin (〈em〉iro〈/em〉). Our findings provide novel insights on the lifestyle, physiology, antimicrobial, and virulence profiles of 〈em〉E. bugandensis〈/em〉.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Computer Methods and Programs in Biomedicine, Volume 178〈/p〉 〈p〉Author(s): Ángel E. Esteban, Miguel López-Pérez, Adrián Colomer, María A. Sales, Rafael Molina, Valery Naranjo〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Background and objective〈/h6〉 〈p〉Prostate cancer is one of the most common male tumors. The increasing use of whole slide digital scanners has led to an enormous interest in the application of machine learning techniques to histopathological image classification. Here we introduce a novel family of morphological descriptors which, extracted in the appropriate image space and combined with shallow and deep Gaussian process based classifiers, improves early prostate cancer diagnosis.〈/p〉 〈/div〉 〈div〉 〈h6〉Method〈/h6〉 〈p〉We decompose the acquired RGB image in its RGB and optical density hematoxylin and eosin components. Then, we define two novel granulometry-based descriptors which work in both, RGB and optical density, spaces but perform better when used on the latter. In this space they clearly encapsulate knowledge used by pathologists to identify cancer lesions. The obtained features become the inputs to shallow and deep Gaussian process classifiers which achieve an accurate prediction of cancer.〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉We have used a real and unique dataset. The dataset is composed of 60 Whole Slide Images. For a five fold cross validation, shallow and deep Gaussian Processes obtain area under ROC curve values higher than 0.98. They outperform current state of the art patch based shallow classifiers and are very competitive to the best performing deep learning method. Models were also compared on 17 Whole Slide test Images using the FROC curve. With the cost of one false positive, the best performing method, the one layer Gaussian process, identifies 83.87% (sensitivity) of all annotated cancer in the Whole Slide Image. This result corroborates the quality of the extracted features, no more than a layer is needed to achieve excellent generalization results.〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusion〈/h6〉 〈p〉Two new descriptors to extract morphological features from histological images have been proposed. They collect very relevant information for cancer detection. From these descriptors, shallow and deep Gaussian Processes are capable of extracting the complex structure of prostate histological images. The new space/descriptor/classifier paradigm outperforms state-of-art shallow classifiers. Furthermore, despite being much simpler, it is competitive to state-of-art CNN architectures both on the proposed SICAPv1 database and on an external database.〈/p〉 〈/div〉

Beschreibung: 〈p〉Publication date: Available online 4 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics〈/p〉 〈p〉Author(s): Carlos Eduardo Pena, Mauricio G.S. Costa, Paulo Ricardo Batista〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Fungi cellulases are used to degrade cellulose-containing biomass for bioethanol production. Industrial cellulases such as Cel7A from 〈em〉Trichoderma reesei〈/em〉 (〈em〉Tr〈/em〉Cel7A) are critical in this process. Thus, the understanding of structure and dynamics is crucial for engineering variants with improved cellulolytic activity. This cellulase consists of two domains connected by a flexible and highly glycosylated linker. However, the linker flexibility has hindered the determination of Cel7A complete structure. Herein, based on atomic and sparse data, we applied integrative modelling to build a model of the complete enzyme structure. Next, through simulations, we studied the glycosylation effects on the structure and dynamics of a solubilized 〈em〉Tr〈/em〉Cel7A. Essential dynamics analysis showed that O-glycosylation in the linker led to the stabilization of protein overall dynamics. O-linked glycans seem to restrict protein dihedral angles distribution in this region, selecting more elongated conformations. Besides the reduced flexibility, functional interdomain motions occurred in a more concerted way in the glycosylated system. In contrast, in the absence of glycosylation, we observed vast conformational plasticity with the functional domains frequently collapsing. We report here evidence that targeting Cel7A linker flexibility by point mutations including modification of glycosylation sites could be a promising design strategy to improve cellulase activity.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S1570963919301207-ga1.jpg" width="500" alt="Unlabelled Image" title="Unlabelled Image"〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 92〈/p〉 〈p〉Author(s): Bin Zhong, Zeyin Jiang, Zhenhuang Chen, Kazue Ishihara, Huilin Mao, Shanghong Wang, Gang Lin, Chengyu Hu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Recently, studies have shown that IκB kinase β (IKKβ), a critical kinase in the nucleus factor kappa-B (NF-κB) pathway, participates in inflammatory responses associated with unfolded protein response (UPR) and plays an important role in ER stress-induced cell death. The unfolded protein response (UPR), which is a regulatory system to restore cellular homeostasis in the endoplasmic reticulum (ER), such as oxidative stress, bacterial infection, and virus invasion. The UPR pathways have been reported to be involved in immune responses in mammals, including the classical NF-κB pathway. However, the molecular mechanism of their crosstalk remains to be elucidated. Previously, we demonstrated that IKKβ also has some conserved functions between fish and human, as grass carp (〈em〉Ctenopharyngodon idella〈/em〉) IKKβ (CiIKKβ) can activate NF-κB pathway. In this study, we found that CiIKKβ level in nucleus was elevated under ER stress and CiIKKβ can interact with grass carp X-box-binding protein 1 (CiXBP1S), a key transcription factor in UPR. Consistently, fluorescent histochemical analysis of grass carp kidney (CIK) cells indicated that CiIKKβ and CiXBP1S colocalized under ER stress. Furthermore, overexpression of CiIKKβ in CIK cells enhanced ER stress tolerance by regulating UPR signaling and resulted in the significant increase of cell viability.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Journal of Hydrology: Regional Studies, Volume 24〈/p〉 〈p〉Author(s): Dagnachew Daniel Molla, Tenalem Ayenew Tegaye, Christopher G. Fletcher〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Study region〈/h6〉 〈p〉The volcano-tectonic lakes basin of Abaya-Chamo is part of the Main Ethiopian Rift system and exhibits large variations in geomorphology, physiography and climate between the rift floor and the plateau.〈/p〉 〈/div〉 〈div〉 〈h6〉Study focus〈/h6〉 〈p〉Despite the importance of streamflow for water resources management and planning in the basin, many of the rivers there are ungauged. To make quantitative estimates of streamflow for spatially resolved water availability in such a highly heterogeneous environment, therefore, requires numerical modeling. This study is the first to quantify the surface and shallow groundwater resources in Abaya-Chamo, and to validate the physically fully distributed hydrologic model WetSpass under highly data-limited conditions, in a complex two-lake environment.〈/p〉 〈/div〉 〈div〉 〈h6〉New hydrological insights〈/h6〉 〈p〉Simulated total river flow and estimated baseflow were verified at 15 gauging stations, with a good agreement. The WetSpass model is shown to be suitable for such a complex setting with a correlation coefficient of 0.95 and 0.97 for total flow and baseflow respectively at a statistically significant level (p-value 〈 0.05). The simulated annual water budget reveals that 74.6% of the 22.1 billion lit/yr in total precipitation in the basin is lost through evapotranspiration, 15.7% through surface runoff, and only 9.7% recharges the groundwater system. The simulations also revealed the surface runoff and groundwater recharge are the most sensitive to soil textural class, while evapotranspiration depends more strongly on land use.〈/p〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2214581818302623-ga1.jpg" width="159" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Beschreibung: 〈p〉Publication date: September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 92〈/p〉 〈p〉Author(s): Lu-Yun Ni, Qing Han, Hong-Ping Chen, Xiao-Chun Luo, An-Xing Li, Xue-Ming Dan, Yan-Wei Li〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Macrophage expressed gene 1 (Mpeg1) is a molecule that can form pores and destroy the cell membrane of invading pathogens. In this study, we identified two Mpeg1 isoforms from the orange-spotted grouper (〈em〉Epinephelus coioides〈/em〉) and named them EcMpeg1a and EcMpeg1b. Predicted proteins of the two EcMpeg1s contained a signal peptide, a conserved membrane attack complex/perforin (MACPF) domain, a transmembrane segment, and an intracellular region. Sequence alignment demonstrated that two EcMpeg1 proteins share a high sequence identity with that of other teleosts. Tissue distribution analysis showed that EcMpeg1s were expressed in all tissues tested in healthy grouper, with the highest expression in the head kidney and spleen. After infection with the ciliate parasite 〈em〉Cryptocaryon irritans〈/em〉, expression of the two EcMpeg1s was significantly upregulated in the spleen and gills. Furthermore, the recombinant EcMpeg1a showed antiparasitic and antibacterial activity against Gram-negative and -positive bacteria, whereas EcMpeg1b had an inhibitory effect only against Gram-positive bacteria. These results indicated that EcMpeg1s play an important role in the host response against invading pathogens.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Geoforum, Volume 105〈/p〉 〈p〉Author(s): Eric Nost, Morgan Robertson, Rebecca Lave〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉We present results from a Q-method survey on a key question in water governance and reflect on Q-method as an approach that quantitatively distinguishes qualitative subject-positions. The survey was conducted with the Q-TIP platform, which we designed for the study and is now open to all researchers (〈a href="https://qtip.geography.wisc.edu/" target="_blank"〉https://qtip.geography.wisc.edu/〈/a〉). Our study asked how stream restoration should be evaluated in state regulatory programs. Streams are dynamic and multi-scalar geomorphological, chemical, biological, as well as socio-cultural systems and it is not obvious what good restoration means or how it should be assessed. Across the stream restoration community we found four different priorities, each of which differently characterizes the feasibility of assessing outcomes. These four perspectives were that metrics of success should: (a) be rigorous and site-focused; (b) be simple and easy to implement in the field; (c) capture complexity; (d) reflect innovations in watershed planning, ecosystem functions, and stakeholder inclusion. These subject-positions on assessment do not, however, map cleanly onto informant profession or background, and a single informant can hold more than one view. Despite relatively limited uptake in geography, Q offers the promise of a critical quantitative approach to researching subjectivity in a way that is compatible with poststructural understandings of identity. We use our case material to show that methodological rules of thumb limit Q’s potential, but we demonstrate unconventional approaches. Drawing on the process and results of our survey of stream restoration practitioners, we argue that Q-method can help in the task of representing subjectivity while respecting its complexity.〈/p〉〈/div〉 〈/div〉

Beschreibung: 〈p〉Publication date: Available online 3 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Molecular Cell〈/p〉 〈p〉Author(s): Konstantinos Boulias, Diana Toczydłowska-Socha, Ben R. Hawley, Noa Liberman, Ken Takashima, Sara Zaccara, Théo Guez, Jean-Jacques Vasseur, Françoise Debart, L. Aravind, Samie R. Jaffrey, Eric Lieberman Greer〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉mRNAs are regulated by nucleotide modifications that influence their cellular fate. Two of the most abundant modified nucleotides are 〈em〉N〈/em〉〈sup〉6〈/sup〉-methyladenosine (m〈sup〉6〈/sup〉A), found within mRNAs, and 〈em〉N〈/em〉〈sup〉6〈/sup〉,2′-〈em〉O〈/em〉-dimethyladenosine (m〈sup〉6〈/sup〉Am), which is found at the first transcribed nucleotide. Distinguishing these modifications in mapping studies has been difficult. Here, we identify and biochemically characterize PCIF1, the methyltransferase that generates m〈sup〉6〈/sup〉Am. We find that PCIF1 binds and is dependent on the m〈sup〉7〈/sup〉G cap. By depleting PCIF1, we generated transcriptome-wide maps that distinguish m〈sup〉6〈/sup〉Am and m〈sup〉6〈/sup〉A. We find that m〈sup〉6〈/sup〉A and m〈sup〉6〈/sup〉Am misannotations arise from mRNA isoforms with alternative transcription start sites (TSSs). These isoforms contain m〈sup〉6〈/sup〉Am that maps to “internal” sites, increasing the likelihood of misannotation. We find that depleting PCIF1 does not substantially affect mRNA translation but is associated with reduced stability of a subset of m〈sup〉6〈/sup〉Am-annotated mRNAs. The discovery of PCIF1 and our accurate mapping technique will facilitate future studies to characterize m〈sup〉6〈/sup〉Am’s function.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S1097276519304393-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Beschreibung: 〈p〉Publication date: Available online 3 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Molecular Cell〈/p〉 〈p〉Author(s): Erdem Sendinc, David Valle-Garcia, Abhinav Dhall, Hao Chen, Telmo Henriques, Jose Navarrete-Perea, Wanqiang Sheng, Steven P. Gygi, Karen Adelman, Yang Shi〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉mRNA modifications play important roles in regulating gene expression. One of the most abundant mRNA modifications is N6,2-O-dimethyladenosine (m6Am). Here, we demonstrate that m6Am is an evolutionarily conserved mRNA modification mediated by the Phosphorylated CTD Interacting Factor 1 (PCIF1), which catalyzes m6A methylation on 2-O-methylated adenine located at the 5′ ends of mRNAs. Furthermore, PCIF1 catalyzes only 5′ m6Am methylation of capped mRNAs but not internal m6A methylation 〈em〉in vitro〈/em〉 and 〈em〉in vivo〈/em〉. To study the biological role of m6Am, we developed a robust methodology (m6Am-Exo-Seq) to map its transcriptome-wide distribution, which revealed no global crosstalk between m6Am and m6A under assayed conditions, suggesting that m6Am is functionally distinct from m6A. Importantly, we find that m6Am does not alter mRNA transcription or stability but negatively impacts cap-dependent translation of methylated mRNAs. Together, we identify the only human mRNA m6Am methyltransferase and demonstrate a mechanism of gene expression regulation through PCIF1-mediated m6Am mRNA methylation.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S1097276519304022-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Beschreibung: 〈p〉Publication date: August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Trends in Pharmacological Sciences, Volume 40, Issue 8〈/p〉 〈p〉Author(s): Alex Zhavoronkov, Polina Mamoshina〈/p〉 〈div xml:lang="en"〉〈div〉〈p〉First published in 2016, predictors of chronological and biological age developed using deep learning (DL) are rapidly gaining popularity in the aging research community. These deep aging clocks can be used in a broad range of applications in the pharmaceutical industry, spanning target identification, drug discovery, data economics, and synthetic patient data generation. We provide here a brief overview of recent advances in this important subset, or perhaps superset, of aging clocks that have been developed using artificial intelligence (AI).〈/p〉〈/div〉〈/div〉