bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modification of Pyrrolo[2,3‐d]pyrimidines by C–H Borylation Followed by Cross‐Coupling or Other Transformations: Synthesis of 6,8‐Disubstituted 7‐Deazapurine Bases
Authors: Klečka Martin , Poštová Slavětínská Lenka , Hocek Michal 
Published: November 2015

AbstractA general access to 4‐substituted 6‐arylpyrrolo[2,3‐d]pyrimidine (6‐substituted 8‐aryl‐7‐deazapurine derivatives) was developed based on iridium‐catalyzed C–H borylations of pyrrolo[2,3‐d]pyrimidines at the 6‐position followed by the Suzuki cross‐coupling reactions or other functional group transformations of the boronates. Biologically relevant 6‐arylpyrrolo[2,3‐d]pyrimidin‐4‐amines (8‐aryl‐7‐deazaadenines) and pyrrolo[2,3‐d]pyrimidin‐4‐ones (–7‐deazahypoxanthines) were synthesized starting from SEM‐protected 4‐methylsulfanyl‐ or 4‐methoxypyrrolo[2,3‐d]pyrimidine. The one‐pot borylation/Suzuki coupling reactions were followed either by demethylation and deprotection to yield deazahypoxanthine bases, or by oxidation of sulfide to sulfone, amination and deprotection to give deazaadenines. In addition, the boronate intermediates were converted into 6‐halo‐ or 6‐(trifluoromethyl)pyrrolo[2,3‐d]pyrimidine (8‐halo‐ or 8‐trifluoromethyl‐7‐deazapurine) derivatives.
Investigation of a Late‐Stage Derivatiza­tion Approach to Isatogens: Discovery of New Reaction Pathways
Authors: Edeson Steven J. , Maduli Elvis J. M. , Swanson Stephen , Procopiou Panayiotis A. , Harrity Joseph P. A. 
Published: November 2015

AbstractWe have developed a new strategy for preparing 2‐substituted indolone N‐oxides (isatogens) by substitution reactions with aryl‐ and alkyl‐organometallic reagents. This approach allows a range of substituents to be incorporated at a late stage and complements existing methods that necessitate their early stage incorporation during substrate preparation. Further chemistry has been found to take place at the nitrone moiety; intramolecular dipolar cycloaddition provides access to angularly fused tricyclic heterocycles. More unusually however, these compounds are prone to further addition by organozinc reagents leading to 2,2‐disubstituted 3‐oxindole products.
Press or pulse exposures determine the environmental fate of cerium nanoparticles in stream mesocosms
Authors: Baker Leanne F. , King Ryan S. , Unrine Jason M. , Castellon Benjamin T. , Lowry Gregory V. , Matson Cole W. 
Published: November 2015

Abstract

Risk-assessment models indicate that stream ecosystems receiving municipal wastewater effluent may have the greatest potential for exposure to manufactured nanoparticles. The authors determined the fate of cerium oxide (CeO2) nanoparticles in outdoor stream mesocosms using 1) 1-time pulse addition of CeO2 nanoparticles, representative of accidental release, and 2) continuous, low-level press addition of CeO2 nanoparticles, representative of exposure via wastewater effluent. The pulse addition led to rapid nanoparticle floc formation, which appeared to preferentially deposit on periphyton in low-energy areas downstream from the location of the input, likely as a result of gravitational sedimentation. Floc formation limited the concentration of suspended nanoparticles in stream water to &lt;5% of target and subsequent downstream movement. In contrast, press addition of nanoparticles led to higher suspended nanoparticle concentrations (77% of target) in stream water, possibly as a result of stabilization of suspended nanoparticles through interaction with dissolved organic carbon. Smaller nanoparticle aggregates appeared to preferentially adsorb to stream surfaces in turbulent sections, where Ce concentrations were highest in the press, likely a result of stochastic encounter with the surface. Streams receiving wastewater effluent containing nanoparticles may lead to exposure of aquatic organisms over a greater spatial extent than a similar amount of nanoparticles from an accidental release. Exposure models must take into account these mechanisms controlling transport and depositional processes. Environ Toxicol Chem 2016;35:1213–1223. © 2015 SETAC
Effects of ivermectin application on the diversity and function of dung and soil fauna: Regulatory and scientific background information
Authors: Adler Nicole , Bachmann Jean , Blanckenhorn Wolf U. , Floate Kevin D. , Jensen John , Römbke Jörg 
Published: November 2015

Abstract

The application of veterinary medical products to livestock can impact soil organisms in manure-amended fields or adversely affect organisms that colonize dung pats of treated animals and potentially retard the degradation of dung on pastures. For this reason, the authorization process for veterinary medicinal products in the European Union includes a requirement for higher-tier tests when adverse effects on dung organisms are observed in single-species toxicity tests. However, no guidance documents for the performance of higher-tier tests are available. Hence, an international research project was undertaken to develop and validate a proposed test method under varying field conditions of climate, soil, and endemic coprophilous fauna at Lethbridge (Canada), Montpellier (France), Zurich (Switzerland), and Wageningen (The Netherlands). The specific objectives were to determine if fecal residues of an anthelmintic with known insecticidal activity (ivermectin) showed similar effects across sites on 1) insects breeding in dung of treated animals, 2) coprophilous organisms in the soil beneath the dung, and 3) rates of dung degradation. By evaluating the effects of parasiticides on communities of dung-breeding insects and soil fauna under field conditions, the test method meets the requirements of a higher-tier test as mandated by the European Union. The present study provides contextual information on authorization requirements for veterinary medicinal products and on the structure and function of dung and soil organism communities. It also provides a summary of the main findings. Subsequent studies on this issue provide detailed information on different aspects of this overall project. Environ Toxicol Chem 2016;35:1914–1923. © 2015 SETAC
Toward a harmonized approach for environmental assessment of human activities in the marine environment
Authors: Tamis Jacqueline E , de Vries Pepijn , Jongbloed Ruud H , Lagerveld Sander , Jak Robbert G , Karman Chris C , Van der Wal Jan Tjalling , Slijkerman Diana ME , Klok Chris 
Published: November 2015

Abstract
With a foreseen increase in maritime activities, and driven by new policies and conventions aiming at sustainable management of the marine ecosystem, spatial management at sea is of growing importance. Spatial management should ensure that the collective pressures caused by anthropogenic activities on the marine ecosystem are kept within acceptable levels. A multitude of approaches to environmental assessment are available to provide insight for sustainable management, and there is a need for a harmonized and integrated environmental assessment approach that can be used for different purposes and variable levels of detail. This article first provides an overview of the main types of environmental assessments: “environmental impact assessment” (EIA), “strategic environmental assessment” (SEA), “cumulative effect assessment” (CEA), and “environmental (or ecological) risk assessment” (ERA). Addressing the need for a conceptual “umbrella” for the fragmented approaches, a generic framework for environmental assessment is proposed: cumulative effects of offshore activities (CUMULEO). CUMULEO builds on the principle that activities cause pressures that may lead to adverse effects on the ecosystem. Basic elements and variables are defined that can be used consistently throughout sequential decision-making levels and diverse methodological implementations. This enables environmental assessment to start at a high strategic level (i.e., plan and/or program level), resulting in early environmental awareness and subsequently more informed, efficient, and focused project-level assessments, which has clear benefits for both industry and government. Its main strengths are simplicity, transparency, flexibility (allowing the use of both qualitative and quantitative data), and visualization, making it a powerful framework to support discussions with experts, stakeholders, and policymakers. Integr Environ Assess Manag 2016;12:632–642. © 2015 SETAC
Low-Level Cadmium Exposure Is Associated With Decreased Bone Mineral Density and Increased Risk of Incident Fractures in Elderly Men: The MrOS Sweden Study
Authors: Wallin Maria , Barregard Lars , Sallsten Gerd , Lundh Thomas , Karlsson Magnus K , Lorentzon Mattias , Ohlsson Claes , Mellström Dan 
Published: November 2015

ABSTRACT

One risk factor for osteoporosis that has attracted increasing attention in recent years is exposure to cadmium. The aim of this study was to examine the associations between low-level cadmium exposure, from diet and smoking, and bone mineral density (BMD) and incident fractures in elderly men. The study population consisted of 936 men from the Swedish cohort of the Osteoporotic Fractures in Men (MrOS) study, aged 70 to 81 years at inclusion (years 2002 to 2004), with reliable data on cadmium in urine (U-Cd) analyzed using inductively coupled plasma mass spectrometry in baseline samples. The participants also answered a questionnaire on lifestyle factors and medical history. BMD was measured at baseline using dual-energy X-ray absorptiometry (DXA) in the total body, hip, and lumbar spine. During the follow-up period (until 2013), all new fractures were registered by date and type. Associations between BMD and U-Cd were assessed using multiple linear regression, and associations between incident fractures and baseline U-Cd were analyzed using Cox regression. In both cases, a number of potential confounders and other risk factors (eg, age, smoking, body mass index [BMI], and physical activity) were included in the models. We found significant negative associations between U-Cd and BMD, with lower BMD (4% to 8%) for all sites in the fourth quartile of U-Cd, using the first quartile as the reference. In addition, we found positive associations between U-Cd and incident fractures, especially nonvertebral osteoporosis fractures in the fourth quartile of U-Cd, with hazard ratios of 1.8 to 3.3 in the various models. U-Cd as a continuous variable was significantly associated with nonvertebral osteoporosis fractures (adjusted hazard ratio 1.3 to 1.4 per μg Cd/g creatinine), also in never-smokers, but not with the other fracture groups (all fractures, hip fractures, vertebral fractures, and other fractures). Our results indicate that even relatively low cadmium exposure through diet and smoking increases the risk of low BMD and osteoporosis-related fractures in elderly men. © 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).
Inhibition of Histone Deacetylases Enhances the Osteogenic Differentiation of Human Periodontal Ligament Cells
Authors: Huynh Nam Cong‐Nhat , Everts Vincent , Pavasant Prasit , Ampornaramveth Ruchanee Salingcarnboriboon 
Published: November 2015

ABSTRACTOne of the characteristics of periodontal ligament (PDL) cells is their plasticity. Yet, the underlying mechanisms responsible for this phenomenon are unknown. One possible mechanism might be related to epigenetics, since histone deacetylases (HDACs) have been shown to play a role in osteoblast differentiation. This study was aimed to investigate the role of HDACs in osteogenic differentiation of human PDL (hPDL) cells. HDAC inhibitor trichostatin A (TSA) had no effect on cell viability as was assessed by MTT assay. Osteogenic and adipogenic differentiation was analyzed by gene expression, ALP activity and mineral deposition. Western blotting was used to investigate the effect of TSA on histone acetylation and protein expression. In the presence of the HDAC inhibitor osteogenic differentiation was induced; osteoblast‐related gene expression was increased significantly. ALP activity and mineral nodule formation were also enhanced. Inhibition of HDACs did not induce differentiation into the adipocyte lineage. hPDL highly expressed HDACs of both class I (HDAC 1, 2, 3) and class II (HDAC 4, 6). During osteogenic differentiation HDAC 3 expression gradually decreased. This was apparent in the absence and presence of the inhibitor. The level of acetylated Histone H3 was increased during osteogenic differentiation. Inhibition of HDAC activity induced hyperacetylation of Histone H3, therefore, demonstrating Histone H3 as a candidate target molecule for HDAC inhibition. In conclusion, hPDL cells express a distinguished series of HDACs and these enzymes appear to be involved in osteogenic differentiation. This finding suggests a potential application of TSA for bone regeneration therapy by hPDL cells. J. Cell. Biochem. 117: 1384–1395, 2016. © 2015 Wiley Periodicals, Inc.
Protein deamidation in biopharmaceutical manufacture: understanding, control and impact
Authors: Gervais David 
Published: November 2015

AbstractUnderstanding of product‐related variants, such as variants with post‐translational modifications, is an important part of biopharmaceutical development. Deamidation is a common post‐translational modification occurring in biopharmaceutical proteins, affecting L‐asparagine (Asn) and to a lesser extent, L‐glutamine (Gln) residues. The rate of deamidation reactions are influenced by factors including protein structure (primary, secondary and higher structure), temperature and pH. In the vast majority of cases, deamidation is undesirable in biopharmaceuticals, and may lead to potential changes in protein structure, function, stability and immunogenicity. Measurement and characterisation of deamidated biopharmaceutical variants may be challenging, particularly with regard to quantitation of the two L‐aspartate isoforms that are created, L‐aspartic acid (Asp) and isoaspartate (isoAsp). Deamidation may occur intracellularly or during biopharmaceutical manufacture and storage, and must be understood, minimised and controlled, particularly in a regulatory context. Process control strategies that have been employed to date include alterations to fermentation steps, additives to cell cultures, chromatographic separation of charge variants and protein engineering to remove deamidation‐prone Asn residues. However, the impact of deamidated forms of biopharmaceuticals should also be thoroughly studied, as they may not necessarily represent deleterious changes to the function of the molecule or the quality of the final product. This mini‐review provides a summary of the current understanding of the origins, control and measurement of deamidation during biopharmaceutical development. © 2015 Society of Chemical Industry
Dynamic sensory description of Rioja Alavesa red wines made by different winemaking practices by using Temporal Dominance of Sensations
Authors: Etaio Iñaki , Meillon Sophie , Pérez‐Elortondo Francisco J , Schlich Pascal 
Published: November 2015

AbstractBACKGROUNDAlthough sensory description of wines in scientific literature is very large, there is an evident lack of studies describing wines from a dynamic approach. The objective of this study was to describe the evolution of the sensations perceived in red wines from Rioja Alavesa by using Temporal Dominance of Sensations (TDS) and also to compare wines made with the two winemaking procedures used in Rioja Alavesa: carbonic maceration (CM) and destemming (DS).RESULTSTen sensory attributes were evaluated in eight wines (four CM and four DS wines) in triplicate by a panel of 16 trained assessors. Red/black berry and woody aromas were dominant firstly, whereas heat, astringent, bitter and pungent sensations were dominant later. CM wines showed higher dominance for woody, spicy, pungent and acid sensations and lower dominance for red/black berry aroma and astringency than DS wines.CONCLUSIONThis study is the first to describe Rioja wines from a dynamic approach and it also provides information about the dynamic sensory differences between wines made by CM or by DS. In this sense, this work shows the usefulness of TDS to describe and differentiate wines and to provide additional information to the conventional static descriptive analysis. © 2015 Society of Chemical Industry
Influence of Hydrophobic Dendrimer Core Structure on the Itraconazole Encapsulation Efficiency
Authors: Elkin Igor , Rabanel Jean‐Michel , Hildgen Patrice 
Published: November 2015

New polyester‐co‐polyether dendritic macromolecules of first generation characterized by different flexibility of their central part (core) are synthesized and proposed as simplified models of new drug encapsulation agents for itraconazole (ITZ), an antifongic agent. Chemical structures of obtained products are characterized by FTIR, UV–vis, 1H and 13C NMR, and GPC techniques, as well as by elemental analysis and mass spectrometry. The absence of cytotoxicity limitation for further applications in drug delivery is evidenced by the results of MTT assay on the murine macrophage cell line RAW‐262.7. To elucidate the role of hydrophobic core structure of dendrimers in the process of ITZ encapsulation, the in silico simulations with reduced model structures are performed. The results of studies in vitro and in silico are found consistent, suggesting that the drug encapsulation efficiency can be determined by the possibility of an effective bending of hydrophobic central core segments of dendrimer around ITZ molecule.
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Charge Correlations for Precise, Coulombically Driven Self Assembly
Authors: Radhakrishna Mithun , Sing Charles E. 
Published: November 2015

Polyelectrolyte materials represent a challenge for polymer physicists, with a research literature that spans decades with little sign of slowing down. The essence of this challenge is how to treat charge correlations on both a theoretical as well as a conceptual basis. Charge correlations are related to the spatial arrangement of charges and can have a strong effect on the equilibrium state of polyelectrolyte systems. Accurate treatment of correlation effects is therefore integral to the design and development of materials consisting of (for example) charged gels, block copolymers, and biopolymers. In this Talents article, recent theoretical developments useful for understanding correlations are discussed. This understanding can shape the development of new materials, exposing new opportunities in precise, sequence‐based control over charge correlations in polymers and their emerging role in charge‐driven self‐assembly.
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Probing Cellulose Acetylation in Binary Mixtures of an Ionic Liquid with Dimethylsulfoxide and Sulfolane by Chemical Kinetics, Viscometry, Spectroscopy, and Molecular Dynamics Simulations
Authors: Nawaz Haq , Pires Paulo A. R. , Arêas Elizabeth P. G. , Malek Naved I. , El Seoud Omar A. 
Published: November 2015

Acetylation of microcrystalline cellulose (MCC) by ethanoic anhydride (Ac2O) in mixtures of the ionic liquid (IL) 1‐allyl‐3‐methylimidazolium chloride and the (structurally related) mole­cular solvents (MSs), dimethylsulfoxide (DMSO) and sulfolane (Sulfn), is studied. Values of the reaction third‐order rate constants, k3, are calculated from conductivity data; they are linearly dependent on c(IL), due to (cellulose‐solvent) complex formation, as corroborated by Fourier Transform Infrared (FTIR) spectroscopy. The observed order of reactivity (IL/DMSO > IL/Sulfn) is explained by examining differences in the following properties of the MCC‐IL/MS solutions: macroscopic (viscosity); microscopic (empirical polarity and basicity), and from the results of molecular dynamics simulations. The latter indicate faster reactant diffusion in IL/DMSO and more interaction between the biopoly­mer hydroxyl groups and the ions of the IL.
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α7 nicotinic receptor agonists reduce levodopa‐induced dyskinesias with severe nigrostriatal damage
Authors: Zhang Danhui , McGregor Matthew , Bordia Tanuja , Perez Xiomara A. , McIntosh J. Michael , Decker Michael W. , Quik Maryka 
Published: November 2015

AbstractBackgroundABT‐126 is a novel, safe, and well‐tolerated α7 nicotinic receptor agonist in a Phase 2 Alzheimer's disease study. We tested the antidyskinetic effect of ABT‐126 in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine–treated squirrel monkeys with moderate and more severe nigrostriatal damage.MethodsMonkeys (n = 21, set 1) were lesioned with 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine 1‐2×. When parkinsonian, they were gavaged with levodopa (10 mg/kg)/carbidopa (2.5 mg/kg) twice daily and dyskinesias rated. They were then given nicotine in drinking water (n = 5), or treated with vehicle (n = 6) or ABT‐126 (n = 10) twice daily orally 30 min before levodopa. Set 1 was then re‐lesioned 1 to 2 times for a total of 3 to 4 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine injections. The antidyskinetic effect of ABT‐126, nicotine, and the β2* nicotinic receptor agonist ABT‐894 was re‐assessed. Another group of monkeys (n = 23, set 2) were lesioned with 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine only 1× to 2×. They were treated with levodopa/carbidopa, administered the α7 agonist ABT‐107 (n = 6), ABT‐894 (n = 6), nicotine (n = 5), or vehicle (n = 6) and dyskinesias evaluated. All monkeys were euthanized and the dopamine transporter measured.ResultsWith moderate nigrostriatal damage (1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine 1×‐2×), ABT‐126 dose‐dependently decreased dyskinesias (∼60%), with similar results seen with ABT‐894 (∼60%) or nicotine (∼60%). With more severe damage (1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine 3‐4×), ABT‐126 and nicotine reduced dyskinesias, but ABT‐894 did not. The dopamine transporter was 41% and 8.9% of control, with moderate and severe nigrostriatal damage, respectively. No drug modified parkinsonism.ConclusionThe novel α7 nicotinic receptor drug ABT‐126 reduced dyskinesias in monkeys with both moderate and severe nigrostriatal damage. ABT‐126 may be useful to reduce dyskinesias in both early‐ and later‐stage Parkinson's disease. © 2015 International Parkinson and Movement Disorder Society
Clinical spectrum of valosin containing protein (VCP)‐opathy
Authors: Kazamel Mohamed , Sorenson Eric J. , McEvoy Kathleen M. , Jones Lyell K. , Leep‐Hunderfund Andrea N. , Mauermann Michelle L. , Milone Margherita 
Published: November 2015

ABSTRACTIntroduction: Valosin containing protein (VCP) mutations cause a rare disorder characterized by hereditary inclusion body myopathy, Paget disease of bone (PDB), and frontotemporal dementia (FTD) with variable penetrance. VCP mutations have also been linked to amyotrophic lateral sclerosis and Charcot‐Marie‐Tooth disease type 2. Methods: Review of clinical, serological, electrophysiological, and myopathological findings of 6 VCP‐opathy patients from 4 unrelated families. Results: Patients manifested muscle weakness between ages 40 and 53 years and developed predominant asymmetric limb girdle weakness. One patient had distal weakness at onset and co‐existing peripheral neuropathy. Another patient had PDB, 1 had mild cognitive deficits, and 1 had FTD. All patients had myopathic and neurogenic electromyographic findings with predominant neurogenic changes in 2. Rimmed vacuoles were infrequent, while neurogenic changes were prominent in muscle biopsies. Conclusions: VCP‐opathy is a multifaceted disorder in which myopathy and peripheral neuropathy can coexist. The electrophysiological and pathological neurogenic changes raise the possibility of coexisting motor neuron involvement. Muscle Nerve, 2015 Muscle Nerve 54: 94–99, 2016 Muscle Nerve 54: 94–99, 2016