bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phytochemical and biological investigation of the extracts of Nigella sativa L. seed waste
Authors: Michel Camilia G. , El‐Sayed Nesrine S. , Moustafa Sherifa F. , Ezzat Shahira M. , Nesseem Demiana I. , El‐Alfy Taha S. 
Published: February 2011

AbstractDifferent extracts of Nigella sativa L. seed waste; aqueous (AE) 200 mg/kg, ethanol 70% (EE) 250 mg/kg and hexane (HE) 10 mg/kg, were evaluated for their hepatoprotective activities. They were administered orally, once daily, for 5 consecutive days. On day 5, liver injury was induced in animals by a single i.p. injection of carbon tetrachloride (10 mg/kg b. w. of 0.25% (v/v). Hepatoxicity produced, was evaluated by both biochemical and histopathological investigations. The aqueous extract attenuated the CCl4‐induced liver damage likely due to the decrease of proinflammatory cytokines and T‐cell proliferation. This was noticed by a significant decrease in both serum and tissue cytokines; tumor necrosis factor‐alpha (TNF‐α), interferon‐gamma (INF‐γ) and interlukin‐beta (IL‐1β), in the markers of liver functions; bilirubin and glutamic pyruvic transaminase (GPT) and in the oxidative stress markers; malondialdehyde (MDA) and glutathione content (GSH). Fractionation of this extract was performed and its component, protein, saponin, and polyphenol fractions were evaluated by appropriate analytical procedures. The crude protein of the seed waste reached 36.85% while protein fingerprint showed four bands ranging from 91.97 KD and 29.00 KD. The saponin content was evaluated through the determination of the haemolytic index and reached 15.56 mg/g dry powder. Finally, Folin Ciocalteu method was used for the determination of the total polyphenols. The same biochemical and histopathological studies were again performed on the different fractions of the aqueous extract; protein fraction (PF) 10 mg/kg, saponin fraction (SF) 5 mg/kg and polyphenol fraction (FF) 10 mg/kg. The biochemical changes were improved only by the protein fraction (PF) of the seed waste of Nigella sativa. This was manifested by a significant reduction in both serum and tissue cytokines in the liver markers and in the oxidative stress markers. Moreover, liver histopathology showed that (PF) reduced the incidence of liver lesions including hepatic cells cloudy swelling, lymphocytes infiltration, hepatic necrosis and fibrous connective tissue proliferation induced by CCl4 in mice. From this study, it is concluded that the protein fraction of the aqueous extract of Nigella sativa seed waste exhibited a promising hepatoprotective effect in the management of different liver disorders. Copyright © 2011 John Wiley & Sons, Ltd.
Simultaneous estimation of atorvastatin and its two metabolites from human plasma by ESI‐LC‐MS/MS
Authors: Ghosh Chinmoy , Jain Ina , Gaur Shashank , Patel Niraj , Upadhyay Anita , Chakraborty Bhaswat S. 
Published: February 2011

AbstractA selective, sensitive, and fast high performance liquid chromatography (HPLC) method with mass spectrometric (MS) detection mode has been developed and validated completely in human plasma. Atorvastatin (ATO), p‐hydroxy atorvastatin (p‐HATO), o‐hydroxy atorvastatin (o‐HATO) and internal standard (IS) are extracted from human plasma via solid phase extraction (SPE) technique. After elution, the solution is evaporated, then reconstituted with 250 µL of Mobile Phase and analyzed using HPLC/MS/MS system. An isocratic mode is used to separate interference peaks using a Symmetry C‐18, 75 × 4.6 mm ID, 3.5 µ, column. The m/z of ATO, o‐HATO and p‐HATO are 559.2/440.2, 575.3/440.4 and 575.0/440.4 respectively. Linearity ranges are 0.05 to 252.92 ng/mL for ATO, p‐HATO and o‐HATO respectively. Calibration functions, lower limit of quantitation (LLOQ), stability, intra‐ and inter‐day reproducibility, accuracy, and recovery are estimated. This method is free from matrix effects and any abnormal ionization. This method was successfully applied to a single dose 80 mg tablet bioequivalence (BE) study of Atorvastatin. Copyright © 2011 John Wiley & Sons, Ltd.
Voltammetric determination of isoproterenol using multiwall carbon nanotubes‐ionic liquid paste electrode
Authors: Ensafi Ali A. , Karimi‐Maleh H. 
Published: February 2011

AbstractA sensitive and selective electrochemical method for the determination of isoproterenol (ISPT) was developed using multiwall carbon nanotubes and a room temperature ionic liquid (i.e. 1‐butyl‐3‐methylimidazolium hexafluoro phosphate, ([C4mim]‐[PF6])). This multiwall carbon nanotubes ionic liquid electrode (MWCNTILEE) is a very good alternative to previously described electrodes because the electrocatalytic effect is achieved without any electrode modification. The oxidation peak potentials in cyclic voltammogram of ISPT on MWCNTILEE was occurred around 470 mV vs Ag/AgCl (at pH 6.0) while this peak potential at carbon paste electrode was appeared around 605 mV at the same scan rate of 100 mV s−1. The electrochemical parameters such as diffusion coefficient and charge transfer resistance were determined using cyclic voltammetry and electrochemical impedance spectroscopy. Under the optimized conditions, the peak current was linear to ISPT concentration over the concentration range of 1.0 to 520 µmol L−1 using differential pulse voltammetry. The detection limit was 0.85 µmol L−1. The proposed method was successfully applied to the determination of ISPT in both ampoules and urine samples. Copyright © 2011 John Wiley & Sons, Ltd.
The planar cell polarity pathway in vertebrate development
Authors: Wansleeben Carolien , Meijlink Frits 
Published: February 2011

AbstractDirecting the orientation of cells in three dimensions is a fundamental aspect of many of the processes underlying the generation of the appropriate shape and function of tissues and organs during embryonic development. In an epithelium, this requires not only the establishment of apicobasal polarity, but also cell arrangement in a specific direction in the plane of the cell sheet. The molecular pathway central to regulating this planar cell polarity (PCP) was originally discovered in the fruit fly Drosophila melanogaster and has more recently been shown to act in a highly analogous way in vertebrates, involving a strongly overlapping set of genes. Mutant studies and molecular analyses have led to insights into the role of ordered planar cell polarity in the development of a wide variety of organs and tissues. In this review, we give an overview of recent developments in the study of planar polarity signaling in vertebrates. Developmental Dynamics 240:616–626, 2011. © 2011 Wiley‐Liss, Inc.
Novel type II collagen reporter mice: New tool for assessing collagen 2α1 expression in vivo and in vitro
Authors: Tryfonidou Marianna A. , Lunstrum Gregory P. , Hendriks Kristyanne , Riemers Frank M. , Wubbolts Richard , Hazewinkel H.A.W. , Degnin Catherine R. , Horton William A. 
Published: February 2011

AbstractWe report the generation of a new mouse strain harboring a Col2‐pd2EGFP reporter transgene; pd2EGFP has a much shorter half‐life than EGFP, making it a near real‐time reporter for Col2α1 expression in vivo and in vitro. In the post‐natal growth plate, pd2EGFP fluorescence was expressed in almost all proliferative chondrocytes and in some hypertrophic chondrocytes based on localization with type X collagen. In articular cartilage, pd2EGFP fluorescence diminished over time, nicely illustrating the decrease of type II collagen synthesis in articular chondrocytes during growth. Monolayers of FACS‐sorted chondrocytes from P1‐2 mice showed faster loss of pd2EGFP compared to EGFP, reflecting rapid chondrocyte de‐differentiation. High‐density culture of FACS‐pd2EGFP‐ growth plate chondrocytes revealed the typical temporal expression pattern in which type II collagen preceded type X collagen matrix deposition. The Col2‐pd2EGFP reporter mouse will be a valuable tool for studies of growth plate chondrocyte biology. Developmental Dynamics 240:663–673, 2011. © 2011 Wiley‐Liss, Inc.
The emerging face of primary cilia
Authors: Zaghloul Norann A. , Brugmann Samantha A. 
Published: February 2011

AbstractPrimary cilia are microtubule‐based organelles that serve as hubs for the transduction of various developmental signaling pathways includingHedgehog, Wnt, FGF, and PDGF. Ciliary dysfunction contributes to a range of disorders, collectively known as the ciliopathies. Recently, interest has grown in these syndromes, particularly among craniofacial biologists, as many known and putative ciliopathies have severe craniofacial defects. Herein we discuss the current understanding of ciliary biology and craniofacial development in an attempt to gain insight into the molecular etiology for craniofacial ciliopathies, and uncover a characteristic ciliopathic craniofacial gestalt. genesis 49:231–246, 2011. © 2011 Wiley‐Liss, Inc.
Estrogen‐induced protection against experimental autoimmune encephalomyelitis is abrogated in the absence of B cells
Authors: Bodhankar Sheetal , Wang Chunhe , Vandenbark Arthur A. , Offner Halina 
Published: February 2011

AbstractIncreased remissions in multiple sclerosis (MS) during pregnancy suggest that elevated levels of sex steroids exert immunoregulatory activity. Estrogen (E2=17β‐estradiol) protects against experimental autoimmune encephalomyelitis (EAE), but the cellular basis for E2‐induced protection remains unclear. Studies demonstrate that depletion of B cells prior to induction of EAE exacerbates disease severity, implicating regulatory B cells. We thus evaluated pathogenic and E2‐induced protective mechanisms in B‐cell‐deficient (μMT−/−) mice. EAE‐protective effects of E2 were abrogated in μMT−/− mice, with no reduction in disease severity, cellular infiltration or pro‐inflammatory factors in the central nervous system compared to untreated controls. E2 treatment of WT mice selectively upregulated expression of PD‐L1 on B cells and increased the percentage of IL‐10‐producing CD1dhighCD5+ regulatory B cells. Upregulation of PD‐L1 was critical for E2‐mediated protection since E2 did not inhibit EAE in PD‐L1−/− mice. Direct treatment of B cells with E2 significantly reduced proliferation of MOG35–55‐specific T cells that required estrogen receptor‐α (ERα). These results demonstrate, for the first time, a requirement for B cells in E2‐mediated protection against EAE involving direct E2 effects on regulatory B cells mediated through ERα and the PD‐1/PD‐L1 negative co‐stimulatory pathway. E2‐primed B cells may represent an important regulatory mechanism in MS and have strong implications for women receiving current MS therapies that cause B‐cell depletion.
Immune inhibitory receptors: Essential regulators of phagocyte function
Authors: Steevels Tessa A. M. , Meyaard Linde 
Published: February 2011

AbstractPhagocytes, including neutrophils, monocytes, and macrophages, play a crucial role in host defense by recognition and elimination of invading pathogens. Phagocytic cells produce reactive oxygen species (ROS), inflammatory cytokines, and chemokines, leading to bacterial killing and to recruitment and activation of additional immune cells. However, inflammatory mediators are potentially harmful for the host and their production is therefore tightly controlled by multiple regulatory mechanisms. One such mechanism is immune suppression by immune inhibitory receptors, which are increasingly acknowledged as potent regulators of the immune response. So far, research has focused on the role of these receptors in the regulation of NK cells, B cells, and T cells. Importantly, an accumulating number of inhibitory receptors have been identified on phagocytes. Here, we review the role of inhibitory receptors in the regulation of phagocyte cytokine production, migration, apoptosis, ROS production, and phagocytosis. Furthermore, we discuss the intracellular mechanisms utilized by distinct inhibitory receptors to regulate specific phagocyte functions. We demonstrate that inhibitory receptors are important regulators of the immune response, which bacteria can use to their advantage.
The Hydrogenase Subcomplex of the NAD+‐Reducing [NiFe] Hydrogenase from Ralstonia eutropha – Insights into Catalysis and Redox Interconversions
Authors: Lauterbach Lars , Liu Juan , Horch Marius , Hummel Phillip , Schwarze Alexander , Haumann Michael , Vincent Kylie A. , Lenz Oliver , Zebger Ingo 
Published: February 2011

AbstractThe O2‐tolerant, NAD+‐reducing soluble [NiFe] hydrogenase (SH) from Ralstonia eutropha H16, HoxHYFUI2, is a complex enzyme, harboring multiple redox cofactors: a [NiFe] active site, an electron relay of iron‐sulfur clusters, and two noncovalently bound flavin mononucleotides (FMN). The interplay and functional role of these cofactors is so far not understood in detail. In the present study, the isolated HoxHY module was investigated, which represents the smallest active subcomplex of a [NiFe] hydrogenase. Direct electrochemical studies and solution assays showed that the as‐isolated HoxHY is initially catalytically inactive, but after reductive activation at low potentials, exhibits both H2 oxidation and H+ reduction, consistent with the role of the SH in bidirectional catalysis. The overpotential relative to E(2H+/H2) is minimal, facilitating coupling of the closely spaced 2H+/H2 and NAD+/NADH half reactions in the SH. Methyl viologen reduction assays revealed that H2 oxidation by HoxHY is enhanced on addition of excess FMN, in line with results from optical spectroscopy which indicate that FMN is present at substoichiometric levels in as‐isolated HoxHY. X‐ray absorption spectroscopy suggested one 4Fe4S cluster in addition to the active site in HoxHY. FTIR investigations confirmed that the active site iron atom has a “standard” ligation, i.e., one CO and two cyanide ligands. At least two novel oxidized states were detected by FTIR, both of which could be reductively activated by artificial electron donors, such as dithionite, and by the native electron donor H2 in the presence of additional FMN. The flavin cofactor also appears to stabilize the active site, providing further evidence for its importance in HoxHY. All reduced states of the [NiFe] site previously identified for standard [NiFe] hydrogenases and for the native SH within living cells were detected in FTIR spectra of HoxHY with the exception of the intermediate Nia‐C species. Electrochemical experiments show that incubation of active HoxHY with O2 at high potentials causes slow inactivation, but activity is recovered within seconds at potentials below –170 mV at 30 °C, even in the presence of 2 % O2. This behavior is consistent with the HoxHY moiety of the SH remaining active in the presence of O2 at the potential of the NAD+/NADH pool in vivo.
Mercury speciation and biomagnification in the food web of Caddo Lake, Texas and Louisiana, USA, a subtropical freshwater ecosystem
Authors: Chumchal Matthew M , Rainwater Thomas R , Osborn Steven C , Roberts Aaron P , Abel Michael T , Cobb George P , Smith Philip N , Bailey Frank C 
Published: February 2011

Abstract
We studied the biomagnification of total mercury and methylmercury in a subtropical freshwater lake, Caddo Lake, Texas and Louisiana, USA. The present study is unique in that it not only included invertebrates (seven species) and fish (six species) but also an amphibian (one species), reptiles (three species), and mammals (three species). Nonfish vertebrates such as those included in the present study are often not included in assessments of trophic transfer of Hg. Mean trophic position (determined using stable isotopes of nitrogen) ranged from 2.0 (indicative of a primary consumer) to 3.8 (indicative of a tertiary consumer). Mean total Hg concentrations ranged from 36 to 3,292 ng/g dry weight in muscle and whole body and from 150 to 30,171 ng/g dry weight in liver. Most of the Hg in muscle and whole-body tissue was found as methylmercury, and at least 50% of the Hg found in liver was in the inorganic form (with the exception of largemouth bass, Micropterus salmoides). Mercury concentrations were positively correlated with trophic position, indicating that biomagnification occurs in the food web of Caddo Lake. The food web magnification factors (FWMFs; slope of the relationship between mean Hg concentration and trophic position) for both total Hg and methylmercury were similar to those observed in other studies. Because most of the total Hg in consumers was methylmercury, the FWMF for methylmercury was not significantly different from the FWMF for total Hg. Some vertebrates examined in the present study had low Hg concentrations in their tissues similar to those observed in invertebrates, whereas others had concentrations of Hg in their tissues that in previous studies have been associated with negative health consequences in fish. Environ. Toxicol. Chem. 2011; 30:1153–1162. © 2011 SETAC
Frequency of KRAS, BRAF, and NRAS mutations in colorectal cancer
Authors: Vaughn Cecily P. , ZoBell Scott D. , Furtado Larissa V. , Baker Christine L. , Samowitz Wade S. 
Published: February 2011

AbstractMutational analysis of KRAS codons 12 and 13 is standard for patients with metastatic colorectal cancer since mutations in these codons predict lack of response to anti‐EGFR therapies. However, even among patients whose tumors are wildtype for KRAS codons 12 and 13, only a subset respond to therapy. Since additional activating mutations downstream of EGFR may also play a role in treatment resistance, we sought to establish the frequency of these mutations. We evaluated 2121 colorectal tumors for mutations in codons 12 and 13 of the KRAS gene. A subset of these samples, comprised of 513 samples wildtype for KRAS codons 12 and 13, were tested for mutations in codons 61 and 146 of KRAS, codon 600 of BRAF, and codons 12, 13, and 61 of NRAS. Mutation status was determined by targeted pyrosequencing. Mutations in KRAS codon 12 or 13 were identified in 900/2121 (42.4%) samples. Of the 513 wildtype samples tested for additional mutations, 78 samples were mutant for BRAF, 19 for KRAS codon 61, 17 for KRAS codon 146, and 26 for NRAS. In total, 140/513 (27.3%) tumors wildtype for KRAS codons 12 and 13 harbored a mutation in another of the RAS pathway genes. While further study is needed to determine the full therapeutic implications of mutations in these codons, mutational testing of these codons may be useful for identifying a significant proportion of patients who may also be resistant to anti‐EGFR therapies. © 2011 Wiley‐Liss, Inc.
Integrative genomic profiling reveals conserved genetic mechanisms for tumorigenesis in common entities of non‐Hodgkin's lymphoma
Authors: Green Michael R. , Aya‐Bonilla Carlos , Gandhi Maher K. , Lea Rod A. , Wellwood Jeremy , Wood Peter , Marlton Paula , Griffiths Lyn R. 
Published: February 2011

AbstractRecent developments in genomic technologies have resulted in increased understanding of pathogenic mechanisms and emphasized the importance of central survival pathways. Here, we use a novel bioinformatic based integrative genomic profiling approach to elucidate conserved mechanisms of lymphomagenesis in the three commonest non‐Hodgkin's lymphoma (NHL) entities: diffuse large B‐cell lymphoma, follicular lymphoma, and B‐cell chronic lymphocytic leukemia. By integrating genome‐wide DNA copy number analysis and transcriptome profiling of tumor cohorts, we identified genetic lesions present in each entity and highlighted their likely target genes. This revealed a significant enrichment of components of both the apoptosis pathway and the mitogen activated protein kinase pathway, including amplification of the MAP3K12 locus in all three entities, within the set of genes targeted by genetic alterations in these diseases. Furthermore, amplification of 12p13.33 was identified in all three entities and found to target the FOXM1 oncogene. Amplification of FOXM1 was subsequently found to be associated with an increased MYC oncogenic signaling signature, and siRNA‐mediated knock‐down of FOXM1 resulted in decreased MYC expression and induced G2 arrest. Together, these findings underscore genetic alteration of the MAPK and apoptosis pathways, and genetic amplification of FOXM1 as conserved mechanisms of lymphomagenesis in common NHL entities. Integrative genomic profiling identifies common central survival mechanisms and highlights them as attractive targets for directed therapy. © 2011 Wiley‐Liss, Inc.
Fusion gene microarray reveals cancer type‐specificity among fusion genes
Authors: Løvf Marthe , Thomassen Gard O. S. , Bakken Anne Cathrine , Celestino Ricardo , Fioretos Thoas , Lind Guro E. , Lothe Ragnhild A. , Skotheim Rolf I. 
Published: February 2011

AbstractDetection of fusion genes for diagnostic purposes and as a guide to treatment is well‐established in hematological malignancies, and the prevalence of fusion genes in epithelial cancers is also increasingly appreciated. To study whether established fusion genes are present within additional cancer types, we have used an updated version of our fusion gene microarray in a systematic survey of reported fusion genes in multiple cancer types. We assembled a comprehensive database of published fusion genes, including those reported only in individual studies and samples, and fusion genes resulting from deep sequencing of cancer genomes and transcriptomes. From the total set of 548 fusion genes, we designed 599,839 oligonucleotides, targeting both chimeric transcript junctions as well as sequences internal to each of the fusion gene partners. We investigated the presence of fusion genes in a series of 67 cell lines representing 15 different cancer types. Data from ten leukemia cell lines with known fusion gene status were used to develop an automated scoring algorithm, and in five cell lines the correct fusion gene was the top scoring hit, and one came second. Two additional fusion genes, BCAS4‐BCAS3 in the MCF‐7 breast cancer cell line and CCDC6‐RET in the TPC‐1 thyroid cancer cell line were validated as true positive fusion transcripts. However, these fusion genes were not new to these cancer types, and none of 548 fusion genes were identified from a novel cancer type. We therefore find it unlikely that the assayed fusion genes are commonly present across multiple cancer types. © 2011 Wiley‐Liss, Inc.
Reconstructing landscape and vegetation through multiple proxy indicators: A geoarchaeological examination of the St. Louis site, Saskatchewan, Canada
Authors: Cyr Howard , McNamee Calla , Amundson Leslie , Freeman Andrea 
Published: February 2011

AbstractThe St. Louis site, located in the Plains–Parkland transition zone along the South Saskatchewan River, in Saskatchewan, Canada, is a multiple‐component site consisting of stratified floodplain alluvium with multiple, weakly developed soils. Human occupation at the site spans the Late Paleoindian to Middle Precontact periods (10,000–5,000 14C yr B.P.), a time poorly represented archaeologically on the Northern Plains. The dearth of early–middle Holocene‐age archaeological sites is often attributed to reduced inhabitability of the Northern Plains during the Hypsithermal, a period of maximum aridity and limited water availability. Stable isotope and phytolith data from the site indicate increased temperatures during the Hypsithermal and an expansion of Northern Plains grasslands into north‐central Saskatchewan. Although characterized by increased xeric conditions, human occupation at the St. Louis site, as well as the predominance of C3 grasses, attests to the habitability of Northern Plains river systems during this time period. © 2011 Wiley Periodicals, Inc.