bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of culture density on biomass production and light utilization efficiency of Synechocystis sp. PCC 6803
Authors: Straka Levi , Rittmann Bruce E.
Published: October 2017

The viability of large‐scale microalgae cultivation depends on providing optimal growth conditions, for which a key operational parameter is culture density. Using Synechocystis sp. PCC 6803, we conducted a series of fixed‐density, steady‐state experiments and one batch‐growth experiment to investigate the role of culture density on biomass production and light utilization efficiency. In all cases, the fixed‐density, steady‐state experiments and batch‐growth experiment showed good agreement. The highest biomass production rates (260 mg L−1 d−1) and efficiency for converting light energy to biomass (0.80 μg (μmol photons)−1) occurred together at a culture density near 760 mg L−1, which approximately corresponded to the lowest culture density where almost all incident light was absorbed. The ratio of OD680/OD735 increased with culture density up to the point of maximum productivity, where it plateaued (at a value of 2.4) for higher culture densities. This change in OD680/OD735 indicates a photoacclimation effect that depended on culture density. Very high culture densities led to a sharp decline in efficiency of biomass production per photons absorbed, likely due to a combination of increased decay relative to growth, metabolic changes due to cell‐cell interactions, and photodamage due to mixing between regions with high light intensity and zero light intensity.
Directed evolution of polypropylene and polystyrene binding peptides
Authors: Rübsam Kristin , Weber Lina , Jakob Felix , Schwaneberg Ulrich
Published: October 2017

Surface functionalization of biological inert polymers (e.g., polypropylene PP; polystyrene PS) with material binding peptides facilitates an efficient immobilization of enzymes, bioactive peptides or antigens at ambient temperature in water. The developed robust directed evolution protocol enables to tailor polymer binding anchor peptides (PBPs) for efficient binding under application conditions. Key for a successful directed evolution campaign was to develop an epPCR protocol with a very high mutation frequency (60 mutations/kb) to ensure sufficient diversity in PBPs (47 aas LCI: “liquid chromatography peak I”; 44 aas TA2: “Tachystatin A2”). LCI and TA2 were genetically fused to the reporter egfp to quantify peptide binding on PP and PS by fluorescence analysis. The Peptide‐Polymer evolution protocol (PePevo protocol) was validated in two directed evolution campaigns for two PBPs and polymers (LCI: PP; TA2: PS). Surfactants were used as selection pressure for improved PBP binders (non‐ionic surfactant Triton X‐100; 1 mM for LCI‐PP // anionic surfactant LAS; 0.5 mM for TA2‐PS). PePevo yielded an up to three fold improved PP‐binder (LCI‐M1‐PP: I24T, Y29H, E42 K and LCI‐M2‐PP: D31V, E42G) and an up to six fold stronger PS‐binder (TA2‐M1‐PS: R3S, L6P, V12 K, S15P, C29R, R30L, F33S, Y44H and TA2‐M2‐PS: F9C, C24S, G26D, S31G, C41S, Y44Q).
Effect of an acute moderate‐exercise session on metabolic and inflammatory profile of PPAR‐α knockout mice
Authors: Silveira Loreana S. , Pimentel Gustavo D. , Souza Camila O. , Biondo Luana A. , Teixeira Alexandre Abílio S. , Lima Edson A. , Batatinha Helena A. P. , Rosa Neto José C. , Lira Fábio S.
Published: October 2017

Peroxisome proliferator‐activated receptors (PPARs) play a major role in metabolism and inflammatory control. Exercise can modulate PPAR expression in skeletal muscle, adipose tissue, and macrophages. Little is known about the effects of PPAR‐α in metabolic profile and cytokine secretion after acute exercise in macrophages. In this context, the aim of this study was to understand the influence of PPAR‐α on exercise‐mediated immune metabolic parameters in peritoneal macrophages. Mice C57BL/6 (WT) and PPAR‐α knockout (KO) were examined in non‐exercising control (n = 4) or 24 hours after acute moderate exercise (n = 8). Metabolic parameters (glucose, non‐esterified fatty acids, total cholesterol [TC], and triacylglycerol [TG]) were assessed in serum. Cytokine concentrations (IL‐1β, IL‐6, IL‐10, TNF‐α, and MCP‐1) were measured from peritoneal macrophages cultured or not with LPS (2.5 μg/mL) and Rosiglitazone (1 μM). Exercised KO mice exhibited low glucose concentration and higher TC and TG in serum. At baseline, no difference in cytokine production between the genotypes was observed. However, IL‐1β was significantly higher in KO mice after LPS stimulus. IL‐6 and IL‐1β had increased concentrations in KO compared with WT, even after exercise. MCP‐1 was not restored in exercised KO LPS group. Rosiglitazone was not able to reduce proinflammatory cytokine production in KO mice at baseline level or associated with exercise. Acute exercise did not alter mRNA expression in WT mice. Conclusion: PPAR‐α seems to be needed for metabolic glucose homeostasis and anti‐inflammatory effect of acute exercise. Its absence may induce over‐expression of pro‐inflammatory cytokines in LPS stimulus. Moreover, moderate exercise or PPAR‐γ agonist did not reverse this response.
The micronome of mesenchymal stromal cells is partially responsive to inflammation
Authors: Fayyad‐Kazan Hussein , Fayyad‐Kazan Mohammad , Merimi Makram , Meuleman Nathalie , Bron Dominique , Lagneaux Laurence , Najar Mehdi
Published: October 2017

Mesenchymal stromal cells (MSCs) display a special immunological profile that allows their potential use as immunotherapeutic cells. Nowadays, foreskin (FSK) represents a valuable reservoir of MSCs with International Society for Cellular Therapy (ISCT) compliant criteria and relevant functional properties. However, their mode of action is poorly understood and needs to be more elucidated to optimize their therapeutic use. Because microRNAs (miRNAs) act as key regulators in a wide variety of biological processes, we decided to establish the micronome of FSK‐MSCs, the influence of inflammation and the predicted target pathways. Here, we provide the full list of unchanged and additional four differentially expressed miRNAs, miR‐199b, ‐296‐3p and ‐589‐5p being downregulated whilst miR‐146‐3p being upregulated, in MSCs following their exposure to a cocktail of proinflammatory cytokines. MicroRNA target prediction in addition to Pathway enrichment analysis performed using miRNet, showed that miR‐296‐3p is linked to antigen processing and presentation pathway. Collectively, our data indicate that the micronome of FSK‐MSCs is partially responsive to inflammation. Differentially expressed miRNAs are subsequently modulated by inflammation and seem to be involved in regulating the immunological fate of FSK‐MSCs. These miRNAs deserve more attention in order to optimize MSC‐based therapy and achieve the appropriate therapeutic effect.
Na‐Doped C70 Fullerene/N‐Doped Graphene/Fe‐Based Quantum Dot Nanocomposites for Sodium‐Ion Batteries with Ultrahigh Coulombic Efficiency
Authors: Wang Chunlian , Zhang Yang , He Wen , Zhang Xudong , Yang Guihua , Wang Zhaoyang , Ren Manman , Wang Lianzhou
Published: October 2017

Na‐doped C70 fullerene (Na‐C70)/N‐doped graphene (N‐GN)/Fe‐based nanocomposites (Na‐C70/N‐GN/FBNCs) with the multiple morphologies are fabricated through an in situ one‐step method with multifunction sodium lignosulfonate (SLS) as the structural template and the main raw material. Fe‐based quantum dots (FBQDs) can be embeded in the ordered mesoporous hybrid carbon structure of Na‐C70 and N‐GN through a spontaneous chelation reaction of SLS with iron ions and carbonization under relatively mild hydrothermal treatment. We investigate the influences of the molar ratio of SLS/Fe on the structure, components, and electrochemical properties of the nanocomposites. Its unique hybrid carbon structure offers metallicity and superconductivity, countless bonding sites of Na ions, and facilitates the transfer of electrons and Na ions during prolonged cycling. The nanocomposites for sodium‐ion batteries anodes can achieve the highest discharge capacities of 1898 mAh g−1 at a current density of 1000 mA g−1, and can retain a reversible capacity of 238 mAh g−1 after 100 cycles, which are significantly better than those of lithium‐ion batteries. The discharge and charge capacities at 1 A g−1 after 30th cycles are 356 and 119 mAh g−1, respectively, with an ultrahigh coulombic efficiency of 299 % and the highest coulombic efficiency of 463 % after 220 cycles.
Porous Ni−Mo−S Nanowire Network Film Electrode as a High‐Efficiency Bifunctional Electrocatalyst for Overall Water Splitting
Authors: Ma Zizai , Meng Huijie , Wang Mei , Tang Bin , Li Jinping , Wang Xiaoguang
Published: October 2017

Developing noble‐metal‐free electrocatalysts with excellent activity and stability for the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is essential for promoting the generation of H2 by electrocatalytic water splitting. Herein, a novel 3D self‐supported Ni−Mo−S nanowire network film electrode was prepared by facile electroplating nickel−molybdenum on nickel foam followed by sulfurization as bifunctional catalysts for both HER and OER. Electrochemical measurements reveal that superb high catalytic activity and durability is acquired on the Ni−Mo−S electrode, which can afford an electrocatalytic current density of 100 mA cm−2 with an overpotential of 290 mV for the HER and an overpotential of 390 mV for the OER in alkaline medium. Coupled with the superior and robust OER catalytic activity, an alkaline electrolyzer that can achieve 100 mA cm−2 at a cell voltage of 2.0 V was constructed by applying Ni−Mo−S||Ni−Mo−S for overall water splitting, thus indicating a homogeneous, cost‐effective, and earth‐abundant material system for highly efficient H2 production.
Highly Conductive Hierarchical C/C Composites to Eliminate Conductive Agent in EDLC Electrodes
Authors: Chang Panpan , Wang Chengyang , Kinumoto Taro , Tsumura Tomoki , Chen Mingming , Toyoda Masahiro
Published: October 2017

Invited for this month's cover picture is the group of Professor Mingming Chen at Tianjin University (China) and Professor Masahiro Toyoda at Oita University (Japan). The cover picture shows a typical frame‐filling C/C composite, in which graphene guarantees rapid electron conduction and fast ion transmission, and numerous nanoporous carbons derived from amphiphilic carbonaceous materials (ACM) provide sufficient micropores to accumulate electric double layers for energy storage. Nowadays, although carbon black (CB) has no contribution to specific capacitance, it is still indispensable when fabricating an EDLC electrode to guarantee a satisfactory power output of whole EDLCs. Therefore, there arises an appeal for conductive EDLC electrode materials. In our work, aiming at a CB‐free EDLC electrode, we constructed a series of porous frame‐filling type C/C composites that have both ample specific surface area (SSA) and adequate electrical conductivity (e‐conductivity). Read the full text of the Article at 10.1002/celc.201700650.
Self‐Assembly through Noncovalent Preorganization of Reactants: Explaining the Formation of a Polyfluoroxometalate
Authors: Schreiber Roy E. , Avram Liat , Neumann Ronny
Published: October 2017

High‐order elementary reactions in homogeneous solutions involving more than two molecules are statistically improbable and very slow to proceed. They are not generally considered in classical transition‐state or collision theories. Yet, rather selective, high‐yield product formation is common in self‐assembly processes that require many reaction steps. On the basis of recent observations of crystallization as well as reactions in dense phases, it is shown that self‐assembly can occur by preorganization of reactants in a noncovalent supramolecular assembly, whereby directing forces can lead to an apparent one‐step transformation of multiple reactants. A simple and general kinetic model for multiple reactant transformation in a dense phase that can account for many‐bodied transformations was developed. Furthermore, the self‐assembly of polyfluoroxometalate anion [H2F6NaW18O56]7− from simple tungstate Na2WO2F4 was demonstrated by using 2D 19F–19F NOESY, 2D 19F–19F COSY NMR spectroscopy, a new 2D 19F{183W} NMR technique, as well as ESI‐MS and diffusion NMR spectroscopy, and the crucial involvement of a supramolecular assembly was found. The deterministic kinetic reaction model explains the reaction in a dense phase and supports the suggested self‐assembly mechanism. Reactions in dense phases may be of general importance in understanding other self‐assembly reactions.
Approaches for Selective Synthesis of Ullazine Donor–Acceptor Systems
Authors: Drigo Nikita A. , Paek Sanghyun , Huckaba Aron J. , Schouwink Pascal A. , Tabet Nouar , Nazeeruddin Mohammad K.
Published: October 2017

Methods for effective synthesis for the four possible isomeric 3,9‐diphenylullazine carboxaldehydes and reactive halogen intermediates are described. Ullazine donor–acceptor (D–A) dyes were studied using UV/Vis, photoluminescence (PL) spectroscopy and cyclic voltammetry. X‐ray single crystal diffraction analysis independently confirmed the structures of two key intermediates. A D–A dye based on ullazine with dihexylmalonate acceptor was tested as a dopant‐free hole‐transporting material (HTM) in a perovskite solar cell, exhibiting promising power conversion efficiency (PCE) reaching 13.07 %.
Applying complexity theory to explain partner cooperation: The role of transaction cost‐related factors and elements of relational exchanges
Authors: Xue Jinjie , Lu Shaokai , Shi Benshan , Yang Xia
Published: October 2017

Using complexity theory, we seek to better understand the configurations of causal factors stimulating joint ventures' cooperation in Chinese manufacturing context. To this end, we adopt two dominant perspectives of transaction cost economics and relational exchange theory to identify transaction cost‐related factors and elements of relational exchanges as critical factors in joint ventures' cooperation. We apply fuzzy‐set qualitative comparative analysis on a sample of 268 joint venture partners to test research propositions. The findings indicate a need for competence trust and goodwill trust and also show that extorting rent cost should be emphasized. Results reveal those six configurations of causal factors that explain high intention to cooperate. Copyright © 2017 ASAC. Published by John Wiley & Sons, Ltd.
Generation and Characterization of Functional Human Hypothalamic Neurons
Authors: Kirwan Peter , Jura Magdalena , Merkle Florian T.
Published: October 2017

Neurons in the hypothalamus orchestrate homeostatic physiological processes and behaviors essential for life. Defects in the function of hypothalamic neurons cause a spectrum of human diseases, including obesity, infertility, growth defects, sleep disorders, social disorders, and stress disorders. These diseases have been studied in animal models such as mice, but the rarity and relative inaccessibility of mouse hypothalamic neurons and species‐specific differences between mice and humans highlight the need for human cellular models of hypothalamic diseases. We and others have developed methods to differentiate human pluripotent stem cells (hPSCs) into hypothalamic neurons and related cell types, such as astrocytes. This protocol builds on published studies by providing detailed step‐by‐step instructions for neuronal differentiation, quality control, long‐term neuronal maintenance, and the functional interrogation of hypothalamic cells by calcium imaging. Together, these protocols should enable any group with appropriate facilities to generate and study human hypothalamic cells. © 2017 by John Wiley & Sons, Inc.
Harnessing Meta‐analysis to Refine an Oncology Patient Population for Physiology‐Based Pharmacokinetic Modeling of Drugs
Authors: Schwenger Emily , Reddy Venkatesh Pilla , Moorthy Ganesh , Sharma Pradeep , Tomkinson Helen , Masson Eric , Vishwanathan Karthick
Published: October 2017

Certain oncology compounds exhibit fundamental pharmacokinetic (PK) disparities between healthy and malignant conditions. Given the effects of tumor‐associated inflammation on enzyme and transporter expression, we performed a meta‐analysis of CYP‐ and transporter‐sensitive substrate clinical PK to quantitatively compare enzyme and transporter abundances between healthy volunteers (HV) and cancer patients (CP). Hepatic and intestinal CYP1A2, CYP2C19, and CYP3A4 abundance were subsequently adjusted via Simcyp's sensitivity analysis tool. Of the 11 substrates we investigated, seven displayed marked exposure differences >1.25‐fold between CP and HV. Although CP studies are limited, meta‐analysis‐based reduction in CYP1A2, CYP2C19, and CYP3A4 enzyme abundances in a virtual oncology population effectively captures CP‐PK for caffeine, theophylline, midazolam, simvastatin, omeprazole, and a subset of oncology compounds. These changes allow extrapolation from HV to CP, enhancing predictive capability; therefore, conducting simulations in this CYP‐modified oncology (MOD‐CP) population provides a more relevant characterization of CP‐PK.
Photoinduced Charge Separation in Semiconductor‐Quantum‐Dot/Organic‐Molecule Hybrids
Authors: Tkachenko Nikolai V.
Published: October 2017

Semiconductor colloidal quantum dot/organic molecule nanohybrids are gaining momentum due to the relative ease with which an efficient photoinduced charge transfer in the desired direction can be achieved between the dot and the molecule. At the same time analysis of the experimental studies of such systems, and in particular transient absorption spectroscopy data, is a challenging task because of the statistical nature of hybrid formation and the complex kinetics of the photoreactions. This Minireview aims to find common ground for comparing the photoinduced charge‐separation reactions in quantum dot/organic molecule hybrids. It also discusses a common set of parameters which would help to compare different quantum dot/molecule hybrids as well as progress in developing design principles to achieve controllable photoinduced charge separation in such hybrids.
Optimal control of an invasive species using a reaction‐diffusion model and linear programming
Authors: Bonneau Mathieu , Johnson Fred A. , Smith Brian J. , Romagosa Christina M. , Martin Julien , Mazzotti Frank J.
Published: October 2017

Managing an invasive species is particularly challenging as little is generally known about the species’ biological characteristics in its new habitat. In practice, removal of individuals often starts before the species is studied to provide the information that will later improve control. Therefore, the locations and the amount of control have to be determined in the face of great uncertainty about the species characteristics and with a limited amount of resources. We propose framing spatial control as a linear programming optimization problem. This formulation, paired with a discrete reaction‐diffusion model, permits calculation of an optimal control strategy that minimizes the remaining number of invaders for a fixed cost or that minimizes the control cost for containment or protecting specific areas from invasion. We propose computing the optimal strategy for a range of possible model parameters, representing current uncertainty on the possible invasion scenarios. Then, a best strategy can be identified depending on the risk attitude of the decision‐maker. We use this framework to study the spatial control of the Argentine black and white tegus (Salvator merianae) in South Florida. There is uncertainty about tegu demography and we considered several combinations of model parameters, exhibiting various dynamics of invasion. For a fixed one‐year budget, we show that the risk‐averse strategy, which optimizes the worst‐case scenario of tegus’ dynamics, and the risk‐neutral strategy, which optimizes the expected scenario, both concentrated control close to the point of introduction. A risk‐seeking strategy, which optimizes the best‐case scenario, focuses more on models where eradication of the species in a cell is possible and consists of spreading control as much as possible. For the establishment of a containment area, assuming an exponential growth we show that with current control methods it might not be possible to implement such a strategy for some of the models that we considered. Including different possible models allows an examination of how the strategy is expected to perform in different scenarios. Then, a strategy that accounts for the risk attitude of the decision‐maker can be designed.
Carbon dioxide and submersed macrophytes in lakes: linking functional ecology to community composition
Authors: Titus John E. , Pagano Angela M.
Published: October 2017

Evaluating plant community response to atmospheric CO2 rise is critical to predicting ecosystem level change. Freshwater lakes offer a model system for examining CO2 effects as submersed macrophyte species differ greatly in their growth responses to CO2 enrichment, and free CO2 concentrations among these habitats show a wide range of natural, spatial variation. We determined free CO2 concentrations in the water column and sediment porewater in littoral zones with pH < 6.0 in Adirondack Mountain (New York, USA) lakes, and derived a community CO2 responsiveness index (CCRI) based on quantitative sampling of 15 submersed macrophyte communities coupled with greenhouse‐derived growth responses to CO2 enrichment of constituent species to test two hypotheses: (1) CCRI, which is higher for communities dominated by species with greater growth responses to CO2 enrichment, is positively correlated to free [CO2] in the water column, and (2) in natural communities, the percent of sediment CO2‐using species, which are relatively unresponsive to CO2 enrichment, is negatively correlated to free [CO2]. A significant positive correlation (P = 0.003) between our physiologically based CCRI and the concentration of free CO2 in the water column supported our primary hypothesis that sites with higher levels of free CO2 are dominated by species with greater growth responses to CO2 enrichment. Our CCRI is also highly significantly correlated (P < 0.001) to the first axis scores for the same vegetation data from polar ordination. Finally, the relative importance of species that use sediment CO2 as a photosynthetic carbon source is significantly negatively correlated (P = 0.029) with the concentration of free CO2 in the water column. Our results indicate that natural variations in CO2 levels are important determinants of submersed macrophyte community composition. Further, we demonstrate the utility of a physiologically‐based index of community composition, our CCRI, as an ecologically valid measure of community response to CO2.
Zinc(II) Coordination Frameworks Based on Benzobisimidazole: The Role of the Methyl Substituent
Authors: Bunzen Hana , Mahmood Farah , Grzywa Maciej , Volkmer Dirk
Published: October 2017

Three ZnII coordination frameworks (CFs) based on benzobisimidazole were prepared by utilizing organic ligands containing methyl groups in the 2‐position of the imidazole rings. The molecular structures of the prepared CFs were revealed by single‐crystal XRD. The influence of the methyl group on the crystal packing motifs of the materials was investigated and compared to structurally related compounds without methyl groups in the 2‐position of the imidazole rings, which were prepared under the same or very similar reaction conditions. The thermal stability of the prepared CFs was investigated by variable‐temperature powder XRD and thermogravimetric analysis, and their photoluminescence properties are reported.
Organocatalytic Asymmetric Dimerization of γ‐Hydroxyenones to Acetals and Theoretical Investigations into the Diastereoselection
Authors: Mondal Buddahdeb , Mondal Keshab , Satpati Priyadarshi , Pan Subhas Chandra
Published: October 2017

A method for the organocatalytic, highly enantioselective, and moderately diastereoselective dimerization (redox isomerization/acetal formation) of γ‐hydroxyenones is disclosed. The stereogenic acetal products were obtained via hemiacetal intermediates followed by a cyclization reaction. With bifunctional thiourea catalysts, high yields and excellent enantioselectivities were achieved for a variety of acetal products under mild reaction conditions. In addition, detailed DFT calculations were performed to investigate the mechanism of this reaction, and these calculations suggested that the diastereoselectivity was due to a kinetically controlled process.
Application of a One‐Pot Friedel–Crafts Alkylation/Michael Addition Methodology to the Asymmetric Synthesis of Ergoline Derivatives
Authors: Despotopoulou Christina , McKeon Sean C. , Connon Robert , Coeffard Vincent , Müller‐Bunz Helge , Guiry Patrick J.
Published: October 2017

Herein, we report a short and facile stereoselective route to ergoline derivatives. The key steps are a one‐pot Friedel–Crafts alkylation/Michael addition sequence which, in the absence of chiral ligands, affords the trans‐trans‐stereoisomer in 44 % yield as a racemate. Screening of a range of chiral bisoxazoline ligands allowed this sequence to proceed in 42–55 % yields (six examples), with up to 99 % ee. This approach allows for the first time, substitution at the C4‐position and the introduction of 3 chiral centres in one pot. An interesting, base‐mediated conversion of the trans‐trans‐stereoisomer to the cis‐cis‐stereoisomer was discovered and both stereoisomers were characterized by X‐ray crystallography.
Diffuse brain damage in normal tension glaucoma
Authors: Giorgio Antonio , Zhang Jian , Costantino Francesco , De Stefano Nicola , Frezzotti Paolo
Published: October 2017

Brain changes within and beyond the visual system have been demonstrated in primary open angle glaucoma (POAG), the most common type of glaucoma. These changes have been often interpreted as a neurodegenerative process due, at least partially, to the raised intraocular pressure (IOP). In this context, normal tension glaucoma (NTG), a form of POAG with IOP <21 mm Hg despite the typical glaucomatous findings, represents the most suitable model of glaucoma to test the validity of this hypothesis. We acquired multimodal brain MRI in NTG patients (n = 17) and compared them with demographically matched groups of POAG patients with raised IOP (n = 17) and normal controls (NC, n = 29). Voxelwise statistics was performed with nonparametric permutation testing.

Both NTG and POAG patients showed, compared to NC, significantly more gray matter atrophy in both the visual system and in nonvisual brain regions and altered diffusion tensor imaging‐derived anatomical connectivity (AC; lower fractional anisotropy and/or higher diffusivities). Compared with NTG, POAG had both more atrophic visual cortex and higher axial diffusivity in nonvisual regions. Functional connectivity (FC) with respect to NC was altered in NTG at short‐range level [visual network (VN), ventral attention network] and in POAG at long‐range level (between secondary VN and limbic network). FC of POAG was higher than NTG in both VN and executive network.

This study provides further evidence that diffuse structural and functional abnormalities across glaucoma brain may be, at least partially, independent of raised IOP and the consequent retinal degeneration. This further defines glaucoma as a condition with neurodegeneration spreading. Hum Brain Mapp 39:532–541, 2018. © 2017 Wiley Periodicals, Inc.
Integrated genome analysis of uterine leiomyosarcoma to identify novel driver genes and targetable pathways
Authors: Cuppens Tine , Moisse Matthieu , Depreeuw Jeroen , Annibali Daniela , Colas Eva , Gil‐Moreno Antonio , Huvila Jutta , Carpén Olli , Zikán Michal , Matias‐Guiu Xavier , Moerman Philippe , Croce Sabrina , Lambrechts Diether , Amant Frédéric
Published: October 2017

Uterine leiomyosarcomas (uLMS) are rare, aggressive malignancies for which limited treatment options are available. To gain novel molecular insights into uLMS and identify potential novel therapeutic targets, we characterized 84 uLMS samples for genome‐wide somatic copy number alterations, mutations, gene fusions and gene expression and performed a data integration analysis. We found that alterations affecting TP53, RB1, PTEN, MED12, YWHAE and VIPR2 were present in the majority of uLMS. Pathway analyses additionally revealed that the PI3K/AKT/mTOR, estrogen‐mediated S‐phase entry and DNA damage response signaling pathways, for which inhibitors have already been developed and approved, frequently harbored genetic changes. Furthermore, a significant proportion of uLMS was characterized by amplifications and overexpression of known oncogenes (CCNE1, TDO2), as well as deletions and reduced expression of tumor suppressor genes (PTEN, PRDM16). Overall, it emerged that the most frequently affected gene in our uLMS samples was VIPR2 (96%). Interestingly, VIPR2 deletion also correlated with unfavorable survival in uLMS patients (multivariate analysis; HR = 4.5, CI = 1.4–14.3, p = 1.2E‐02), while VIPR2 protein expression was reduced in uLMS vs. normal myometrium. Moreover, stimulation of VIPR2 with its natural agonist VIP decreased SK‐UT‐1 uLMS cell proliferation in a dose‐dependent manner. These data suggest that VIPR2, which is a negative regulator of smooth muscle cell proliferation, might be a novel tumor suppressor gene in uLMS. Our work further highlights the importance of integrative molecular analyses, through which we were able to uncover the genes and pathways most frequently affected by somatic alterations in uLMS.
Improvement of refractory pruritus after lipoprotein‐apheresis in arthrogryposis‐renal failure‐cholestasis syndrome
Authors: Rosales A. , Muñoz M. , Madrid A. , Chocron S. , Hernández J. M. , Ariceta G.
Published: October 2017

Accumulation of bile acids can lead to invalidating pruritus in cholestatic patients. Few reports exist on the influence of lipoprotein‐apheresis (LA) on plasma level of total bile acids (tBA). We report of significant decrease in tBA levels and drastic improvement of pruritus in a 5‐year‐old girl with arthrogryposis‐renal failure‐cholestasis syndrome. We present LA as a suitable rescue treatment option in therapy‐refractory cholestasis‐associated pruritus, at least as bridge until a long‐term solution such as entero‐biliary anastomosis or transplantation is possible.
Patients’ and therapists’ experiences of general change mechanisms during bug‐in‐the‐eye and delayed video‐based supervised cognitive‐behavioral therapy. A randomized controlled trial
Authors: Probst Thomas , Jakob Marion , Kaufmann Yvonne M. , Müller‐Neng Julia M. B. , Bohus Martin , Weck Florian
Published: October 2017

Objective

This secondary analysis of a randomized controlled trial investigated whether bug‐in‐the‐eye (BITE) supervision (live computer‐based supervision during a psychotherapy session) affects the manner in which patients and therapists experience general change mechanisms (GCMs) during cognitive‐behavioral therapy (CBT).

Method

A total of 23 therapists were randomized either to the BITE condition or the control condition (delayed video‐based [DVB] supervision). After each session, both patients (BITE: n = 19; DVB: n = 23) and therapists (BITE: n = 11; DVB: n = 12) completed the Helping Alliance Questionnaire (HAQ) and the Bernese Post Session Report (BPSR). The HAQ total score and the 3 secondary factors of the BPSR (interpersonal experiences, intrapersonal experiences, problem actuation) functioned as GCMs. Multilevel models were performed.

Results

For patients, GCMs did not develop differently between BITE and DVB during CBT. Therapists rated the alliance as well as interpersonal and intrapersonal experiences not significantly different between BITE and DVB during CBT, but they perceived problem actuation to increase significantly more in BITE than in DVB (p < .05).

Conclusion

BITE supervision might be helpful in encouraging CBT therapists to apply interventions, which focus on the activation of relevant problems and related emotions.
Remediation of soil contaminated by PAHs and TPH using alkaline activated persulfate enhanced by surfactant addition at flow conditions
Authors: Lominchar Miguel A , Lorenzo David , Romero Arturo , Santos Aurora
Published: October 2017

BACKGROUND

Remediation of a soil polluted with fuel oil #2 and polycyclic aromatic hydrocarbons (PAHs) has been carried out by alkaline activated persulfate (PS). The effect of surfactant addition on the abatement of TPH and PAHs was studied. Accordingly, four runs were performed at flow conditions using: only water, only surfactant (15 g L‐1 of Verusol‐3), activated persulfate (210 mmol L‐1 PS and 840 mmol L‐1 NaOH) and surfactant (15 g L‐1 Verusol) with activated persulfate (210 mmol L‐1 PS and 840 mmol L‐1 NaOH).

RESULTS

Washing with water was found to achieve negligible desorption of the pollutants. Washing with surfactant or a combination of surfactant and oxidant completely removed the contaminants from soil, however only the addition of oxidant yielded an aqueous effluent without pollutants. When adding activated persulfate alone (without surfactant), about 30% residual contamination remained in the soil.

CONCLUSION

Results suggest that the combined application of surfactant and alkali persulfate produces a significant improvement in the elimination of organic compounds such as fuel oil #2 and PAHs. © 2017 Society of Chemical Industry
Design and Synthesis of Some New Quinoxaline‐Based Heterocycles
Authors: El Azab Islam H. , Elkanzi Nadia A. A. , Gobouri Adil A.
Published: October 2017

Considering quinoxaline as a privileged structure for developing probes of impressive therapeutic potentials, some new azole and azine conjugates of quinoxaline were synthesized. Thus, ethyl 3‐amino‐1,4‐dihydroquinoxaline‐2‐carboxylate (2) was prepared as one‐pot three‐component product and incorporated in a series of manipulations including cyclocondensation reactions to afford a series of pharmacophoric motif conjugates 8–12, 14, 15–17, 20–23, 24–29, 30–37, and 38–43 in fair yields. The newly synthesized were characterized by IR, 1H NMR, 13C NMR, and mass spectral data.
Molecular characterization of hepatitis C virus in end‐stage renal disease patients under hemodialysis
Authors: Alves da Silva Rafael , de Souza Todão Jardelina , Kamitani Fernando Luiz , Silva Antonio Eduardo Benedito , de Carvalho‐Filho Roberto José , Ferraz Maria Lucia Cardoso Gomes , de Carvalho Isabel Maria Vicente Guedes
Published: October 2017

New direct‐acting antiviral (DAA) agents are in development or already approved for the treatment of chronic hepatitis C virus (HCV) infection. The effectiveness of these drugs is related to the previous existence of resistant variants. Certain clinical conditions can allow changes in immunological characteristics of the host and even modify genetic features of viral populations. The aim of this study was to perform HCV molecular characterization from samples of end‐stage renal disease patients on hemodialysis (ESRD‐HD). Nested PCR and Sanger sequencing were used to obtain genetic information from the NS5B partial region of a cohort composed by 86 treatment‐naïve patients. Genomic sequences from the Los Alamos databank were employed for comparative analysis. Bioinformatics methodologies such as phylogenetic reconstructions, informational entropy, and mutation analysis were used to analyze datasets separated by geographical location, HCV genotype, and renal function status. ESRD‐HD patients presented HCV genotypes 1a (n = 18), 1b (n = 16), 2a (n = 2), 2b (n = 2), and 3a (n = 4). Control subjects were infected with genotypes 1a (n = 11), 1b (n = 21), 2b (n = 4), and 3a (n = 8). Dataset phylogenetic reconstruction separated HCV subtype 1a into two distinct clades. The entropy analysis from the ESRD‐HD group revealed two amino acid positions related to an epitope for cytotoxic T lymphocytes and T helper cells. Genotype 1a was found to be more diverse than subtype 1b. Also, genotype 1a ERSD‐HD patients had a higher mean of amino acids changes in comparison to control group patients. The identification of specific mutations on epitopes and high genetic diversity within the NS5B HCV partial protein in hemodialysis patients can relate to host immunological features and geographical distribution patterns. This genetic diversity can affect directly the new DAA's resistance mechanisms.
Establishment of a platform for molecular and immunological characterization of the RNA‐dependent‐RNA‐polymerase NS5B of an Egyptian HCV isolate
Authors: Gewaid Hossam , Mesalam Ahmed A. , Ibrahim Ahmed A. , Abdel Shafy Dina N. , Abdel Shafy Rola N. , Emara Nahed , Hamdy Soha M. , Gewaid Mohy , Bahgat Mahmoud M.
Published: October 2017

The present work aimed at establishing a platform to enable frequent characterization of the HCV RNA‐dependent‐RNA‐polymerase from Egyptian clinical isolates. Subjecting amplified HCV‐NS5B coding gene from Egyptian patient's serum to sequencing, multiple alignment, and phylogenetic analysis confirmed its subtype 4a origin. Nucleotide sequence analysis revealed presence of an additional start codon at the beginning of the NS5B gene. Peptide sequence alignment demonstrated presence of unique amino acid residues in our 4a‐NS5B sequence distinct from the JFH‐1‐NS5B sequence as well as unique amino acids compared to other genotypes. The distinct molecular structure of the herein characterized 4a‐NS5B from the 2a‐JFH‐1‐NS5B was further demonstrated both in the built 3D models and the Ramachandran plots corresponding to each structure. Both the unique amino acid residues and 3D structure of the 4a‐NS5B may influence both genotype 4a replication rate and response to therapy in comparison to other genotypes. Many resistance mutations to polymerase inhibitors were found both in ours and other genotypes' sequences. The presence of the required amino acid motifs for the RNA dependent RNA polymerase activity encouraged to clone the NS5B570‐encoding sequence downstream CMV promotor in a mammalian expression vector. Such construct was used for both prokaryotic expression in bacteria and for DNA immunization. Successful mammalian expression and induction of specific immune response were demonstrated by ELISA and Western blotting. The potential of both the raised antibodies and the expressed NS5B to differentiate between HCV‐infected and control human sera were demonstrated which reflect their diagnostic value.
DNA detection of JC and BK virus in archival urine cytospin slides
Authors: de Assis Patricia G. , de Souza Carvalho Carlos Eduardo , Soares da Mota e Silva Marcelo , da Costa Carvalho Maria da Gloria
Published: October 2017

To identify decoy cells, cytological examination was performed in urine cytospin slides. Decoy cells are related to Polyomaviruses (JC virus [JCV] and BK virus [BKV]), which are recognized worldwide due to potential infection and morbidity in kidney transplant recipients. Cytologically, it is difficult to evaluate the cytopathic effect of JCV and BKV in urine of patients with urothelial neoplasia. For this reason, there is a need for molecular approaches. To evaluate the incidence of BKV and JCV DNA in archival slides of urine cytospin material with benign and malignant characteristics. A total of 176 urine specimens were used for cytological examination of neoplastic or decoy cells. The samples were analyzed for the presence of JCV and BKV, by polymerase chain reaction (PCR) in DNA Isolated from archival slides of urine cytospin material. A typical samples (n = 48) were compared with the remaining 128 samples without atypia/neoplasia for the presence of JCV or BKV DNA. A statistically nonsignificant result was observed correlating the presence of JCV or BKV. The results show that DNA Isolated from archival slides of urine cytospin material can be used for detection of BKV and JCV.
Fluorine‐19 magnetic resonance imaging probe for the detection of tau pathology in female rTg4510 mice
Authors: Yanagisawa Daijiro , Ibrahim Nor Faeizah , Taguchi Hiroyasu , Morikawa Shigehiro , Kato Tomoko , Hirao Koichi , Shirai Nobuaki , Sogabe Takayuki , Tooyama Ikuo
Published: October 2017

Aggregation of tau into neurofibrillary tangles (NFTs) is characteristic of tauopathies, including Alzheimer's disease. Recent advances in tau imaging have attracted much attention because of its potential contributions to early diagnosis and monitoring of disease progress. Fluorine‐19 magnetic resonance imaging (19F‐MRI) may be extremely useful for tau imaging once a high‐quality probe has been formulated. In this investigation, a novel fluorine‐19–labeling compound has been developed as a probe for tau imaging using 19F‐MRI. This compound is a buta‐1,3‐diene derivative with a polyethylene glycol side chain bearing a CF3 group and is known as Shiga‐X35. Female rTg4510 mice (a mouse model of tauopathy) and wild‐type mice were intravenously injected with Shiga‐X35, and magnetic resonance imaging of each mouse's head was conducted in a 7.0‐T horizontal‐bore magnetic resonance scanner. The 19F‐MRI in rTg4510 mice showed an intense signal in the forebrain region. Analysis of the signal intensity in the forebrain region revealed a significant accumulation of fluorine‐19 magnetic resonance signal in the rTg4510 mice compared with the wild‐type mice. Histological analysis showed fluorescent signals of Shiga‐X35 binding to the NFTs in the brain sections of rTg4510 mice. Data collected as part of this investigation indicate that 19F‐MRI using Shiga‐X35 could be a promising tool to evaluate tau pathology in the brain.
Rigid‐layer Raman‐active modes in N‐layer transition metal dichalcogenides: interlayer force constants and hyperspectral Raman imaging
Authors: Froehlicher Guillaume , Lorchat Etienne , Zill Olivia , Romeo Michelangelo , Berciaud Stéphane
Published: October 2017

We report a comparative study of rigid‐layer Raman‐active modes in N‐layer transition metal dichalcogenides. Trigonal prismatic (2Hc, such as MoSe2, MoTe2, WS2, and WSe2) and distorted octahedral (1T', such as ReS2 and ReSe2) phases are considered. The Raman‐active in‐plane interlayer shear modes and out‐of‐plane interlayer breathing modes appear as well‐defined features with wavenumbers in the range 0−40cm−1. These rigid‐layer modes are well described by an elementary linear chain model from which the interlayer force constants are readily extracted. Remarkably, these force constants are all found to be of the same order of magnitude. Finally, we show that the prominent interlayer shear and breathing mode features allow high‐precision hyperspectral Raman imaging of N‐layer domains within a given transition metal dichalcogenide flake. Copyright © 2017 John Wiley & Sons, Ltd.
Acoustic Radiation Force Impulse Quantification in the Evaluation of Thyroid Elasticity in Pediatric Patients With Hashimoto Thyroiditis
Authors: Yucel Serap , Ceyhan Bilgici Meltem , Kara Cengiz , Can Yilmaz Gulay , Aydin H. Murat , Elmali Muzaffer , Tomak Leman , Saglam Dilek
Published: October 2017

Objectives

To evaluate the parenchymal elasticity of the thyroid gland with acoustic radiation force impulse imaging in pediatric patients with Hashimoto thyroiditis and to compare it with healthy volunteers.

Methods

Twenty‐six patients with Hashimoto thyroiditis and 26 healthy volunteers between 6 and 17 years were included. The shear wave velocity (SWV) values of both thyroid lobes in both groups were evaluated.

Results

The age and sex characteristics of the controls and patients with Hashimoto thyroiditis were similar. The SWV of the thyroid gland in patients with Hashimoto thyroiditis (mean ± SD, 1.67 ± 0.63 m/s) was significantly higher than that in the control group (1.30 ± 0.13 m/s; P < .001). There was no significant difference between the thyroid lobes in both groups. A receiver operating characteristic curve analyses showed an optimal cutoff value of 1.41 m/s, with 73.1% sensitivity, 80.8% specificity, a 79.2 % positive predictive value, and a 75.0% negative predictive value (area under the curve, 0.806; P < .001). In patients with Hashimoto thyroiditis, there was a positive correlation between the SWV values versus anti‐thyroperoxidase (Pearson r = 0.46; P = .038). There were no correlations between age, body mass index, thyroid function test results, and anti‐thyroglobulin values and versus SWV values. Also, no significant differences were seen between the groups for gland size, gland vascularity, and l‐thyroxine treatment.

Conclusions

Acoustic radiation force impulse elastography showed a significant difference in the stiffness of the thyroid gland between children with Hashimoto thyroiditis and the healthy group. Using acoustic radiation force impulse elastography immediately after a standard ultrasound evaluation may predict chronic autoimmune thyroiditis.
Correlation Between the Thymic‐Thoracic Ratio and Cardiac Axis in Healthy Fetuses
Authors: Zhao Ge , Liu Jing , Meng Tao
Published: October 2017

Objectives

The aim of this study was to assess the correlation between the thymic‐thoracic ratio and cardiac axis in healthy fetuses.

Methods

The fetal thymic‐thoracic ratio and cardiac axis were measured in 220 healthy fetuses. The normal ranges of the fetal thymic‐thoracic ratio and cardiac axis for each gestational week were established. The Pearson correlation coefficient was calculated to analyze the relationship between the thymic‐thoracic ratio and cardiac axis.

Results

The mean fetal thymic‐thoracic ratio increased slightly throughout the pregnancy, from 0.33 at 17 weeks' gestation to 0.37 at 37 weeks. No statistically significant correlation was found between the thymic‐thoracic ratio and cardiac axis in healthy fetuses.

Conclusions

In healthy fetuses, the thymus occupies an increasingly larger portion of the upper mediastinum when the pregnancy advances. The cardiac axis is not affected by the thymic‐thoracic ratio in healthy fetuses.
Snowshoe hare multi‐level habitat use in a fire‐adapted ecosystem
Authors: Gigliotti Laura C. , Jones Benjamin C. , Lovallo Matthew J. , Diefenbach Duane R.
Published: October 2017

Prescribed burning has the potential to improve habitat for species that depend on pyric ecosystems or other early successional vegetation types. For species that occupy diverse plant communities over the extent of their range, response to disturbances such as fire might vary based on post‐disturbance vegetation dynamics among plant communities. Although responses of snowshoe hares (Lepus americanus) to fire have been studied in conifer‐dominated forests in northern parts of the species’ range, there is a lack of information on snowshoe hare habitat use in fire‐dependent communities in southern parts of their range. We used global positioning system (GPS) and very high frequency (VHF) radio‐collars to monitor the habitat use of 32 snowshoe hares in a scrub‐oak (Quercus ilicifolia)‐pitch pine (Pinus rigida) barrens complex in northeastern Pennsylvania where prescribed fire has been used for habitat restoration. The area contained stands that underwent prescribed burning 1–6 years prior to our study. Also, we investigated fine‐scale determinants of habitat use within stands. We found that regardless of season, hares did not select for areas that had been burned within 6 years prior. Hares primarily used stands of older scrub oak, conifer, or hardwoods, which contained dense understory vegetation and canopy cover. Hare habitat use also was positively associated with stand edges. Our results suggest that hares do not respond to prescribed burning of scrub oak in the short‐term. In addition, by focusing on structural determinants of habitat use, rather than broad‐scale characteristics such as stand type, management strategies for snowshoe hares can be adapted over the extent of their range despite the multitude of different land cover types across which the species occurs. © 2017 The Wildlife Society.