bluuebunny/crossref_metadata_2025_split huggingface dataset:
Obesity: Its Status as a Disease
Authors: Hofmann Bjørn 
Published: November 2016

Abstract

Is obesity a disease? Yes, World Health Organization (WHO) and other authoritative institutions say so, is the standard answer. However, by investigating these sources and some standard definitions of disease, the answer becomes much less obvious. According to naturalist and hybrid definitions of disease, obesity does not qualify as a disease, but according to several normativist conceptions of disease, it does. This undecidedness gives leeway for a wide range of pragmatic arguments for and against making obesity a disease. Using social conceptions of disease to make obesity a disease calls for careful reflection, as they may be based on contested aesthetic, moral and other social norms. History is full of examples where socially defined diseases later have been heavily criticised. Homosexuality, dissiency, drapetomania and attention deficit hyperactivity disorder (ADHD) are some examples.

Key Concepts

Obesity is defined as an excess of adipose tissue (BMI ≥ 30 kg m
2
).

Disease is defined in many ways, and in general, definitions are classified as naturalist, normativist or hybrid.

A naturalist definition of disease defines disease in terms of characteristics in nature.

A normativist definition of disease defines disease in terms of norms (and values), and as such depends on social conventions.

Hybrid definitions of disease refer both to natural and social phenomena.

Obesity is not a disease according to naturalist conceptions of disease.

Obesity may very well be a disease according to normativist definitions of disease.

Pragmatic arguments for making obesity a disease yet lack convincing evidence.
Zuordnung der Rückgrat‐ und Seitenketten‐Protonen in vollständig protonierten Proteinen durch Festkörper‐NMR‐Spektroskopie: Mikrokristalle, Sedimente und Amyloidfibrillen
Authors: Stanek Jan , Andreas Loren B. , Jaudzems Kristaps , Cala Diane , Lalli Daniela , Bertarello Andrea , Schubeis Tobias , Akopjana Inara , Kotelovica Svetlana , Tars Kaspars , Pica Andrea , Leone Serena , Picone Delia , Xu Zhi‐Qiang , Dixon Nicholas E. , Martinez Denis , Berbon Mélanie , Mammeri Nadia El , Noubhani Abdelmajid , Saupe Sven , Habenstein Birgit , Loquet Antoine , Pintacuda Guido 
Published: November 2016

AbstractWir beschreiben die empfindliche Messung von α‐Protonen in vollständig protonierten Proteinen durch Festkörper‐NMR‐Spektroskopie mit Rotation um den magischen Winkel (MAS) von 100–111 kHz. Die exzellente Auflösung in der Cα‐Hα‐Ebene wird für fünf Proteine gezeigt, darunter Mikrokristalle, ein sedimentierter Komplex, ein Kapsid und Amyloidfibrillen. Ausgehend davon wurde ein Satz 3D‐Spektren für die sequenzspezifische Zuordnung der Rückgrat‐ und der aliphatischen Seitenketten‐Resonanzen entwickelt. Dabei wurden nur 500 μg Probe verwendet. Diese Entwicklungen beschleunigen strukturelle Untersuchungen von biomolekularen Komplexen, die nur in Submilligramm‐Mengen verfügbar sind, ohne die Notwendigkeit einer Deuterierung.
Insight into the Interfacial Process and Mechanism in Lithium–Sulfur Batteries: An In Situ AFM Study
Authors: Lang Shuang‐Yan , Shi Yang , Guo Yu‐Guo , Wang Dong , Wen Rui , Wan Li‐Jun 
Published: November 2016

AbstractLithium–sulfur (Li–S) batteries are highly appealing for large‐scale energy storage. However, performance deterioration issues remain, which are highly related to interfacial properties. Herein, we present a direct visualization of the interfacial structure and dynamics of the Li–S discharge/charge processes at the nanoscale. In situ atomic force microscopy and ex situ spectroscopic methods directly distinguish the morphology and growth processes of insoluble products Li2S2 and Li2S. The monitored interfacial dynamics show that Li2S2 nanoparticle nuclei begin to grow at 2 V followed by a fast deposition of lamellar Li2S at 1.83 V on discharge. Upon charging, only Li2S depletes from the interface, leaving some Li2S2 undissolved, which accumulates during cycling. The galvanostatic precipitation of Li2S2 and/or Li2S is correlated to current rates and affects the specific capacity. These findings reveal a straightforward structure–reactivity correlation and performance fading mechanism in Li–S batteries.
Stacking and Electrostatic Interactions Drive the Stereoselectivity of Silylium‐Ion Asymmetric Counteranion‐Directed Catalysis
Authors: Seguin Trevor J. , Wheeler Steven E. 
Published: November 2016

AbstractComputational analysis shows that the enantioselectivity of asymmetric Lewis‐acid organocatalysis of the Diels–Alder cycloaddition of cyclopentadiene to cinnamates arises from stacking interactions that favor the addition of the diene to the more hindered face of the dienophile, while electrostatic interactions control the diastereoselectivity by selectively stabilizing the endo transition state. These results not only explain the stereoselectivity of these silylium‐ion‐ACDC reactions but should also guide the development of more effective ion‐pairing asymmetric organocatalysts.
Capturing Excited States in the Fast‐Intermediate Exchange Limit in Biological Systems Using 1H NMR Spectroscopy
Authors: Steiner Emilie , Schlagnitweit Judith , Lundström Patrik , Petzold Katja 
Published: November 2016

AbstractChanges in molecular structure are essential for the function of biomolecules. Characterization of these structural fluctuations can illuminate alternative states and help in correlating structure to function. NMR relaxation dispersion (RD) is currently the only method for detecting these alternative, high‐energy states. In this study, we present a versatile 1H R1ρ RD experiment that not only extends the exchange timescales at least three times beyond the rate limits of 13C/15N R1ρ and ten times for CPMG experiments, but also makes use of easily accessible probes, thus allowing a general description of biologically important excited states. This technique can be used to extract chemical shifts for the structural characterization of excited states and to elucidate complex excited states.
Ruthenation of Non‐stacked Guanines in DNA G‐Quadruplex Structures: Enhancement of c‐MYC Expression
Authors: Rodríguez Jéssica , Mosquera Jesús , Couceiro José R. , Vázquez M. Eugenio , Mascareñas José L. 
Published: November 2016

AbstractGuanine quadruplexes (GQs) are compact four‐stranded DNA structures that play a key role in the control of a variety of biological processes, including gene transcription. Bulky ruthenium complexes featuring a bipyridine, a terpyridine, and one exchangeable ligand ([Ru(terpy)(bpy)X]n+) are able to metalate exposed guanines present in the GQ of the c‐MYC promoter region that are not involved in quadruplex base pairing. qRT‐PCR and western‐blot experiments indicated that the complexes promote a remarkable increase in the expression of this oncogene. We also show that exchangeable thioether ligands (X=RSR′, Met) allow regulation of the metalating activity of the complex with visible light.
Assembly of Terpenoid Cores by a Simple, Tunable Strategy
Authors: Lahtigui Ouidad , Emmetiere Fabien , Zhang Wei , Jirmo Liban , Toledo‐Roy Samira , Hershberger John C. , Macho Jocelyn M. , Grenning Alexander J. 
Published: November 2016

AbstractOxygenated, polycyclic terpenoid natural products have important biological activities. Although total synthesis of such terpenes is widely studied, synthetic strategies that allow for controlled placement of oxygen atoms and other functionality remains a challenge. Herein, we present a simple, scalable, and tunable synthetic strategy to assemble terpenoid‐like polycycloalkanes from cycloalkanones, malononitrile, and allylic electrophiles, abundantly available reagent classes.
Long Distance Measurements up to 160 Å in the GroEL Tetradecamer Using Q‐Band DEER EPR Spectroscopy
Authors: Schmidt Thomas , Wälti Marielle A. , Baber James L. , Hustedt Eric J. , Clore G. Marius 
Published: November 2016

AbstractCurrent distance measurements between spin‐labels on multimeric protonated proteins using double electron–electron resonance (DEER) EPR spectroscopy are generally limited to the 15–60 Å range. Here we show how DEER experiments can be extended to dipolar evolution times of ca. 80 μs, permitting distances up to 170 Å to be accessed in multimeric proteins. The method relies on sparse spin‐labeling, supplemented by deuteration of protein and solvent, to minimize the deleterious impact of multispin effects and substantially increase the apparent spin‐label phase memory relaxation time, complemented by high sensitivity afforded by measurements at Q‐band. We demonstrate the approach using the tetradecameric molecular machine GroEL as an example. Two engineered surface‐exposed mutants, R268C and E315C, are used to measure pairwise distance distributions with mean values ranging from 20 to 100 Å and from 30 to 160 Å, respectively, both within and between the two heptameric rings of GroEL. The measured distance distributions are consistent with the known crystal structure of apo GroEL. The methodology presented here should significantly expand the use of DEER for the structural characterization of conformational changes in higher order oligomers.
Ionized calcium‐binding adaptor molecule 1 positive macrophages and HO‐1 up‐regulation in intestinal muscularis resident macrophages
Authors: Mikkelsen Hanne B. , Huizinga Jan D. , Larsen Jytte O. , Kirkeby Svend 
Published: November 2016

ABSTRACTSmall intestinal muscularis externa macrophages have been associated with interstitial cells of Cajal. They have been proposed to play various roles in motility disorders and to take part in a microbiota‐driven regulation of gastrointestinal motility. Our objective was to understand the reaction of resident macrophages of the musculature to a pro‐inflammatory stimulator, lipopolysaccharide (LPS). Mice were injected with LPS or saline and sacrificed after 6 hr. Whole mounts were stained with antibodies toward CD169, ionized calcium‐binding adaptor molecule 1 (iba1) (microglial/macrophage marker) and heme oxygenase‐1 (HO‐1). Cell densities were measured using unbiased stereology. Results: iba1pos cells showed an overall higher density than CD169pos and HO‐1pos cells. Most HO‐1pos and iba1pos cells were positive for CD 169 in serosa and at Auerbach's plexus (AP). At the deep muscular plexus, mainly iba1pos cells were present, and were mostly CD169neg; a few HO‐1pos cells were present. Conclusions: A new subset of resident macrophages in the intestinal muscularis externa was discovered, identified as iba1pos CD169neg. HO‐1 is constitutively present in most macrophages in serosa and at AP, suggesting a M2 phenotype. LPS‐treatment results in an up‐regulation of HO‐1pos/CD169neg cells in serosa and at AP. Anat Rec, 300:1114–1122, 2017. © 2016 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists
Excited State Intramolecular Proton Transfer in Ethynyl‐Extended Regioisomers of 2‐(2′‐Hydroxyphenyl)benzothiazole: Effects of the Position and Electronic Nature of Substituent Groups
Authors: Wang Qin , Xu Longfei , Niu Yahui , Wang Yuxiu , Yuan Mao‐Sen , Zhang Yanrong 
Published: November 2016

AbstractAlthough the organic dyes based on excited state intramolecular proton transfer (ESIPT) mechanism have attracted significant attention, the structure‐property relationship of ESIPT dyes needs to be further exploited. In this paper, three series of ethynyl‐extended regioisomers of 2‐(2′‐hydroxyphenyl)benzothiazole (HBT), at the 3′‐, 4′‐ and 6‐positions, respectively, have been synthesized. Changes in the absorption and emission spectra were correlated with the position and electronic nature of the substituent groups. Although 4′‐ and 6‐substituted HBT derivatives exhibited absorption bands at longer wavelengths, the keto‐emission of 3′‐substituted HBT derivatives was found at a substantially longer wavelength. The gradual red‐shifted fluorescence emission was found for 3′‐substituted HBT derivatives where the electron‐donating nature of substituent group increased, which was opposite to what was observed for 4′‐ and 6‐substituted HBT derivatives. The results derived from the theoretical calculations were in conformity with the experimental observations. Our study could potentially provide experimental and theoretical basis for designing novel ESIPT dyes that possess unique fluorescent properties.
Flow‐cytometric screening of aggregation‐inhibitors using a fluorescence‐assisted intracellular method
Authors: Lindberg Hanna , Sandersjöö Lisa , Meister Sebastian W. , Uhlén Mathias , Löfblom John , Ståhl Stefan 
Published: November 2016

AbstractAggregation of misfolded peptides and proteins is a key event in several neurodegenerative diseases. Suggested treatments of such disorders aim to inhibit the initial aggregation process. Here, we have developed an intracellular, function‐based screening method, intended for isolation of aggregation‐inhibitors from combinatorial protein libraries by flow‐cytometric cell sorting. The method is based on fusion of aggregation‐prone peptides to a fluorescent protein, functioning as a solubility reporter. Co‐expression of a protein‐based aggregation‐inhibitor should prevent aggregation and thus increase the whole‐cell fluorescence. We evaluated the method using the aggregation‐prone Alzheimer's‐related amyloid‐β (Aβ) peptide in fusion to green‐fluorescent protein (GFP), and an Aβ aggregation‐inhibiting Affibody molecule. To adapt the method for library applications, the inhibitor was linked to an mCherry reporter for normalization of protein expression levels. We found that aggregation propensity correlates with fluorescence intensity, as co‐expression of the Affibody‐inhibitor increased the whole‐cell fluorescence relative to a non‐inhibitor. Employing improved cultivation parameters, we furthermore demonstrated efficient rescue from aggregation of an α‐synuclein‐derived protein using a different type of aggregation‐inhibitor. Importantly, we also showed that the Aβ aggregation‐inhibiting Affibody molecule could be isolated from a 1:10,000 background of non‐inhibitors, with around 3,500‐fold enrichment, in one cycle of fluorescence‐based cell sorting. In conclusion, our new method represents a promising approach for generation of novel protein‐based aggregation‐inhibitors.
Metabolic characterization of the early stage of hepatic fibrosis in rat using GC‐TOF/MS and multivariate data analyses
Authors: Jiang Hui , Song Jun‐mei , Gao Peng‐fei , Qin Xiu‐juan , Xu Shuang‐zhi , Zhang Jia‐fu 
Published: November 2016

AbstractThe aim of this study was to explore the changes in the urine metabolic spectrum in rats with the early stage of liver fibrosis using gas chromatography–time of flight/mass spectrometry (GC‐TOF/MS), try to search for potential biomarkers and elucidate the probably metabonomic pathogenesis. The early stage of liver fibrosis was established with a single subcutaneous injection of carbon tetrachloride twice each week for 4 weeks continuously. At the end of the experiment, GC‐TOF/MS technology with multivariate statistical approaches such as principal component analysis, partial least squares‐discriminant analysis and orthogonal partial least squares‐discriminant analysis was used to analyze the changes in the metabolic spectrum trajectory and identify potential biomarkers. Twelve potential biomarkers in the model group, such as succinic acid, threonine and lactose, were selected, which indicate that the metabonomic pathogenesis of the early stage of liver fibrosis may be related to disorders of energy metabolism, amino acid metabolism and fatty acid metabolism.
Using virtual laboratories in teaching natural sciences: An example of physics courses in university
Authors: Daineko Yevgeniya , Dmitriyev Viktor , Ipalakova Madina 
Published: November 2016

ABSTRACTThinking outside of the box is an important part of education. However, using innovative teaching methods in education can be very challenging for educators. They are directly involved into a teaching process and upcoming changes should be well planned and the impact of the introduced innovations/changes should be estimated in advance. Innovations can be also challenging for a management part of a particular higher education institution, whose major goal is to organize a smooth learning process. Current work presents software empowered innovation in the domain of teaching physics at universities. Authors demonstrate how particular software artefacts could be possible integrated into existing curriculum in order to help students at universities in mastering particular natural science subject (e.g., “Physics‐1,” “Physics‐2”). Software is based on the ideas of virtual laboratories, whether implementation is based on Microsoft. NET XNA Framework and 3D modeling. Paper shows that the introduction of modern information and computer technologies along with the traditional forms of education are significantly enhancing teaching experience and improving education quality. © 2016 Wiley Periodicals, Inc. Comput Appl Eng Educ 25:39–47, 2017; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.21777
Follistatin‐like protein 1 contributes to dendritic cell and T‐lymphocyte activation in nasopharyngeal carcinoma patients by altering nuclear factor κb and Jun N‐terminal kinase expression
Authors: Wang Hong , Wu Senyong , Huang Shiping , Yin Shaolin , Zou Guilong , Huang Kuan'en , Zhang Zhe , Tang Anzhou , Wen Wensheng 
Published: November 2016

Follistatin‐like protein 1 (FSTL1) is a newly characterized protein that can regulate the immune response in various ways. Dendritic cells (DCs) are central to immune regulation. In this study, we explored the impact of FSTL1 on DC activity in nasopharyngeal carcinoma (NPC) patients. The surface expression of CD40, CD86, and HLA‐DR on DCs was analyzed and showed significantly elevated expression levels, indicating DC maturity. After FSTL1 was added to DCs collected from NPC patients (n = 50), controls (n = 47), and healthy donors (n = 10), interferon γ secretion and T‐cell receptor expression in cytotoxic T lymphocytes were also investigated. In the experimental groups, the expression of the critical immune protein nuclear factor (NF)‐κb was upregulated, whereas Jun N‐terminal kinase (JNK) was downregulated. Our findings demonstrate that FSTL1 plays a critical role in immune regulation, enhancing the antigen presentation ability of DCs by up‐regulating NF‐κb expression and down‐regulating JNK expression.
Renal sympathetic denervation: Recalculating…
Authors: Belardi Jorge A. , Albertal Mariano 
Published: November 2016

Key Points

Renal sympathetic denervation may serve as a treatment alternative in patients with resistant systemic arterial hypertension.
Ablation at the proximal and distal renal artery branches with an irrigated catheter did not lead to better blood pressure reduction than proximal ablation alone.
Pitfalls in study design prevent from drawing definite conclusions in the present randomized study.
Careful design of randomized trials is essential to delineate the role of RD with saline‐irrigation catheters.
Covalent Functionalization of Nanosheets of MoS2 and MoSe2 by Substituted Benzenes and Other Organic Molecules
Authors: Vishnoi Pratap , Sampath Archana , Waghmare Umesh V. , Rao C. N. R. 
Published: November 2016

AbstractCovalent functionalization has been effectively employed to attach benzene functionalities to MoS2 and MoSe2 nanosheets by the reaction with para‐substituted iodobenzenes bearing −OCH3, −H, and −NO2 as the substituents, where the electron‐donating and electron‐withdrawing power of the para substituent varies significantly. The functionalization is based on the formation of a C−S or C−Se linkage at the expense of the C−I bond on reaction of the iodobenzene with electron‐rich 1T‐MoS2 or 1T‐MoSe2. The degree of functionalization is in the range 4–24 % range, the value increases with the electron‐withdrawing power of the para substituent. Semiconducting 2H‐MoS2 and 2H‐MoSe2 nanosheets can also be functionalized with iodobenzene by carrying out the reaction in the presence of a Pd0 catalyst. We have also carried out functionalization of 1T‐MoS2 with pyrene, coumarin, and porphyrin derivatives. By using first‐principles density functional calculations, we show that the bonding of the functional groups with the 1T phase is stronger than with the 2H phase. This is reflected in notable changes in the electronic structure of the former upon functionalization; a gap opens up in the electronic spectrum of the 1T phase. Functionalization with para‐substituted benzenes leads to a change in the work function.
Triethynylmethanol Derivatives: Stable Acetylenic Building Blocks for Surface Chemistry
Authors: Prenzel Dominik , Sander Tim , Gebhardt Julian , Soni Himadri , Hampel Frank , Görling Andreas , Maier Sabine , Tykwinski Rik R. 
Published: November 2016

AbstractThe synthesis of non‐conjugated, carbon‐rich building blocks is described, based on a basic scaffold of triethynylmethanol (TEtM). The substitution of the ethynyl groups can be easily varied (including R3Si, H, Br), and this allows structural tuning for stabilization, synthetic derivatization, and adsorption on Ag(111) or Au(111). X‐ray crystallography helps to explain the surprising stability of the selected derivatives in the solid state, and an unusual form of hydrogen bonding is identified from these analyses. Preliminary efforts to achieve surface‐based reactions on Ag(111) and Au(111) are outlined experimentally and computationally.
Catalytic Strategies for Diastereodivergent Synthesis
Authors: Lin Lili , Feng Xiaoming 
Published: November 2016

AbstractChiral molecules with multiple stereocenters are widely distributed in nature and drugs. Asymmeric catalysis has allowed the formation of a chiral molecule's enantiomers with equal ease by applying the enantiomeric pair of a chiral catalyst. However, the diastereodivergent synthesis is a great challenge because the formation of one of the diastereomers is inherently preferred in most reactions. Under the efforts of chemists, elegant strategies have been developed to full control of absolute and relative stereochemical configurations. In this Minireview, we highlight the significant advances achieved in this field, and present the diastereo‐control mechanism in the appropriate place on the expectation that new diastereodivergent strategies can be inspired and more types of enantioselective diastereodivergent reactions can be realized.
Copper‐Mediated Selective Hydroxylation of a Non‐activated C−H Bond in Steroids: A DFT Study of Schönecker's Reaction
Authors: Gupta Puneet , Diefenbach Martin , Holthausen Max C. , Förster Moritz 
Published: November 2016

AbstractThe regio‐ and stereoselective copper‐mediated hydroxylation of a non‐activated aliphatic C−H bond in steroids by dioxygen, initially reported by Schönecker et al. (Angew. Chem. Int. Ed. 2003, 42, 3240–3244), has recently evolved into a valuable synthetic tool. In the present work, a detailed mechanistic density functional theory (DFT) study addressing the origin of the remarkable selectivity of Schönecker's reaction is reported. The applied BLYP‐D3/def2‐TZVP(SDD) level of DFT is benchmarked against experimental and coupled‐cluster reference data. The resulting mechanistic scenario involves formation of a bis‐μ‐oxo dicopper complex as key intermediate. In this complex three C−H bonds of the pendant steroid ligand are predisposed towards intramolecular activation by the bis‐μ‐oxo dicopper core. The lowest activation barrier (12.0 kcal mol−1) is computed for β‐hydroxylation at the C12 position, in agreement with the experimental observations. Natural bond orbital (NBO) analysis reveals stabilizing orbital interactions that favor the β‐hydroxylation pathway over competing reaction channels.