bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

ABSTRACTLignin 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

ObjectiveThe 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.MethodsThe 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.ResultsCD4+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.ConclusionOur 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

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

ObjectiveTo 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.MethodsA 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.ResultsConsistent 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.ConclusionThe 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

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

AbstractSustainable 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

BACKGROUNDFew 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.METHODSInformation 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.RESULTSNo 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.CONCLUSIONOverall, 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.
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

AbstractMetabolic 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

ABSTRACTHuman 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

ABSTRACTLasso 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

ABSTRACTPlants 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

ABSTRACTWe 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

ABSTRACTBiological 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.