bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro–targeted gene identification in patients with hepatitis C using a genome-wide microarray technology #
Authors: Hagist Susanne , Sültmann Holger , Millonig Gunda , Hebling Ulrike , Kieslich Dörthe , Kuner Rupert , Balaguer Sabrina , Seitz Helmut-Karl , Poustka Annemarie , Mueller Sebastian 
Published: October 2008

Abstract
Iron in association with reactive oxygen species (ROS) is highly toxic, aggravating oxidative stress reactions. Increased iron not only plays an important role in the progression of hereditary hemochromatosis (HH) but also in common liver diseases such as chronic hepatitis C. The underlying mechanisms of hepatitis C virus (HCV)-mediated iron accumulation, however, are poorly understood. We introduce an in vitro–targeted approach to identify ROS/iron-regulated genes in patients with HCV using a genome-wide DNA microarray. The sensitivity of the 32,231 complementary DNA clone-carrying microarray was approximately 20% as estimated by detecting target genes of the genome-wide transcription factor hypoxia inducible factor 1α. Upon in vitro challenge to iron and oxidative stress, 265 iron-related and 1326 ROS-related genes could be identified in HepG2 cells; 233 significantly regulated genes were found in patients with mild (HCV) or severe (HH) iron deposition. Notably, 17 of the in vitro–selected genes corresponded to the genes identified in patients with HCV or HH. Among them, natriuretic peptide precursor B (NPPB) was the only iron-regulated gene identified in vitro that was differentially regulated between HCV and HH. Reverse-transcription polymerase chain reaction confirmed most of the microarray-identified genes in an even larger group of patients (n = 12). In patients with HCV, these included genes that are associated with RNA processing (MED9/NFAT, NSUN2), proliferation, differentiation, hypoxia, or iron metabolism (ISG20, MIG6, HIG2, CA9, NDRG1), whereas none of the nine known iron-related genes showed significant differences between HCV and HH. Conclusion: Although high-density microarray technology is less suitable for routine liver diagnosis, its use in combination with prior in vitro selection is a powerful approach to identify candidate genes relevant for liver disease. (Hepatology 2009;49:378–386.)
Missense mutations and single nucleotide polymorphisms in ABCB11 impair bile salt export pump processing and function or disrupt pre-messenger RNA splicing #
Authors: Byrne Jane A. , Strautnieks Sandra S. , Ihrke Gudrun , Pagani Franco , Knisely A. S. , Linton Kenneth J. , Mieli-Vergani Giorgina , Thompson Richard J. 
Published: October 2008

Abstract
The gene encoding the human bile salt export pump (BSEP), ABCB11, is mutated in several forms of intrahepatic cholestasis. Here we classified the majority (63) of known ABCB11 missense mutations and 21 single-nucleotide polymorphisms (SNPs) to determine whether they caused abnormal ABCB11 pre-messenger RNA splicing, abnormal processing of BSEP protein, or alterations in BSEP protein function. Using an in vitro minigene system to analyze splicing events, we found reduced wild-type splicing for 20 mutations/SNPs, with normal mRNA levels reduced to 5% or less in eight cases. The common ABCB11 missense mutation encoding D482G enhanced aberrant splicing, whereas the common SNP A1028A promoted exon skipping. Addition of exogenous splicing factors modulated several splicing defects. Of the mutants expressed in vitro in CHO-K1 cells, most appeared to be retained in the endoplasmic reticulum and degraded. A minority had BSEP levels similar to wild-type. The SNP variant A444 had reduced levels of protein compared with V444. Treatment with glycerol and incubation at reduced temperature overcame processing defects for several mutants, including E297G. Taurocholate transport by two assessed mutants, N490D and A570T, was reduced compared with wild-type. Conclusion: This work is a comprehensive analysis of 80% of ABCB11 missense mutations and single-nucleotide polymorphisms at pre-mRNA splicing and protein processing/functional levels. We show that aberrant pre-mRNA splicing occurs in a considerable number of cases, leading to reduced levels of normal mRNA. Thus, primary defects at either the protein or the mRNA level (or both) contribute significantly to BSEP deficiency. These results will help to develop mutation-specific therapies for children and adults suffering from intrahepatic cholestasis due to BSEP deficiency. (Hepatology 2008.)
The novel CD4+CD25+ regulatory T cell effector molecule fibrinogen-like protein 2 contributes to the outcome of murine fulminant viral hepatitis #
Authors: Shalev Itay , Wong Kit Man , Foerster Katharina , Zhu Yi , Chan Cecilia , Maknojia Asif , Zhang Jianhua , Ma Xue-Zhong , Yang Xiao Chun , Gao Julia Fang , Liu Hao , Selzner Nazia , Clark David A. , Adeyi Oyedele , Phillips James M. , Gorczynski Reginald R. , Grant David , McGilvray Ian , Levy Gary 
Published: October 2008

Abstract
Fulminant viral hepatitis (FH) remains an important clinical problem in which the underlying pathogenesis is not well understood. Here, we present insight into the immunological mechanisms involved in FH caused by murine hepatitis virus strain 3 (MHV-3), indicating a critical role for CD4+CD25+ regulatory T cells (Tregs) and production of the novel Treg effector molecule FGL2. Before infection with MHV-3, susceptible BALB/cJ mice had increased numbers of Tregs and expression of fgl2 messenger RNA (mRNA) and FGL2 protein compared with resistant A/J mice. After MHV-3 infection, plasma levels of FGL2 in BALB/cJ mice were significantly increased, correlating with increased percentage of Tregs. Treatment with anti-FGL2 antibody completely inhibited Treg activity and protected susceptible BALB/cJ mice against MHV-3-liver injury and mortality. Adoptive transfer of wild-type Tregs into resistant fgl2
−/− mice increased their mortality caused by MHV-3 infection, whereas transfer of peritoneal exudate macrophages had no adverse effect. Conclusion: This study demonstrates that FGL2 is an important effector cytokine of Tregs that contributes to susceptibility to MHV-3–induced FH. The results further suggest that targeting FGL2 may lead to the development of novel treatment approaches for acute viral hepatitis infection. (Hepatology 2009.)
14‐3‐3β‐Rac1‐p21 activated kinase signaling regulates Akt1‐mediated cytoskeletal organization, lamellipodia formation and fibronectin matrix assembly
Authors: Somanath Payaningal R. , Byzova Tatiana V. 
Published: October 2008

AbstractAkt1 belongs to the three‐gene Akt family and functions as a serine–threonine kinase regulating phosphorylation of an array of substrates and mediating cellular processes such as cell migration, proliferation, survival, and cell cycle. Our previous studies have established the importance of Akt1 in angiogenesis and absence of Akt1 resulted in impaired integrin activation, adhesion, migration, and extracellular matrix assembly by endothelial cells and fibroblasts. In this study, we identify the downstream signaling pathways activated by Akt1 in the regulation of these cellular events. We demonstrate here that Akt1 is necessary for the growth factor stimulated activation of 14‐3‐3β‐Rac1‐p21 activated kinase (Pak) pathway in endothelial cells and fibroblasts. While activation of Akt1 resulted in translocation of Rac1 to membrane ruffles, enhanced Rac1 activity, Pak1 phosphorylation, and lamellipodia formation, resulting in enhanced adhesion and assembly of fibronectin, inhibition of Akt1 resulted in inhibition of these processes due to impaired Rac1‐Pak signaling. Formation of lamellipodia, adhesion, and fibronectin assembly by myristoylated Akt1 expression in NIH 3T3 fibroblasts was inhibited by co‐expression with either dominant negative Rac1 or dominant negative Pak1. In contrast, impaired lamellipodia formation, adhesion, and fibronectin assembly by dominant negative‐Akt1 expression was rescued by co‐expression with either constitutively active‐Rac1 or ‐Pak1. Moreover, previously reported defects in adhesion and extracellular matrix assembly by Akt1−/− fibroblasts could be rescued by expression with either active‐Rac1 or ‐Pak1, implying the importance of Rac1‐Pak signaling in growth factor stimulated cytoskeletal assembly, lamellipodia formation and cell migration in endothelial cells and fibroblasts downstream of Akt1 activation. J. Cell. Physiol. 218: 394–404, 2009. © 2008 Wiley‐Liss, Inc.
Preparation of sodium carboxymethyl cellulose from paper sludge
Authors: He Xiaojia , Wu Shaozu , Fu Dongkang , Ni Jinren 
Published: October 2008

AbstractBACKGROUND: This paper describes the reuse of paper sludge, an industrial solid waste, for the preparation of sodium carboxymethyl cellulose (CMC). The process includes pretreatment, basification and etherification.RESULTS: The optimal pretreatment condition involved the addition of 6.7% hydrochloric acid to the paper sludge for 30 min at 70 °C. The order of factors influencing the effect of reaction was: etherification temperature > sodium hydroxide dose > basification temperature > etherification time > sodium chloroacetate dose. The optimal preparation condition of CMC was: mpapersludge: msodiumhydroxide: msodiumchloroacetate = 0.9:0.8:1.15; basification at 40 °C; etherification at 60 °C for 1 h. Under these conditions, certified CMC with viscosity less than 20 mPa· s, DS more than 0.50 and purity more than 90% was produced. The results of Fourier transform infrared (FTIR) and X‐ray diffraction (XRD) spectra analyses indicated that the product has characteristics of high degree of substitution (DS) and low crystallinity. The coated paper using CMC prepared from paper sludge as a water retention agent can meet the quality standards of GB/T 10335.1‐2005.CONCLUSION: Preparation of CMC from paper sludge can be considered a feasible alternative, generating value‐added product and contributing to solving environmental problems resulting from paper sludge. Copyright © 2008 Society of Chemical Industry
Reactive extraction of propionic acid using tri‐n‐octylamine, tri‐n‐butyl phosphate and aliquat 336 in sunflower oil as diluent
Authors: Keshav Amit , Wasewar Kailas L. , Chand Shri 
Published: October 2008

AbstractBACKGROUND: Propionic acid is widely used in chemical and allied industries and can be produced by biocultivation in a clean and environmentally friendly route. Recovery of the acid from the dilute stream from the bioreactor is an economic problem. Reactive extraction is a promising method of recovering the acid but suffers from toxicity problems of the solvent employed. There is thus a need for a non‐toxic solvent or a combination of less toxic extractants in a non‐toxic diluent that can recover acid efficiently.RESULTS: The effect of different extractants (tri‐n‐butylphosphate (TBP), tri‐n‐octylamine (TOA) and Aliquat 336) and their mixed binary solutions in sunflower oil diluent was studied to find the best extractant‐sunflower oil combination. Equilibrium complexation constant, KE, values of 4.02, 3.13 and 1.87 m3 kmol−1 were obtained for propionic acid extraction using Aliquat 336, TOA and TBP, respectively, in sunflower oil. The effect of different modifiers (1‐decanol, methylisobutyl ketone, butyl acetate and dodecanol) on the extraction was also studied and it was found that modifiers enhance extraction, with 1‐decanol found to be the best.CONCLUSION: The problem of toxicity in reactive extraction can be reduced by using a non‐toxic diluent (sunflower oil) or a modifier in a non‐toxic solvent, with the extractant. The addition of modifiers was found to improve the extraction. Copyright © 2008 Society of Chemical Industry
Normal ultrasound anatomy of the triangular fibrocartilage of the wrist: A study on cadavers and on healthy subjects
Authors: Pesquer Lionel , Scepi Michel , Bihan Morgan , Vialle Romain , Richer Jean Pierre , Roumy Jérôme , Tasu Jean‐Pierre 
Published: October 2008

AbstractPurpose.To report the normal sonographic anatomy of the triangular fibrocartilage (TFC) of the wrist in cadavers and volunteers.Method.Five hands from cadavers were examined sonographically before and after wrist dissection, during which the TFC was marked with surgical wires. Twenty volunteers without wrist limitation or pain, and without any history of wrist disease or inflammatory arthritis (mean age, 26 years (range,19–45 years) were also examined.Results.Sonograms showed that the meniscus and the TFC were clearly separated. The meniscus appeared as a triangular structure that was homogeneous and slightly hyperechoic. Compared with the meniscus, the TFC appeared hypoechoic. The same patterns were observed for cadavers and volunteers. In 3 volunteers (15%), the TFC was not visualized.Conclusions.Using high‐resolution ultrasound systems, the TFC can be separated from meniscus. However, vizualization of the TFC remains limited due to its deep location and the presence of acoustic shadowing from bony structures. © 2008 Wiley Periodicals, Inc. J Clin Ultrasound 2009
Sonography of postpartum uterine inversion from acute to chronic stage
Authors: Momin Asif A. , Saifi Shenaz G. A. , Pethani Nargis R. , Mitha Sharifa H. 
Published: October 2008

AbstractWe report the sonographic appearance of postpartum uterine inversion progressing from acute partial to chronic stage after an 8‐week interval. The delay in diagnosis was partly due to the patient's stable clinical condition except for minor vaginal discharge and bleeding. The diagnosis of chronic inversion on the follow‐up sonographic examination prompted clinicians to undertake surgical repair. Our case shows that the prompt use of sonography during labor and in the peripartum should be sufficient to establish the diagnosis of this serious postpartum complication, which can result in shock or even death. Sonography findings can be considered characteristic and fairly accurate in this condition. © 2008 Wiley Periodicals, Inc. J Clin Ultrasound 2009
Colorimetric recognizing of biologically important anions based on anion‐induced tautomerism of the sensor
Authors: Shao Jie , Yu Xudong , Lin Hai , Lin Huakuan 
Published: October 2008

AbstractThe anion sensing ability of compound 1 based on a novel 2,4‐dinitrophenylhydrazone derivative was studied through “naked‐eye” experiment, UV–Vis spectral titration, and 1H NMR titration. Sensor 1 was synthesized through a simple method with high yield. The solution of host 1 turned deep purple from light purple in the presence of the strong basic anions and turned yellow upon addition of the weak basic anions, respectively. The results could be explained on the basis of transfer of the tautomeric equilibrium of sensor 1 induced by anions with different basicity. Copyright © 2008 John Wiley & Sons, Ltd.
ESI+MS/MS confirmation of canine ivermectin toxicity
Authors: Lehner A. F. , Petzinger E. , Stewart J. , Lang D. G. , Johnson M. B. , Harrison L. , Seanor J. W. , Tobin T. 
Published: October 2008

AbstractIvermectin is a semisynthetic macrocyclic lactone anthelmintic of the avermectin family derived fromStreptomycesfermentation products. Avermectins are used as antiparasitic agents in domestic animals; although considered relatively safe, one must consider animal species, breed, weight, and age in dosage determinations.In January 2006, two canines were presented to the UK Livestock Disease Diagnostic Center after dying from suspected ivermectin overdoses [30–50 mg/kg body weight]. To confirm this clinical diagnosis we developed a rapid, sensitive semiquantitative ElectroSpray Ionization–Mass Spectrometry (ESI/MS) method for ivermectin in canine tissue samples. Pharmaceutical ivermectin contains two ivermectins differing by a single methyl group, and each compound forms interpretation‐confounding adducts with tissue Na+and K+ions. We now report that ivermectin administration was clearly confirmed by comparison with standard and dosage forms of ivermectin, and simple proportionalities based on mass spectral intensity of respective molecular ions allowed semiquantitative estimates of injection site tissue concentrations of 20 and 40 µg/g tissue (wet weight) in these animals, consistent with the history of ivermectin administration and the clinical signs observed.There is a distinct need for both rapid detection and confirmation of toxic exposures in veterinary diagnostics, whether for interpretation of clinical cases antemortem or for forensic reasons postmortem. It is vital that interpreters of analytical results have appropriate guidance in the scientific literature and elsewhere so as to enable clear‐cut answers. The method presented here is suitable for routine diagnostic work in that it allows rapid extraction of ivermectin from tissue samples, avoids the need for high‐performance liquid chromatography and allows ready interpretation of the multiple ivermectin species seen by ESI+MS/MS in samples originating from veterinary dosage forms. Copyright © 2008 John Wiley & Sons, Ltd.
Accurate mass analysis of N‐acyl‐homoserine‐lactones and cognate lactone‐opened compounds in bacterial isolates of Pseudomonas aeruginosa PAO1 by LC‐ESI‐LTQ‐FTICR‐MS
Authors: Cataldi Tommaso R. I. , Bianco Giuliana , Abate Salvatore 
Published: October 2008

AbstractN‐acyl‐homoserine‐lactones (AHSLs) are widely conserved signal molecules present in quorum sensing systems of Gram‐negative bacteria such as Pseudomonas aeruginosa. We present here the results obtained with a hybrid linear trap/Fourier transform ion cyclotron resonance (LTQ‐FTICR) mass spectrometer used to investigate the occurrence of AHSLs and cognate N‐acyl‐homoserines (AHSs) in bacterial isolates of P. aeruginosa (strain PAO1). Two hydrolysed AHSs were found in significant amounts, most likely formed through the lactone opening of N‐3‐oxo‐decanoyl‐L‐homoserine‐lactone (3OC10‐HSL) and N‐3‐oxo‐dodecanoyl‐L‐homoserine‐lactone (3OC12‐HSL). Structure elucidation of these ring‐opened molecules, i.e. N‐3‐oxo‐decanoyl‐L‐homoserine (3OC10‐HS), and N‐3‐oxo‐dodecanoyl‐L‐homoserine (3OC12‐HS), which are not detected by bacterial biosensors, was performed by high‐resolution and accurate mass measurements upon liquid chromatography (LC) and confirmed by tandem MS in the LTQ analyser. Assignment of chemical formula, with mass spectra in the form of [M + H]+, was significantly expedited by extracted ion chromatograms (XICs) because the number of potentially plausible formulae for each protonated signalling molecule was considerably reduced a priori by the LC behaviour, the high mass measurement accuracy available in FTICR mass spectra and the isotopic patterns. At least two concentration levels were observed in spent culture supernatants of P. aeruginosa: compounds at a relatively high content (5–15 µM) that is C4‐HSL, 3OC10‐HS, and 3OC12‐HS and those occurring at a lower content (<0.2 µM) that is C6‐HSL and C8‐HSL. The implications of this work extend to a great variety of Gram‐negative bacteria. Copyright © 2008 John Wiley & Sons, Ltd.
Analysis of flavonoids: Tandem mass spectrometry, computational methods, and NMR
Authors: March Raymond , Brodbelt Jennifer 
Published: October 2008

AbstractDue to the increasing understanding of the health benefits and chemopreventive properties of flavonoids, there continues to be significant effort dedicated to improved analytical methods for characterizing the structures of flavonoids and monitoring their levels in fruits and vegetables, as well as developing new approaches for mapping the interactions of flavonoids with biological molecules. Tandem mass spectrometry (MS/MS), particularly in conjunction with liquid chromatography (LC), is the dominant technique that has been pursued for elucidation of flavonoids. Metal complexation strategies have proven to be especially promising for enhancing the ionization of flavonoids and yielding key diagnostic product ions for differentiation of isomers. Of particular value is the addition of a chromophoric ligand to allow the application of infrared (IR) multiphoton dissociation as an alternative to collision‐induced dissociation (CID) for the differentiation of isomers. CID, including energy‐resolved methods, and nuclear magnetic resonance (NMR) have also been utilized widely for structural characterization of numerous classes of flavonoids and development of structure/activity relationships.The gas‐phase ion chemistry of flavonoids is an active area of research particularly when combined with accurate mass measurement for distinguishing between isobaric ions. Applications of a variety of ab initio and chemical computation methods to the study of flavonoids have been reported, and the results of computations of ion and molecular structures have been shown together with computations of atomic charges and ion fragmentation. Unambiguous ion structures are obtained rarely using MS alone. Thus, it is necessary to combine MS with spectroscopic techniques such as ultraviolet (UV) and NMR to achieve this objective. The application of NMR data to the mass spectrometric examination of flavonoids is discussed. Copyright © 2008 John Wiley & Sons, Ltd.
Five cases of β‐ureidopropionase deficiency detected by GC/MS analysis of urine metabolome
Authors: Kuhara T. , Ohse M. , Inoue Y. , Shinka T. 
Published: October 2008

AbstractThe clinical presentation of inborn errors of pyrimidine degradation varies considerably from asymptomatic to severe neurological illness. We have reported a method to screen for and make a chemical diagnosis of β‐ureidopropionase deficiency, leading to the discovery of the first asymptomatic case of this disease. In this method, the recovery of β‐ureidopropionate and β‐ureidoisobutyrate, the key biomarkers, was very high,and the adoption of GC/MS and targeted analysis enabled us to simultaneously obtain information related and unrelated to pyrimidine metabolism. The present study reports the results of a large‐scale screening of 24 000 newborns using dried urine on filter paper. Identification of a total of four asymptomatic patients among newborns suggests the high incidence (1/6000) of this disease in Japan. While these newborns were asymptomatic, two additional cases detected at the age of 5 years as well as 3 months with this method for high‐risk screening had autism and West syndrome, respectively.The key biomarkers and α‐ureidobutyrate used as an internal standard were found to give not only their di‐trimethylsilyl derivatives but also tri‐trimethylsilyl derivatives, upon derivatization. The mass spectra and retention times of their tri‐trimethylsilyl derivatives and data handling for quantification of the markers are presented.Identification of individuals with defects in pyrimidine metabolism would realize personalized medication in cancer chemotherapy with pyrimidine analogs such as 5‐fluorouracil. Copyright © 2008 John Wiley & Sons, Ltd.