bluuebunny/crossref_metadata_2025 huggingface dataset:
The Histone Deacetylase Sirtuin 1 Is Reduced in Systemic Sclerosis and Abrogates Fibrotic Responses by Targeting Transforming Growth Factor β Signaling
Authors: Wei Jun , Ghosh Archit K. , Chu Haiyan , Fang Feng , Hinchcliff Monique E. , Wang Jiucun , Marangoni Roberta Goncalves , Varga John
Published: February 2015

Objective

Persistent fibroblast activation underlies skin fibrosis in systemic sclerosis (SSc), but the transcriptional and epigenetic mechanisms controlling this process are not well understood. In view of the potent influence of acetylation status governing tissue fibrosis, we undertook this study to investigate the expression of the antiaging deacetylase enzyme sirtuin 1 (SIRT1) in SSc and its effects on fibrotic responses in vitro and in vivo.

Methods

Tissue expression of SIRTs was interrogated from publicly available genome‐wide expression data sets and by immunohistochemistry. The effects of SIRT1 on modulating fibrotic responses, as well as the underlying mechanisms, were examined in human and mouse fibroblasts in culture and in an experimental fibrosis model in the mouse.

Results

Analysis of transcriptome data revealed a selective reduction of SIRT1 messenger RNA (mRNA) levels in SSc skin biopsy samples as well as a negative correlation of SIRT1 mRNA with the skin score. Cellular SIRT1 levels were suppressed in normal fibroblasts exposed to hypoxia or platelet‐derived growth factor and were constitutively down‐regulated in SSc fibroblasts. Activation of SIRT1 attenuated fibrotic responses in skin fibroblasts and skin organ cultures, while genetic or pharmacologic inhibition of SIRT1 had profibrotic effects. The antifibrotic effects of SIRT1 were due in part to decreased expression and function of the acetyltransferase p300. In mice, experimentally induced skin fibrosis was accompanied by reduced SIRT1 expression in lesional tissue fibroblasts, and both fibrosis and loss of SIRT1 in these mice were mitigated by treatment with a SIRT1 activator.

Conclusion

SIRT1 has antifibrotic effects, and its reduced tissue expression in patients with SSc might have a direct causal role in progression of fibrosis. Pharmacologic modulation of SIRT1 in these patients therefore might represent a potential treatment strategy.
Bioactivity in an Aggrecan 32‐mer Fragment Is Mediated via Toll‐like Receptor 2
Authors: Lees Sophie , Golub Suzanne B. , Last Karena , Zeng Weiguang , Jackson David C. , Sutton Philip , Fosang Amanda J.
Published: February 2015

Objective

To determine whether an aggrecan 32‐mer fragment derived from dual ADAMTS and matrix metalloproteinase (MMP) cleavage in the aggrecan interglobular domain was bioactive and, if so, to elucidate its mechanism of action.

Methods

Mouse primary chondrocytes, synovial fibroblasts, or peritoneal macrophages, human primary chondrocytes, and cells or cell lines from myeloid differentiation factor 88 (MyD88)–deficient and Toll‐like receptor 2 (TLR‐2)–deficient mice were stimulated with synthetic mouse 32‐mer peptide, human 32‐mer peptide, a 32‐mer scrambled peptide, or native, glycosylated 32‐mer peptide. Cells stimulated with 32‐mer peptide were analyzed for changes in messenger RNA (mRNA) expression by quantitative polymerase chain reaction. Conditioned medium was analyzed for levels of interleukin‐6 protein by an AlphaLISA or for levels of MMP‐3 and MMP‐13 protein by Western blotting. NF‐κB activation was measured in a luciferase reporter assay.

Results

Treatment of mouse cells or cartilage explants with 32‐mer peptide or scrambled peptide revealed that the 32‐mer peptide, but not the scrambled peptide, had antianabolic, procatabolic, and proinflammatory bioactivity in vitro. Chondrocytes, synovial fibroblasts, and macrophages from MyD88‐deficient mice failed to respond to 32‐mer peptide stimulation. A macrophage cell line derived from TLR‐2–deficient mice also failed to respond to 32‐mer peptide stimulation. Stimulation of human chondrocytes with human 32‐mer peptide increased the expression of catabolic markers at the mRNA and protein levels. Mouse and human 32‐mer peptide stimulated NF‐κB activation in a TLR‐2–dependent reporter assay, and the response of chondrocytes from both species to native, glycosylated 32‐mer peptide was similar to the response to synthetic peptides.

Conclusion

The aggrecan 32‐mer fragment is a novel endogenous ligand of TLR‐2 with the potential to accelerate cartilage destruction in vivo.
Brief Report: Articular Ankle Fracture Results in Increased Synovitis, Synovial Macrophage Infiltration, and Synovial Fluid Concentrations of Inflammatory Cytokines and Chemokines
Authors: Furman Bridgette D. , Kimmerling Kelly A. , Zura Robert D. , Reilly Rachel M. , Zlowodzki Michal P. , Huebner Janet L. , Kraus Virginia B. , Guilak Farshid , Olson Steven A.
Published: February 2015

Objective

The inflammatory response following an articular fracture is thought to play a role in the development of posttraumatic arthritis (PTA) but has not been well characterized. The objective of this study was to characterize the acute inflammatory response, both locally and systemically, in joint synovium, synovial fluid (SF), and serum following articular fracture of the ankle. We hypothesized that intraarticular fracture would alter the synovial environment and lead to increased local and systemic inflammation.

Methods

Synovial tissue biopsy specimens, SF samples, and serum samples were collected from patients with an acute articular ankle fracture (n = 6). Additional samples (normal, ankle osteoarthritis [OA], and knee OA [n = 6 per group]) were included for comparative analyses. Synovial tissue was assessed for synovitis and macrophage count. SF and serum were assessed for cytokines (interferon‐γ [IFNγ], interleukin‐1β [IL‐1β], IL‐6, IL‐8, IL‐10, IL‐12p70, and tumor necrosis factor α) and chemokines (eotaxin, eotaxin 3, IFNγ‐inducible 10‐kd protein, monocyte chemotactic protein 1 [MCP‐1], MCP‐4, macrophage‐derived chemokine, macrophage inflammatory protein 1β, and thymus and activation–regulated chemokine).

Results

Synovitis scores were significantly higher in ankle fracture tissue compared with normal ankle tissue (P = 0.007), and there was a trend toward an increased abundance of CD68+ macrophages in ankle fracture synovium compared with normal knee synovium (P = 0.06). The concentrations of all cytokines and chemokines were elevated in the SF of patients with ankle fracture compared with those in SF from OA patients with no history of trauma. Only the concentration of IL‐6 was significantly increased in the serum of patients with ankle fracture compared with normal serum (P = 0.027).

Conclusion

Articular fracture of the ankle increased acute local inflammation, as indicated by increased synovitis, increased macrophage infiltration into synovial tissue, and increased SF concentrations of biomarkers of inflammation. Characterizing the acute response to articular fracture provides insight into the healing process and may help to identify patients who may be at greater risk of PTA.
Microvascular Abnormalities in Adjuvant‐Induced Arthritis: Relationship to Macrovascular Endothelial Function and Markers of Endothelial Activation
Authors: Totoson Perle , Maguin‐Gaté Katy , Nappey Maude , Prati Clément , Wendling Daniel , Demougeot Céline
Published: February 2015

Objective

To determine the time course of microvascular abnormalities and the link with macrovascular endothelial function and circulating markers of endothelial activation in adjuvant‐induced arthritis (AIA) in rats.

Methods

Microvascular function/structure and mechanics were studied in third‐order mesenteric arteries subjected to flow and/or pressure on day 4 (preclinical arthritis), day 11 (very early arthritis), day 33 (severe disease), and day 90 (when inflammation has resolved) after AIA induction. Macrovascular function was studied in aortic rings, and blood pressure, plasma levels of C‐reactive protein (CRP), intercellular adhesion molecule 1 (ICAM‐1), and vascular cell adhesion molecule 1 (VCAM‐1) were measured at each time point.

Results

Mesenteric flow‐mediated vasodilation was significantly reduced from very early arthritis to chronic disease, whereas increased microvascular arterial stiffness was evident only on day 33. Macrovascular endothelial dysfunction was observed only on day 33. Thus, on day 90, whereas rats with AIA recovered normal macrovascular endothelial function, microvascular endothelial function remained impaired. No correlation was found between micro‐ and macrovascular endothelial function throughout the course of arthritis (r = 0.180, P = 0.229). Furthermore, no correlation was found between CRP levels, ICAM‐1 levels, and endothelial function whatever the vascular bed. AIA was not associated with change in blood pressure or VCAM levels.

Conclusion

Our findings indicate that microvascular endothelial dysfunction occurs earlier than macrovascular endothelial dysfunction and microvascular arterial stiffness during arthritis, suggesting that microvascular endothelial function would be a valuable tool for the early assessment of cardiovascular risk in RA. Neither the ICAM‐1 level nor the CRP level is a good marker of micro‐ or macrovascular endothelial dysfunction.
Glucocorticoid‐Induced Leucine Zipper Governs the Therapeutic Potential of Mesenchymal Stem Cells by Inducing a Switch From Pathogenic to Regulatory Th17 Cells in a Mouse Model of Collagen‐Induced Arthritis
Authors: Luz‐Crawford P. , Tejedor G. , Mausset‐Bonnefont A. L. , Beaulieu E. , Morand E. F. , Jorgensen C. , Noël D. , Djouad F.
Published: February 2015

Objective

Mesenchymal stem cells (MSCs) are potent immunosuppressive cells that have shown promise in the treatment of rheumatoid arthritis (RA). Deciphering the intrinsic characteristics of MSCs that correlate with their biologic activity will facilitate their clinical use. Recently, the role of glucocorticoid‐induced leucine zipper (GILZ) in the development of RA has been documented. The aim of this study was to evaluate whether GILZ expression by MSCs may contribute to their therapeutic effect.

Methods

MSCs were isolated from GILZ‐deficient (GILZ−/−) mice and wild‐type mice. MSCs (1 × 106 cells) were injected twice via the tail vein into mice with collagen‐induced arthritis (CIA).

Results

In vitro, we showed that GILZ is a key factor involved in the immunosuppressive potential of MSCs. MSCs derived from GILZ−/− mice did not suppress the proliferation of CD4+ T cells and were less efficient than MSCs derived from WT mice in altering Th17 cell polarization. Thus, we investigated the role of GILZ in an experimental model of arthritis and demonstrated that although WT MSCs significantly reduced paw swelling in arthritic mice, GILZ−/− MSCs did not. Moreover, the magnitude of the effects of GILZ−/− MSCs on Th17 cell frequency was significantly lower than that of WT MSCs. The therapeutic effect of MSCs correlated with the generation of Treg cells bearing the CD4 + RORγt+IL‐17low IL‐10+ signature, and Th17 cell polarization was GILZ dependent.

Conclusion

This study demonstrates that GILZ has an essential role in the therapeutic effectiveness of MSCs in arthritis by favoring Th17 cell polarization toward a regulatory phenotype. Therefore, potentiation of GILZ expression in MSCs could represent a means to enhance their therapeutic effect in autoimmune diseases.
A Reactive Oxygen Species–Mediated Loop Maintains Increased Expression of NADPH Oxidases 2 and 4 in Skin Fibroblasts From Patients With Systemic Sclerosis
Authors: Spadoni Tatiana , Svegliati Baroni Silvia , Amico Donatella , Albani Lisa , Moroncini Gianluca , Avvedimento Enrico V. , Gabrielli Armando
Published: February 2015

Objective

Reactive oxygen species (ROS) contribute to the pathogenesis of fibrosis in systemic sclerosis (SSc; scleroderma), and NADPH oxidase (NOX) is an important source of ROS. Since the role of single NOX isoforms has not been previously investigated in SSc, this study was undertaken to assess the expression of NOX in SSc fibroblasts compared to normal healthy cells and to analyze their role in cell activation.

Methods

Expression of NOX isoforms in dermal fibroblasts from patients with SSc and healthy control subjects was analyzed by real‐time polymerase chain reaction, immunoblotting, and immunofluorescence. NOX isoforms were silenced using small interfering RNA. Production of ROS was measured by fluorometry and confocal microscopy.

Results

Scleroderma fibroblasts showed up‐regulation of NOX‐2 and NOX‐4 protein and messenger RNA (mRNA) expression. Treatment of the cells with diphenyleneiodonium, a nonselective inhibitor of flavin‐containing enzymes, and silencing of NOX2 and NOX4 decreased the production of ROS as well as the expression of type I collagen and α‐smooth muscle actin in SSc fibroblasts. ROS generated by NOX‐2 and NOX‐4 were involved in DNA damage and activation of a DNA repair checkpoint. Incubation of healthy control fibroblasts with platelet‐derived growth factor (PDGF) or with IgG isolated from SSc patient serum enhanced the expression of NOX2 and NOX4 mRNA, via ROS, in a time‐dependent manner. Treatment with actinomycin D, a transcription inhibitor, reversed the effects of PDGF stimulation but not the effects of SSc IgG.

Conclusion

Both NOX2 and NOX4 generate ROS in SSc fibroblasts and play a critical role in cell activation and DNA damage. Expression of NOX‐2 and NOX‐4 in SSc fibroblasts is maintained by a ROS‐mediated loop.
Semaphorin 4D Contributes to Rheumatoid Arthritis by Inducing Inflammatory Cytokine Production: Pathogenic and Therapeutic Implications
Authors: Yoshida Yuji , Ogata Atsushi , Kang Sujin , Ebina Kousuke , Shi Kenrin , Nojima Satoshi , Kimura Tetsuya , Ito Daisuke , Morimoto Keiko , Nishide Masayuki , Hosokawa Takashi , Hirano Toru , Shima Yoshihito , Narazaki Masashi , Tsuboi Hideki , Saeki Yukihiko , Tomita Tetsuya , Tanaka Toshio , Kumanogoh Atsushi
Published: February 2015

Objective

Semaphorin 4D (Sema4D)/CD100 has pleiotropic roles in immune activation, angiogenesis, bone metabolism, and neural development. We undertook this study to investigate the role of Sema4D in rheumatoid arthritis (RA).

Methods

Soluble Sema4D (sSema4D) levels in serum and synovial fluid were analyzed by enzyme‐linked immunosorbent assay. Cell surface expression and transcripts of Sema4D were analyzed in peripheral blood cells from RA patients, and immunohistochemical staining of Sema4D was performed in RA synovium. Generation of sSema4D was evaluated in an ADAMTS‐4–treated monocytic cell line (THP‐1 cells). The efficacy of anti‐Sema4D antibody was evaluated in mice with collagen‐induced arthritis (CIA).

Results

Levels of sSema4D were elevated in both serum and synovial fluid from RA patients, and disease activity markers were correlated with serum sSema4D levels. Sema4D‐expressing cells also accumulated in RA synovium. Cell surface levels of Sema4D on CD3+ and CD14+ cells from RA patients were reduced, although levels of Sema4D transcripts were unchanged. In addition, ADAMTS‐4 cleaved cell surface Sema4D to generate sSema4D in THP‐1 cells. Soluble Sema4D induced tumor necrosis factor α (TNFα) and interleukin‐6 (IL‐6) production from CD14+ monocytes. IL‐6 and TNFα induced ADAMTS‐4 expression in synovial cells. Treatment with an anti‐Sema4D antibody suppressed arthritis and reduced proinflammatory cytokine production in CIA.

Conclusion

A positive feedback loop involving sSema4D/IL‐6 and TNFα/ADAMTS‐4 may contribute to the pathogenesis of RA. The inhibition of arthritis by anti‐Sema4D antibody suggests that Sema4D represents a potential therapeutic target for RA.
Rapid induction of omega‐3 fatty acids (EPA) in Nannochloropsis sp. by UV‐C radiation
Authors: Sharma Kalpesh , Schenk Peer M.
Published: February 2015

Omega‐3 fatty acids, such as eicosapentaenoic acid (EPA), provide substantial health benefits. As global fish stocks are declining and in some cases are contaminated with heavy metals, there is a need to find more sustainable land‐based sources of these essential fatty acids. The oleaginous microalga Nannochloropsis sp. has been identified as a highly efficient producer of omega‐3 fatty acids. In this study, we present a new process to rapidly induce biosynthesis of essential fatty acids, including EPA in Nannochloropsis sp. BR2. Short exposure to UV‐C at a dose of 100 or 250 mJ/cm2 led to a significant increase in total cellular lipid contents when compared to mock‐treated controls. A low dosage of 100 mJ/cm2 also led to a twofold increase in total EPA content within 24 h that constituted 30% of total fatty acids and up to 12% of total dry weight at higher dosages. UV‐C radiation may find uses as an easily applicable external inducer for large‐scale production of omega‐3 production from microalgae. Biotechnol. Bioeng. 2015;112: 1243–1249. © 2015 Wiley Periodicals, Inc.
Comparison of CT numbers of organs before and after plastination using standard S‐10 technique
Authors: Shanthi Pauline , Singh Rabi Raja , Gibikote Sridhar , Rabi Suganthy
Published: February 2015

Plastination is the art of preserving biological tissues with curable polymers. Imaging with plastinates offers a unique opportunity for radiographic, anatomical, pathological correlation to elucidate complex anatomical relationships. The aim of this study was to make plastinates from cadavers using the standard S‐10 plastination technique and to compare the radiological properties of the tissue before and afterwards to examine the suitability of plastinates as phantoms for planning radiotherapy treatment. An above‐diaphragm and a below‐diaphragm specimen were obtained from a male and a female cadaver, respectively, and subjected to the standard S‐10 plastination technique. CT images were obtained before and after plastination and were compared using Treatment Planning System for anatomical accuracy, volume of organs, and CT numbers. The plastinated specimens obtained were dry, robust, and durable. CT imaging of the plastinated specimens showed better anatomical detail of the organs than the preplastinate. Organ volumes were estimated by contouring the organs' outline in the CT images of the preplastinated and postplastinated specimens, revealing an average shrinkage of 25%. CT numbers were higher in the plastinated specimens except in bones and air‐filled cavities such as the maxillary air sinus. Although plastination by the standard S‐10 technique preserves anatomical accuracy, it increases the CT numbers of the organs because of the density of silicone, making it unsuitable for radiation dosimetry. Further improvements of the technique could yield more suitable plastinated phantoms. Clin. Anat. 28:431–435, 2015. © 2015 Wiley Periodicals, Inc.
From face‐to‐face to distance LMS‐mediated collaborative learning situations with GLUE!
Authors: Alario‐Hoyos Carlos , Gómez‐Sánchez Eduardo , Bote‐Lorenzo Miguel L. , Asensio‐Pérez Juan I. , Vega‐Gorgojo Guillermo , Ruiz‐Calleja Adolfo
Published: February 2015

GLUE! is an integration architecture that allows teachers to easily set up an LMS environment with several external tools to carry out complex collaborative learning situations in distance settings. Though its effectiveness in alleviating the burden on teachers of deploying and enacting such situations has been studied elsewhere, there are no studies in the literature analyzing the impact, in terms of learning achievement, of turning traditional face‐to‐face collaborative learning situations into distance LMS‐mediated ones with the support of integration approaches such as the GLUE! architecture. This paper compares the learning achievement in a distance LMS‐mediated collaborative learning situation supported by GLUE! and in the equivalent face‐to‐face in a non‐technological setting. The conclusions of this comparison, along with the fact that GLUE! significantly reduces the set up effort, suggest that GLUE! is a good choice for turning traditional face‐to‐face collaborative learning situations into distance LMS‐mediated ones without significant negative effects in the learning achievement. © 2015 Wiley Periodicals, Inc. Comput Appl Eng Educ 23:527–536, 2015; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.21623
CAS and real life problems to learn basic concepts in Linear Algebra course
Authors: Caridade C. M. R. , Encinas A. H. , Martín‐Vaquero J. , Queiruga‐Dios A.
Published: February 2015

In this paper we examine the effect of the use of a Computer Algebra System (CAS) to solve interdisciplinary problems. We have been working for some years in the application of mathematics to different engineering problems, the main reason was to improve the motivation of our students and to make possible for them to connect and apply what they learn in Linear Algebra class to other engineering subjects. We describe a case study with students of Electromechanical and Mechanical Engineering from the Coimbra Institute of Engineering and from Geological and Industrial Engineering students from the University of Salamanca in a Linear Algebra course. The study involves the application of digital image processing to develop the basic skills of Linear Algebra. Furthermore, we include the results of a pre‐test and post‐test control group study using that application in the classroom. The results indicate that the experiences were very enriching for the students in different subjects. We tested at different centers from two different countries with similar results. © 2015 Wiley Periodicals, Inc. Comput Appl Eng Educ 23:567–577, 2015; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.21627
Using IBM SPSS modeler to improve undergraduate mathematical modelling competence
Authors: Xiao Xiang , Xu Honglei , Xu Shouzhi
Published: February 2015

This paper is concerned with the problem of improving undergraduate mathematical modelling competence in the current big data world. Firstly, we review the renowned teacher's seven‐step, student's four‐step and a six‐step modelling cycles to explain mathematical modelling competence. The six‐step modelling cycle is also used in Common Core State Standards for Mathematics (CCSSM) in the United States. Based on these previous modelling cycles, we propose a new five‐phase modelling cycle by use of the tool named IBM SPSS Modeler in accordance with Cross Industry Standard Process for Data Mining (CRISP‐DM). A teaching case will be presented to apply these methodologies to undergraduates’ mathematical modelling lessons. It is shown that teachers can use IBM SPSS Modeler to improve student's mathematical modelling competence by understanding and practicing the process of five‐phase modelling. © 2015 Wiley Periodicals, Inc. Comput Appl Eng Educ 23:603–609, 2015; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.21632
Predictive Models for Thermal Behavior of Chemicals with Quantitative Structure‐Property Relationships
Authors: Baati Nadia , Nanchen Annik , Stoessel Francis , Meyer Thierry
Published: February 2015

Most processes in the chemical industry involve potentially hazardous steps. It is thus of critical importance to perform risk assessments and to know the thermal behavior of the chemicals at stake. A widely used thermal analysis, differential scanning calorimetry, allows verifying if the compounds are stable towards heat or if they decompose above certain temperatures. This information helps setting the appropriate handling and storage conditions for safe operations. The time and resources needed for these experimental investigations would be reduced if the testing phase could be better targeted and guided using reliable predictive methods. This work helps to answer these needs by proposing predictive models for thermal stability based on the quantitative structure‐property relationships method.
An Innovative Approach for Adsorption Column Modeling
Authors: Boyadjiev Christo , Boyadjiev Boyan , Popova‐Krumova Petya , Doichinova Maria
Published: February 2015

An new methody for physical and chemical adsorption modeling in column apparatuses is presented. A convection‐diffusion model is obtained in the approximations of the continua mechanics, where the mathematical point is equivalent to the medium elementary volume which is sufficiently small with respect to the column volume and at the same time sufficiently large with respect to the intermolecular volumes of the medium. The created convection‐diffusion type model allows performing qualitative analysis of the process and obtaining the effect of the velocity radial nonuniformity in the column. An average concentration model is applied for quantitative description of physical and chemical adsorption in the column apparatus. The methods for model equation solutions and model parameter identifications are described.
In Situ‐Formed, Amorphous, Oxygen‐Enabled Germanium Anode with Robust Cycle Life for Reversible Lithium Storage
Authors: Sun Xiaolei , Si Wenping , Xi Lixia , Liu Bo , Liu Xuejun , Yan Chenglin , Schmidt Oliver G.
Published: February 2015

An oxygen‐enabled germanium anode for lithium‐ion batteries has been obtained for the first time through the local electron‐stimulated reaction of oxygen molecules with gaseous germanium. Benefiting from the incorporation of oxygen atoms, this material can effectively suppress the agglomeration of germanium particles, tolerate the substantial volume change, and reduce the strain/stress generated during lithiation/delithiation. As demonstrated, the oxygen‐enabled germanium anode shows significantly enhanced electrochemical performance compared to the untreated germanium anode. The oxygen‐enabled electrode exhibits a high reversible lithium‐storage capacity (≈1200 mAh g−1), extremely robust cycle life, and superior rate capability. The proposed concept presented in this work is feasible and valuable for other group IV materials (Si, Sn), potentially leading to high‐performance electrochemical energy‐storage and conversion devices.
CBr4‐Mediated Cross‐Dehydrogenative Coupling Reaction of Amines
Authors: Huo Congde , Xie Haisheng , Wu Mingxia , Jia Xiaodong , Wang Xicun , Chen Fengjuan , Tang Jing
Published: February 2015

A novel CBr4‐mediated dehydrogenative Povarov/aromatization tandem reaction of glycine derivatives with alkenes, leading to complex quinoline derivatives, and a CBr4‐mediated dehydrogenative CH functionalization of N‐aryl tetrahydroisoquinolines with nucleophiles to form CC and CP bonds are reported. The reactions were performed under very simple and mild reaction conditions; only CBr4 was used as a promoter. A plausible mechanism involving a radical process is proposed.
Tannery Effluent Treatment by Microfiltration through Ceramic Membrane for Water Reuse: Assessment of Environmental Impacts
Authors: Bhattacharya Priyankari , Ghosh Sourja , Swarnakar Snehashikta , Mukhopadhyay Aniruddha
Published: February 2015

The performance evaluation of an indigenously developed ceramic membrane from a clay–alumina mixture was evaluated toward microfiltration treatment of tannery effluent from a secondary clarifier. The study was aimed at observing the reuse efficiency of the membrane treated effluent using Pistia sp. as plant model and Poecilia sp. as fish model. About 70–86% chemical oxygen demand removal and 85% total organic carbon removal was achieved in the ceramic membrane based microfiltration process. The comet assay of Pistia sp. leaves showed formation of DNA tail in the untreated effluent suggesting DNA damage whereas no such observations were noted in treated water. Oxidative stress biomarkers like guaiacol peroxidase, superoxide dismutase, etc., in both Pistia sp. and Poecilia sp. increased considerably in untreated effluent, whereas the treated water values were close to that of control. The overall process demonstrated that microfiltration by ceramic membranes might prove as effective means of wastewater reuse for aquaculture, agriculture, as well as in industrial sectors.
Highly Selective Continuous‐Flow Synthesis of Potentially Bioactive Deuterated Chalcone Derivatives
Authors: Hsieh Chi‐Ting , Ötvös Sándor B. , Wu Yang‐Chang , Mándity István M. , Chang Fang‐Rong , Fülöp Ferenc
Published: February 2015

The selective synthesis of various dideuterochalcones as potentially bioactive deuterium‐labeled products is presented, by means of the highly controlled partial deuteration of antidiabetic chalcone derivatives. The benefits of continuous‐flow processing in combination with on‐demand electrolytic D2 gas generation has been exploited to avoid over‐reaction to undesired side products and to achieve selective deuterium addition to the carbon–carbon double bond of the starting enones without the need for unconventional catalysts or expensive special reagents. The roles of pressure, temperature, and residence time proved crucial for the fine‐tuning of the sensitive balance between the product selectivity and the reaction rate. The presented flow‐chemistry‐based deuteration technique lacks most of the drawbacks of the classical batch methods, and is convenient, time‐ and cost‐efficient, and safe.
A Chalcone‐Based Highly Selective and Sensitive Chromofluorogenic Probe for Trivalent Metal Cations
Authors: Santos‐Figueroa Luis E. , Llopis‐Lorente Antoni , Royo Santiago , Sancenón Félix , Martínez‐Máñez Ramón , Costero Ana M. , Gil Salvador , Parra Margarita
Published: February 2015

A new chalcone‐based probe for the chromofluorogenic sensing of trivalent (Al3+, Fe3+, Cr3+, Ga3+, In3+ and As3+) over mono‐ and divalent cations and anions is reported. In the presence of trivalent metal cations, the probe was able to display a remarkable color change from yellow to colorless that was clearly visible to the naked eye. Also, the initial strong yellow emission was gradually quenched and substituted by a weakly shifted band.
Cannabis and the maturing brain: Role in psychosis development
Authors: Crocker CE , Tibbo PG
Published: February 2015

A common viewpoint has proliferated that cannabis use is mostly harmless. Some argue that by not supporting its use, we are missing a great therapeutic opportunity. The general public view on cannabis may partially be a result of poor knowledge translation. In fact, the “war on drugs” approach has not allowed for basic education on the varied effects of cannabis on the brain, especially at highly critical phases of brain development such as adolescence.
Reference intervals for leukocyte subsets in adults: Results from a population‐based study using 10‐color flow cytometry
Authors: Melzer Susanne , Zachariae Silke , Bocsi Jozsef , Engel Christoph , Löffler Markus , Tárnok Attila
Published: February 2015

Background

Reference intervals for leukocyte subsets from peripheral blood are helpful for the understanding of disease states and therapy effects.

Methods

We performed in‐depth immunophenotyping for 608 healthy German adults from the Leipzig region from 40 to 79 years by 10‐color flow cytometry (FCM) to gain reference information for various leukocyte subsets including subsets of granulocytes, monocytes and lymphocytes.

Results

First, we derived gender‐ and age‐specific reference intervals for males and females from 40 to 59 and from 60 to 79 years, respectively. Second, we further investigated the influence of gender and age on leukocyte counts. We found significantly higher cell counts for monocytes (P < 0.001) and NK cells (P < 0.001) in men, whereas women had higher counts for B cells (P < 0.001), Th cells (P < 0.001) and regulatory T cells (P = 0.008). Furthermore, with increasing age, a decrease in Tc cells (about 8% within 5 years) and an increase in NK cells (<4% within 5 years) were observed.

Conclusion

In future research, it should be investigated whether these are real ageing effects that can be confirmed in longitudinal studies. Furthermore, it is important to understand if the Tc cell count drop is functionally compensated by the increase of NK cells. © 2015 International Clinical Cytometry Society
A comparative analysis reveals weak relationships between ecological factors and beta diversity of stream insect metacommunities at two spatial levels
Authors: Heino Jani , Melo Adriano S. , Bini Luis Mauricio , Altermatt Florian , Al‐Shami Salman A. , Angeler David G. , Bonada Núria , Brand Cecilia , Callisto Marcos , Cottenie Karl , Dangles Olivier , Dudgeon David , Encalada Andrea , Göthe Emma , Grönroos Mira , Hamada Neusa , Jacobsen Dean , Landeiro Victor L. , Ligeiro Raphael , Martins Renato T. , Miserendino María Laura , Md Rawi Che Salmah , Rodrigues Marciel E. , Roque Fabio de Oliveira , Sandin Leonard , Schmera Denes , Sgarbi Luciano F. , Simaika John P. , Siqueira Tadeu , Thompson Ross M. , Townsend Colin R.
Published: February 2015

The hypotheses that beta diversity should increase with decreasing latitude and increase with spatial extent of a region have rarely been tested based on a comparative analysis of multiple datasets, and no such study has focused on stream insects. We first assessed how well variability in beta diversity of stream insect metacommunities is predicted by insect group, latitude, spatial extent, altitudinal range, and dataset properties across multiple drainage basins throughout the world. Second, we assessed the relative roles of environmental and spatial factors in driving variation in assemblage composition within each drainage basin. Our analyses were based on a dataset of 95 stream insect metacommunities from 31 drainage basins distributed around the world. We used dissimilarity‐based indices to quantify beta diversity for each metacommunity and, subsequently, regressed beta diversity on insect group, latitude, spatial extent, altitudinal range, and dataset properties (e.g., number of sites and percentage of presences). Within each metacommunity, we used a combination of spatial eigenfunction analyses and partial redundancy analysis to partition variation in assemblage structure into environmental, shared, spatial, and unexplained fractions. We found that dataset properties were more important predictors of beta diversity than ecological and geographical factors across multiple drainage basins. In the within‐basin analyses, environmental and spatial variables were generally poor predictors of variation in assemblage composition. Our results revealed deviation from general biodiversity patterns because beta diversity did not show the expected decreasing trend with latitude. Our results also call for reconsideration of just how predictable stream assemblages are along ecological gradients, with implications for environmental assessment and conservation decisions. Our findings may also be applicable to other dynamic systems where predictability is low.
Regional hippocampal damage in heart failure
Authors: Woo Mary A. , Ogren Jennifer A. , Abouzeid Christiane M. , Macey Paul M. , Sairafian Kevin G. , Saharan Priya S. , Thompson Paul M. , Fonarow Gregg C. , Hamilton Michele A. , Harper Ronald M. , Kumar Rajesh
Published: February 2015

Aims

Heart failure (HF) patients show cognitive and mood impairments, including short‐term memory loss and depression, that have an adverse impacting on quality of life and self‐care management. Brain regions, including the hippocampus, a structure significantly involved in memory and mood, show injury in HF, but the integrity of specific hippocampal subregions is unclear.

Methods and results

To assess regional hippocampal volume loss, we evaluated 17 HF patients (mean age ± SD, 54.4 ± 2.0 years; 12 male, left ventricular ejection fraction 28.3 ± 6.8%; New York Heart Association class II/III 94%/6%) and 34 healthy control subjects (52.3 ± 1.3 years; 24 male) using high‐resolution T1‐weighted magnetic resonance imaging and evaluated localized surface changes with morphometric procedures. Hippocampi were manually outlined, and volumes calculated from normalized tracings. Volume differences between groups were assessed by two‐sample t‐tests, and regional differences were assessed by surface morphometry. Patients with HF exhibited smaller hippocampal volumes than controls (right 3060 ± 146 mm3 vs. 3478 ± 94 mm3, P = 0.02; left 3021 ± 145 mm3 vs. 3352 ± 98 mm3, P = 0.06). Volume reductions were detected principally in CA1, an area integral to an array of learning and memory functions, as well as in mid to posterior CA3 and subiculum.

Conclusion

The hippocampus shows regional volume reduction in HF, which may contribute to short‐term memory loss and depression associated with the condition.
Differences in n‐alkane profiles between olives and olive leaves as potential indicators for the assessment of olive leaf presence in virgin olive oils
Authors: Mihailova Alina , Abbado Dimitri , Pedentchouk Nikolai
Published: February 2015

The olive (Olea europaea) is one of the most important crops in the Mediterranean region for economic and culinary reasons. Cuticular waxes coat olives and olive leaves and play a significant role in plant physiology and resistance against environmental stresses. The present study describes n‐alkane profiles in cuticular waxes of olives and leaves of three Italian varieties (Frantoio, Leccino and Maraiolo) during different stages of olive development. Additionally, the study investigates the differences between n‐alkane profiles of extra virgin olive oils with low and high leaf content. Olive leaves are characterised by the predominance of n‐alkanes with longer carbon chains (n‐C29‐C33) compared with olives (n‐C25‐C29). During all stages of olive ripening period, n‐alkane average chain length (ACL) values of olive leaves are significantly higher compared with those of olives. Extra virgin olive oils with admixture of leaves have significantly different n‐alkane profiles than those free from leaf material.

Practical applications: The results of this study will contribute significantly to the currently very limited information on n‐alkane data from olive tree varieties used for oil production. The presence of leaves increases the concentrations of long chain n‐alkanes (n‐C31‐C35) in extra virgin olive oils, therefore studying the differences between n‐alkane profiles of olives and olive leaves could help establishing the presence of leaf material in produced extra virgin olive oils. Information about the relative and absolute concentrations of n‐alkanes in olives, olive leaves and olive oil will also be useful for biochemical and metabolic studies of the olive tree.

Significant differences in n‐alkane profiles of olives and olive leaves can be used for detecting the presence of leaf material in virgin olive oils.
Dynamics of omega‐3 long chain polyunsaturated fatty acid incorporation in egg yolk by autotrophic microalgal supplementation
Authors: Lemahieu Charlotte , Bruneel Charlotte , Termote‐Verhalle Romina , Muylaert Koenraad , Foubert Imogen , Buyse Johan
Published: February 2015

Four different microalgal species (Phaeodactylum tricornutum, Isochrysis galbana, Nannochloropsis oculata, and Chlorella fusca) in two doses (125 and 250 mg ALA + EPA + DHA per 100 g feed) were supplemented to the diet of laying hens to examine the impact on the dynamics of long chain omega‐3 polyunsaturated fatty acid (n‐3 LC‐PUFA) incorporation in the egg and yolk color changes. However, no major differences in dynamics of these parameters were observed between the species and between the supplementation doses. The maximum n‐3 LC‐PUFA content was observed after 14 days supplementation, except for the highest supplementation doses of Phaeodactylum and Nannochloropsis. In this case, the maximal value was obtained after 10 days. After a few days of wash‐out, still an enrichment of n‐3 LC‐PUFA was observed, except for the lowest dose of Chlorella. Due to the enrichment of carotenoids in the egg, originating from microalgae, the yolk color changed. Concomitant with the delay of n‐3 LC‐PUFA incorporation, also a delay of yolk color changes was observed. After 7 days of microalgal supplementation, again a stable yolk color was obtained and after 10 days of wash‐out, the yolk color returned to the standard yolk color in most cases.

Practical applications: Knowledge of the dynamics of n‐3 LC‐PUFA and carotenoid incorporation is very important to know how long the microalgae need to be supplemented in to the diet of the laying hens in order to find a compromise between omega‐3 and pigment levels to be stated on eggs' labels and the cost of the treatment. From an economical viewpoint, it is interesting to evaluate the supplementation of different microalgal species and different doses, since this could lead to different impacts on the economical aspect of the use of microalgae in the diet of laying hens.

Microalgae were supplemented into the diets of laying hens and the impact of this supplementation on long chain omega‐3 polyunsaturated fatty acid incorporation into the egg and yolk color changes was examined.
Fatty acid profile of seashore mallow (Kosteletzkya pentacarpos) seed oil and properties of the methyl esters
Authors: Knothe Gerhard , Moser Bryan R.
Published: February 2015

In recent literature, seashore mallow (Kosteletzkya pentacarpos; also known previously as Kosteletzkya virginica) seed oil was reported as a potential alternative feedstock for biodiesel. In the present work, the fatty acid profile of K. pentacarpos is shown to correspond to that of other plants in the Malvaceae family by containing approximately 6% fatty acids with cyclic moieties, namely malvalic acid as well as dihydrosterculic acid. Previously determined properties of biodiesel from seashore mallow are discussed under the aspect of the fatty acid profile. The 1H‐ and 13C‐NMR spectra of K. pentacarpos methyl esters, which confirm the fatty acid profile, are also discussed.

Practical applications: This article discusses the fatty acid profile of the seed oils of Kosteletzkya species. This is significant for evaluating potential applications of these oils. This is demonstrated by evaluating biodiesel fuel properties from the results.

The seed oils of Kosteletzkya species contain malvalic acid and other acids with cyclic moieties.
Eicosapentaenoic acid (EPA) production by an oleaginous fungus Mortierella alpina expressing heterologous the Δ17‐desaturase gene under ordinary temperature
Authors: Okuda Tomoyo , Ando Akinori , Negoro Hiroaki , Muratsubaki Tatsuya , Kikukawa Hiroshi , Sakamoto Takaiku , Sakuradani Eiji , Shimizu Sakayu , Ogawa Jun
Published: February 2015

The oleaginous fungus Mortierella alpina is known to accumulate eicosapentaenoic acid (EPA) only when cultivated at a low temperature (below 15°C). Here, we investigated EPA production at an ordinary temperature (28°C) by expressing the Saprolegnia diclina Δ17 desaturase gene (sdd17m) in M. alpina ST1358, an ω3‐desaturation activity‐defective mutant derived from M. alpina 1S‐4. Expression of the exogenous gene was confirmed by EPA accumulation in transformants at both 28 and 12°C. The EPA content in total lipids produced by transformants was over 20% at 28°C. Bench‐scale fermentation with a 5‐L jar fermentor showed that EPA content reached 26.4% of total fatty acids, and EPA production reached 1.8 g/L. This is the first study to report the accumulation of EPA in M. alpina at an ordinary temperature, and provide a platform technology for the industrial production of EPA using M. alpina as a promising source for EPA.

Practical applications: This achievement shows the potential of M. alpina for industrial production of EPA at lower cost compared to conventional transgenic organisms such as plants and yeasts. The composition of fatty acids produced by M. alpina transformants was simple and did not contain unusual fatty acids compared with that of fish oils, so it may be acceptable for general consumers. Low‐cost, large‐scale, and high‐purity EPA supply by M. alpina will also lead to development of academic research on physiological functions of EPA and its derivatives.

The oleaginous fungus Mortierella alpina accumulates eicosapentaenoic acid (EPA) only when cultivated at a low temperature (below 15°C). Here, we investigated EPA production at an ordinary temperature (28°C) by expressing the Saprolegnia diclina Δ17 desaturase gene (sdd17m) in M. alpina. The transformants with the sdd17m gene produced EPA (>20% in total lipids) at 28°C.
Synthetic Route to Rare Isoindolones Derivatives
Authors: Oukoloff Killian , Buron Frédéric , Routier Sylvain , Jean Ludovic , Renard Pierre‐Yves
Published: February 2015

The isoindolone scaffold is present in many biologically active compounds. Here, we have developed a shorter and more efficient synthesis of tetrahydropyrido[2,1‐a]isoindolone. The key step of this approach is a cyclization to form the γ‐lactam ring under Shibasaki's conditions. Thus, tetrahydropyrido[2,1‐a]isoindolone and superior analogues, namely hexahydroazepino[2,1‐a]isoindolone and hexahydroazocino[2,1‐a]isoindolone, have been prepared in only three steps in 39, 25, and 19 % overall yields, respectively. This novel strategy offers a shorter alternative to existing procedures.
Copper(I)‐Catalyzed (Z)‐β‐(Tosyloxy)alkenyl Iodide Synthesis from (Aryl)[(E)‐β‐(tosyloxy)alkenyl]iodonium Tosylates: Diversity‐Oriented Synthesis of Trisubstituted Alkenes
Authors: Mondal Keshab , Pan Subhas Chandra
Published: February 2015

The first stereoselective synthesis of (Z)‐β‐(tosyloxy)alkenyl iodide has been developed from (aryl)[(E)‐β‐(tosyloxy)alkenyl]iodonium tosylates by using a CuI catalyst. The products of this reaction have been utilized for the diversity‐oriented synthesis of trisubstituted alkenes, and a formal synthesis of the anticancer compound (Z)‐tamoxifen is described.
Novel Amperometric Tri‐Enzyme Biosensor for Lysine Determination in Pharmaceutical Products and Food Samples
Authors: Bóka Beáta , Korózs Marietta , Nánási Márta , Adányi Nóra
Published: February 2015

An enzyme‐based amperometric biosensor was developed for the determination of the lysine content of pharmaceutical products, food and feed samples. Lysine decarboxylase (EC 4.1.1.18) from Bacterium cadaveris was coupled with diamine oxidase (EC 1.4.3.6) from Pisum sativum and horseradish peroxidase (EC 1.11.1.7). The enzymes were co‐immobilized on a graphite electrode with an Os polymer. The biosensor worked in flow injection analysis system (FIA). Optimal working conditions were pH 7.0 and −50 mV potential vs. Ag/AgCl. The linear measuring range was 0.005–0.500 mM. Different pharmaceutical products and feed samples were analysed by the lysine biosensor and by HPLC method for validation.