bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of lipase‐catalyzed polymerization of benzyl malolactonate through a design of experiment approach
Authors: Casajus Hubert , Tranchimand Sylvain , Wolbert Dominique , Nugier‐Chauvin Caroline , Cammas‐Marion Sandrine
Published: November 2016

Polyesters are polymers of choice in the design of drug delivery systems as a result of their good biocompatibility and their (bio)degradability. Such polyesters are mainly obtained by polymerization techniques using chemically based initiators whose presence in the final materials, even at trace levels, might induce toxic effects on in vivo uses. Therefore, lipases‐catalyzed ring opening polymerization (ROP) of lactones might be considered as interesting solutions. In this context, we have studied the possibilities to use lipase‐catalyzed ROP of the benzyl malolactonate (MLABe) to obtain the poly(benzyl malate), PMLABe. A Design of Experiment (DoE) approach has been elaborated to identify the important parameters having a significant influence on the polymerization reaction and on the characteristics of the obtained PMLABe. Such DoE technique allowed us to select conditions for lipase‐catalyzed ROP of MLABe leading to PMLABe with a mass‐average molar mass of around 10,000 g/mol with a dispersity of 1.4. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44604.
Locomotor Hand Postures, Carpal Kinematics During Wrist Extension, and Associated Morphology in Anthropoid Primates
Authors: Orr Caley M.
Published: November 2016

The biomechanics of wrist extension (or dorsiflexion) are important for understanding functional adaptation of the primate hand because extension mobility varies with habitual locomotor hand posture and facilitates certain manipulative tasks. Here, intercarpal kinematics are employed to investigate mechanisms underlying wrist extension in a sample of anthropoids representing various arboreal and terrestrial locomotor modes. Carpal kinematics are studied using computed‐tomography of cadaveric forelimbs, and these data are combined with a morphometric analysis of biomechanically‐informative anatomical features. The results indicate that stiff‐wristed knuckle‐walking chimpanzees and digitigrade baboons are characterized by low ranges of motion (ROMs) at the radiocarpal and midcarpal complexes. Palmigrade‐capable monkeys have high extension ROMs at both the radiocarpus and midcarpus, while palmigrade‐capable orangutans achieve wrist extension through moderate radiocarpal ROMs and high midcarpal ROMs. Morphometrics demonstrate that a more projecting dorsal ridge of the distal radius corresponds with low‐to‐moderate radioscaphoid mobility in the apes, but that baboons resemble palmigrade‐capable monkeys in this metric. Thus, the dorsal ridge of the radius alone is not a good indicator of wrist mobility and hand posture. However, the extent of the lunate's articular arc on the dorsum of the capitate head is correlated with midcarpal mobility across taxa. These findings suggest that although a precise relationship between wrist extension ROM and morphology is difficult to define, the presence of a pronounced dorsal ridge combined with an abbreviated dorsal capitate articular arc reflects limited overall dorsiflexion with attendant constraints on the adoption of palmigrade hand postures. Anat Rec, 300:382–401, 2017. © 2016 Wiley Periodicals, Inc.
Identification of 8‐Hydroxyquinoline Derivatives Active Against Somatic V658F Mutant JAK1‐Dependent Cells
Authors: Kiss Róbert , Bajusz Dávid , Baskin Rebekah , Tóth Katalin , Monostory Katalin , Sayeski Peter P. , Keserű György M.
Published: November 2016

Janus kinases (JAKs) and their gain‐of‐function mutants have been implicated in a range of oncological, inflammatory, and autoimmune conditions, which has sparked great research interest in the discovery and development of small‐molecule JAK inhibitors. Two molecules are currently marketed as JAK inhibitors, but due to the displayed side effects (owing to their suboptimal selectivities among the various JAK subtypes) new JAK inhibitors are still sought after. We present the results of an extensive virtual screening campaign based on a multi‐step screening protocol involving ligand docking. The screening yielded five new, experimentally validated inhibitors of JAK1 with 8‐hydroxyquinoline as a novel hinge‐binding scaffold. The compounds did not only display favorable potencies in a JAK1V658F‐driven cell‐based assay but were also shown to be non‐cytotoxic on rat liver cells.
Brief Report: Partial‐ and Full‐Thickness Focal Cartilage Defects Contribute Equally to Development of New Cartilage Damage in Knee Osteoarthritis: The Multicenter Osteoarthritis Study
Authors: Guermazi Ali , Hayashi Daichi , Roemer Frank W. , Niu Jingbo , Quinn Emily K. , Crema Michel D. , Nevitt Michael C. , Torner James , Lewis Cora E. , Felson David T.
Published: November 2016

Objective

To determine the risk of incident cartilage damage at follow‐up in subregions that are undamaged at baseline, by comparing tibiofemoral joint compartments with a baseline focal partial‐thickness or full‐thickness cartilage defect against compartments without any baseline cartilage damage, in knees with and those without radiographic osteoarthritis (OA).

Methods

We included participants in the Multicenter Osteoarthritis Study for whom there were semiquantitative magnetic resonance imaging readings at baseline and at 30 months. We estimated the risk of incident cartilage defects developing in tibiofemoral compartments with prevalent partial‐thickness and full‐thickness cartilage defects in only one subregion within the compartment, using tibiofemoral compartments with no baseline cartilage defects as a referent. Logistic regression with generalized estimating equations was used for all analyses, with adjustments for confounders.

Results

A total of 374 compartments (359 knees) were included, and 140 knees (39%) had radiographic OA. Compared to compartments with no baseline cartilage defects, those with partial‐thickness (adjusted odds ratio 1.62 [95% confidence interval 1.06–2.47]) and full‐thickness (adjusted odds ratio 1.92 [95% confidence interval 1.00–3.66]) cartilage defects in a subregion had a higher risk of incident cartilage defects in other subregions in the same compartment.

Conclusion

Prevalent focal cartilage defects, regardless of defect depth, in a single subregion within a tibiofemoral joint compartment increase the risk of developing new cartilage damage in other subregions of the same compartment for middle‐aged to elderly persons with or at high risk of knee OA.
Regulation of Chondrocyte Survival in Mouse Articular Cartilage by p63
Authors: Taniguchi Yuki , Kawata Manabu , Ho Chang Song , Mori Daisuke , Okada Keita , Kobayashi Hiroshi , Sugita Shurei , Hosaka Yoko , Inui Hiroshi , Taketomi Shuji , Yano Fumiko , Ikeda Toshiyuki , Akiyama Haruhiko , Mills Alea A. , Chung Ung‐il , Tanaka Sakae , Kawaguchi Hiroshi , Saito Taku
Published: November 2016

Objective

Transcription factor p63, of the p53 family, regulates cell proliferation, survival, and apoptosis in various cells and tissues. This study was undertaken to examine the expression and roles of p63 transcript variants in the mouse growth plate and articular chondrocytes.

Methods

For in vivo analyses, we generated Cre‐mediated TAp63α‐transgenic and TAp63γ‐transgenic mice. To induce tissue‐specific overexpression or deletion in chondrocytes, chondroprogenitor cells, or early limb bud mesenchymal cells, we used Col2a1‐Cre, Sox9‐Cre, and Prx1‐Cre mice, respectively. We analyzed osteoarthritis (OA) development with aging or surgically induced instability in Prx1‐Cre;p63fl/fl (P–conditional knockout) mice.

Results

Among major variants, TAp63α and TAp63γ are highly expressed in mouse primary costal and articular chondrocytes. The p63 protein was predominantly localized in the hypertrophic zone of the embryonic limb cartilage, and in the middle zone of articular cartilage. No obvious change was observed in skeletal growth of TAp63α‐transgenic mice, Sox9‐Cre;p63fl/fl, or P–conditional knockout mice, while that of TAp63γ‐transgenic mice was impaired due to ectopic apoptosis and the resulting decreased number of chondrocytes. Expression of proapoptotic genes including bax, noxa, puma, and fas was increased in TAp63γ‐transgenic mouse chondrocytes, and their transcription was probably sustained by p53 in p63–conditional knockout mouse chondrocytes because both proteins were coexpressed in the growth plate. In contrast, p53 was expressed in the superficial zone of articular cartilage, differently from p63. Notably, P–conditional knockout mice showed significant resistance to OA development, with suppression of chondrocyte apoptosis in the aging and surgical models.

Conclusion

We demonstrated regulation of chondrocyte survival in articular cartilage by p63.
“Patients with amyotrophic lateral sclerosis (ALS) are usually nice persons”—How physicians experienced in ALS see the personality characteristics of their patients
Authors: Mehl Theresa , Jordan Berit , Zierz Stephan
Published: November 2016

Introduction

Physicians experienced in the treatment of patients with amyotrophic lateral sclerosis (ALS) occasionally describe these patients as “nice” persons.

Methods

ALS experienced physicians (n = 36) were asked to assess the personality characteristics of ALS patients using a multidimensional personality questionnaire based on the five‐factor model of personality. Control groups consisted of physicians experienced in Myasthenia gravis (MG) (n = 21) and lung cancer (LC) (n = 36).

Results

In the dimension Agreeableness ALS patients were rated significantly higher than the other groups (p < .001). This was mainly due to the high scores for converse adjective pairs “stubborn—compliant” and “selfish—helpful”.

Discussion

The dimension Agreeableness is very similar to “niceness”. Results support the anecdotal description of ALS patients as “nice” persons. Personality characteristics of ALS patients differentiate them from other patient groups. It remains open whether the “nice” personality structure is linked to the susceptibility to the disease.
Superior Catalytic Performance of Hierarchically Micro‐Meso‐Macroporous CuAlPO‐5 for the Oxidation of Aromatic Amines under Mild Conditions
Authors: Ke Qingping , Wu Mingzhou , Yu Huizhen , Lu Guanzhong
Published: November 2016

Aromatic nitro compounds are versatile building blocks for organic synthesis because of easy transformation of the nitro group into other diverse functional groups. Herein, hierarchical mesoporous–macroporous CuAlPO‐5 was prepared and found to exhibit excellent catalytic activity and stability for the oxidation of aromatic amines to nitroarenes. For the oxidation of bulky aromatic amine molecules (e.g., 1‐naphthalenamine), hierarchical CuAlPO‐5 exhibited higher selectivity to the product than homogeneous Cu catalysts and higher catalytic activity than traditional microporous CuAlPO‐5; the former was attributed to shape selectivity to the product and the latter was attributed to improved diffusion of bulky molecules inside the meso‐ and macropores. After CuAlPO‐5 was used five times in the oxidation of 4‐bromoaniline, >98.6 % conversion and 98.1 % selectivity to the product were obtained. This shows the potential and attractiveness of this method for the preparation of nitroarenes by the selective oxidation of organic amines.
Liquid‐to‐Particle Mass Transfer in a Structured‐Bed Minireactor
Authors: Templis Chrysovalantis C. , Papayannakos Nikos G.
Published: November 2016

Liquid‐to‐particle mass transfer effects in a string pellet minireactor were studied by applying the diffusion‐controlled copper dissolution technique. Structured beds were formed with cylindrical particles in spiral and vertical configurations and operated with liquid and gas‐liquid feeds in upflow mode. Single‐ and two‐phase flow experiments were conducted to study the effects of the gas and the liquid superficial velocities on the liquid‐to‐particle mass transfer coefficient. Computational fluid dynamics calculations were performed to study the effect of the arrangement of the particles in the reactor tube on the liquid‐to‐particle effective mass transfer coefficient for the single‐phase flow. Correlations of the mass transfer coefficient with the operating conditions were derived.
d‐ Versus l‐Glucose Conjugation: Mitochondrial Targeting of a Light‐Activated Dual‐Mode‐of‐Action Ruthenium‐Based Anticancer Prodrug
Authors: Lameijer Lucien N. , Hopkins Samantha L. , Brevé Tobias G. , Askes Sven H. C. , Bonnet Sylvestre
Published: November 2016

Light‐activated ruthenium polypyridyl anticancer prodrugs often suffer from poor water solubility, poor selectivity, and/or ill‐defined intracellular targets. Coordination of the d‐ or l‐glucose thioether ligand 3 (2‐(2‐(2‐(methylthio)ethoxy)ethoxy)ethyl‐β‐glucopyranoside) to the highly lipophilic ruthenium complex [Ru(tpy)(dppn)(H2O)]2+ ([1]2+; dppn=benzo[i]dipyrido‐[3,2‐a:2′,3′‐c]phenazine, tpy=2,2′:6′,2′′‐terpyridine) solved all these problems at once. The two enantiomers of [Ru(tpy)(dppn)(3)][PF6]2, [d‐2][PF6]2 and [l‐2][PF6]2, were soluble in water, which allowed the influence of the chirality of the glucose moiety on uptake, toxicity, and intracellular localization of the prodrug to be probed without changing any other physicochemical properties. Both compounds showed mild, but different, cytotoxicity in A549 (human lung carcinoma) and MCF‐7 (human breast adenocarcinoma) cancer cells in the dark, whereas following low doses of visible light irradiation (3.1 J cm−2 at λ = 454 nm), a similar, but high cytotoxicity (EC50 < 1 μm), was observed. Irrespective of the chirality, both slightly emissive Ru complexes were found in the mitochondria, and two modes of action may contribute to light‐induced cell death: 1) the glucose thioether ligand is photosubstituted by water, thus [1]2+, which interacts with DNA at an exceptionally high 400:1 base pair/Ru ratio, is released; 2) both [1]2+ and [2]2+ produce massive amounts of singlet oxygen, which leads to very efficient photodynamic DNA cleavage.
Study of (Cyclic Peptide)–Polymer Conjugate Assemblies by Small‐Angle Neutron Scattering
Authors: Koh Ming Liang , FitzGerald Paul A. , Warr Gregory G. , Jolliffe Katrina A. , Perrier Sébastien
Published: November 2016

We present a fundamental study into the self‐assembly of (cyclic peptide)–polymer conjugates as a versatile supramolecular motif to engineer nanotubes with defined structure and dimensions, as characterised in solution using small‐angle neutron scattering (SANS). This work demonstrates the ability of the grafted polymer to stabilise and/or promote the formation of unaggregated nanotubes by the direct comparison to the unconjugated cyclic peptide precursor. This ideal case permitted a further study into the growth mechanism of self‐assembling cyclic peptides, allowing an estimation of the cooperativity. Furthermore, we show the dependency of the nanostructure on the polymer and peptide chemical functionality in solvent mixtures that vary in the ability to compete with the intermolecular associations between cyclic peptides and ability to solvate the polymer shell.
Fluorogenic Behaviour of the Hetero‐Diels–Alder Ligation of 5‐Alkoxyoxazoles with Maleimides and their Applications
Authors: Renault Kévin , Jouanno Laurie‐Anne , Lizzul‐Jurse Antoine , Renard Pierre‐Yves , Sabot Cyrille
Published: November 2016

Fluorogenic reactions are largely underrepresented in the toolbox of chemoselective ligations despite their tremendous potential, particularly in chemical biology and biochemistry. In this respect, we have investigated in full detail the fluorescence behaviour of the azaphthalamide, a scaffold which is generated through a hetero‐Diels–Alder reaction of 5‐alkoxyoxazole and maleimide derivatives under mild conditions that are compatible with, among others, peptide chemistry. The scope and limitations of such a fluorogenic labelling strategy were examined through four distinct applications, which target enzymatic activities or bioorthogonal reactions.
The Design, Synthesis, and Evaluation of 1,5,7‐Trisubstituted‐3‐Pyridyl‐Xanthones for Use as Insecticides Starting from Pyripyropene A
Authors: Fuse Shinichiro , Matsumura Keisuke , Johmoto Kohei , Uekusa Hidehiro , Tanaka Hiroshi , Hirose Tomoyasu , Sunazuka Toshiaki , Ōmura Satoshi , Takahashi Takashi
Published: November 2016

A readily accessible template of 1,5,7‐trisubstituted‐3‐pyridyl‐xanthones was designed starting from naturally occurring pyripyropene A for agrichemical development. Our originally developed Ag2CO3‐mediated oxidative cyclization enabled ready access to the key scaffold, 1,5,7‐trihydroxy‐3‐chloro‐xanthone. The chemo‐ and regioselective sequential introduction of four substituents to the scaffold rapidly afforded the desired, structurally diverse 1,5,7‐trisubstituted‐3‐pyridyl‐xanthones. An evaluation of insecticidal activity revealed that one of the synthesized compounds retained insecticidal activity against vetch aphid and green peach aphid. The observed insecticidal spectrum was similar to that of pyripyropene A. The developed template could be a valuable aid for future agrichemical development.
Synthesis of Structurally Varied 1,3‐Disiloxanediols and Their Activity as Anion‐Binding Catalysts
Authors: Diemoz Kayla M. , Wilson Sean O. , Franz Annaliese K.
Published: November 2016

A series of new 1,3‐disiloxanediols has been synthesized, including naphthyl‐substituted and unsymmetrical siloxanes, and demonstrated as a new class of anion‐binding catalysts. In the absence of anions, diffusion‐ordered spectroscopy (DOSY) displays self‐association of 1,3‐disiloxanediols through hydrogen‐bonding interactions. Binding constants determined for 1,3‐disiloxanediol catalysts indicate strong hydrogen‐bonding and anion‐binding abilities with unsymmetrical siloxanes displaying different hydrogen‐bonding abilities for each silanol group.
Single Heteroatom Substitutions in the Efavirenz Oxazinone Ring Impact Metabolism by CYP2B6
Authors: Cox Philip M. , Bumpus Namandjé N.
Published: November 2016

Previously, we observed that the oxazinone ring is important for cytochrome P450 2B6 (CYP2B6) activity toward efavirenz ((4S)‐6‐chloro‐4‐(2‐cyclopropylethynyl)‐1,4‐dihydro‐4‐(trifluoromethyl)‐2H‐3,1‐benzoxazin‐2‐one), a CYP2B6 substrate used to treat HIV. To further understand the structural characteristics of efavirenz that render it a CYP2B6 substrate, we tested the importance of each heteroatom of the oxazinone ring. We assembled a panel of five analogues: 6‐chloro‐4‐(2‐cyclopropylethynyl)‐1,4‐dihydro‐2‐methyl‐4‐(trifluoromethyl)‐2H‐3,1‐benzoxazine (1), (4S)‐6‐chloro‐4‐[(1E)‐2‐cyclopropylethenyl]‐3,4‐dihydro‐4‐(trifluoromethyl)‐2(1H)‐quinazolinone (2), (4S)‐6‐chloro‐4‐(2‐cyclopropylethynyl)‐3,4‐dihydro‐4‐(trifluoromethyl)‐2(1H)‐quinazolinone (3), 6‐chloro‐4‐(cyclopropylethynyl)‐3,4‐dihydro‐4‐(trifluoromethyl)‐2(1H)‐quinolinone (4), and 6‐chloro‐4‐(cyclopropylethynyl)‐4‐(trifluoromethyl)‐4H‐benzo[d][1,3]dioxin‐2‐one (5). The metabolism of compounds 1–5 was investigated using human liver microsomes, individual P450s, and mass spectrometry or UV/Vis absorbance detection. Steady‐state analysis of CYP2B6 metabolism of 1–5 showed KM values ranging from 0.3‐ to 3.9‐fold different from that observed for efavirenz (KM: 3.6±1.7 μm). The lowest KM values, approximating 1 μm, were observed for the metabolism of 1, whereas the greatest KM value, 14±6.4 μm, was found for 4. Our work reveals that analogues with heteroatom changes in the oxazinone ring are still CYP2B6 substrates, although the changes in KM suggest altered substrate binding.
Modeling Drug‐Induced Neuropathy Using Human iPSCs for Predictive Toxicology
Authors: Ohara R , Imamura K , Morii F , Egawa N , Tsukita K , Enami T , Shibukawa R , Mizuno T , Nakagawa M , Inoue H
Published: November 2016

Drugs under development can cause unpredicted toxicity in humans due to differential drug responsiveness between humans and other disease models, resulting in clinical trial failures. Human induced pluripotent stem cells (iPSCs) are expected to represent a useful tool for toxicity testing. However, among many assays, appropriate cellular assays for predicting neurotoxicity in an iPSC‐based model are still uncertain. Here we generated neurons from iPSCs of Charcot–Marie–Tooth disease (CMT) patients. Some CMT patients are sensitive to anticancer drugs and present with an adverse reaction of neuropathy. We analyzed cellular phenotypes and found that mitochondria in neurites of CMT neurons were morphologically shorter and showed slower mobility compared to control. A neurosphere assay showed that treatment with drugs known to cause neuropathy caused mitochondrial aggregations in neurites with adenosine triphosphate shortage in both CMT and control neurons, although more severely in CMT. These findings suggest that the genetically susceptible model could provide a useful tool to predict drug‐induced neurotoxicity.
Investigation of Methane Oxidation Reactions Over a Dual‐Bed Catalyst System using 18O Labelled DRIFTS coupling
Authors: Richard Melissandre , Duprez Daniel , Bion Nicolas , Can Fabien
Published: November 2016

Low loading Pd‐supported (0.2 wt % Pd) Y‐stabilized zirconia (YSZ) and LaMnO3 (LM) perovskite were associated to study the partial oxidation of methane using labelled 18O2 in the gas phase. Synthesis gas production was demonstrated to occur through an indirect reaction in which oxygen is first consumed in the total methane combustion. A Mars–van Krevelen mechanism was observed over Pd/YSZ at 425 °C to yield C16O2 and C16O. A significant enhancement of the Pd/YSZ catalyst activity was achieved by the association of LM–Pd/YSZ in a dual catalyst bed, resulting in a significant increase of the oxidation rate. Vibration bands of adsorbed formate species, assumed to be intermediates to the gas production, were observed by diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) coupling experiments. It was proposed that LM enables the generation of highly active singlet O2, which is activated on the YSZ oxygen vacancies to assist a rapid recovery of surface PdO and increase formate decomposition into CO and H2 in Pd‐supported catalyst.
The Planktonic Relationship Between Fluid‐Like Electrodes and Bacteria: Wiring in Motion
Authors: Tejedor‐Sanz Sara , Quejigo Jose Rodrigo , Berná Antonio , Esteve‐Núñez Abraham
Published: November 2016

We have explored a new concept in bacteria‐electrode interaction based on the use of fluid‐like electrodes and planktonic living cells. We show for the first time that living in a biofilm is not a strict requirement for Geobacter sulfurreducens to exchange electrons with an electrode. The growth of planktonic electroactive G. sulfurreducens could be supported by a fluid‐like anode as soluble electron acceptors and with electron transfer rates similar to those reported for electroactive biofilms. This growth was maintained by uncoupling the charge (catabolism) and discharge (extracellular respiration) processes of the cells. Our results reveal a novel method to culture electroactive bacteria in which every single cell in the medium could be instantaneously wired to a fluid‐like electrode. Direct extracellular electron transfer is occurring but with a new paradigm behind the bacteria–electrode interaction.
One‐Component Aluminum(heteroscorpionate) Catalysts for the Formation of Cyclic Carbonates from Epoxides and Carbon Dioxide
Authors: Martínez Javier , Castro‐Osma José A. , Alonso‐Moreno Carlos , Rodríguez‐Diéguez Antonio , North Michael , Otero Antonio , Lara‐Sánchez Agustín
Published: November 2016

New neutral and zwitterionic chiral NNO‐donor scorpionate ligands 1 and 2 were designed to obtain new mononuclear and dinuclear NNO‐heteroscorpionate aluminum complexes. Reaction of 1 with [AlR3] (R=Me, Et) in a 1:1 or 1:2 molar ratio afforded the neutral mononuclear alkyl complexes [AlR2(κ2‐bpzappe)] {R=Me (3), Et (4); bpzappeH=2,2‐bis(3,5‐dimethylpyrazol‐1‐yl)‐1‐[4‐(dimethylamino)phenyl]‐1‐phenylethanol} and bimetallic complexes [{AlR2(κ2‐bpzappe)}(μ‐O){AlR3}] [R=Me (5), Et (6)]. By reaction of complexes 3–6 with PhCH2Br, mononuclear and dinuclear cationic aluminum complexes [AlR2(κ2‐bbpzappe)]Br {R=Me (7), Et (8); bbpzappeH=N‐benzyl‐4‐[2,2‐bis(3,5‐dimethyl‐1H‐pyrazol‐1‐yl)‐1‐hydroxy‐1‐phenylethyl]‐N,N‐dimethylbenzenaminium bromide} and [{AlR2(κ2‐bbpzappe)}(μ‐O){AlR3}]Br [R=Me (9), Et (10)] were synthesized. Both neutral aluminum complexes in the presence of Bu4NBr and cationic aluminum complexes were investigated as catalysts for cyclic carbonate formation from epoxides and carbon dioxide. Amongst them, complex 10 was found to be an efficient one‐component catalyst for the synthesis of cyclic carbonates from both monosubstituted and internal epoxides and was shown to have broad substrate scope.
Low dose IL‐2 increase regulatory T cells and elevate platelets in a patient with immune thrombocytopenia
Authors: Zhang Jiakui , Ruan Yanjie , Shen Yuanyuan , Tao Qianshan , Wang Huiping , Tao Lili , Pan Yin , Fang Huizi , Wang Yiping , Zhai Zhimin
Published: November 2016

Immune thrombocytopenia (ITP) is an autoimmune disorder in which its immune system destroys platelets and leads to haemorrhage symptom. Recent studies have found that regulatory T cells (Tregs) in peripheral blood, bone marrow, and spleen were reduced in ITP patients and recovered after effective ITP therapy. Low‐dose Interleukin‐2 (IL‐2) has been reported recently to increase Tregs and used to treat autoimmune disease including graft‐versus‐host disease (GVHD) after organ transplantation and HCV‐related autoimmune vasculitis. However, it is unknown whether IL‐2 is able to treat ITP. We have used low‐dose IL‐2 (1.0 million IU/day) on 5 consecutive days per week for 4 weeks in a 36‐year‐old patient with ITP. The result has shown that low‐dose IL‐2 induces expansion of Tregs significantly and increase platelet count was gradually from 36 × 109/L to maximum 85 × 109/L. No side effects of IL‐2 have been found. This result suggested that low‐dose of IL‐2 may have therapeutic potential for ITP. © 2016 International Clinical Cytometry Society
A Computational Mechanistic Study of Metal‐Catalyzed Remote C–H Functionalizations – Insights into the Origin of Regioselectivity and the Role of Acid
Authors: Xu Yilu , Yang Shengwen , Du Lijuan , Li Juan
Published: November 2016

The metal‐catalyzed remote C–H functionalization of quinoline N‐oxide was investigated systematically through density functional theory calculations. We found that the coordination of the N‐oxide moiety to a metal center greatly lowered the barrier to C–H activation and made C8–H activation favorable, regardless of the metal center (Ir, Rh, or Pd). For IrIII and RhIII systems, the active catalyst was identified from several candidates as [Cp*M(OAc)]+ (M = Ir or Rh, Cp* = pentamethylcyclopentadienyl) because the N‐oxide moiety in quinoline N‐oxide can coordinate to the metal center in the [Cp*M(OAc)]+ system. The cleavage of the C8–H bond was favored over the C2–H cleavage because the transition state in the former case is a five‐membered metallacycle, whereas that for the latter is a four‐membered metallacycle. For the PdII system, the absence or presence of a phosphine ligand enabled C8–H or C2–H bond functionalization in quinoline N‐oxide. This is attributed to the occurrence or not of the coordination of the N‐oxide moiety to the Pd center. Acid additives play a key role in the catalytic cycle for IrIII‐catalyzed C8 amidation because the protodemetalation step contributes to the overall rate‐determining barrier, on the basis of an energetic span model.
β‐Amyrin Biosynthesis: Effect of Steric Bulk at the 6‐, 10‐ and 15‐Positions in the 2,3‐Oxidosqualene Backbone on Polycyclisation Cascades
Authors: Terasawa Yuri , Sasaki Yusuke , Yamaguchi Yuki , Takahashi Kazunari , Hoshino Tsutomu
Published: November 2016

β‐Amyrin synthase incubation experiments have been conducted to determine the influence of steric effects at the 6‐, 10‐ and 15‐positions of 2,3‐oxidosqualene on the polycyclisation pathway. Nor‐ and ethyl‐substituted oxidosqualene analogues were synthesised. Cyclisation of the ethyl‐substituted analogues did not occur, but the nor analogues underwent a polycyclisation cascade to yield fully cyclised products with 6/6/6/6/6‐fused pentacyclic scaffolds generated via a final oleanyl cation. Previously, we reported that 19‐ and 23‐ethyl‐substituted analogues underwent polycyclisation reactions. Therefore, the catalytic domain involved in earlier cyclisation steps is notably compact. In contrast, the catalytic domain in the later cyclisation steps is more loosely packed (less compact) to accommodate the bulky ethyl group. The reaction cavities for recognising branched methyl groups are discussed by comparing β‐amyrin synthase with other triterpene cyclases such as lanosterol and hopene synthases.
Facile one‐pot preparation of a novel imidazolium‐based monolith by thiol–ene click chemistry for capillary liquid chromatography
Authors: Zhang Peng , Yang Haiguan , Chen Tao , Qin Yuemei , Ye Fanggui
Published: November 2016

In this work, a novel imidazolium‐based monolith was fabricated through a simple route. With 1‐vinyl‐3‐octadecylimidazolium bromide and ethylene dimethacrylate as monomers, pentaerythritol tetra‐(3‐mercaptopropionate) as crosslinker, AIBN as thermal initiator, the monolith was facilely fabricated by one‐pot thiol–ene click chemistry. The influences of both the content of monomer/crosslinker and porogenic systems on the morphology, and permeability of the monolith were studied. The optimal reaction conditions were used to prepare a homogeneous and permeable monolith. The optimal preparation of monolithic column was characterized by scanning electron microscopy, Fourier transform infrared spectrometry, X‐ray photoelectron spectroscopy, and thermogravimetric analysis. High efficiency and quick separation of alkylbenzenes, styrene and ethylbenzene, polycyclic aromatic hydrocarbon, phenols, anilines, and aromatic acids were achieved. The minimum plate height of this monolith were determined as 11.42 μm for thiourea and 13.26 μm for benzene. All results indicated that thiol–ene click chemistry provides a quick way for the fabrication of imidazolium‐based monolith.
Confinement effects on electroconvective instability
Authors: Andersen Mathias B. , Wang Karen M. , Schiffbauer Jarrod , Mani Ali
Published: November 2016

We present an analysis of hydrodynamic effects in systems involving ion transport from an aqueous electrolyte to an ion‐selective surface. These systems are described by the Poisson–Nernst–Planck and Navier–Stokes equations. Historically, such systems were modeled by one‐dimensional geometries with spatial coordinate in the direction of transport and normal to the ion‐selective surface. Rubinstein and Zaltzman [JFM 579, 173–226 (2007)] showed that when such systems are unbounded in the transverse directions, a hydrodynamic instability can occur. This instability, referred to as electroconvective instability, leads to advective mixing, which results in overlimiting transport rates significantly beyond what is predicted from one‐dimensional models. In this study, we present an analysis of electroconvection in confined systems, considering a broad range of applications including microfluidic systems and porous media. Our analysis reveals that full confinement in the transverse directions significantly suppresses electroconvection and overlimiting current. However, when at least one transverse direction allows for flow escape, such as in thin but wide channels or in porous media, the onset of instability is only weakly affected by confinement. We will also present a review of relevant literature and discuss how the present study resolves the contradictory contrasts between the results of recent work on this topic.
Impacts of process parameters optimization on the performance of the annular single chamber microbial fuel cell in wastewater treatment
Authors: Nouri Parisa , Najafpour Darzi Ghasem
Published: November 2016

Energy harvest from optimized annular single chamber microbial fuel cell (ASCMFC) with novel configuration, which treats chocolate industry wastewater, was investigated. In this study, optimization of operational parameters of the ASCMFC in terms of efficiency water‐soluble organic matter reduction and capability of electricity generation was evaluated. During the experiment, effluent from the anode compartment was examined through current and power density curves for variation in temperature and pH, chemical oxygen demand (COD), and turbidity removal, and substrate concentration. The performance analyzed at different temperature ranges such as 25, 30, 35, and 40°C, which showed 88% increase by uprising temperature from 25 to 35°C. The ASCMFC was used to produce electricity by adjusting pH between 5 and 9 at resistance of 100 Ω. Under the condition of pH 7 power density (16.75 W/m3) was highest, which means natural pH is preferred to maximize microbial activities. Wastewater concentration with COD of 700 and 1400 mg/L were investigated to determine its affection on current production. Reduction of current density was observed due to decrease in wastewater concentration. Significant reduction in COD and turbidity of effluent were 91 and 78%, respectively. The coulombic efficiency of 45.1% was achieved.
Role of the momentum interpolation mechanism of the Roe scheme in shock instability
Authors: Ren Xiao‐dong , Gu Chun‐wei , Li Xue‐song
Published: November 2016

The shock instability phenomenon is a well‐known problem for hypersonic flow computation by the shock‐capturing Roe scheme. The pressure checkerboard is another well‐known problem for low‐Mach‐number flow computation. The momentum interpolation method (MIM) is necessary for low‐Mach‐number flows to suppress the pressure checkerboard problem, and the pressure‐difference‐driven modification for cell face velocity can be regarded as a version of the MIM by subdividing the numerical dissipation of the Roe scheme. In this paper, MIM has been discovered through analysis and numerical tests to have the most important function in shock instability. MIM should be completely removed for nonlinear flows. However, the unexpected MIM is activated on the cell face nearly parallel to the flow for the high‐Mach‐number flows or low‐Mach‐number cells in numerical shock. Therefore, MIM should be retained for low‐Mach‐number flows and be completely removed for high‐Mach‐number flows and low‐Mach‐number cells in numerical shock. For such conditions, two coefficients are designed on the basis of the local Mach number and a shock detector. Thereafter, the improved Roe scheme is proposed. This scheme considers the requirement of MIM for incompressible and compressible flows, and is validated for good performance of numerical tests. An acceptable result can also be obtained with only the Mach number coefficient for general practical computation. Therefore, the objective of decreasing rather than increasing numerical dissipation to cure shock instability can be achieved with simple modification. Moreover, the mechanism of shock instability has been profoundly understood, in which MIM plays the most important role, although it is not the only factor. Copyright © 2016 John Wiley & Sons, Ltd.
Exome copy number variation detection: Use of a pool of unrelated healthy tissue as reference sample
Authors: Wenric Stephane , Sticca Tiberio , Caberg Jean‐Hubert , Josse Claire , Fasquelle Corinne , Herens Christian , Jamar Mauricette , Max Stéphanie , Gothot André , Caers Jo , Bours Vincent
Published: November 2016

An increasing number of bioinformatic tools designed to detect CNVs (copy number variants) in tumor samples based on paired exome data where a matched healthy tissue constitutes the reference have been published in the recent years. The idea of using a pool of unrelated healthy DNA as reference has previously been formulated but not thoroughly validated. As of today, the gold standard for CNV calling is still aCGH but there is an increasing interest in detecting CNVs by exome sequencing. We propose to design a metric allowing the comparison of two CNV profiles, independently of the technique used and assessed the validity of using a pool of unrelated healthy DNA instead of a matched healthy tissue as reference in exome‐based CNV detection. We compared the CNV profiles obtained with three different approaches (aCGH, exome sequencing with a matched healthy tissue as reference, exome sequencing with a pool of eight unrelated healthy tissue as reference) on three multiple myeloma samples. We show that the usual analyses performed to compare CNV profiles (deletion/amplification ratios and CNV size distribution) lack in precision when confronted with low LRR values, as they only consider the binary status of each CNV. We show that the metric‐based distance constitutes a more accurate comparison of two CNV profiles. Based on these analyses, we conclude that a reliable picture of CNV alterations in multiple myeloma samples can be obtained from whole‐exome sequencing in the absence of a matched healthy sample.
Geochemical and stable carbon isotope composition variations of natural gases in tight sandstones from the West Sichuan Basin, China
Authors: Chen Dongxia , Pang Xiongqi , Yan Qingxia , Liu Yuchen , Mou Jiawen , Lv Chang
Published: November 2016

Recent exploration has revealed the great potential of gas resources, complicated gas distributions and geochemical characteristics of natural gases in tight sandstones of the West Sichuan Basin, China (WSBC). The chemical, stable carbon and light hydrocarbon compositions of natural gases from WSBC were investigated to assess the genesis, sources, and migration pattern leading to variations in the geochemical and stable carbon isotope compositions. The analysis shows that the natural gas in the Jurassic tight sandstones occurs as dry gas or wet gas in some places; however, most of the gas in the deep Triassic tight sandstones is apparently dry gas. Carbon isotope distributions increased in the order δ13C1 < δ13C2 < δ13C3 < δ13C4. The light hydrocarbon content increased in the order of chain (i.e. non‐cyclic) alkanes, cycloalkanes, and aromatic hydrocarbons. Relatively high ethane carbon isotope values and methylcyclohexane contents indicated the presence of lacustrine coal‐formed gases. The Jurassic natural gas is in a lower thermally mature stage and possibly originated from a mixture of T3X3 and T3X5 black mudstones. The deep Triassic natural gas was possibly originated in the deep source rocks because the gas has a relatively higher thermal maturity. Positive correlations between burial depth and methane content, dryness coefficient, δ13C1, and δ13C1–δ13C2 for the deep Triassic gas suggest that the migration distance was short and the source was nearby or the gas accumulated in situ. The chemical compositions and geological studies revealed that the fractionation of the Jurassic natural gases in a tight reservoir was predominantly caused by vertical migration rather than the maturity of the local source rocks. Copyright © 2016 John Wiley & Sons, Ltd.
Mortality salience reduces the discrimination between in‐group and out‐group interactions: A functional MRI investigation using multi‐voxel pattern analysis
Authors: Feng Chunliang , Azarian Bobby , Ma Yina , Feng Xue , Wang Lili , Luo Yue‐Jia , Krueger Frank
Published: November 2016

As a fundamental concern of human beings, mortality salience impacts various human social behaviors including intergroup interactions; however, the underlying neural signature remains obscure. Here, we examined the neural signatures underlying the impact of mortality reminders on in‐group bias in costly punishment combining a second‐party punishment task with multivariate pattern analysis of fMRI data. After mortality salience (MS) priming or general negative affect priming, participants received offers from racial in‐group and out‐group proposers and decided how to punish proposers by reducing their payoffs. We revealed that MS priming attenuated in‐group bias and dampened the discriminated activation patterns pertaining to group identities in regions previously implicated in costly punishment, including dorsomedial prefrontal cortex, temporo‐parietal junction, anterior cingulate cortex, and dorsolateral prefrontal cortex. The group identity represented in multivariate patterns of activity of these regions predicted in‐group bias for the control condition, i.e., the stronger discriminative representations of group identities in these regions; the larger was the in‐group bias. Furthermore, the in‐group bias was reliably decoded by distributed activation patterns in the punishment‐related networks but only in the control condition and not in the MS condition. These findings elucidate the neural underpinnings of the effects of mortality reminders on intergroup interaction. Hum Brain Mapp 38:1281–1298, 2017. © 2016 Wiley Periodicals, Inc.
BAD TIMES, SLIMMER CHILDREN?
Authors: Bellés‐Obrero Cristina , Jiménez‐Martín Sergi , Vall‐Castello Judit
Published: November 2016

Although the majority of the literature has confirmed that recessions are beneficial for adults' health and babies' outcomes at delivery, this effect should not necessarily be the same for children. In this paper, we study the effect of business cycle conditions on infant underweight, overweight, and obesity. We exploit eight waves of repeated cross‐sectional data (1987–2012) of the Spanish National Health Survey for children aged 2–15 and use the regional unemployment rate of the trimester of the interview as a proxy for the business cycle phase at the local level. We find that an increase in the unemployment rate is associated with lower obesity incidence, especially for children under 6 years old and over 12 years old. However, economic shocks also proof to have potentially negative consequences as they increase the prevalence of infant underweight for the same age groups.

Moreover, we show that the possible mechanisms through which the cycle is impacting infant obesity is the nutritional composition of the children's diet, as well as, increases in the frequency of exercise. We provide some evidence that suggests that the impact of business cycle conditions on infant weight disorders have little objective health consequences in the short run. However, the potential long‐term effects may become important as underweight during childhood is associated with worse outcomes later in life. Copyright © 2016 John Wiley & Sons, Ltd.
The ubiquitin ligase UBE4A inhibits prostate cancer progression by targeting interleukin‐like EMT inducer (ILEI)
Authors: Sun Yanan , Jia Xiaopeng , Gao Qiang , Liu Xing , Hou Lianguo
Published: November 2016

Epithelial to mesenchymal transition (EMT) is an important prerequisite for metastasis to secondary organs. Interleukin‐like EMT inducer (ILEI) protein has been shown to translationally upregulated during EMT and metastatic progression as a consequence of aberrant TGF‐β signaling. Our initial evaluation of FAM3C (encoding ILEI) and ILEI expression in normal prostate (PCS‐440‐010) and prostate cancer cell lines (DU145, LNCaP, and PC3) revealed detectable protein expression in only LNCaP cell line even though all cell lines tested had comparable FAM3C expression. Given that PC3 and DU145 cell lines did not have detectable ILEI expression hinted at additional level of regulation of ILEI expression. Treatment with MG‐132 resulted in robust detection of ILEI in the PCS‐440‐010, PC3 and DU145 cell lines, suggesting that at least in these cell lines, ILEI is actively degraded by the proteasome. Mass spectrometric analysis of FLAG immunoprecipitates of untreated and MG‐132 treated FLAG‐ILEI transfected cells indicated that UBE4A and UBE3C ubiquitin ligases were interacting with ILEI. Ectopic overexpression of UBE4A, but not UBE3C, resulted in destabilization of ILEI in LNCaP cells, whereas RNAi‐mediated silencing of UBE4A in PCS‐440‐010, PC3 and DU145 cell lines resulted in robust accumulation of ILEI, indicating UBE4A as the cognate ubiquitin ligase for ILEI. Co‐immunoprecipitation experiments established direct interaction of endogenous ILEI and UBE4A. Furthermore, co‐immunoprecipitation of FLAG‐tagged ILEI in cells co‐transfected with either HA‐UBE4A or HA‐UBE3C revealed robust polyubiquitinated smear of ILEI in cells transfected with UBE4A, but not UBE3C, thus confirming UBE4A as the ubiquitin ligase for ILEI degradation. Ectopic overexpression of UBE4A, but not UBE3C, in cells was downregulated in vitro migration and invasion in these cells. Cumulatively, our data reveals a novel post‐translational regulatory mechanism of regulating ILEI1 expression, a protein required for metastatic progression in prostate cancer cells. © 2016 IUBMB Life, 69(1):16–21, 2017
Raine Syndrome (OMIM #259775), Caused By FAM20C Mutation, Is Congenital Sclerosing Osteomalacia With Cerebral Calcification (OMIM 259660)
Authors: Whyte Michael P , McAlister William H , Fallon Michael D , Pierpont Mary Ella , Bijanki Vinieth N , Duan Shenghui , Otaify Ghada A , Sly William S , Mumm Steven
Published: November 2016

In 1985, we briefly reported infant sisters with a unique, lethal, autosomal recessive disorder designated congenital sclerosing osteomalacia with cerebral calcification. In 1986, this condition was entered into Mendelian Inheritance In Man (MIM) as osteomalacia, sclerosing, with cerebral calcification (MIM 259660). However, no attestations followed. Instead, in 1989 Raine and colleagues published an affected neonate considering unprecedented the striking clinical and radiographic features. In 1992, “Raine syndrome” entered MIM formally as osteosclerotic bone dysplasia, lethal (MIM #259775). In 2007, the etiology emerged as loss-of-function mutation of FAM20C that encodes family with sequence similarity 20, member C. FAM20C is highly expressed in embryonic calcified tissues and encodes a kinase (dentin matrix protein 4) for most of the secreted phosphoproteome including FGF23, osteopontin, and other regulators of skeletal mineralization. Herein, we detail the clinical, radiological, biochemical, histopathological, and FAM20C findings of our patients. Following premortem tetracycline labeling, the proposita's non-decalcified skeletal histopathology after autopsy indicated no rickets but documented severe osteomalacia. Archival DNA revealed the sisters were compound heterozygotes for a unique missense mutation and a novel deletion in FAM20C. Individuals heterozygous for the missense mutation seemed to prematurely fuse their metopic suture and develop a metopic ridge sometimes including trigonocephaly. Our findings clarify FAM20C's role in hard tissue formation and mineralization, and show that Raine syndrome is congenital sclerosing osteomalacia with cerebral calcification. © 2016 American Society for Bone and Mineral Research.

Abstract

In 1985, we briefly characterized “congenital sclerosing osteomalacia with cerebral calcification” (CSOCC) in infant sisters. Later, Raine syndrome (RNS) became known, with FAM20C deactivation discovered in 2007. FAM20C is a kinase for the secreted phosphoproteome, including FGF23 and SIBLINGs that regulate mineralization. We find the sisters carried two unique mutations in FAM20C. Skeletal histopathology indicated severe osteomalacia yet no rickets. Our findings clarify FAM20C's role in osteogenesis and hard tissue mineralization, and show RNS is CSOCC.