bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of individual cubicle research on the social interactions and individual behavior of brown capuchin monkeys (Sapajus apella)
Authors: Ruby Suzanne , Buchanan‐Smith Hannah M.
Published: July 2015

Primates are increasingly being tested individually in purpose‐built research centers within zoos. The voluntary nature of research testing indicates that participation is enriching for the primate subjects, but previous studies have generally focused only on stress‐related behavior, indicating that the research does not have a negative effect. Few data are available on the effects that individual research may have on social behavior, yet given primates' complex social lives and their responses to how conspecifics are treated, it is important to determine whether individual testing impacts upon their social interactions. The current study compared the social and individual behavior of 11 brown capuchin monkeys (Sapajus apella) between three conditions: (1) directly after undergoing individual testing, (2) a control, and (3) upon returning to the group having voluntarily left. The results indicate that individual and stress‐related behaviors were affected very little by individual research testing and that social behaviors increased. However, although affiliative interactions were enhanced, aggressive interactions were also seen to increase in the condition following individual testing compared with the return to group condition. Suggestions for minimizing the negative interactions are given. Provided that these suggestions are taken into account by researchers, our results provide support for developing research centers within zoos given the important findings emerging on our closest living relatives, combined with the potentially positive effects the research has on their welfare. Am. J. Primatol. 77:1097–1108, 2015. © 2015 Wiley Periodicals, Inc.
Setting the stage for medieval plague: Pre‐black death trends in survival and mortality
Authors: DeWitte Sharon N.
Published: July 2015

OBJECTIVES

The 14th‐century Black Death was one of the most devastating epidemics in human history, killing tens of millions of people in a short period of time. It is not clear why mortality rates during the epidemic were so high. One possibility is that the affected human populations were particularly stressed in the 14thcentury, perhaps as a result of repeated famines in areas such as England. This project examines survival and mortality in two pre‐Black Death time periods, 11–12thcenturies vs 13thcentury CE, to determine if demographic conditions were deteriorating before the epidemic occurred.

MATERIALS AND METHODS

This study is done using a sample of individuals from several London cemeteries that have been dated, in whole or in part, either to the 11–12thcenturies (n = 339) or 13thcentury (n = 258). Temporal trends in survivorship and mortality are assessed via Kaplan–Meier survival analysis and by modeling time period as a covariate affecting the Gompertz hazard of adult mortality.

RESULTS

The age‐at‐death distributions from the two pre‐Black Death time periods are significantly different, with fewer older adults in 13thcentury. The results of Kaplan–Meier survival analysis indicate reductions in survival before the Black Death, with significantly lower survival in the 13thcentury (Mantel Coxp < 0.001). Last, hazard analysis reveals increases in mortality rates before the Black Death.

CONCLUSIONS

Together, these results suggest that health in general was declining in the 13thcentury, and this might have led to high mortality during the Black Death. This highlights the importance of considering human context to understand disease in past and living human populations. Am J Phys Anthropol 158:441–451, 2015. © 2015 Wiley Periodicals, Inc.
Inferring the genetic history of lactase persistence along the Italian peninsula from a large genomic interval surrounding the LCT gene
Authors: De Fanti Sara , Sazzini Marco , Giuliani Cristina , Frazzoni Federica , Sarno Stefania , Boattini Alessio , Marasco Elena , Mantovani Vilma , Franceschi Claudio , Moral Pedro , Garagnani Paolo , Luiselli Donata
Published: July 2015

Objective

Although genetic variants related to lactase persistence in European populations were supposed to have firstly undergone positive selection in farmers from the Balkans and Central Europe, demographic and evolutionary dynamics that subsequently shaped the distribution of this adaptive trait across the continent have still to be elucidated. To deepen the knowledge about potential routes of diffusion of lactase persistence to Western Europe we investigated variation at a large genomic region surrounding the LCT gene along the Italian peninsula, a geographical area that played a key role in population movements responsible for Neolithic diffusion across Europe.

Methods

By genotyping 40 highly selected SNPs in more than 400 Italian individuals we described gradients of nucleotide and haplotype variation potentially related to lactase persistence and compared them with those observed in several European and Mediterranean human groups.

Results

Multiple migratory events responsible for earlier introduction of the examined alleles in Italy than in Northern European regions could be invoked. Different demic processes occurred along the western and eastern sides of the peninsula were also inferred via linkage disequilibrium and population structure analyses.

Conclusion

The appreciable genetic continuum observed between people from Northern or Central‐Western Italy and Central European populations suggested a local arrival of lactase persistence‐related variants mainly via overland routes. On the contrary, diversity of Central‐Eastern and Southern Italian groups entailed also gene flow from South‐Eastern Mediterranean regions, in accordance to the earlier entrance of the Neolithic in Southern Italy via maritime population movements along the Mediterranean coastlines. Am J Phys Anthropol 158:708–718, 2015. © 2015 Wiley Periodicals, Inc.
Post‐Mortem evaluation of amyloid‐dopamine terminal positron emission tomography dementia classifications
Authors: Albin Roger L. , Fisher‐Hubbard Amanda , Shanmugasundaram Krithika , Koeppe Robert A. , Burke James F. , Camelo‐Piragua Sandra , Lieberman Andrew P. , Giordani Bruno , Frey Kirk A.
Published: July 2015

Clinical classification of early dementia and mild cognitive impairment (MCI) is imprecise. We reported previously that molecular imaging classification of early dementia and MCI with dual amyloid and dopamine terminal positron emission tomography differs significantly from expert clinical classification. We now report pathological diagnoses in a substantial subset of our previously imaged subjects. Among 36 subjects coming to autopsy, imaging classifications and pathological diagnosis were concordant in 33 cases (κ = 0.85). This approach enhanced specificity of Alzheimer's disease diagnosis. The strong concordance of imaging‐based classifications and pathological diagnoses suggests that this imaging approach will be useful in establishing more accurate and convenient classification biomarkers for dementia research. Ann Neurol 2015;78:Ann Neurol 2015;78:679–696
Spatial, Hysteretic, and Adaptive Host–Guest Chemistry in a Metal–Organic Framework with Open Watson–Crick Sites
Authors: Cai Hong , Li Mian , Lin Xiao‐Rong , Chen Wei , Chen Guang‐Hui , Huang Xiao‐Chun , Li Dan
Published: July 2015

Biological and artificial molecules and assemblies capable of supramolecular recognition, especially those with nucleobase pairing, usually rely on autonomous or collective binding to function. Advanced site‐specific recognition takes advantage of cooperative spatial effects, as in local folding in protein–DNA binding. Herein, we report a new nucleobase‐tagged metal–organic framework (MOF), namely ZnBTCA (BTC=benzene‐1,3,5‐tricarboxyl, A=adenine), in which the exposed Watson–Crick faces of adenine residues are immobilized periodically on the interior crystalline surface. Systematic control experiments demonstrated the cooperation of the open Watson–Crick sites and spatial effects within the nanopores, and thermodynamic and kinetic studies revealed a hysteretic host–guest interaction attributed to mild chemisorption. We further exploited this behavior for adenine–thymine binding within the constrained pores, and a globally adaptive response of the MOF host was observed.
Construction of Versatile and Functional Nanostructures Derived from CO2‐based Polycarbonates
Authors: Wang Yanyan , Fan Jingwei , Darensbourg Donald J.
Published: July 2015

The construction of amphiphilic polycarbonates through epoxides/CO2 coupling is a challenging aim to provide more diverse CO2‐based functional materials. In this report, we demonstrate the facile preparation of diverse and functional nanoparticles derived from a CO2‐based triblock polycarbonate system. By the judicious use of water as chain‐transfer reagent in the propylene oxide/CO2 polymerization, poly(propylene carbonate (PPC) diols are successfully produced and serve as macroinitiators in the subsequent allyl glycidyl ether/CO2 coupling reaction. The resulting ABA triblock polycarbonate can be further functionalized with various thiols by radical mediated thiol–ene click chemistry, followed by self‐assembly in deionized water to construct a versatile and functional nanostructure system. This class of amphiphilic polycarbonates could embody a powerful platform for biomedical applications.
A Twist‐Bend Nematic (NTB) Phase of Chiral Materials
Authors: Gorecka Ewa , Vaupotič Nataša , Zep Anna , Pociecha Damian , Yoshioka Jun , Yamamoto Jun , Takezoe Hideo
Published: July 2015

New chiral dimers consisting of a rod‐like and cholesterol mesogenic units are reported to form a chiral twist‐bend nematic phase (NTB*) with heliconical structure. The compressibility of the NTB phase made of bent dimers was found to be as large as in smectic phases, which is consistent with the nanoperiodic structure of the NTB phase. The atomic force microscopy observations in chiral bent dimers revealed a periodicity of about 50 nm, which is significantly larger than the one reported previously for non‐chiral compounds (ca. 10 nm).
A Functional Role for Aβ in Metal Homeostasis? N‐Truncation and High‐Affinity Copper Binding
Authors: Mital Mariusz , Wezynfeld Nina E. , Frączyk Tomasz , Wiloch Magdalena Z. , Wawrzyniak Urszula E. , Bonna Arkadiusz , Tumpach Carolin , Barnham Kevin J. , Haigh Cathryn L. , Bal Wojciech , Drew Simon C.
Published: July 2015

Accumulation of the β‐amyloid (Aβ) peptide in extracellular senile plaques rich in copper and zinc is a defining pathological feature of Alzheimer′s disease (AD). The Aβ1–x (x=16/28/40/42) peptides have been the primary focus of CuII binding studies for more than 15 years; however, the N‐truncated Aβ4–42 peptide is a major Aβ isoform detected in both healthy and diseased brains, and it contains a novel N‐terminal FRH sequence. Proteins with His at the third position are known to bind CuII avidly, with conditional log K values at pH 7.4 in the range of 11.0–14.6, which is much higher than that determined for Aβ1–x peptides. By using Aβ4–16 as a model, it was demonstrated that its FRH sequence stoichiometrically binds CuII with a conditional Kd value of 3×10−14 M at pH 7.4, and that both Aβ4–16 and Aβ4–42 possess negligible redox activity. Combined with the predominance of Aβ4–42 in the brain, our results suggest a physiological role for this isoform in metal homeostasis within the central nervous system.
Boronate‐Affinity Glycan‐Oriented Surface Imprinting: A New Strategy to Mimic Lectins for the Recognition of an Intact Glycoprotein and Its Characteristic Fragments
Authors: Bie Zijun , Chen Yang , Ye Jin , Wang Shuangshou , Liu Zhen
Published: July 2015

Lectins possess unique binding properties and are of particular value in molecular recognition. However, lectins suffer from several disadvantages, such as being hard to prepare and showing poor storage stability. Boronate‐affinity glycan‐oriented surface imprinting was developed as a new strategy for the preparation of lectin‐like molecularly imprinted polymers (MIPs). The prepared MIPs could specifically recognize an intact glycoprotein and its characteristic fragments, even within a complex sample matrix. Glycan‐imprinted MIPs could thus prove to be powerful tools for important applications such as proteomics, glycomics, and diagnostics.
Rhodium‐Catalyzed CH Annulation of Nitrones with Alkynes: A Regiospecific Route to Unsymmetrical 2,3‐Diaryl‐Substituted Indoles
Authors: Yan Hao , Wang Haolong , Li Xincheng , Xin Xiaoyi , Wang Chunxiang , Wan Boshun
Published: July 2015

The direct CH annulation of anilines or related compounds with internal alkynes provides straightforward access to 2,3‐disubstituted indole products. However, this transformation proceeds with poor regioselectivity in the synthesis of unsymmetrically 2,3‐diaryl substituted indoles. Herein, we report the rhodium(III)‐catalyzed CH annulation of nitrones with symmetrical diaryl alkynes as an alternative method to prepare 2,3‐diaryl‐substituted N‐unprotected indoles with two different aryl groups. One of the aryl substituents is derived from NC‐aryl ring of the nitrone and the other from the alkyne substrate, thus providing the indole products with exclusive regioselectivity.
A Reaction of Triazoles with Thioesters to Produce β‐Sulfanyl Enamides by Insertion of an Enamine Moiety into the Sulfur–Carbonyl Bond
Authors: Miura Tomoya , Fujimoto Yoshikazu , Funakoshi Yuuta , Murakami Masahiro
Published: July 2015

N‐Sulfonyl‐1,2,3‐triazoles react with thioesters in the presence of a rhodium(II) catalyst to produce β‐sulfanyl enamides in a stereoselective manner. The reaction proceeds through generation of an α‐imino rhodium carbene complex, nucleophilic addition of the sulfur atom of a thioester onto the carbenoid carbon atom, and subsequent intramolecular migration of the acyl group from the sulfur atom to the imino nitrogen atom. The method is successfully applied to a ring‐expansion reaction of thiolactones, thus leading to the formation of sulfur‐containing lactams.
Dynamic Expression of DNA Complexation with Self‐assembled Biomolecular Clusters
Authors: Bartolami Eline , Bessin Yannick , Gervais Virginie , Dumy Pascal , Ulrich Sébastien
Published: July 2015

We report herein the implementation of a dynamic covalent chemistry approach to the generation of multivalent clusters for DNA recognition. We show that biomolecular clusters can be expressed in situ by a programmed self‐assembly process using chemoselective ligations. The cationic clusters are shown, by fluorescence displacement assay, gel electrophoresis and isothermal titration calorimetry, to effectively complex DNA through multivalent interactions. The reversibility of the ligation was exploited to demonstrate that template effects occur, whereby DNA imposes component selection in order to favor the most active DNA‐binding clusters. Furthermore, we show that a chemical effector can be used to trigger DNA release through component exchange reactions.
A Simple NMR‐Based Method for Studying the Spatial Distribution of Linkers within Mixed‐Linker Metal–Organic Frameworks
Authors: Krajnc Andraž , Kos Tomaž , Zabukovec Logar Nataša , Mali Gregor
Published: July 2015

The spatial distribution of different linkers within mixed‐linker metal–organic frameworks crucially influences the properties of such materials. A simple and robust approach based on 1H spin‐diffusion magic‐angle‐spinning nuclear magnetic resonance measurements and modeling of spin‐diffusion curves is presented; this approach facilitates the distinction between homogeneous and clustered distributions. The performance of the approach is demonstrated with an example of an aluminum‐based metal–organic material DUT‐5, which has framework consisting of biphenyl and bipyridyl dicarboxylic linkers. The distribution is shown to be homogeneous in this material. The approach could be applied to studying other spatially disordered crystalline materials.
Visible‐Light‐Induced Click Chemistry
Authors: Mueller Jan O. , Schmidt Friedrich G. , Blinco James P. , Barner‐Kowollik Christopher
Published: July 2015

A rapid and catalyst‐free cycloaddition system for visible‐light‐induced click chemistry is reported. A readily accessible photoreactive 2H‐azirine moiety was designed to absorb light at wavelengths above 400 nm. Irradiation with low‐energy light sources thus enables efficient small‐molecule synthesis with a diverse range of multiple‐bond‐containing compounds. Moreover, in order to demonstrate the efficiency of the current approach, quantitative ligation of the photoactivatable chromophore with functional polymeric substrates was performed and full conversion with irradiation times of only 1 min at ambient conditions was achieved. The current report thus presents a highly efficient method for applications involving selective cycloaddition to electron‐deficient multiple‐bond‐containing materials.
Single‐Vehicular Delivery of Antagomir and Small Molecules to Inhibit miR‐122 Function in Hepatocellular Carcinoma Cells by using “Smart” Mesoporous Silica Nanoparticles
Authors: Yu Changmin , Qian Linghui , Uttamchandani Mahesh , Li Lin , Yao Shao Q.
Published: July 2015

MicroRNAs (miRNAs) regulate a variety of biological processes. The liver‐specific, highly abundant miR‐122 is implicated in many human diseases including cancer. Its inhibition has been found to result in a dramatic loss in the ability of Hepatitis C virus (HCV) to infect host cells. Both antisense technology and small molecules have been used to independently inhibit endogenous miR‐122 function, but not in combination. Intracellular stability, efficient delivery, hydrophobicity, and controlled release are some of the current challenges associated with these novel therapeutic methods. Reported herein is the first single‐vehicular system, based on mesoporous silica nanoparticles (MSNs), for simultaneous cellular delivery of miR‐122 antagomir and small molecule inhibitors. The controlled release of both types of inhibitors depends on the expression levels of endogenous miR‐122, thus enabling these drug‐loaded MSNs to achieve combination inhibition of its targeted mRNAs in Huh7 cells.
A comparative study of hydroxyl‐ and carboxylate‐functionalized imidazolium and benzimidazolium salts as precursors for N‐heterocyclic carbene ligands
Authors: Allegue Andrés , Albert‐Soriano María , Pastor Isidro M.
Published: July 2015

The preparation of imidazolium and benzimidazolium salts with hydroxyl or carboxylate functions has been achieved using straightforward synthetic pathways. These salts in combination with palladium(II) acetate give active catalytic systems for Suzuki reaction. A comparative study has been performed, which has revealed that both the heterocycle and the functional group are important for the catalytic activity and stability of the catalyst. Copyright © 2015 John Wiley & Sons, Ltd.
Cryopreservation of adhered mammalian cells on a microfluidic device: Toward ready‐to‐use cell‐based experimental platforms
Authors: Kondo Eitaro , Wada Ken‐Ichi , Hosokawa Kazuo , Maeda Mizuo
Published: July 2015

In this paper, we describe cryopreservation of mammalian cells in the adhered state on a microfluidic device (microdevice) for the first time. HeLa, NIH3T3, MCF‐7, and PC12 cells were cultured on a microdevice in which a commercial polystyrene dish surface was used as the cell adhesion surface. Without cell‐detaching treatment, the microdevice was stored in a freezer at −80°C. After thawing, we observed a greater number of live cells on the microdevice than those on a control culture dish. Although the effectiveness of the microdevice varied depending on the cell type and surface coating, the trend was consistent. We confirmed that the phenotype of the PC12 cells to differentiate into neuron‐like cells was kept after the on‐chip cryopreservation, and that the results of cytotoxicity test of cisplatin against the HeLa cells were essentially unchanged by the on‐chip cryopreservation. These findings will open up a new possibility of ready‐to‐use cell‐based experimental platforms. Biotechnol. Bioeng. 2016;113: 237–240. © 2015 Wiley Periodicals, Inc.
Structural and functional characteristics of virgin and fouled Protein A MabSelect resin cycled in a monoclonal antibody purification process
Authors: Zhang Shaojie , Xu Kerui , Daniels William , Salm Jeffrey , Glynn Judy , Martin Joseph , Gallo Christopher , Godavarti Ranga , Carta Giorgio
Published: July 2015

The structural and functional characteristics of the Protein A MabSelect resin are determined for a virgin sample and for samples removed from a column that had been operated in an antibody capture process which had shown losses in product recovery over fewer than 20 cycles. Compared to the virgin resin, the cycled samples show reduced porosity and apparent pore size based on inverse size exclusion chromatography while transmission electron microscopy (TEM) shows accumulation of foulants on the cycled resin. Adsorption isotherms, batch adsorption kinetics, and batch desorption kinetics, obtained using the antibody in purified form, show that the cycled samples have about 10% lower binding capacity and slower mass transfer. Confocal scanning laser microscopy shows, however, that different degrees of fouling exist for different beads in the cycled samples, which may correspond to the existence of areas exposed to minimal or no flow in the process column. Replacing the standard cleaning procedure with an improved multi‐step cleaning protocol prevented the accumulation of foulants in the resin beads, as evident from TEM, and resulted in a stable operation with high recovery. Biotechnol. Bioeng. 2016;113: 367–375. © 2015 Wiley Periodicals, Inc.
Three‐dimensional matrix stiffness and adhesive ligands affect cancer cell response to toxins
Authors: Zustiak Silviya Petrova , Dadhwal Smritee , Medina Carlos , Steczina Sonette , Chehreghanianzabi Yasaman , Ashraf Anisa , Asuri Prashanth
Published: July 2015

There is an immediate need to develop highly predictive in vitro cell‐based assays that provide reliable information on cancer drug efficacy and toxicity. Development of biomaterial‐based three‐dimensional (3D) cell culture models as drug screening platforms has recently gained much scientific interest as 3D cultures of cancer cells have been shown to more adequately mimic the in vivo tumor conditions. Moreover, it has been recognized that the biophysical and biochemical properties of the 3D microenvironment can play key roles in regulating various cancer cell fates, including their response to chemicals. In this study, we employed alginate‐based scaffolds of varying mechanical stiffness and adhesive ligand presentation to further explore the role of 3D microenvironmental cues on glioblastoma cell response to cytotoxic compounds. Our experiments suggested the ability of both matrix stiffness and cell‐matrix adhesions to strongly influence cell responses to toxins. Cells were found to be more susceptible to the toxins when cultured in softer matrices that emulated the stiffness of brain tissue. Furthermore, the effect of matrix stiffness on differential cell responses to toxins was negated by the presence of the adhesive ligand RGD, but regained when integrin‐based cell‐matrix interactions were inhibited. This study therefore indicates that both 3D matrix stiffness and cell‐matrix adhesions are important parameters in the design of more predictive in vitro platforms for drug development and toxicity screening. Biotechnol. Bioeng. 2016;113: 443–452. © 2015 Wiley Periodicals, Inc.
Development of a core outcome set for research and audit studies in reconstructive breast surgery
Authors: Potter S , Holcombe C , Ward J A , Blazeby J M , Brookes S T , Cawthorn S J , Harcourt D , Macefield R , Warr R , Weiler-Mithoff E , Williamson P R , Wilson S
Published: July 2015

Background

Appropriate outcome selection is essential if research is to guide decision-making and inform policy. Systematic reviews of the clinical, cosmetic and patient-reported outcomes of reconstructive breast surgery, however, have demonstrated marked heterogeneity, and results from individual studies cannot be compared or combined. Use of a core outcome set may improve the situation. The BRAVO study developed a core outcome set for reconstructive breast surgery.

Methods

A long list of outcomes identified from systematic reviews and stakeholder interviews was used to inform a questionnaire survey. Key stakeholders defined as individuals involved in decision-making for reconstructive breast surgery, including patients, breast and plastic surgeons, specialist nurses and psychologists, were sampled purposively and sent the questionnaire (round 1). This asked them to rate the importance of each outcome on a 9-point Likert scale from 1 (not important) to 9 (extremely important). The proportion of respondents rating each item as very important (score 7–9) was calculated. This was fed back to participants in a second questionnaire (round 2). Respondents were asked to reprioritize outcomes based on the feedback received. Items considered very important after round 2 were discussed at consensus meetings, where the core outcome set was agreed.

Results

A total of 148 items were combined into 34 domains within six categories. Some 303 participants (51·4 per cent) (215 (49·5 per cent) of 434 patients; 88 (56·4 per cent) of 156 professionals) completed and returned the round 1 questionnaire, and 259 (85·5 per cent) reprioritized outcomes in round 2. Fifteen items were excluded based on questionnaire scores and 19 were carried forward to the consensus meetings, where a core outcome set containing 11 key outcomes was agreed.

Conclusion

The BRAVO study has used robust consensus methodology to develop a core outcome set for reconstructive breast surgery. Widespread adoption by the reconstructive community will improve the quality of outcome assessment in effectiveness studies. Future work will evaluate how these key outcomes should best be measured.
Measurement of ceftazidime concentration in human plasma by ultra‐performance liquid chromatography–tandem mass spectrometry. Application to critically ill patients and patients with osteoarticular infections
Authors: Rigo‐Bonnin Raül , Cobo‐Sacristán Sara , Padullés Ariadna , Ribera Alba , Arbiol‐Roca Ariadna , Murillo Óscar , Sabater‐Riera Joan , Alía Pedro
Published: July 2015

Ceftazidime is an antibiotic belonging to the third generation of the cephalosporin family. It is indicated in the treatment of serious, simple or mixed bacterial infections, and its administration in continuous or intermittent infusion allows optimization of the concentration of antibiotic to keep it above the minimum inhibitory concentration. We developed and validated a chromatographic method by ultra‐performance liquid chromatography–tandem mass spectrometry to measure ceftazidime concentration in human plasma. Following extraction with acetonitrile and 1,2‐dichloroethane, the chromatographic separation was achieved using an Acquity ® UPLC ® BEHTM (2.1 × 100 mm i.d., 1.7 µm) reverse‐phase C18 column, with a water–acetonitrile linear gradient containing 0.1% formic acid at a 0.4 mL/min flow rate. Ceftazidime and its internal standard (cefotaxime) were detected by electrospray ionization mass spectrometry in positive ion multiple reaction monitoring mode using mass‐to‐charge transitions of 547.0 → 467.9/396.1 and 456.0 → 395.8/324.1, respectively. The limit of quantification was 0.58 mg/L and linearity was observed in the range 0.58–160 mg/L. Coefficients of variation and absolute relative biases were <9.8 and 8.4%. The mean recovery for ceftazidime was 74.4 ± 8.1%. Evaluation of the matrix effect showed ion enhancement, and no carry‐over was observed. The validated method could be applied to daily clinical laboratory practice to measure the concentration of ceftazidime in plasma. Copyright © 2015 John Wiley & Sons, Ltd.
LC‐MS/MS determination of 1‐O‐acetylbritannilactone in rat plasma and its application to a preclinical pharmacokinetic study
Authors: Li Huajun , Li Wei , Yu Min , Jiang Ligang
Published: July 2015

A novel, rapid and sensitive LC‐MS/MS method for the determination of 1‐O‐Acetylbritannilactone (ABL), a sesquiterpene lactone abundant in Inula britannica, was developed and validated using heteroclitin D as internal standard. Separation was achieved on a reversed phase Hypersil Gold C18 column (50 × 4.6 mm, i.d., 3.0 µm) using isocratic elution with methanol–5 mM ammonium acetate buffer aqueous solution (80:20, v/v) at a flow rate of 0.4 mL/min. Calibration curve was linear (r > 0.99) in a concentration range of 1.60–800 ng/mL with the lower limit of quantification of 1.60 ng/mL. Intra‐ and inter‐day accuracy and precision were validated by relative error (RE) and relative standard deviation (RSD) values, respectively, which were both less than ±15%. The validated method has been successfully applied to a pharmacokinetic study of ABL in rats. The elimination half‐lives were 0.412 ± 0.068, 0.415 ± 0.092 and 0.453 ± 0.071 h after a single intravenous administration of 0.14, 0.42, and 1.26 mg/kg ABL, respectively. The area under the plasma concentration–time curve from time zero to the last quantifiable time point and from time zero to infinity and the plasma concentrations at 2 min were linearly related to the doses tested. Copyright © 2015 John Wiley & Sons, Ltd.
Diagnostic accuracy for major depression in multiple sclerosis using self‐report questionnaires
Authors: Fischer Anja , Fischer Marcus , Nicholls Robert A. , Lau Stephanie , Poettgen Jana , Patas Kostas , Heesen Christoph , Gold Stefan M.
Published: July 2015

Objective

Multiple sclerosis and major depressive disorder frequently co‐occur but depression often remains undiagnosed in this population. Self‐rated depression questionnaires are a good option where clinician‐based standardized diagnostics are not feasible. However, there is a paucity of data on diagnostic accuracy of self‐report measures for depression in multiple sclerosis (MS). Moreover, head‐to‐head comparisons of common questionnaires are largely lacking. This could be particularly relevant for high‐risk patients with depressive symptoms. Here, we compare the diagnostic accuracy of the Beck Depression Inventory (BDI) and 30‐item version of the Inventory of Depressive Symptomatology Self‐Rated (IDS‐SR30) for major depressive disorder (MSS) against diagnosis by a structured clinical interview.

Methods

Patients reporting depressive symptoms completed the BDI, the IDS‐SR30 and underwent diagnostic assessment (Mini International Neuropsychiatric Interview, M.I.N.I.). Receiver‐Operating Characteristic analyses were performed, providing error estimates and false‐positive/negative rates of suggested thresholds.

Results

Data from n = 31 MS patients were available. BDI and IDS‐SR30 total score were significantly correlated (r = 0.82). The IDS‐SR30total score, cognitive subscore, and BDI showed excellent to good accuracy (area under the curve (AUC) 0.86, 0.91, and 0.85, respectively).

Conclusion

Both the IDS‐SR30 and the BDI are useful to quantify depressive symptoms showing good sensitivity and specificity. The IDS‐SR30 cognitive subscale may be useful as a screening tool and to quantify affective/cognitive depressive symptomatology.
Inhibition of MCL‐1 by obatoclax sensitizes Sp2/0‐Ag14 hybridoma cells to glutamine deprivation‐induced apoptosis
Authors: Harnett Curtis C. , Abusneina Abdelmuhsen , Clément Julie , Gauthier Eric R.
Published: July 2015

For several cancer cell types, the lack of an adequate supply of the amino acidl‐glutamine (Gln) triggers apoptosis, a phenomenon termed Gln addiction. In this report, we examined the role of the anti‐apoptotic proteins of the B‐cell lymphoma 2 (BCL‐2) protein family in the survival of Sp2/0‐Ag14 (Sp2/0) mouse hybridoma cells, a cell line that undergoes apoptosis within minutes of Gln deprivation. Western blot analysis revealed that myeloid cell leukaemia 1 (MCL‐1) was expressed at much higher levels than BCL‐2, B‐cell lymphoma extra‐large and BCL‐2‐like protein 2 making it the prominent pro‐survival BCL‐2 family member in this hybridoma. Gln deprivation triggered a progressive decrease in MCL‐1 protein levels, which coincided with the decrease in Sp2/0 cell survival. Moreover, Sp2/0 cells were much more sensitive to the broad Bcl‐2 homology domain‐3 (BH3) mimetic obatoclax (which targets MCL‐1) than to the more selective drug ABT‐737 (which does not target MCL‐1). Finally, we show that obatoclax sensitizes Sp2/0 cells to apoptosis following Gln starvation. All together, the data presented here reveal that modulation of the pro‐survival protein MCL‐1 is an important step in the sequence of events leading to the initiation of apoptosis in Gln‐starved Sp2/0 cells. Cancer cells require an adequate supply ofl‐glutamine for their survival. Using a mouse hybridoma cell line that is exquisitely sensitive to glutamine starvation, we show that the levels of the pro‐survival BCL‐2 family protein MCL‐1 decrease upon glutamine starvation in a manner that correlates with the loss of cell viability. Moreover, inhibiting MCL‐1 with the drug obatoclax sensitizes hybridoma cells to glutamine starvation. Thus, in some cancer cells, glutamine starvation triggers the inactivation of pro‐survival proteins. Our data suggest that the combined inhibition of glutamine biosynthesis pathways and BCL‐2 proteins may prove effective against some cancers. Copyright © 2015 John Wiley & Sons, Ltd.
LINE‐1 hypomethylation induced by reactive oxygen species is mediated via depletion of S‐adenosylmethionine
Authors: Kloypan Chiraphat , Srisa‐art Monpicha , Mutirangura Apiwat , Boonla Chanchai
Published: July 2015

Whether long interspersed nuclear element‐1 (LINE‐1) hypomethylation induced by reactive oxygen species (ROS) was mediated through the depletion of S‐adenosylmethionine (SAM) was investigated. Bladder cancer (UM‐UC‐3 and TCCSUP) and human kidney (HK‐2) cell lines were exposed to 20 μM H2O2 for 72 h to induce oxidative stress. Level of LINE‐1 methylation, SAM and homocysteine (Hcy) was measured in the H2O2‐exposed cells. Effects of α‐tocopheryl acetate (TA), N‐acetylcysteine (NAC), methionine, SAM and folic acid on oxidative stress and LINE‐1 methylation in the H2O2‐treated cells were explored. Viabilities of cells treated with H2O2 were not significantly changed. Intracellular ROS production and protein carbonyl content were significantly increased, but LINE‐1 methylation was significantly decreased in the H2O2‐treated cells. LINE‐1 methylation was restored by TA, NAC, methionine, SAM and folic acid. SAM level in H2O2‐treated cells was significantly decreased, while total glutathione was significantly increased. SAM level in H2O2‐treated cells was restored by NAC, methionine, SAM and folic acid; while, total glutathione level was normalized by TA and NAC. Hcy was significantly decreased in the H2O2‐treated cells and subsequently restored by NAC. In conclusion, in bladder cancer and normal kidney cells exposed to H2O2, SAM and Hcy were decreased, but total glutathione was increased. Treatments with antioxidants (TA and NAC) and one‐carbon metabolites (SAM, methionine and folic acid) restored these changes. This pioneer finding suggests that exposure of cells to ROS activates glutathione synthesis via the transsulfuration pathway leading to deficiency of Hcy, which consequently causes SAM depletion and eventual hypomethylation of LINE‐1. Copyright © 2015 John Wiley & Sons, Ltd.
A Bi‐enzymatic Convergent Cascade for ε‐Caprolactone Synthesis Employing 1,6‐Hexanediol as a ‘Double‐Smart Cosubstrate’
Authors: Bornadel Amin , Hatti‐Kaul Rajni , Hollmann Frank , Kara Selin
Published: July 2015

A bi‐enzymatic cascade consisting of a Baeyer–Villiger monooxygenase and an alcohol dehydrogenase (ADH) was designed in a convergent fashion to utilise two molar equivalents of cyclohexanone (CHO) and one equivalent of 1,6‐hexanediol as a ‘double‐smart cosubstrate’ to produce ε‐caprolactone (ECL) with water as sole by‐product. The convergent enzymatic cascade reaction reported herein, is performed at ambient conditions in water, is self‐sufficient with respect to cofactor, and incorporates all starting materials into the desired product, ECL. Among different enzymes explored, the reaction catalysed by cyclohexanone monooxygenase from Acinetobacter sp. NCIMB 9871 coupled with ADH from Thermoanaerobacter ethanolicus showed the best results, reaching 91 % conversion of CHO after 24 h with a product titre of 2 g L−1. Scale‐up of the coupled system (50 mL) performed better than the small‐scale reactions and >99 % conversion of CHO and ECL concentration of 20 mM were achieved within 18 h.
Nanoporosity, Inclusion Chemistry, and Spin Crossover in Orthogonally Interlocked Two‐Dimensional Metal–Organic Frameworks
Authors: Romero‐Morcillo Tania , De la Pinta Noelia , Callejo Lorena M. , Piñeiro‐López Lucía , Muñoz M. Carmen , Madariaga Gotzon , Ferrer Sacramento , Breczewski Tomasz , Cortés Roberto , Real José A.
Published: July 2015

[Fe(tvp)2(NCS)2] (1) (tvp=trans‐(4,4′‐vinylenedipyridine)) consists of two independent perpendicular stacks of mutually interpenetrated two‐dimensional grids. This uncommon supramolecular conformation defines square‐sectional nanochannels (diagonal≈2.2 nm) in which inclusion molecules are located. The guest‐loaded framework 1@guest displays complete thermal spin‐crossover (SCO) behavior with the characteristic temperature T1/2 dependent on the guest molecule, whereas the guest‐free species 1 is paramagnetic whatever the temperature. For the benzene–guest derivatives, the characteristic SCO temperature T1/2 decreases as the Hammet σp parameter increases. In general, the 1@guest series shows large entropy variations associated with the SCO and conformational changes of the interpenetrated grids that leads to a crystallographic‐phase transition when the guest is benzonitrile or acetonitrile/H2O.
Pincer‐Type Complexes for Catalytic (De)Hydrogenation and Transfer (De)Hydrogenation Reactions: Recent Progress
Authors: Werkmeister Svenja , Neumann Jacob , Junge Kathrin , Beller Matthias
Published: July 2015

Pincer complexes are becoming increasingly important for organometallic chemistry and organic synthesis. Since numerous applications for such catalysts have been developed in recent decades, this Minireview covers progress in their use as catalysts for (de)hydrogenation and transfer (de)hydrogenation reactions during the last four years. Aside from noble‐metal‐based pincer complexes, the corresponding base metal complexes are also highlighted and their applications summarized.
Syntheses, Spectroscopic, Electrochemical, and Third‐Order Nonlinear Optical Studies of a Hybrid Tris{ruthenium(alkynyl)/(2‐phenylpyridine)}iridium Complex
Authors: Zhao Huajian , Simpson Peter V. , Barlow Adam , Moxey Graeme J. , Morshedi Mahbod , Roy Nivya , Philip Reji , Zhang Chi , Cifuentes Marie P. , Humphrey Mark G.
Published: July 2015

The synthesis of fac‐[Ir{N,C1′‐(2,2′‐NC5H4C6H3‐5′‐CC‐1‐C6H2‐3,5‐Et2‐4‐CCC6H4‐4‐CCH)}3] (10), which bears pendant ethynyl groups, and its reaction with [RuCl(dppe)2]PF6 to afford the heterobimetallic complex fac‐[Ir{N,C1′‐(2,2′‐NC5H4C6H3‐5′‐CC‐1‐C6H2‐3,5‐Et2‐4‐CCC6H4‐4‐CC‐trans‐[RuCl(dppe)2])}3] (11) is described. Complex 10 is available from the two‐step formation of iodo‐functionalized fac‐tris[2‐(4‐iodophenyl)pyridine]iridium(III) (6), followed by ligand‐centered palladium‐catalyzed coupling and desilylation reactions. Structural studies of tetrakis[2‐(4‐iodophenyl)pyridine‐N,C1′](μ‐dichloro)diiridium 5, 6, fac‐[Ir{N,C1′‐(2,2′‐NC5H4C6H3‐5′‐CC‐1‐C6H2‐3,5‐Et2‐4‐CCH)}3] (8), and 10 confirm ligand‐centered derivatization of the tris(2‐phenylpyridine)iridium unit. Electrochemical studies reveal two (5) or one (6–10) Ir‐centered oxidations for which the potential is sensitive to functionalization at the phenylpyridine groups but relatively insensitive to more remote derivatization. Compound 11 undergoes sequential Ru‐centered and Ir‐centered oxidation, with the potential of the latter significantly more positive than that of Ir(N,C′‐NC5H4‐2‐C6H4‐2)3. Ligand‐centered π–π* transitions characteristic of the Ir(N,C′‐NC5H4‐2‐C6H4‐2)3 unit red‐shift and gain in intensity following the iodo and alkynyl incorporation. Spectroelectrochemical studies of 6, 7, 9, and 11 reveal the appearance in each case of new low‐energy LMCT bands following formal IrIII/IV oxidation preceded, in the case of 11, by the appearance of a low‐energy LMCT band associated with the formal RuII/III oxidation process. Emission maxima of 6–10 reveal a red‐shift upon alkynyl group introduction and arylalkynyl π‐system lengthening; this process is quenched upon incorporation of the ligated ruthenium moiety on proceeding to 11. Third‐order nonlinear optical studies of 11 were undertaken at the benchmark wavelengths of 800 nm (fs pulses) and 532 nm (ns pulses), the results from the former suggesting a dominant contribution from two‐photon absorption, and results from the latter being consistent with primarily excited‐state absorption.
Carboxylated, Fe‐Filled Multiwalled Carbon Nanotubes as Versatile Catalysts for O2 Reduction and H2 Evolution Reactions at Physiological pH
Authors: Bracamonte M. Victoria , Melchionna Michele , Stopin Antoine , Giulani Angela , Tavagnacco Claudio , Garcia Yann , Fornasiero Paolo , Bonifazi Davide , Prato Maurizio
Published: July 2015

The development of new electrocatalysts for the oxygen reduction reaction (ORR) and hydrogen evolution reaction (HER) at physiological pH is critical for several fields, including fuel cells and biological applications. Herein, the assembly of an electrode based on carboxyl‐functionalised hydrophilic multiwalled carbon nanotubes (MWCNTs) filled with Fe phases and their excellent performance as electrocatalysts for ORR and HER at physiological pH are reported. The encapsulated Fe dramatically enhances the catalytic activity, and the graphitic shells play a double role of efficiently mediating the electron transfer to O2 and H2O reactants and providing a cocoon that prevents uncontrolled Fe oxidation or leaching.
Comprehensive Study of the Organic‐Solvent‐Free CDI‐Mediated Acylation of Various Nucleophiles by Mechanochemistry
Authors: Métro Thomas‐Xavier , Bonnamour Julien , Reidon Thomas , Duprez Anthony , Sarpoulet Jordi , Martinez Jean , Lamaty Frédéric
Published: July 2015

Acylation reactions are ubiquitous in the synthesis of natural products and biologically active compounds. Unfortunately, these reactions often require the use of large quantities of volatile and/or toxic solvents, either for the reaction, purification or isolation of the products. Herein we describe and discuss the possibility of completely eliminating the use of organic solvents for the synthesis, purification and isolation of products resulting from the acylation of amines and other nucleophiles. Thus, utilisation of N,N′‐carbonyldiimidazole (CDI) allows efficient coupling between carboxylic acids and various nucleophiles under solvent‐free mechanical agitation, and water‐assisted grinding enables both the purification and isolation of pure products. Critical parameters such as the physical state and water solubility of the products, milling material, type of agitation (vibratory or planetary) as well as contamination from wear are analysed and discussed. In addition, original organic‐solvent‐free conditions are proposed to overcome the limitations of this approach. The calculations of various green metrics are included, highlighting the particularly low environmental impact of this strategy.
Experimental Evidence on the Formation of Ethene through Carbocations in Methanol Conversion over H‐ZSM‐5 Zeolite
Authors: Wang Chao , Yi Xianfeng , Xu Jun , Qi Guodong , Gao Pan , Wang Weiyu , Chu Yueying , Wang Qiang , Feng Ningdong , Liu Xiaolong , Zheng Anmin , Deng Feng
Published: July 2015

The methanol to olefins conversion over zeolite catalysts is a commercialized process to produce light olefins like ethene and propene but its mechanism is not well understood. We herein investigated the formation of ethene in the methanol to olefins reaction over the H‐ZSM‐5 zeolite. Three types of ethylcyclopentenyl carbocations, that is, the 1‐methyl‐3‐ethylcyclopentenyl, the 1,4‐dimethyl‐3‐ethylcyclopentenyl, and the 1,5‐dimethyl‐3‐ethylcyclopentenyl cation were unambiguously identified under working conditions by both solid‐state and liquid‐state NMR spectroscopy as well as GC‐MS analysis. These carbocations were found to be well correlated to ethene and lower methylbenzenes (xylene and trimethylbenzene). An aromatics‐based paring route provides rationale for the transformation of lower methylbenzenes to ethene through ethylcyclopentenyl cations as the key hydrocarbon‐pool intermediates.
Recent Progress toward the Introduction of Functionalized Difluoromethylated Building Blocks onto C(sp2) and C(sp) Centers
Authors: Belhomme Marie‐Charlotte , Besset Tatiana , Poisson Thomas , Pannecoucke Xavier
Published: July 2015

Fluorine chemistry is a field undergoing tremendous expansion. Although much attention has been paid to the introduction of the fluorine atom and the CF3 group, less interest has been devoted to the introduction of functionalized fluorinated building blocks, in sharp contrast with the high versatility of the fluorinated products. In this Minireview, the most relevant methods for the introduction of difluoromethylated building blocks are summarized. Access to difluoromethylated arenes, alkenes, and alkynes is highlighted and special attention is paid to explanation of the reaction mechanism.
Cobalt‐Catalyzed Cross‐Coupling of 3‐ and 4‐Iodopiperidines with Grignard Reagents
Authors: Gonnard Laurine , Guérinot Amandine , Cossy Janine
Published: July 2015

A cobalt‐catalyzed cross‐coupling between 3‐ and 4‐iodopiperidines and Grignard reagents is disclosed. The reaction is an efficient, cheap, chemoselective, and flexible way to functionalize piperidines. This coupling was used as the key step to realize a short synthesis of (±)‐preclamol. Some mechanistic investigations were conducted that highlight the formation of radical intermediates.
Bifunctional Indenyl‐Derived Receptors for Fluoride Chelation and Detection
Authors: Tirfoin Rémi , Abdalla Joseph A. B. , Aldridge Simon
Published: July 2015

Anion receptors based on a [CpFe(indenyl)] scaffold offer the possibility for the incorporation of adjacent Lewis acidic functions onto a six‐membered carbocyclic framework, while at the same time retaining the colorimetric/electrochemical reporter mechanisms available to synthetically simpler ferrocene systems. Thus, [CpFe(indenyl)] systems featuring mutually ortho BMes2 and PPh2Me+ substituents (with either 4,5 or 5,6 regiochemistry) are accessible which are capable of cooperative fluoride ion fixation. Simultaneous binding at the borane and phosphonium centres can be established by spectroscopic, structural and computational approaches, and is responsible for the favourable thermodynamics associated with F− uptake. Thus, in contrast to simple BMes2 systems, the binding of fluoride is found to be more favourable than the uptake of cyanide (which interacts only with the borane Lewis acid). Moreover, in the case of a 4‐(MePh2P)‐5‐(Mes2B)‐7‐Me‐indenyl derivative, fluoride chelation is signalled not only by a large cathodic shift in the FeII/FeIII potential (>500 mV in THF), but also by a distinct colour change from green (for the free receptor) to maroon for the adduct.