bluuebunny/crossref_metadata_2025 huggingface dataset:
Open issues in neutrino astrophysics
Authors: Volpe Cristina
Published: July 2013

Neutrinos of astrophysical origin are messengers produced in stars, in explosive phenomena like core‐collapse supernovae, in the accretion disks around black holes, or in the Earth's atmosphere. Their fluxes and spectra encode information on the environments that produce them. Such fluxes are modified in characteristic ways when neutrinos traverse a medium. Here the current understanding of neutrino flavour conversion in media is summarized. The importance of this domain for astrophysical observations is emphasized. Examples are given of the fundamental properties that research into astrophysical neutrinos has uncovered, or might reveal in the future.
Effect of irradiation on the composition and thermal properties of softwood kraft lignin and styrene grafted lignin
Authors: Ayoub Ali , Venditti Richard A. , Jameel Hasan , Chang Hou‐Min
Published: July 2013

Lignin is an abundant, underutilized natural resource that has potential to be used as a biomaterial but is currently hampered in its use by not being uniform in structure and composition and is thermally unstable due to phenolic group. To address these issues and modify its thermal properties, softwood kraft lignin was modified using γ‐irradiation at low doses with and without styrene present and characterized. Irradiation of kraft lignin alone with γ‐radiation shows an initial decrease in molecular weight due to chain scission up to about 10 kGy followed by an increase in molecular weight due to crosslinking. NMR results indicate a decrease of about 15% in the OH content of the lignin with 30 kGy irradiation. Thermal properties such as Tg, free volume and ΔCp follow accordingly. Irradiation at very low dosages was determined to facilitate the grafting of styrene monomer to lignin, decreasing the OH content by 23%. This effect increased the hydrophobicity of the material, depressed the value of Tg, increased the ΔCp, increased the mobility in the liquid state, and made the material more thermally stable relative to the lignin alone, thus improving its processability at high temperatures. Both the irradiation of lignin alone and the grafting of styrene to lignin increased the yield of mass during pyrolysis and the activation energy for mass loss relative to untreated lignin alone. This work has demonstrated that the application of low dosages of γ‐irradiation is a promising method to attach functional molecules onto lignin for use in various applications. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 39743.
Enhanced Activity of Akt in Teff Cells From Children With Lupus Nephritis Is Associated With Reduced Induction of Tumor Necrosis Factor Receptor–Associated Factor 6 and Increased OX40 Expression
Authors: Kshirsagar Sudhir , Binder Elisabeth , Riedl Magdalena , Wechselberger Gottfried , Steichen Elisabeth , Edelbauer Monika
Published: July 2013

Objective

The breakdown of peripheral tolerance mechanisms is central to the pathogenesis of systemic lupus erythematosus (SLE). Although true Treg cells in patients with SLE exhibit intact suppressive activity, Teff cells are resistant to suppression. The underlying mechanisms are incompletely understood. This study was undertaken to examine the Akt signaling pathway and molecules that may alter its activity in T cells in lupus patients.

Methods

The Akt pathway and its regulators were analyzed in Teff and Treg cells from children with lupus nephritis and controls using flow cytometry and real‐time quantitative polymerase chain reaction. T cell proliferation was assessed by analysis of 5,6‐carboxyfluorescein succinimidyl ester dilution.

Results

CD4+CD45RA−FoxP3low and FoxP3− Teff cells from children with lupus nephritis expressed high levels of activated Akt, resulting in the down‐regulation of the proapoptotic protein Bim and an enhanced proliferative response. The induction of tumor necrosis factor receptor–associated factor 6 (TRAF6) was impaired, and TRAF6 levels inversely correlated with Akt activity. Although the expression of OX40 was enhanced on Teff cells from children with lupus nephritis compared to controls, OX40 stimulation failed to significantly increase TRAF6 expression in cells from patients, in contrast to those from healthy controls, but resulted in further increased Akt activation that was reversed by blockade of OX40 signaling. Moreover, inhibition of Akt signaling markedly decreased the proliferation of Teff cells from lupus patients.

Conclusion

Our findings indicate that hyperactivation of the Akt pathway in Teff cells from children with lupus nephritis is associated with reduced induction of TRAF6 and up‐regulation of OX40, which may cause Teff cell resistance to Treg cell–mediated suppression.
Role of ADAM‐17, p38 MAPK, Cathepsins, and the Proteasome Pathway in the Synthesis and Shedding of Fractalkine/CX3CL1 in Rheumatoid Arthritis
Authors: Jones Brian A. , Riegsecker Sharayah , Rahman Ayesha , Beamer Maria , Aboualaiwi Wissam , Khuder Sadik A. , Ahmed Salahuddin
Published: July 2013

Objective

To evaluate the mechanism of fractalkine (FKN)/CX3CL1 synthesis and shedding in rheumatoid arthritis synovial fibroblasts (RASFs) and in rat adjuvant‐induced arthritis (AIA).

Methods

The effect of tumor necrosis factor α (TNFα) and/or interferon‐γ (IFNγ) on FKN synthesis and shedding in human RASFs was determined over time by immunostaining, quantitative reverse transcription–polymerase chain reaction, and Western blotting. The role of protease enzymes and signaling pathways was evaluated using chemical inhibitors and small interfering RNA (siRNA). The activity of 20S proteasome in the lysates and the DNA binding of NF‐κB/p65 in the nuclear fractions were evaluated. The in vivo relevance of these findings was examined in rat AIA.

Results

In RASFs, stimulation with the combination of TNFα and IFNγ induced cellular expression of FKN within 24 hours. Activation of ADAM‐17, but not ADAM‐10, partly mediated the proteolytic shedding and release of soluble FKN (sFKN) following TNFα/IFNγ stimulation for 24–72 hours. Compared with control siRNA, ADAM‐17 siRNA markedly inhibited TNFα/IFNγ‐induced sFKN production (by ∼33%). TNFα/IFNγ‐induced sFKN release was markedly suppressed by inhibitors of ADAM‐17, p38 MAPK, proteasome, or cathepsin inhibitor but not by inhibitors of caspase 3 or calpain. TNFα/IFNγ‐induced proteasome activity also correlated with rapid degradation of IκBα and p38 MAPK phosphorylation. In vivo findings showed increased FKN expression in the joints of rats with AIA, which correlated with increased expression of ADAM‐17 and phospho–p38 MAPK.

Conclusion

Our results provide new understanding of the role of ADAM‐17, p38 MAPK, cathepsins, and the proteasome pathway in FKN expression and shedding. Regulating these pathways may suppress FKN‐mediated inflammation and tissue destruction.
Familial Risks and Heritability of Rheumatoid Arthritis: Role of Rheumatoid Factor/Anti–Citrullinated Protein Antibody Status, Number and Type of Affected Relatives, Sex, and Age
Authors: Frisell Thomas , Holmqvist Marie , Källberg Henrik , Klareskog Lars , Alfredsson Lars , Askling Johan
Published: July 2013

Objective

To estimate familial aggregation of rheumatoid arthritis (RA) in 3 large population‐representative samples and to test if familial aggregation is affected by rheumatoid factor (RF)/anti–citrullinated protein antibody (ACPA) status, type of relative, sex, and age at onset of RA.

Methods

A register‐based nested case–control study was performed in the Swedish total population. Data on patients with RA were ascertained through the nationwide Swedish Patient Register (n = 88,639), the clinical Swedish Rheumatology Quality Register (n = 11,519), and the Epidemiological Investigation of Rheumatoid Arthritis case–control study (n = 2,871). Data on first‐ and second‐degree relatives were obtained through the Swedish Multigeneration Register. Familial risks were calculated using conditional logistic regression.

Results

Consistent across data sources, the familial odds ratio for RA was ∼3 in first‐degree relatives of RA patients and 2 in second‐degree relatives. Familial risks were similar among siblings, parents, and offspring. Familial aggregation was not modified by sex, but was higher in RA patients with early‐onset disease and in RF/ACPA‐positive RA patients. The observed familial risks were consistent with a heritability of ∼50% for ACPA‐positive RA and ∼20% for ACPA‐negative RA.

Conclusion

The pattern of risks suggests that familial factors influence RA in men and women equally and that these factors are of less importance for late‐onset RA. Familial factors are more important for seropositive RA, but there is significant familial overlap between seropositive RA and seronegative RA. Even if the familial risk is assumed to be completely due to genetics, the observed risks suggest that heritability of RA is lower than previously reported, in particular for ACPA‐negative RA.
Skin Gene Expression Correlates of Severity of Interstitial Lung Disease in Systemic Sclerosis
Authors: Assassi Shervin , Wu Minghua , Tan Filemon K. , Chang Jeffrey , Graham Tiffany A. , Furst Daniel E. , Khanna Dinesh , Charles Julio , Ferguson Emma C. , Feghali‐Bostwick Carol , Mayes Maureen D.
Published: July 2013

Objective

We undertook this hypothesis‐generating study to identify skin transcripts correlating with severity of interstitial lung disease (ILD) in systemic sclerosis (SSc).

Methods

Skin biopsy samples from 59 patients enrolled in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) cohort or an open‐label imatinib study (baseline visit) were examined by global gene expression analysis using Illumina HT‐12 arrays. Skin transcripts correlating with concomitantly obtained forced vital capacity (FVC) values and the modified Rodnan skin thickness score (MRSS) were identified by quantitative trait analysis. Also, immunofluorescence staining for selected transcripts was performed in affected skin and lung tissue. Plasma levels of CCL2, soluble SELP, and soluble P‐selectin glycoprotein ligand 1 (sPSGL‐1) were examined in all patients enrolled in the GENISOS cohort (n = 266).

Results

Eighty‐two skin transcripts correlated significantly with FVC. This gene list distinguished patients with more severe ILD (FVC <70% predicted) in unsupervised hierarchical clustering analysis (P < 0.001). These genes included SELP, CCL2, and matrix metalloproteinase 3, which are involved in extravasation and adhesion of inflammatory cells. Among the FVC correlates, 8 genes (CCL2, HAPLN3, GPR4, ADCYAP1, WARS, CDC25B, PLP1, and STXBP6) also correlated with the MRSS. Immunofluorescence staining revealed that SELP and CCL2 were also overexpressed in affected skin and lung tissue from SSc patients compared to those from controls. Plasma levels of CCL2 and sPSGL‐1 correlated with concomitantly obtained FVC values (r = −0.22, P = 0.001 and r = 0.17, P = 0.015, respectively). This relationship was independent of potential confounders (age, sex, ethnicity, smoking status, anti–topoisomerase I positivity, treatment with immunosuppressive agents, MRSS, disease type, and disease duration).

Conclusion

A limited number of skin transcripts including genes involved in extravasation and adhesion of inflammatory cells correlate with severity of ILD.
Managing a second‐generation crop portfolio through sustainable intensification: Examples from the USA and the EU
Authors: Heaton Emily A. , Schulte Lisa A. , Berti Marisol , Langeveld Hans , Zegada‐Lizarazu Walter , Parrish David , Monti Andrea
Published: July 2013

Sustainable intensification of agricultural systems has been suggested – in addition to reducing waste and changing consumption habits – as a way to increase food, feed, fuel, and fiber security in the twenty‐first century. Here we describe three primary strategies of agricultural intensification – conventional intensification, temporal intensification, and spatial intensification – and how they can be used to manage and integrate food and second‐generation crop portfolios. While each strategy has individual merits, combining them to meet case‐specific targets may achieve optimum results. Multiple experiments and examples from the USA and the EU illustrate the potential of combining these approaches for agroecological intensification that can provide ecosystem services while maintaining or increasing economic output, thus striking a balance between ‘land sparing’ and ‘land sharing’. Management strategies will vary by the types of markets available, e.g., food, fuel and/or ecosystem services, and the scale of markets supplied, e.g., small heat and power vs. large cellulosic ethanol. Future research should holistically and methodologically evaluate the trade‐offs between different management strategies. © 2013 Society of Chemical Industry and John Wiley & Sons, Ltd
Early prenatal exposure to air pollution and its associations with birth defects in a state‐wide birth cohort from North Carolina
Authors: Vinikoor‐Imler Lisa C. , Davis J. Allen , Meyer Robert E. , Luben Thomas J.
Published: July 2013

BACKGROUND

Few studies have examined the potential relationship between air pollution and birth defects. The objective of this study was to investigate whether maternal exposure to particulate matter (PM2.5) and ozone (O3) during pregnancy is associated with birth defects among women living throughout North Carolina.

METHODS

Information on maternal and infant characteristics was obtained from North Carolina birth certificates and health service data (2003–2005) and linked with information on birth defects from the North Carolina Birth Defects Monitoring Program. The 24‐hr PM2.5 and O3 concentrations were estimated using a hierarchical Bayesian model of air pollution generated by combining modeled air pollution predictions from the U.S. Environmental Protection Agency's Community Multi‐Scale Air Quality model with air monitor data from the Environmental Protection Agency's Air Quality System. Maternal residence was geocoded and assigned pollutant concentrations averaged over weeks 3 to 8 of gestation. Binomial regression was performed and adjusted for potential confounders.

RESULTS

No association was observed between either PM2.5 or O3 concentrations and most birth defects. Positive effect estimates were observed between air pollution and microtia/anotia and lower limb deficiency defects, but the 95% confidence intervals were wide and included the null.

CONCLUSION

Overall, this study suggested a possible relationship between air pollution concentration during early pregnancy and certain birth defects (e.g., microtia/anotia, lower limb deficiency defects), although this study did not have the power to detect such an association. The risk for most birth defects does not appear to be affected by ambient air pollution. Birth Defects Research (Part A) 97:696–701, 2013. © 2013 Wiley Periodicals, Inc.
Translational paradigms in scientific and clinical imaging of cardiac development
Authors: Gregg Chelsea L. , Butcher Jonathan T.
Published: July 2013

Congenital heart defects (CHD) are the most prevalent congenital disease, with 45% of deaths resulting from a congenital defect due to a cardiac malformation. Clinically significant CHD permit survival upon birth, but may become immediately life threatening. Advances in surgical intervention have significantly reduced perinatal mortality, but the outcome for many malformations is bleak. Furthermore, patients living while tolerating a CHD often acquire additional complications due to the long‐term systemic blood flow changes caused by even subtle anatomical abnormalities. Accurate diagnosis of defects during fetal development is critical for interventional planning and improving patient outcomes. Advances in quantitative, multidimensional imaging are necessary to uncover the basic scientific and clinically relevant morphogenetic changes and associated hemodynamic consequences influencing normal and abnormal heart development. Ultrasound is the most widely used clinical imaging technology for assessing fetal cardiac development. Ultrasound‐based fetal assessment modalities include motion mode (M‐mode), two dimensional (2D), and 3D/4D imaging. These datasets can be combined with computational fluid dynamics analysis to yield quantitative, volumetric, and physiological data. Additional imaging modalities, however, are available to study basic mechanisms of cardiogenesis, including optical coherence tomography, microcomputed tomography, and magnetic resonance imaging. Each imaging technology has its advantages and disadvantages regarding resolution, depth of penetration, soft tissue contrast considerations, and cost. In this review, we analyze the current clinical and scientific imaging technologies, research studies utilizing them, and appropriate animal models reflecting clinically relevant cardiogenesis and cardiac malformations. We conclude with discussing the translational impact and future opportunities for cardiovascular development imaging research. Birth Defects Research (Part C) 99:106–120, 2013. © 2013 Wiley Periodicals, Inc.
Exposure to diethylstilbestrol during sensitive life stages: A legacy of heritable health effects
Authors: Reed Casey E. , Fenton Suzanne E.
Published: July 2013

Diethylstilbestrol (DES) is a potent estrogen mimic that was predominantly used from the 1940s to the 1970s by pregnant women in hopes of preventing miscarriage. Decades later, DES is known to enhance breast cancer risk in exposed women and cause a variety of birth‐related adverse outcomes in their daughters such as spontaneous abortion, second trimester pregnancy loss, preterm delivery, stillbirth, and neonatal death. Additionally, children exposed to DES in utero suffer from sub/infertility and cancer of reproductive tissues. DES is a pinnacle compound that demonstrates the fetal basis of adult disease. The mechanisms of cancer and endocrine disruption induced by DES are not fully understood. Future studies should focus on common target tissue pathways affected and the health of the DES grandchildren. Birth Defects Research (Part C) 99:134–146, 2013. © 2013 Wiley Periodicals, Inc.
Basic concepts and principles of stoichiometric modeling of metabolic networks
Authors: Maarleveld Timo R. , Khandelwal Ruchir A. , Olivier Brett G. , Teusink Bas , Bruggeman Frank J.
Published: July 2013

Metabolic networks supply the energy and building blocks for cell growth and maintenance. Cells continuously rewire their metabolic networks in response to changes in environmental conditions to sustain fitness. Studies of the systemic properties of metabolic networks give insight into metabolic plasticity and robustness, and the ability of organisms to cope with different environments. Constraint‐based stoichiometric modeling of metabolic networks has become an indispensable tool for such studies. Herein, we review the basic theoretical underpinnings of constraint‐based stoichiometric modeling of metabolic networks. Basic concepts, such as stoichiometry, chemical moiety conservation, flux modes, flux balance analysis, and flux solution spaces, are explained with simple, illustrative examples. We emphasize the mathematical definitions and their network topological interpretations.
Cycloviolacin O2 (CyO2) suppresses productive infection and augments the antiviral efficacy of nelfinavir in HIV‐1 infected monocytic cells
Authors: Gerlach Samantha L. , Yeshak Mariamawit , Göransson Ulf , Roy Upal , Izadpanah Reza , Mondal Debasis
Published: July 2013

Human immunodeficiency virus type‐1 (HIV‐1), the etiologic agent of acquired immune deficiency syndrome (AIDS), is a global pandemic causing millions of deaths annually. Highly active antiretroviral therapy (HAART) greatly enhances lifespan but eventually causes debilitating side effects, in part, due to their chronic administration required to suppress HIV‐1 replication. If treatment is discontinued, viral suppression is lost and dormant replication‐competent monocytic cell reservoirs become reactivated, leading to viral recrudescence and progression to AIDS. Therefore, novel strategies to circumvent obstacles to HIV‐1 therapy are critically needed. We evaluated the potentially therapeutic effects of cycloviolacin O2 (CyO2) on cell viability (MTT assay), membrane disruption (SYTOX Green uptake), p24 production [enzyme‐linked immunosorbent assays (ELISA)], and proviral integration (PCR amplification) in U1 cells; a monocytic cell model of HIV‐1 latency and reactivation. We demonstrate, for the first time, that CyO2 (0.5–5.0 μM) kills productively infected cells. Sub‐toxic concentrations (<0.5 μM) of CyO2 disrupted plasma membranes in both latently‐infected and productively‐infected U1 cells and enhanced the antiviral efficacy of nelfinavir, a HIV‐1 protease inhibitor (HPI). Interestingly, CyO2 also decreased virus production by activated U1 cells; however, this effect was not due to suppression of integrated provirus in U1 cells. This suggested that, in addition to the known pore‐forming ability of cyclotides, a novel mode of antiviral activity may exist for CyO2. Our data indicate that CyO2 may be a promising candidate for the targeting HIV‐1 reservoirs in monocytes, and their inclusion in adjuvant therapy approaches may augment the efficacy of HPIs and ultimately facilitate virus elimination. © 2013 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 100: 471–479, 2013.
Lasso peptides from proteobacteria: Genome mining employing heterologous expression and mass spectrometry
Authors: Hegemann Julian D. , Zimmermann Marcel , Zhu Shaozhou , Klug Dennis , Marahiel Mohamed A.
Published: July 2013

Lasso peptides are natural products with a unique three dimensional structure resembling a lariat knot. They are from ribosomal origin and are post‐translationally modified by two enzymes (B and C), one of which shares little similarity to enzymes outside of lasso peptide biosynthetic gene clusters and as such is a useful target for genome mining. In this study, we demonstrate a B protein–centric genome mining approach through which we were able to identify 102 putative lasso peptide biosynthetic gene clusters from a total of 87 different proteobacterial strains. Ten of these clusters were cloned into the pET41a expression vector, optimized through incorporation of a ribosomal binding site and heterologously expressed in Escherichia coli BL21(DE3). All 12 predicted lasso peptides (namely burhizin, caulonodin I, caulonodin II, caulonodin III, rhodanodin, rubrivinodin, sphingonodin I, sphingonodin II, syanodin I, sphingopyxin I, sphingopyxin II, and zucinodin) were detected by high‐resolution Fourier transform mass spectrometry and their proposed primary structure was confirmed through tandem mass spectrometry. High yields (ranging from 0.4 to 5.2 mg/L) were observable for eight of these compounds, while thermostability assays revealed five new representatives of heat labile lasso peptides. © 2013 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 100: 527–542, 2013.
Thionin‐like peptides from Capsicum annuum fruits with high activity against human pathogenic bacteria and yeasts
Authors: Taveira Gabriel B. , Mathias Luciana S. , da Motta Olney V. , Machado Olga L. T. , Rodrigues Rosana , Carvalho André O. , Teixeira‐Ferreira André , Perales Jonas , Vasconcelos Ilka M. , Gomes Valdirene M.
Published: July 2013

Plants defend themselves against pathogens with production of antimicrobial peptides (AMPs). Herein we describe the discovery of a new antifungal and antibacterial peptide from fruits of Capsicum annuum that showed similarity to an already well characterized family of plant AMPs, thionins. Other fraction composed of two peptides, in which the major peptide also showed similarity to thionins. Among the obtained fractions, fraction 1, which is composed of a single peptide of 7 kDa, was sequenced by Edman method and its comparative sequence analysis in database (nr) showed similarity to thionin‐like peptides. Tests against microorganisms, fraction 1 presented inhibitory activity to the cells of yeast Saccharomyces cerevisiae, Candida albicans, and Candida tropicalis and caused growth reduction to the bacteria species Escherichia coli and Pseudomonas aeruginosa. Fraction 3 caused inhibitory activity only for C. albicans and C. tropicalis. This fraction was composed of two peptides of ∼7 and 10 kDa, and the main protein band correspondent to the 7 kDa peptide, also showed similarity to thionins. This plasma membrane permeabilization assay demonstrates that the peptides present in the fractions 1 and 3 induced changes in the membranes of all yeast strains, leading to their permeabilization. Fraction 1 was capable of inhibiting acidification of the medium of glucose‐induced S. cerevisiae cells 78% after an incubation time of 30 min, and opposite result was obtained for C. albicans. Experiments demonstrate that the fraction 1 and 3 were toxic and induced changes in the membranes of all yeast strains, leading to their permeabilization. © 2013 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 102: 30–39, 2014.
Synthesis and conformational properties of a TOAC doubly spin‐labeled analog of the medium‐length, membrane active peptaibiotic ampullosporin a as revealed by cd, fluorescence, and EPR spectroscopies
Authors: Milov Alexander D. , Tsvetkov Yuri D. , Bortolus Marco , Maniero Anna Lisa , Gobbo Marina , Toniolo Claudio , Formaggio Fernando
Published: July 2013

We describe the challenging solid‐phase synthesis of the medium‐length (14 amino‐acid residues) peptaibiotic ampullosporin A, originally extracted from the fungusSepedonium ampullosporum,and an analog doubly spin labeled (at positions 3 and 13) with the stable nitroxyl free‐radical 4‐amino‐1‐oxyl‐2,2,6,6‐tetramethylpiperidine‐4‐carboxylic acid (TOAC). The results of a circular dichrosim investigation in methanol strongly support the view that both peptides are essentially right‐handed helical, in particular endowed with a large population of α‐helical conformers. We also observed a significant quenching effect from the TOAC3nitroxyl radical on the fluorescence of Trp1, compatible with that expected when both residues are closely located on the same helix segment. Combined continuous wave and pulsed electron‐electron double resonance electron paramagnetic resonance methodologies converge on the conclusion obtained from the other aforementioned spectroscopies, namely, that the [TOAC3,13] ampullosporin A analog is mostly folded in the α‐helical conformation. A liposome leakage assay demonstrated that the membrane‐modifying properties of thisbis‐labeled analog are remarkable and even slightly superior to those of the natural peptaibiotic itself. © 2013 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 102: 40–48, 2014.
Liquid chromatography–tandem mass spectrometry of porphyrins and porphyrinogens in biological materials: separation and identification of interfering poly(ethylene) glycol by travelling wave ion mobility spectrometry/tandem mass spectrometry
Authors: Benton Christopher M. , Lim Chang Kee , Moniz Caje , Jones Donald J. L.
Published: July 2013

Biological and clinical samples for porphyrin and porphyrinogen analyses by liquid chromatography–tandem mass spectrometry (LC‐MS/MS) are often contaminated with poly(ethylene)glycol (PEG), which complicates the interpretation of mass spectra and characterisation of new porphyrin metabolites. Two contaminating PEG molecules (m/z 833 and m/z 835) were completely separated from uroporphyrin I (m/z 831) by travelling wave ion mobility spectrometry and characterised by tandem mass spectrometry. One of the PEG species (m/z 835) also co‐eluted with uroporphyrinogen I (m/z 837) and was unresolvable by travelling wave ion mobility spectrometry/MS, therefore contaminating the MS/MS mass spectra owing to isotope distribution. These PEG species, with the [M + H]+ ions at m/z at 833 and/or m/z 835, co‐eluted with uroporphyrin I and uroporphyrinogen I by LC‐MS/MS and could be wrongly identified as uroporphomethenes. Copyright © 2013 John Wiley & Sons, Ltd.
Online lifestyle consumption community dynamics: A practice‐based analysis
Authors: Närvänen Elina , Kartastenpää Elina , Kuusela Hannu
Published: July 2013

The purposes of this study were to identify and categorize the discursive practices through which consumers negotiate a lifestyle‐related identity in online lifestyle consumption communities. The empirical case is a very active community of consumers who adhere to the low‐carb/high‐fat diet. The paper contributes to communal consumption literature by showing how a lifestyle identity and the community evolve together. Focusing on an online community with lifestyle focus differentiates this study from previous research because nutritional choices influence the consumers' everyday life in a comprehensive manner. By employing a netnographic analysis on discussion board messages, 11 discursive practices are identified. These practices are categorized according to confirming/challenging and self‐directed/community‐directed dimensions. The paper provides a typology of online community dynamics, emphasizing the importance of challenging practices for community development. It also has important implications for companies who wish to understand food lifestyles and develop online platforms for their customers.

Copyright © 2013 John Wiley & Sons, Ltd.
Bismuth Tri‐ and Tetraarylcarboxylates: Crystal Structures, In Situ X‐ray Diffraction, Intermediates and Luminescence
Authors: Feyand Mark , Köppen Milan , Friedrichs Gernot , Stock Norbert
Published: July 2013

A systematic investigation of the systems Bi3+/carboxylic acid/HNO3 for the tri‐ and tetracarboxylic acids pyromellitic acid (H4Pyr), trimellitic acid (H3Tri) and trimesic acid (H3BTC) acid led to the discovery of five new bismuth carboxylates. Structural characterisation allowed the influence of the linker geometry and the Bi3+:linker molar ratio in the starting solution on the crystal structure to be determined. The crystallisation of three selected compounds was investigated by in situ energy‐dispersive X‐ray diffraction. Three new crystalline intermediates were observed within minutes, and two of them could be isolated by quenching of the reaction mixture. Their crystal structures were determined from laboratory and synchrotron X‐ray powder diffraction data and allowed a possible reaction pathway to be established. In depth characterisation of the luminescence properties of the three bismuth pyromellate compounds was carried out. Fluorescence and phosphorescence could be assigned to (mainly) ligand‐ and metal‐based transitions. The polymorphs of Bi(HPyr) exhibit different luminescence properties, although their structures are very similar. Surprisingly, doping of the three host structures with Eu3+ and Tb3+ ions was only successful for one of the polymorphs.
Determination of the Enantiomeric Purity of the Antiasthmatic Drug Montelukast by Means of 1H NMR Spectroscopy
Authors: Redondo Jordi , Capdevila Anna , Ciudad Sonia
Published: July 2013

In order to define an enantioselective nuclear magnetic resonance (NMR) method for the antiasthmatic drug montelukast, a series of nine easily available products were evaluated as NMR chiral solvating agents (CSAs): D‐dibenzoyltartaric acid, D‐ditoluoyltartaric acid, (+)‐camphorsulfonic acid, (S)‐BINOL, (S)‐3,3’‐diphenyl‐2,2’‐binaphthyl‐1,1’‐diol, (R)‐3,3'′‐di‐9‐anthracenyl‐1,1'′‐bi‐2‐naphthol, (R)‐3,3'′‐di‐9‐phenanthrenyl‐1,1'′‐bi‐2‐naphthol, Pirkle's alcohol, and (−)‐cinchonidine. It was proved that most of the studied agents constitute diastereomeric complexes with both drug enantiomers in CD2Cl2 or CDCl3 solutions, thus permitting the direct 1H NMR detection of the unwanted S‐enantiomer, even at levels of 0.75%. (−)‐Cinchonidine was found to be the more convenient CSA in terms of NMR enantiodiscrimination power and ease of experimental requirements. The final method was validated and applied to the fast monitoring of the optical purity of montelukast “in‐process” samples, circumventing the need for tedious and slower analytical procedures like enantioselective chromatography or capillary electrophoresis. In addition, a method for the enantiopurity control of the commercial drug (montelukast sodium salt) was also established using (S)‐BINOL as NMR CSA. Chirality 25: 780–786, 2013. © 2013 Wiley Periodicals, Inc.
Morphology and ultrastructure of medial rectus subgroup motoneurons in the macaque monkey
Authors: Erichsen Jonathan T. , Wright Nicholas F. , May Paul J.
Published: July 2013

There are two muscle fiber types in extraocular muscles: those receiving a single motor endplate, termed singly innervated fibers (SIFs), and those receiving multiple small terminals along their length, termed multiply innervated fibers (MIFs). In monkeys, these two fiber types receive input from different motoneuron pools: SIF motoneurons found within the extraocular motor nuclei, and MIF motoneurons found along their periphery. For the monkey medial rectus muscle, MIF motoneurons are found in the C‐group, while SIF motoneurons lie in the A‐ and B‐groups. We analyzed the somatodendritic morphology and ultrastructure of these three subgroups of macaque medial rectus motoneurons to better understand the structural determinants controlling the two muscle fiber types. The dendrites of A‐ and B‐group motoneurons lay within the oculomotor nucleus, but those of the C‐group motoneurons were located outside the nucleus, and extended into the preganglionic Edinger–Westphal nucleus. A‐ and B‐group motoneurons were very similar ultrastructurally. In contrast, C‐group motoneurons displayed significantly fewer synaptic contacts on their somata and proximal dendrites, and those contacts were smaller in size and lacked dense‐cored vesicles. However, the synaptic structure of C‐group distal dendrites was quite similar to that observed for A‐ and B‐group motoneurons. Our anatomical findings suggest that C‐group MIF motoneurons have different physiological properties than A‐ and B‐group SIF motoneurons, paralleling their different muscle fiber targets. Moreover, primate C‐group motoneurons have evolved a special relationship with the preganglionic Edinger–Westphal nucleus, suggesting these motoneurons play an important role in near triad convergence to support increased near work requirements. J. Comp. Neurol. 522:626–641, 2014. © 2013 Wiley Periodicals, Inc.
Cross‐modal reorganization of cortical afferents to dorsal auditory cortex following early‐ and late‐onset deafness
Authors: Kok Melanie A. , Chabot Nicole , Lomber Stephen G.
Published: July 2013

Cat auditory cortex is known to undergo cross‐modal reorganization following deafness, such that behavioral advantages in visual motion detection are abolished when a specific region of deaf auditory cortex, the dorsal zone (DZ), is deactivated. The purpose of the present investigation was to examine the connectional adaptations that might subserve this plasticity. We deposited biotinylated dextran amine (BDA; 3,000 MW), a retrograde tracer, unilaterally into the posterior portion of the suprasylvian fringe, corresponding to area DZ of hearing, early‐deafened (onset <1 month), and late‐deafened (onset >3 months) cats to reveal cortical afferent projections. Overall, the pattern of cortical projections to DZ was similar in both hearing and deafened animals. However, there was a progressive increase in projection strength among hearing and late‐ and early‐deafened cats from an extrastriate visual cortical region known to be involved in the processing of visual motion, the posterolateral lateral suprasylvian area (PLLS). Additionally, although no such change was documented for the posteromedial lateral suprasylvian area (PMLS), labeled neurons were present within a subregion of PMLS devoted to foveal vision in both late‐ and early‐deafened animals but not in hearing controls. PMLS is also an extrastriate visual motion processing area and is widely considered to be the homolog of primate middle temporal area. No changes in auditory cortical connectivity were observed among groups. These observations suggest that amplified cortical projections from extrastriate visual areas involved in visual motion processing to DZ may contribute to the cross‐modal reorganization that functionally manifests as superior visual motion detection ability in the deaf animal. J. Comp. Neurol. 522:654–675, 2014. © 2013 Wiley Periodicals, Inc.
Subcellular localization of intercellular adhesion molecule‐5 (telencephalin) in the visual cortex is not developmentally regulated in the absence of matrix metalloproteinase‐9
Authors: Kelly Emily A. , Tremblay Marie‐Eve , Gahmberg Carl G. , Tian Li , Majewska Ania K.
Published: July 2013

The telencephalon‐associated intercellular adhesion molecule‐5 (telencephalin; ICAM‐5) regulates dendritic morphology in the developing brain. In vitro studies have shown that ICAM‐5 is found predominantly within dendrites and immature dendritic protrusions, with reduced expression in mushroom spines, suggesting that ICAM‐5 downregulation is critical for the maturation of synaptic structures. However, developmental expression of ICAM‐5 has not been explored in depth at the ultrastructural level in intact brain tissue. To investigate the ultrastructural localization of ICAM‐5 with transmission electron microscopy, we performed immunoperoxidase histochemistry for ICAM‐5 in mouse visual cortex at postnatal day (P)14, a period of intense synaptogenesis, and at P28, when synapses mature. We observed the expected ICAM‐5 expression in dendritic protrusions and shafts at both P14 and P28. ICAM‐5 expression in these dendritic protrusions decreased in prevalence with developmental age to become localized predominantly to dendritic shafts by P28. To understand better the relationship between ICAM‐5 and the endopeptidase metalloproteinase‐9 (MMP‐9), which mediates ICAM‐5 cleavage following glutamate activation during postnatal development, we also explored ICAM‐5 expression in MMP‐9 null animals. This analysis revealed a similar expression of ICAM‐5 in dendritic elements at P14 and P28; however, an increased prevalence of ICAM‐5 was noted in dendritic protrusions at P28 in the MMP‐9 null animals, indicating that, in the absence of MMP‐9, there is no developmental shift in ICAM‐5 subcellular localization. Our ultrastructural observations shed light on possible functions mediated by ICAM‐5 and their regulation by extracellular proteases. J. Comp. Neurol. 522:676–688, 2013. © 2013 Wiley Periodicals, Inc.
Topographic organization of orbitofrontal projections to the parahippocampal region in rats
Authors: Kondo Hideki , Witter Menno P.
Published: July 2013

The parahippocampal region, which comprises the perirhinal, postrhinal, and entorhinal cortices, as well as the pre‐ and parasubiculum, receives inputs from several association cortices and provides the major cortical input to the hippocampus. This study examined the topographic organization of projections from the orbitofrontal cortex (OFC) to the parahippocampal region in rats by injecting anterograde tracers, biotinylated dextran amine (BDA) and Phaseolus vulgaris‐leucoagglutinin (PHA‐L), into four subdivisions of OFC. The rostral portion of the perirhinal cortex receives strong projections from the medial (MO), ventral (VO), and ventrolateral (VLO) orbitofrontal areas and the caudal portion of lateral orbitofrontal area (LO). These projections terminate in the dorsal bank and fundus of the rhinal sulcus. In contrast, the postrhinal cortex receives a strong projection specifically from VO. All four subdivisions of OFC give rise to projections to the dorsolateral parts of the lateral entorhinal cortex (LEC), preferentially distributing to more caudal levels of LEC. The medial entorhinal cortex (MEC) receives moderate input from VO and weak projections from MO, VLO, and LO. The presubiculum receives strong projections from caudal VO but only weak projections from other OFC regions. As for the laminar distribution of projections, axons originating from OFC terminate more densely in upper layers (layers I–III) than in deep layers in the parahippocampal region. These results thus show a striking topographic organization of OFC‐to‐parahippocampal connectivity. Whereas LO, VLO, VO, and MO interact with perirhinal–LEC circuits, the interactions with postrhinal cortex, presubiculum, and MEC are mediated predominantly through the projections of VO. J. Comp. Neurol. 522:772–793, 2014. © 2013 Wiley Periodicals, Inc.
Digital atlas of the zebra finch (Taeniopygia guttata) brain: A high‐resolution photo atlas
Authors: Karten Harvey J. , Brzozowska‐Prechtl Agnieszka , Lovell Peter V. , Tang Daniel D. , Mello Claudio V. , Wang Haibin , Mitra Partha P.
Published: July 2013

We describe a set of new comprehensive, high‐quality, high‐resolution digital images of histological sections from the brain of male zebra finches (Taeniopygia guttata) and make them publicly available through an interactive website (http://zebrafinch.brainarchitecture.org/). These images provide a basis for the production of a dimensionally accurate and detailed digital nonstereotaxic atlas. Nissl‐ and myelin‐stained brain sections are provided in the transverse, sagittal, and horizontal planes, with the transverse plane approximating the more traditional Frankfurt plane. In addition, a separate set of brain sections in this same plane is stained for tyrosine hydroxylase, revealing the distribution of catecholaminergic neurons (dopaminergic, noradrenergic, and adrenergic) in the songbird brain. For a subset of sagittal sections we also prepared a corresponding set of drawings, defining and annotating various nuclei, fields, and fiber tracts that are visible under Nissl and myelin staining. This atlas of the zebra finch brain is expected to become an important tool for birdsong research and comparative studies of brain organization and evolution. J. Comp. Neurol. 521:3702–3715, 2013. © 2013 Wiley Periodicals, Inc.
Are all osteocytes equal? Multiscale modelling of cortical bone to characterise the mechanical stimulation of osteocytes
Authors: Vaughan Ted J. , Verbruggen Stefaan W. , McNamara Laoise M.
Published: July 2013

Bone continuously adapts its internal structure to accommodate the functional demands of its mechanical environment. This process is orchestrated by a network of mechanosensitive osteocytes that respond to external mechanical signals and recruit osteoblasts and osteoclasts to alter bone mass to meet loading demands. Because of the irregular hierarchical microarchitecture of bone tissue, the precise mechanical stimuli experienced by osteocytes located in different regions of the tissue is not well‐understood. The objective of this study is to characterise the local stimulus experienced by osteocytes distributed throughout the tissue structure. Our models predict that an inhomogeneous microstructural strain field contributes to osteocytes receiving vastly different stimuli at the cellular level, depending on their location within the microstructure. In particular, osteocytes located directly adjacent to micropores experienced strain amplifications in their processes of up to nine times the applied global strain. Furthermore, it was found that the principal orientation of lamellar regions was found to contribute significantly to the magnitude of the stimulus being received at the cellular level. These findings indicate that osteocytes are not equal in terms of the mechanical stimulus being received, and we propose that only a subset of osteocytes may be sufficiently stimulated to function as mechanoreceptors. Copyright © 2013 John Wiley & Sons, Ltd.
Dynamics of survival of motor neuron (SMN) protein interaction with the mRNA‐binding protein IMP1 facilitates its trafficking into motor neuron axons
Authors: Fallini Claudia , Rouanet Jeremy P. , Donlin‐Asp Paul G. , Guo Peng , Zhang Honglai , Singer Robert H. , Rossoll Wilfried , Bassell Gary J.
Published: July 2013

Spinal muscular atrophy (SMA) is a lethal neurodegenerative disease specifically affecting spinal motor neurons. SMA is caused by the homozygous deletion or mutation of the survival of motor neuron 1 (SMN1) gene. The SMN protein plays an essential role in the assembly of spliceosomal ribonucleoproteins. However, it is still unclear how low levels of the ubiquitously expressed SMN protein lead to the selective degeneration of motor neurons. An additional role for SMN in the regulation of the axonal transport of mRNA‐binding proteins (mRBPs) and their target mRNAs has been proposed. Indeed, several mRBPs have been shown to interact with SMN, and the axonal levels of few mRNAs, such as the β‐actin mRNA, are reduced in SMA motor neurons. In this study we have identified the β‐actin mRNA‐binding protein IMP1/ZBP1 as a novel SMN‐interacting protein. Using a combination of biochemical assays and quantitative imaging techniques in primary motor neurons, we show that IMP1 associates with SMN in individual granules that are actively transported in motor neuron axons. Furthermore, we demonstrate that IMP1 axonal localization depends on SMN levels, and that SMN deficiency in SMA motor neurons leads to a dramatic reduction of IMP1 protein levels. In contrast, no difference in IMP1 protein levels was detected in whole brain lysates from SMA mice, further suggesting neuron specific roles of SMN in IMP1 expression and localization. Taken together, our data support a role for SMN in the regulation of mRNA localization and axonal transport through its interaction with mRBPs such as IMP1. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 74: 319–332, 2014
The Ptch1DL mouse: A new model to study lambdoid craniosynostosis and basal cell nevus syndrome‐associated skeletal defects
Authors: Feng Weiguo , Choi Irene , Clouthier David E. , Niswander Lee , Williams Trevor
Published: July 2013

Mouse models provide valuable opportunities for probing the underlying pathology of human birth defects. By using an N‐ethyl‐N‐nitrosourea‐based screen for recessive mutations affecting craniofacial anatomy, we isolated a mouse strain, Dogface‐like (DL), with abnormal skull and snout morphology. Examination of the skull indicated that these mice developed craniosynostosis of the lambdoid suture. Further analysis revealed skeletal defects related to the pathology of basal cell nevus syndrome (BCNS) including defects in development of the limbs, scapula, ribcage, secondary palate, cranial base, and cranial vault. In humans, BCNS is often associated with mutations in the Hedgehog receptor PTCH1 and genetic mapping in DL identified a point mutation at a splice donor site in Ptch1. By using genetic complementation analysis we determined that DL is a hypomorphic allele of Ptch1, leading to increased Hedgehog signaling. Two aberrant transcripts are generated by the mutated Ptch1DL gene, which would be predicted to reduce significantly the levels of functional Patched1 protein. This new Ptch1 allele broadens the mouse genetic reagents available to study the Hedgehog pathway and provides a valuable means to study the underlying skeletal abnormalities in BCNS. In addition, these results strengthen the connection between elevated Hedgehog signaling and craniosynostosis. genesis 51:677–689. © 2013 Wiley Periodicals, Inc.