bluuebunny/crossref_metadata_2025 huggingface dataset:
VP7 and VP8* genetic characterization of group A rotavirus genotype G12P[8]: Emergence and spreading in the Eastern Brazilian coast in 2014
Authors: da Silva Marcelle Figueira Marques , Fumian Tulio Machado , de Assis Rosane Maria Santos , Fialho Alexandre Madi , Carvalho‐Costa Filipe Anibal , da Silva Ribeiro de Andrade Juliana , Leite José Paulo Gagliardi
Published: June 2016

Group A rotavirus (RVA) genotype G12 is habitually associated with diarrhea disease (DD) in African children and recently its detection has increased worldwide. A total of 970 stool samples collected from individuals with DD in the Northeastern, Southeastern, and Southern Brazilian regions, Eastern coast, were analyzed and 321 (33%) were positive for RVA and of these, 241 (75%) genotyped as G12P[8]. The rate of RVA positivity was higher among children aged 5–10 years old (60%). All RVA infections observed in adults aged >21 years were G12P[8] (n = 27) showing that this genotype affected older age groups during the year of 2014 in Brazil. Phylogenetic analysis of VP7 and VP8* G12P[8] strains demonstrated an elevated similarity among Brazilian and G12‐III prototypes strains circulating worldwide recently, suggesting that this lineage is associated with the global spread of the G12 genotype, considered as the 6th most prevalent human RVA genotype nowadays; while other G12 lineages remain sporadically detected and usually detected in association with other P genotypes. VP8* analysis revealed that Brazilian strains belong to P[8]‐3 lineage, the single P[8] lineage presently detected in the country. No major nucleotide/amino acid disparities were observed among strains recovered from children and adults for VP7 and VP8* genes. These data are essential to support the surveillance studies, particularly in countries where the RVA vaccine was introduced in their National Immunization Program enabling identification of potential alterations in the epidemiological profile that can impact its efficacy in vaccination programs. J. Med. Virol. 89:64–70, 2017. © 2016 Wiley Periodicals, Inc.
An optogenetic mouse model of rett syndrome targeting on catecholaminergic neurons
Authors: Zhang Shuang , Johnson Christopher M. , Cui Ningren , Xing Hao , Zhong Weiwei , Wu Yang , Jiang Chun
Published: June 2016

Rett syndrome (RTT) is a neurodevelopmental disorder affecting multiple functions, including the norepinephrine (NE) system. In the CNS, NE is produced mostly by neurons in the locus coeruleus (LC), where defects in intrinsic neuronal properties, NE biosynthetic enzymes, neuronal CO2 sensitivity, and synaptic currents have been reported in mouse models of RTT. LC neurons in methyl‐CpG‐binding protein 2 gene (Mecp2) null mice show a high rate of spontaneous firing, although whether such hyperexcitability might increase or decrease the NE release from synapses is unknown. To activate the NEergic axonal terminals selectively, we generated an optogenetic mouse model of RTT in which NEergic neuronal excitability can be manipulated with light. Using commercially available mouse breeders, we produced a new strain of double‐transgenic mice with Mecp2 knockout and channelrhodopsin (ChR) knockin in catecholaminergic neurons. Several RTT‐like phenotypes were found in the tyrosine hydroxylase (TH)‐ChR‐Mecp2−/Y mice, including hypoactivity, low body weight, hindlimb clasping, and breathing disorders. In brain slices, optostimulation produced depolarization and an increase in the firing rate of LC neurons from TH‐ChR control mice. In TH‐ChR control mice, optostimulation of presynaptic NEergic neurons augmented the firing rate of hypoglossal neurons (HNs), which was blocked by the α‐adrenoceptor antagonist phentolamine. Such optostimulation of NEergic terminals had almost no effect on HNs from two or three TH‐ChR‐Mecp2−/Y mice, indicating that excessive excitation of presynaptic neurons does not benefit NEergic modulation in mice with Mecp2 disruption. These results also demonstrate the feasibility of generating double‐transgenic mice for studies of RTT with commercially available mice, which are inexpensive, labor/time efficient, and promising for cell‐specific stimulation. © 2016 Wiley Periodicals, Inc.
Combination of the clustered regularly interspaced short palindromic repeats (CRISPR)‐associated 9 technique with the piggybac transposon system for mouse in utero electroporation to study cortical development
Authors: Cheng Man , Jin Xubin , Mu Lili , Wang Fangyu , Li Wei , Zhong Xiaoling , Liu Xuan , Shen Wenchen , Liu Ying , Zhou Yan
Published: June 2016

In utero electroporation (IUE) is commonly used to study cortical development of cerebrum by downregulating or overexpressing genes of interest in neural progenitor cells (NPCs) of small mammals. However, exogenous plasmids are lost or diluted over time. Furthermore, gene knockdown based on short‐hairpin RNAs may exert nonspecific effects that lead to aberrant neuronal migration. Genomic engineering by the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated 9 (Cas9) system has great research and therapeutic potentials. Here we integrate the CRISPR/Cas9 components into the piggyBac (PB) transposon system (the CRISPR/Cas9‐PB toolkit) for cortical IUEs. The mouse Sry‐related HMG box‐2 (Sox2) gene was selected as the target for its application. Most transduced cortical NPCs were depleted of SOX2 protein as early as 3 days post‐IUE, whereas expressions of SOX1 and PAX6 remained intact. Furthermore, both the WT Cas9 and the D10A nickase mutant Cas9n showed comparable knockout efficiency. Transduced cortical cells were purified with fluorescence‐activated cell sorting, and effective gene editing at the Sox2 loci was confirmed. Thus, application of the CRISPR/Cas9‐PB toolkit in IUE is a promising strategy to study gene functions in cortical NPCs and their progeny. © 2016 Wiley Periodicals, Inc.
Effects of repetitive low‐pressure explosive blast on primary neurons and mixed cultures
Authors: Zander Nicole E. , Piehler Thuvan , Banton Rohan , Benjamin Richard
Published: June 2016

Repetitive mild traumatic brain injury represents a considerable health concern, particularly for athletes and military personnel. For blast‐induced brain injury, threshold shock‐impulse levels required to induce such injuries and cumulative effects with single and/or multiple exposures are not well characterized. Currently, there is no established in vitro experimental model with blast pressure waves generated by live explosives. This study presents results of primary neurons and mixed cultures subjected to our unique in vitro indoor experimental platform that uses real military explosive charges to probe the effects of primary explosive blast at the cellular level. The effects of the blast on membrane permeability, generation of reactive oxygen species (ROS), uptake of sodium ions, intracellular calcium, and release of glutamate were probed 2 and 24 hr postblast. Significant changes in membrane permeability and sodium uptake among the sham, single‐blast‐injured, and triple‐blast‐injured samples were observed. A significant increase in ROS and glutamate release was observed for the triple‐blast‐injured samples compared with the sham. Changes in intracellular calcium were not significant. These results suggest that blast exposure disrupts the integrity of the plasma membrane, leading to the upset of ion homeostasis, formation of ROS, and glutamate release. Published 2016. †This article is a U.S. Government work and is in the public domain in the USA
Effective version of self‐approximation for the Riemann zeta function
Authors: Nakamura Takashi , Pańkowski Łukasz
Published: June 2016

In the paper we prove an effective version of self‐approximation for the Riemann zeta function.
Self‐Assembly of Differently Shaped Protein–Polymer Conjugates through Modification of the Bioconjugation Site
Authors: Huang Aaron , Olsen Bradley D.
Published: June 2016

Self‐assembly of protein–polymer block copolymers is an attractive route for preparing biocatalytic materials. To clarify the effect of bioconjugate shape on self‐assembly without changing the chemical details of either block, four different conjugation sites are selected on the surface of the model globular protein mCherry at residues 3, 108, 131, and 222 to alter the colloidal shape of the bioconjugate. All four mCherry‐b‐poly(N‐isopropylacrylamide) bioconjugates show qualitatively similar phase diagrams, indicating that self‐assembly is robust with respect to changes in conjugation site. However, protein orientation has an effect on the location of the order–disorder transition concentration, and the stability of the disordered micellar phase is shown to be different for each conjugate. Differences in domain spacing also suggest changes in protein orientation within the lamellae.

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Quantitative Measurement of Akinesia in Parkinson's Disease
Authors: Lalvay Lissette , Lara Miguel , Mora Andrea , Alarcón Fernando , Fraga Manuel , Pancorbo Jesús , Marina José Luis , Mena María Ángeles , Lopez Sendón Jose Luis , García de Yébenes Justo
Published: June 2016

Background

There is great interest in developing simple, user‐friendly, and inexpensive tools for the quantification and elucidation of motor deficits in patients with Parkinson's disease (PD). These systems could help to monitor the clinical status of patients with PD, to develop better treatments, and to identify individuals who have subtle motor signs that might pass unnoticed in the conventional neurological examination.

Methods

Mememtum, a smartphone application that allows for the quantification of several parameters of movement, such as regularity, rhythm, and changes in the number of taps while taping with a single finger and with alternating fingers, was developed and then tested in a pilot study in Madrid and in an extensive study in Quito, Ecuador.

Results

Almost all patients could successfully perform single‐finger tapping, but approximately 10% of patients with severe parkinsonism had problems taping with alternating fingers. The results revealed changes in the regularity of the pressure applied while tapping and a reduction in the number of taps on the device screen when alternating tapping among patients who had idiopathic PD and vascular parkinsonism compared with controls and individuals who had prediagnostic motor abnormalities of PD.

Conclusion

Applications available in smartphones could be used for investigation and treatment of patients with PD, but much research is needed to optimize the ideal parameters to be investigated and the potential usefulness of this technique for patients with PD in different stages of the disease.
Outcome on Balance and Gait Following Botulinum Toxin Treatment for Striatal Foot in Parkinson's Disease
Authors: Lindholm Beata , Beckman Anders , Duzynski Wojciech , Ekvall Hansson Eva
Published: June 2016

Background

Striatal foot deformity can shorten the stance phase of gait and impair the ability to stand and walk. Botulinum neurotoxin type A (BoNT A) is a treatment option. However, no previous study has included clinical balance testing in the evaluation of treatment effects. The aim of this study was to evaluate gait and balance in patients with striatal foot deformities and Parkinson's disease (PD) before and after treatment with BoNT A injections.

Method

The study included 10 patients with PD and striatal foot deformity who visited a neurological clinic. The mean ± standard deviation age and PD‐duration was 62.8 ± 8.8 years and 4.9 ± 3.6 years, respectively. Clinical assessment was made before and 4 and 16 weeks after injection and included 5 clinical gait and balance tests. The intensity of distress due to deformities was investigated with a visual analogue scale. Parkinsonian motor status was assessed with the Unified Parkinson's Disease Rating Scale part III (motor part). Based on ordinary clinical examination, electromyography‐guided BoNT A injection was given in affected muscles. Clinically effective doses of BoNT A were used.

Results

Improvements were observed regarding functional, dynamic, and standing balance as well as intensity of distress at 4 weeks but not at 16 weeks compared with baseline.

Conclusions

BoNT A injection treatment improved gait and balance in patients with PD and striatal foot deformities. Multicenter trials are needed; and, to achieve increased power, a randomized, double‐blind controlled design is needed and should focus on the ability of tests to capture subtle changes in gait and balance.
Further Insights in the Binding Mode of Selective Inhibitors to Human PDE4D Enzyme Combining Docking and Molecular Dynamics
Authors: D'Ursi Pasqualina , Guariento Sara , Trombetti Gabriele , Orro Alessandro , Cichero Elena , Milanesi Luciano , Fossa Paola , Bruno Olga
Published: June 2016

Alzheimer′s disease has recently emerged as a possible field of application for PDE4D inhibitors (PDE4DIs). The great structure similarity among the various PDE4 isoforms and, furthermore, the lack of the full length crystal structure of the enzyme, impaired the rational design of new selective PDE4DIs. In this paper, with the aim of exploring new insights into the PDE4D binding, we tackled the problem by performing a computational study based on docking simulations combined with molecular dynamics (D‐MD). Our work uniquely identified the binding mode and the key residues involved in the interaction with a number of in‐house catechol iminoether derivatives, acting as PDE4DIs. Moreover, the new binding mode was tested using a series of analogues previously reported by us and it was used to confirm their key structural features to allow PDE4D inhibition. The binding model disclosed within the current computational study may prove to be useful to further advance the design and synthesis of novel, more potent and selective, PDE4D inhibitors.
Variations in TAS1R taste receptor gene family modify food intake and gastric cancer risk in a Korean population
Authors: Choi Jeong‐Hwa , Lee Jeonghee , Choi Il Ju , Kim Young‐Woo , Ryu Keun Won , Kim Jeongseon
Published: June 2016

Scope

Human taste receptor type 1 (TAS1R, T1R) gene family mediates the perception of umami and sweet tastes and regulates metabolism. This study investigated whether variants in the TAS1R are associated with food intake and susceptibility to gastric cancer (GC).

Methods and results

A total of 1131 Koreans including 377 GC cases were analyzed to determine the dietary intake and genotype for 25 variants in TAS1R genes. Among the genotyped polymorphisms, six loci with a minor allele frequency >0.05 were tested for an association with dietary intake and GC risk. Findings suggest that TAS1R polymorphisms were associated with a variety of food intake that is beyond the known T1R‐taste association. Furthermore, differential consumption for cigarettes and citrus fruits by TAS1R genetic variants may be linked to GC risk in males and females, respectively. Additionally, in males, TAS1R1 rs34160967 heterozygote showed an increased risk of GC (odds ratio: 1.52, 95% confidence interval: 1.10–2.09), independent of dietary intake. However, this GC‐risk effect of TAS1R variants was not evident in females.

Conclusions

Genetic variants in TAS1R were associated with dietary consumption, which may be associated with GC risk. TAS1R1 rs34160967 may also modify the risk for GC independent of diet in Korean males.
Transfer of Semibatch Processes to Continuous Processes with Side Injections—Opportunities and Limitations
Authors: Goerke Thilo , Kohlmann Daniel , Engell Sebastian
Published: June 2016

The transfer of copolymerization processes from discontinuous plants to continuous plants has become a topic of industrial interest in the recent years. The motivations for such a transfer are better product consistency, smaller capital investment, and smaller footprint of the plants. However the experiences of the F3 project show that some copolymerization processes cannot be transferred to continuous production if the product quality must remain the same because in a continuous reactor, feeds can be added only at certain points along the reactor. This paper discusses the transferability of semibatch polymerization processes to a continuous plug‐flow reactor with side injections in a generic fashion. Transferability of a semibatch recipe here means the possibility of the production of the same product in both modes of operation (semibatch and continuous). To determine the limits of the transferability from semibatch to continuous production, a model‐based analysis has been performed based on a simplified kinetic model and realistic kinetic parameters. The ranges of product qualities that can be produced in both modes of operation and the minimum changes in the product qualities, if no 1:1 transfer is possible are determined by means of model‐based optimization. Besides the numerical results, also an analytical treatment is presented. This provides a sound basis for an analysis of the transferability from a kinetic and an economic point of view.

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On a nonoverlapping additive Schwarz method for h‐p discontinuous Galerkin discretization of elliptic problems
Authors: Krzyżanowski Piotr
Published: June 2016

The condition number of a discontinuous Galerkin
finite element discretization preconditioned with a nonoverlapping additive Schwarz method is analyzed. We improve the result of Antonietti and Houston (J Sci Comput 46 (2011), 124–149), where a bound
has been proved for a two‐level nonoverlapping additive Schwarz method with coarse problem using polynomials of degree
on a coarse mesh size
. In a more general framework, where the concurrency of the algorithm is increased by applying solvers on subdomains smaller than the coarse grid cells, we prove that the condition number of the preconditioned system is
where
is the coarse space element degree polynomial and
is the size of subdomain where local problems are solved in parallel. Our result also extends to the case of discontinuous coefficient, piecewise constant on the coarse grid, for a composite continuous–discontinuous Galerkin discretization. © 2016Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 32: 1572–1590, 2016
Influence of liquid‐like polyhedral oligomeric silsesquioxanes derivatives structures on thermal resistance property of their epoxy nanocomposites
Authors: Bai Haipeng , Zheng Yaping , Zheng Diao , Wang Yudeng , Li Mengzhi
Published: June 2016

Four kinds of liquid‐like polyhedral oligomeric silsesquioxanes derivatives (liquid‐Ds) were fabricated and characterized by FTIR, XPS, TGA, and Rheometer. The liquid‐Ds/epoxy nanocomposites were prepared and their thermal resistance properties were tested by TGA. As a result, the thermal resistances properties were improved sharply and influenced by particle sizes, flow abilities, and bonding types of liquid‐Ds. The glass transition temperature improved via adding liquid‐Ds. The increase of crosslinking density was thought as an important factor to these improvements, which was studied by FTIR spectra and gel content of curved nanocomposites. POLYM. COMPOS., 39:1620–1629, 2018. © 2016 Society of Plastics Engineers
Self‐Supporting AuCu@Cu Elongated Pentagonal Bipyramids Toward Neutral Glucose Sensing
Authors: Wang Gang , Jin Zhitong , Zhang Meirong , Wang Zhong‐Sheng
Published: June 2016

Controlling the electronic structure of a catalyst has become an important approach to tune and optimize its antipoisoning ability and catalytic efficiency for a chemical reaction. Using d‐mannitol as a structure‐directing agent to induce size transformation and twinned defects in copper particles, penta‐twinned Cu elongated pentagonal bipyramids as supports have been synthesized, and HAuCl4 is reduced in situ to form an AuCu alloy on the surface of Cu, generating a self‐supporting AuCu@Cu core–shell structure for application as a glucose sensor in a neutral medium. The AuCu@Cu elongated pentagonal bipyramids with 0.42 at% Au show activities comparable with the Au and Pt catalyst but are more tolerant toward Cl− than Au and more tolerant toward H3–xPO4x− than Cu. The mass activity of AuCu@Cu reaches 0.10 A mg−1 of Au at 0.6 V versus Ag/AgCl (3 m KCl) in a pH 8.0 buffer. The self‐supporting AuCu@Cu elongated pentagonal bipyramids are promising catalysts for glucose sensing in a neutral medium. This work offers an effective way to design antitoxic and durable catalysts with ultralow content of noble metal for glucose sensing.
Synthesis of Porous NiO Nanorods as High‐Performance Anode Materials for Lithium‐Ion Batteries
Authors: Li Qian , Huang Gang , Yin Dongming , Wu Yaoming , Wang Limin
Published: June 2016

1D nanostructured metal oxides with porous structure have drawn wide attention to being used as high‐performance anode materials for lithium‐ion batteries (LIBs). This study puts forward a simple and scalable strategy to synthesize porous NiO nanorods with the help of a thermal treatment of metal‐organic frameworks in air. The NiO nanorods with an average diameter of approximately 38 nm are composed of nanosized primary particles. When evaluated as anode materials for LIBs, an initial discharge capacity of 743 mA h g−1 is obtained at a current density of 100 mA g−1, and a high reversible capacity is still maintained as high as 700 mA h g−1 even after 60 charge–discharge cycles. The excellent electrochemical performance is mainly ascribed to the 1D porous structure.
Energetic Characteristics of HMX‐Based Explosives Containing LiH
Authors: Ding Xiao‐Yong , Shu Yuan‐Jie , Liu Ning , Wu Min‐Jie , Zhang Jian‐Guo , Gou Bing‐Wang , Wang Hai‐Min , Wang Cai‐Ling , Dong Shu‐Nan , Wang Wei
Published: June 2016

The high energy density compound octahydro‐1,3,5,7‐tetranitro‐1,3,5,7‐tetrazocine (HMX) and the strong exothermic compound LiH represent an excellent principal explosive and an active fuel, respectively. Herein, the energetic characteristics of HMX‐based explosives are explored by adding LiH as fuel additive. The detonation parameters of HMX‐based explosives containing LiH were tested with free‐field explosion experiments and compared with those of traditional TNT, HMX, and aluminized explosives. The results show that the explosives exhibit higher energy and present preferable explosion effect when LiH is added as an explosive ingredient. The improvement of impulse is more than 32.8 % at 2 m. The shock wave peak overpressure increases by almost 40 % at a distance of 3 m from detonation center specially for the explosive containing both LiH and Al additives. Elemental H and Li are expected to release tremendous energy to effectively improve the explosives instant damage power, but the detonation duration is shorter than that of Al‐containing mixed explosives, which may limit the advantage over Al in the impulse. Li2CO3 powder is the solid product of HMX/LiH, which explains the LiH oxidation during the explosion. The exothermic processes in the formation are the reason for the increased energy of HMX/LiH explosives. These results can provide guidance to a potential energetic system formed by HMX and LiH.
Reactivation of mutant p53: Constraints on mechanism highlighted by principal component analysis of the DNA binding domain
Authors: Ouaray Zahra , ElSawy Karim M. , Lane David P. , Essex Jonathan W. , Verma Chandra
Published: June 2016

Most p53 mutations associated with cancer are located in its DNA binding domain (DBD). Many structures (X‐ray and NMR) of this domain are available in the protein data bank (PDB) and a vast conformational heterogeneity characterizes the various free and complexed states. The major difference between the apo and the holo‐complexed states appears to lie in the L1 loop. In particular, the conformations of this loop appear to depend intimately on the sequence of DNA to which it binds. This conclusion builds upon recent observations that implicate the tetramerization and the C‐terminal domains (respectively TD and Cter) in DNA binding specificity. Detailed PCA analysis of the most recent collection of DBD structures from the PDB have been carried out. In contrast to recommendations that small molecules/drugs stabilize the flexible L1 loop to rescue mutant p53, our study highlights a need to retain the flexibility of the p53 DNA binding surface (DBS). It is the adaptability of this region that enables p53 to engage in the diverse interactions responsible for its functionality. Proteins 2016; 84:1443–1461. © 2016 Wiley Periodicals, Inc.
Defect states in LiFeAs as seen by low‐temperature scanning tunneling microscopy and spectroscopy
Authors: Schlegel R. , Nag P. K. , Baumann D. , Beck R. , Wurmehl S. , Büchner B. , Hess C.
Published: June 2016

We present a microscopic investigation of frequently observed impurity‐induced states in stoichiometric LiFeAs using low‐temperature scanning tunneling microscopy and spectroscopy (STM/STS). Our data reveal seven distinct well‐defined defects which are discernible in topographic measurements. Depending on their local topographic symmetry, we are able to assign five defect types to specific lattice sites at the Li, Fe, and As positions. The most prominent result is that two different defect types have a remarkably different impact on the superconducting state. A specific and quite abundant Fe‐defect with ‐symmetry generates significant impurity‐induced additional states primarily at positive bias voltage with pronounced peaks in the on‐site local density of states (LDOS) at about 4 and 12 mV. On the other hand, a ‐symmetric As‐defect causes a significantly enhanced LDOS at both positive and negative bias voltages. We expect that these findings provide fresh input for further experimental and theoretical studies on elucidating the nature of superconductivity in LiFeAs.
Identification of 4‐hydroxynonenal protein targets in rat, mouse and human liver microsomes by two‐dimensional liquid chromatography/tandem mass spectrometry
Authors: Golizeh Makan , Geib Timon , Sleno Lekha
Published: June 2016

Rationale

4‐Hydroxynonenal (HNE), endogenously generated through peroxidation and breakdown of polyunsaturated fatty acids, has been linked to a number of adverse biological effects through carbonylation of essential biomolecules. Covalent binding of HNE to proteins can alter their structure and functions, causing cell damage as well as adverse immune responses. The liver plays a predominant role in metabolic transformations and hepatic proteins are often targeted by reactive metabolites.

Methods

Rat, mouse and human liver microsomes were incubated with HNE, enzymatically digested, and subjected to strong cation‐exchange peptide fractionation prior to liquid chromatography/tandem mass spectrometry (LC/MS/MS) analysis coupled to electrospray ionization quadrupole time‐of‐flight (QqTOF) mass spectrometry. HNE‐modified peptides were detected by probability‐driven peptide spectral matching and comparative analysis between treated and control samples, and confirmed based on accurate mass and high‐resolution MS/MS spectra.

Results

A total of 99, 123 and 51 HNE‐modified peptides were identified in rat, mouse and human liver microsomes related to 76, 103 and 44 target proteins, respectively. Eight proteins were found to be adducted by HNE in all three species, including ATP synthase, carbamoyl phosphate synthase, cytochrome P450 1A2, glutamate dehydrogenase 1, protein ERGIC‐53, protein disulfide‐isomerase, and voltage‐dependent anion‐selective channel protein 1. These proteins play crucial roles in cellular processes and their covalent modification could potentially alter their function and lead to cytotoxicity.

Conclusions

An analytical approach was developed for the identification of in vitro HNE protein targets in rat, mouse and human liver microsomes using two‐dimensional (2D) LC/MS/MS. This approach can be applied to study HNE modification of proteins in vitro and in vivo, providing insight into the toxicology of HNE protein adduction. Copyright © 2016 John Wiley & Sons, Ltd.
Stable 18O‐labeling method for stercobilin and other bilins for metabolomics
Authors: Rudolph Heather L. , Sekera Emily R. , Wood Troy D.
Published: June 2016

Rationale

Bilin tetrapyrroles including stercobilin are unique to mammalian waste; they have been used as markers of source water contamination and may have important diagnostic value in human health conditions. Unfortunately, commercial isotopomers for bilins are not available. Thus, there is a need for isotopomer standards of stercobilin and other bilins for quantification in environmental and clinical diagnostic applications.

Methods

A procedure is described here using H218O to label the carboxylic acid groups of bilin tetrapyrroles. Reaction conditions as a function of temperature and reagent volume were found to produce a mixture of isotopomers, as assessed by electrospray ionization and Fourier transform ion cyclotron resonance mass spectrometry (FTICRMS). Stability as a function of storage time and temperature and in conjunction with solid‐phase extraction (SPE) was assessed.

Results

The highest labeling efficiency was achieved at 70 °C for 8 h, while a stable ratio of the isotopmers could be produced at 60 °C for 4 h. The stability of the isotopic distribution was maintained under storage (room temperature or frozen) for 20 days. It was also stable throughout SPE. The high mass accuracy and resolving power of FTICRMS enables clear distinction between 18O‐labeled bilins from other unlabeled bilins present, avoiding a potential interference in quantitation.

Conclusions

A procedure was developed to label bilins with 18O. The final ratio of the 18O‐labeled bilin isotopomers was reproducible and highly stable for at least 20 days under storage. This ratio was not changed in any statistically significant way even after SPE. Thus a reliable method for producing stable isotopomer ratios for bilins has been achieved. Copyright © 2016 John Wiley & Sons, Ltd.
Intraspecific carbon and nitrogen isotopic variability in foxtail millet (Setaria italica)
Authors: Lightfoot Emma , Przelomska Natalia , Craven Martha , O′Connell Tamsin C. , He Lu , Hunt Harriet V. , Jones Martin K.
Published: June 2016

Rationale

Isotopic palaeodietary studies generally focus on bone collagen from human and/or animal remains. While plant remains are rarely analysed, it is known that plant isotope values can vary as a result of numerous factors, including soil conditions, the environment and type of plant. The millets were important food crops in prehistoric Eurasia, yet little is known about the isotopic differences within millet species.

Methods

Here we compare the stable isotope ratios within and between Setaria italica plants grown in a controlled environment chamber. Using homogenised samples, we compare carbon isotope ratios of leaves and grains, and nitrogen isotope ratios of grains, from 29 accessions of Setaria italica.

Results

We find significant isotopic variability within single leaves and panicles, and between leaves and panicles within the same plant, which must be considered when undertaking plant isotope studies. We find that the leaves and grains from the different accessions have a ca 2‰ range in δ13C values, while the nitrogen isotope values in the grains have a ca 6‰ range. We also find an average offset of 0.9‰ between leaves and grains in their δ13C values.

Conclusions

The variation found is large enough to have archaeological implications and within‐ and between‐plant isotope variability should be considered in isotope studies. The range in δ15N values is particularly significant as it is larger than the typical values quoted for a trophic level enrichment, and as such may lead to erroneous interpretations of the amount of animal protein in human or animal diets. It is therefore necessary to account for the variability in plant stable isotope values during palaeodietary reconstructions. Copyright © 2016 John Wiley & Sons, Ltd.
Contamination risk of stable isotope samples during milling
Authors: Isaac‐Renton M. , Schneider L. , Treydte K.
Published: June 2016

Rationale

Isotope analysis of wood is an important tool in dendrochronology and ecophysiology. Prior to mass spectrometry analysis, wood must be homogenized, and a convenient method involves a ball mill capable of milling samples directly in sample tubes. However, sample‐tube plastic can contaminate wood during milling, which could lead to biological misinterpretations.

Methods

We tested possible contamination of whole wood and cellulose samples during ball‐mill homogenization for carbon and oxygen isotope measurements. We used a multi‐factorial design with two/three steel milling balls, two sample amounts (10 mg, 40 mg), and two milling times (5 min, 10 min). We further analyzed abrasion by milling empty tubes, and measured the isotope ratios of pure contaminants.

Results

A strong risk exists for carbon isotope bias through plastic contamination: the δ13C value of polypropylene deviated from the control by −6.77‰. Small fibers from PTFE filter bags used during cellulose extraction also present a risk as the δ13C value of this plastic deviated by −5.02‰. Low sample amounts (10 mg) showed highest contamination due to increased abrasion during milling (−1.34‰), which is further concentrated by cellulose extraction (−3.38‰). Oxygen isotope measurements were unaffected.

Conclusions

A ball mill can be used to homogenize samples within test tubes prior to oxygen isotope analysis, but not prior to carbon or radiocarbon isotope analysis. There is still a need for a fast, simple and contamination‐free sample preparation procedure. Copyright © 2016 John Wiley & Sons, Ltd.
Automated simultaneous measurement of the δ13C and δ2H values of methane and the δ13C and δ18O values of carbon dioxide in flask air samples using a new multi cryo‐trap/gas chromatography/isotope ratio mass spectrometry system
Authors: Brand Willi A. , Rothe Michael , Sperlich Peter , Strube Martin , Wendeberg Magnus
Published: June 2016

Rationale

The isotopic composition of greenhouse gases helps to constrain global budgets and to study sink and source processes. We present a new system for high‐precision stable isotope measurements of carbon, hydrogen and oxygen in atmospheric methane and carbon dioxide. The design is intended for analyzing flask air samples from existing sampling programs without the need for extra sample air for methane analysis.

Methods

CO2 and CH4 isotopes are measured simultaneously using two isotope ratio mass spectrometers, one for the analysis of δ13C and δ18O values and the second one for δ2H values. The inlet carousel delivers air from 16 sample positions (glass flasks 1‐5 L and high‐pressure cylinders). Three 10‐port valves take aliquots from the sample stream. CH4 from 100‐mL air aliquots is preconcentrated in 0.8‐mL sample loops using a new cryo‐trap system. A precisely calibrated working reference air is used in parallel with the sample according to the Principle of Identical Treatment.

Results

It takes about 36 hours for a fully calibrated analysis of a complete carousel including extractions of four working reference and one quality control reference air. Long‐term precision values, as obtained from the quality control reference gas since 2012, account for 0.04 ‰ (δ13C values of CO2), 0.07 ‰ (δ18O values of CO2), 0.11 ‰ (δ13C values of CH4) and 1.0 ‰ (δ2H values of CH4). Within a single day, the system exhibits a typical methane δ13C standard deviation (1σ) of 0.06 ‰ for 10 repeated measurements.

Conclusions

The system has been in routine operation at the MPI‐BGC since 2012. Consistency of the data and compatibility with results from other laboratories at a high precision level are of utmost importance. A high sample throughput and reliability of operation are important achievements of the presented system to cope with the large number of air samples to be analyzed. Copyright © 2016 John Wiley & Sons, Ltd.
A false positive finding in liquid chromatography/triple quadrupole mass spectrometry analysis by a non‐isobaric matrix component: the case of benzotriazole in urine for human biomonitoring
Authors: Schlittenbauer Linda , Seiwert Bettina , Reemtsma Thorsten
Published: June 2016

Rationale

Multi‐residual methods employing liquid chromatography coupled to triple quadrupole mass spectrometry (LC/MS/MS) with selected reaction monitoring (SRM) are attractive also for human biomonitoring (HBM). A new process is determined that can lead to false positive findings by matrix components that are not isobaric to the analyte of interest.

Methods

Benzotriazole (1H‐BT) was false positively detected in 87 human urine samples analyzed by ultra‐high‐performance‐(UHP)‐LC/MS/MS. The quantifier/qualifier ratio (Q/q ratio) did not match. This was further confirmed by negative results with an optimized gradient. Investigations were performed by UHPLC/high‐resolution (HR)MS and model compounds to reveal the identity of the disturbing matrix compound and the way that it interfered with 1H‐BT detection.

Results

A formula of C7H5NO (m/z 120.0444) was found at the retention time of 1H‐BT (m/z 120.0556) belonging to an in‐source product ion of a heavier co‐eluting compound. Product ion spectra and Q/q ratios of model compounds indicated a benzene sub‐structure with a carbonyl and amine functional group in the ortho‐ or para‐position. Finally, folic acid was confirmed as the disturbing urine component, exhibiting an in‐source fragment with the nominal mass of 1H‐BT and the same product ions as used in the SRM mode for UHPLC/MS/MS monitoring.

Conclusions

Interferences in SRM detection need not be due to co‐eluting isobaric matrix compounds, but can originate from in‐source fragmentation of heavier ions. Rigid quality control measures are recommended for LC/MS/MS analysis, especially for small molecules in complex sample matrices to overcome the selectivity limits of SRM. Copyright © 2016 John Wiley & Sons, Ltd.
Dissociation of doubly charged clusters of lithium acetate: Asymmetric fission and breakdown of the liquid drop model
Authors: Shukla Anil
Published: June 2016

Rationale

Electrospray ionization (ESI) results in the formation of multiply charged cluster ions which then fragment via two competing processes: fission (charge separation) via Coulomb repulsion, and evaporation of one or more neutrals from the fragmenting ion, as described by Rayleigh's liquid drop model. Unimolecular and collision‐induced dissociation (CID) of doubly charged lithium acetate clusters, (CH3COOLi)nLi22+, demonstrated that Coulomb fission via charge separation is the dominant dissociation process with no contribution from the neutral evaporation processes for all such ions from the critical limit to larger cluster ions, although the latter process was normally observed in most earlier studies of multiply charged clusters.

Methods

Doubly and higher charged lithium acetate cluster ions were generated by ESI. Unimolecular and CID of mass selected doubly charged cluster ions above the critical limit were recorded at high resolution using an LTQ Velos Orbitrap mass spectrometer.

Results

Unimolecular and collision‐induced dissociation of doubly charged lithium acetate clusters proceed via symmetric fission processes and the intensity of the fragment ions decreases as the cluster size increases. Dissociations via neutral evaporation of a monomer or larger clusters are not observed.

Conclusions

Doubly charged clusters of lithium acetate above the critical limit dissociate via symmetrical fission processes and not neutral evaporation. These results are clearly in disagreement with the Rayleigh liquid drop model that has been used previously to predict the critical size and explain the fragmentation behavior of multiply charged clusters. Copyright © 2016 John Wiley & Sons, Ltd.
Chemical characterization of α‐pinene secondary organic aerosol constituents using gas chromatography, liquid chromatography, and paper spray‐based mass spectrometry techniques
Authors: Rindelaub Joel D. , Wiley Joshua S. , Cooper Bruce R. , Shepson Paul B.
Published: June 2016

Rationale

Despite ample research into the atmospheric oxidation of α‐pinene, an important precursor to biogenic secondary organic aerosol formation, the identification of its reaction products, specifically organic nitrates, which impact atmospheric NOx concentrations, is still incomplete. This negatively impacts our understanding of α‐pinene oxidation chemistry and its relation to air quality.

Methods

Photochemical chamber experiments were conducted in conjunction with mass spectrometric techniques, including gas chromatography/mass spectrometry (GC/MS), high‐performance liquid chromatography/time‐of‐flight (HPLC/TOF), and paper spray ionization MS, to investigate products from the OH radical initiated oxidation of α‐pinene under high NOx conditions.

Results

Over 30 compounds were tentatively identified, including those newly detected from photochemical chamber studies of α‐pinene oxidation, pinocamphenol, fencholenic aldehyde, and α‐pinene‐derived nitrate isomers. α‐Pinene‐derived hydroxynitrate isomers were successfully detected using chromatographic methods, demonstrating, for the first time, the identification of individual first‐generation organic nitrate products derived from α‐pinene. The application of paper spray ionization to particle‐phase compounds collected on filters represents a novel method for the direct analysis of filter samples at ambient pressure and temperature.

Conclusions

The use of HPLC/TOF and paper spray ionization methods to identify previously unobserved α‐pinene‐derived products helps lower the uncertainty in α‐pinene oxidation chemistry and provides new platforms that can be used to identify and quantify important atmospheric compounds that relate to air quality in a complex sample matrix, such as ambient aerosol particles. Additionally, the use of paper spray ionization for direct filter analysis is a fast, relatively inexpensive sample preparation technique that can be used to reduce sample manipulation from solvent‐induced reactions. Copyright © 2016 John Wiley & Sons, Ltd.
Effect of Nitrogen Donor Disposition on Topology in Cobalt Isophthalate Coordination Polymers Containing Dipyridylamide Ligands
Authors: Sample Alexander D. , O'Donovan Megan E. , LaDuca Robert L.
Published: June 2016

Cobalt coordination complexes containing a substituted isophthalate ligand and hydrogen‐bonding capable dipyridylamide ligands were prepared hydrothermally and structurally characterized by single‐crystal X‐ray diffraction. {[Co(nip)(3‐pina)]n (1) (nip = 5‐nitroisophthalate, 3‐pina = 3‐pyridylisonicotinamide) displays [Co(nip)]n 1D ribbon motifs with embedded {Co2(OCO)2} dimeric units, linked by L‐shaped 3‐pina tethers into a 3D [Co(nip)(3‐pina)]n coordination polymer network with pcu topology. In contrast, {[Co(nip)(4‐pmina)(H2O)]·H2O}n (2) (4‐pmina = 4‐pyridylmethylisonicotinamide) manifests a twofold interpenetrated 66 topology diamondoid network. {[Co(meoip)(3‐pina)]n (3) (meoip = 5‐methoxyisophthalate) has a dimer‐based 3D pcu network as seen in 1. [Co(meoipH)2(4‐pmina)2(H2O)2] (4) contains neutral coordination complexes linked by hydrogen‐bonding into supramolecular ribbons. Thermal properties of these new solids were also investigated.
Self-adaptation and secure information flow in multiparty communications
Authors: Castellani Ilaria , Dezani-Ciancaglini Mariangiola , Pérez Jorge A.
Published: June 2016

We present a comprehensive model of structured communications in which self-adaptation and security concerns are jointly addressed. More specifically, we propose a model of multiparty, self-adaptive communications with access control and secure information flow guarantees. In our model, multiparty protocols (choreographies) are described as global types; security violations occur when process implementations of protocol participants attempt to read or write messages of inappropriate security levels within directed exchanges. Such violations trigger adaptation mechanisms that prevent the violations to occur and/or to propagate their effect in the choreography. Our model is equipped with local and global adaptation mechanisms for reacting to security violations of different gravity; type soundness results ensure that the overall multiparty protocol is still correctly executed while the system adapts itself to preserve the participants’ security.
Density‐dependent reproduction causes winter crashes in a common vole population
Authors: Pinot Adrien , Barraquand Frédéric , Tedesco Edoardo , Lecoustre Vincent , Bretagnolle Vincent , Gauffre Bertrand
Published: June 2016

Common voles in western France exhibit three‐year population cycles with winter crashes after large outbreaks. During the winter of 2011–2012, we monitored survival, reproduction, recruitment and population growth rate of common voles at different densities (from low to outbreak densities) in natura to better understand density dependence of demographic parameters. Between October and April, the number of animals decreased irrespective of initial density. However, the decline was more pronounced when October density was higher (loss of ≈54 % of individuals at low density and 95 % at high density). Using capture‐mark‐recapture models with Pradel's temporal symmetry approach, we found a negative effect of density on recruitment and reproduction. In contrast, density had a slightly positive effect on survival indicating that mortality did not drive the steeper declines in animal numbers at high density. We discuss these results in a population cycle framework, and suggest that crashes after outbreaks could reflect negative effects of density dependence on reproduction rather than changes in mortality rates.
Novelty design in gain flattening filter of ASE source based on fat ultra-long period fiber grating
Authors: Nafchi Fereshteh Mohammadi , Shahi Sharifeh , Shaffaatifar Mohammad Taha , Kanani Mohammad , Noormohammadi Hossein
Published: June 2016

A new type of gain flattening filter for amplified spontaneous emission (ASE) source based on erbium doped fiber (EDF) is proposed and demonstrated by fabricating and writing two series ultra-long period fiber grating (ULPFG) on single mode fiber (SMF-28). The novelty method in this research is based on writing the two ULPFGs as fat gratings. The LPG is written by a simple and available arc-discharge method. The pump power based on single-pass backward pump configuration is around 100 mW, and the average wavelength is near to 974 nm. The gain flattening profile is obtained by 3.4 (±1.7) dB ripple in the wavelength range between 1524 nm and 1565 nm with 41-nm band width.
Use of anti‐Müllerian hormone testing during ovarian reserve screening to identify women at risk of polycystic ovary syndrome
Authors: Safier Lauren Z. , Grossman Lisa C. , Chan Cariann W. , Sauer Mark V. , Lobo Rogerio A. , Douglas Nataki C.
Published: June 2016

Objective

To assess the applicability of anti‐Müllerian hormone (AMH) testing in the identification of women at risk for polycystic ovary syndrome (PCOS) when AMH is used in ovarian reserve screening in the general population.

Methods

A secondary analysis was undertaken of a large cross‐sectional study. Women aged 27–37 years, presently delaying childbearing but interested in future fertility, completed an online questionnaire to assess knowledge and attitudes about ovarian reserve testing, and underwent serum AMH testing between October 2014 and April 2015 in New York, NY, USA. For the secondary analysis, women considered to have elevated AMH levels (≥ 4.7 ng/mL) were invited for physical examination and transvaginal ultrasonography.

Results

Among 97 women who underwent AMH testing, 32 (33.0%) had elevated AMH levels. Hyperandrogenism was reported by 8 (25.0%) women with elevated AMH and none with AMH concentrations lower than 4.7 ng/mL (P < 0.001). Irregular menstrual cycles before hormonal contraceptive use were reported by 16 (24.6%) of 65 women with AMH concentrations lower than 4.7 ng/mL and 11 (34.4%) with elevated AMH (P = 0.34). Of the 20 women with elevated AMH who returned for further evaluation, 16 (80.0%) had polycystic ovaries and 13 (65.0%) were diagnosed with PCOS (Rotterdam criteria).

Conclusion

When AMH levels are used as a screening test for fertility, elevated concentrations can identify women at risk for PCOS.