bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of arachidonic acid on hypoxia‐induced IL‐6 production in mouse ES cells: Involvement of MAPKs, NF‐κB, and HIF‐1α
Authors: Lee Sang Hun , Lee Yu Jin , Han Ho Jae 
Published: November 2009

AbstractThis study examined the role of arachidonic acid (AA) in hypoxia‐induced production of interleukin (IL)‐6 and its related signaling pathways in mouse embryonic stem (ES) cells. Hypoxia with AA induced IL‐6 production, which was mediated by reactive oxygen species (ROS). In addition, hypoxia increased the levels of p38 mitogen‐activated protein kinases (MAPKs) and stress‐activated protein kinase/c‐jun NH2‐terminal kinase (SAPK/JNK) phosphorylation, which were blocked by antioxidant (vitamin C). Inhibition of p38 MAPK and SAPK/JNK blocked hypoxia‐ or hypoxia with AA‐induced nuclear factor‐kappa B (NF‐κB) activation. Furthermore, hypoxia‐induced increase in hypoxia‐inducible factor‐1α (HIF‐1α) expression was regulated by NF‐κB activation. Consequently, the increased HIF‐1α expression induced activation of matrix metalloproteinase (MMP)‐2 and MMP‐9. The expression of each signaling molecule stimulated an increase in IL‐6 production that was greater in hypoxic conditions with AA than with hypoxia alone. Finally, inhibition of IL‐6 production using IL‐6 antibody or soluble IL‐6 receptor attenuated the hypoxia‐induced increases in DNA synthesis of mouse ES cells. In conclusion, AA potentiates hypoxia‐induced IL‐6 production through the MAPKs, NF‐κB, and HIF‐1α pathways in mouse ES cells. J. Cell. Physiol. 222: 574–585, 2010. © 2009 Wiley‐Liss, Inc.
PKB/Akt activation inhibits p53‐mediated HIF1A degradation that is independent of MDM2
Authors: Choy Mun‐Kit , Movassagh Mehregan , Bennett Martin R. , Foo Roger S.‐Y. 
Published: November 2009

AbstractCross‐talk between the two transcription factors, p53 and hypoxia inducible factor 1α (HIF1A), is important in different pathophysiological conditions (Hammond and Giaccia, 2006, Clin Cancer Res 12:5007–5009) such as in the transition from myocardial hypertrophy to cardiac dilatation and heart failure. In that context, p53 induces HIF1A degradation which in turn provokes the transition from compensatory hypertrophy to myocardial thinning and chamber dilatation (Sano et al., 2007, Nature 446:444–448). In order to investigate the mechanism of p53‐induced HIF1A degradation, we used the established in vitro model of deferroxamine (DFX)‐induced HIF1A accumulation in H9c2 cardiac cells (Sano et al., 2007, Nature 446:444–448). Here, we report that opposite to HIF1A accumulation following exposure to DFX, prolonged DFX‐induced p53 activation and HIF1A protein decrease, without any change in Hif1a mRNA. HIF1A protein decrease accompanied upregulated HIF1A ubiquitination. MDM2, an ubiquitin E3 ligase target gene of p53, was upregulated following prolonged DFX, but using p53/Mdm2 double‐null mouse embryonic fibroblasts, we found that p53 upregulated HIF1A ubiquitination and degradation independently of MDM2. Moreover, with prolonged DFX treatment, an enhanced interaction between MDM2 and HIF1A was lacking. Instead, phospho‐Aktser473 was decreased during the phase coinciding with HIF1A degradation, and inhibition of PKB/Akt phosphorylation using PI3K inhibitor (LY294002) upregulated HIF1A ubiquitination. In summary, we propose that p53‐induced HIF1A degradation is not exclusively MDM2‐mediated, but reversible by PKB/Akt phosphorylation. J. Cell. Physiol. 222: 635–639, 2010. © 2009 Wiley‐Liss, Inc.
High glucose increases expression of cyclooxygenase‐2, increases oxidative stress and decreases the generation of nitric oxide in mouse microvessel endothelial cells
Authors: Aljofan Mohamad , Ding Hong 
Published: November 2009

AbstractHyperglycaemia is a key factor that contributes to the development of diabetes‐related microvascular disease. Both cyclooxygenase I and cyclooxygenase II are expressed in endothelial cells and play key roles in the regulation of cardiovascular function. In the current study we tested the hypothesis that hyperglycaemia‐induced increased expression of cyclooxygenase II is a contributing factor both to the increased oxidative stress and to the reduction in the generation of nitric oxide in microvessel endothelial cells following their exposure to high glucose. We demonstrated that the exposure of mouse microvascular endothelial cells to high glucose for 3 days decreased the generation of nitric oxide and enhanced production of superoxide. Western blots illustrated that exposure to high glucose also increased endothelial nitric oxide synthase and cyclooxygenase II protein expression levels and decreased the dimer/monomer ratio of endothelial nitric oxide synthase protein. All the changes induced by the high glucose culture media could be reversed by either the cyclooxygenase II inhibitor CAY10404, the non‐selective cyclooxygenase inhibitor indomethacin or the protein kinase C inhibitor chelerythrine, but not solely by preincubation with the antioxidant and putative NADPH oxidase inhibitor, apocynin. Our data indicate that high glucose induced oxidative stress is linked to an increase in the expression of cyclooxygenase II and a reduced generation of nitric oxide that is associated with an uncoupled endothelial nitric oxide synthase, possibly due to decreased dimer/monomer ratio. J. Cell. Physiol. 222: 669–675, 2010. © 2009 Wiley‐Liss, Inc.
Natural selection coupled with intragenic recombination shapes diversity patterns in the major histocompatibility complex class II genes of the giant panda
Authors: Chen Yi‐Yan , Zhang Ying‐Ying , Zhang He‐Min , Ge Yun‐Fa , Wan Qiu‐Hong , Fang Sheng‐Guo 
Published: November 2009

AbstractAmple variations of the major histocompatibility complex (MHC) genes are essential for vertebrates to adapt to various environmental conditions. In this study, we investigated the genetic variations and evolutionary patterns of seven functional MHC class II genes (one DRA, two DRB, two DQA, and two DQB) of the giant panda. The results showed the presence of two monomorphic loci (DRA and DQB2) and five polymorphic loci with different numbers of alleles (seven at DRB1, six at DRB3, seven at DQA1, four at DQA2, six at DQB1). The presence of balancing selection in the giant panda was supported by the following pieces of evidence: (1) The observed heterozygosity was higher than expected. (2) Amino acid heterozygosity was significantly higher at antigen‐binding sites (ABS) compared with non‐ABS sequences. (3) The selection parameter ω (dN/dS) was significantly higher at ABS compared with non‐ABS sequences. (4) Approximately 95.45% of the positively selected codons (P>0.95) were located at or adjacent to an ABS. Furthermore, this study showed that (1) The Qinling subspecies exhibited high ω values across each locus (all >1), supporting its extensive positive selection. (2) The Sichuan subspecies displayed small ω at DRB1 (ω<0.72) and DQA2 (ω<0.48), suggesting that these sites underwent strong purifying selection. (3) Intragenic recombination was detected in DRB1, DQA1, and DQB1. The molecular diversity in classic Aime‐MHC class II genes implies that the giant panda had evolved relatively abundant variations in its adaptive immunity along the history of host–pathogen co‐evolution. Collectively, these findings indicate that natural selection accompanied by recombination drives the contrasting diversity patterns of the MHC class II genes between the two studied subspecies of giant panda. J. Exp. Zool. (Mol. Dev. Evol.) 314B:208–223, 2010. © 2009 Wiley‐Liss, Inc.
Mystery unsolved: missing limbs in deformed amphibians
Authors: Skelly David K. , Benard Michael F. 
Published: November 2009

AbstractBallengee and Sessions (2009) claim that predatory attacks by small predators such asSympetrumdragonfly larvae are sufficient to explain amphibian limb deformities in which the limb is partly or completely missing. This deformity type, the most common in nature, is not well explained byRibeiroiainfection which has also been nominated as a mechanism for limb deformities. We argue that the conclusions of the Ballanegee and Sessions study are not well founded. In part this is because the authors have provided no quantitative analysis of the association between limb deformities and predator densities. Our own data on frequencies of limb deformities suggest that missing hind limbs are often extremely rare even whenSympetrumand other small predators are common. While predatory attacks may contribute to observations of limb deformities, further study will be required to elucidate their role; other potential mechanisms deserve study as well. It is premature, and counterproductive, to draw any conclusions regarding the mechanisms behind the most common limb deformities recorded in natural populations.J. Exp. Zool. (Mol. Dev. Evol.) 314B:179–181, 2010. © 2009 Wiley‐Liss, Inc.
Radiosynthesis of 4‐[18F]fluoromethyl‐L‐phenylalanine and [18F]FET via a same strategy and automated synthesis module
Authors: Kersemans Ken , Mertens John , Caveliers Vicky 
Published: November 2009

AbstractCurrently there is still a need for more potent amino acid analogues as tumour imaging agents for peripheral tumour imaging with PET as it was recently reported that the success of O‐(2′‐[18F]fluoroethyl)‐L‐tyrosine ([18F]FET) is limited to brain, head and neck tumours. As the earlier described 2‐Amino‐3‐(2‐[18F]fluoromethyl‐phenyl)‐propionic acid (2‐[18F]FMP) suffered from intramolecular‐catalysed defluorination, we synthesized 2‐Amino‐3‐(4‐[18F]fluoromethyl‐phenyl)‐propionic acid (4‐[18F]FMP) as an alternative for tumour imaging with PET. Radiosynthesis of 4‐[18F]FMP, based on Br for [18F] aliphatic nucleophilic exchange, was performed with a customized modular Scintomics automatic synthesis hotboxthree system in a high overall yield of 30% and with a radiochemical purity of \gt 99%. 4‐[18F]FMP was found to be stable in its radiopharmaceutical formulation, even at high radioactivity concentrations. Additionally, for a comparative study, [18F]FET was synthesized using the same setup in 40% overall yield, with a radiochemical purity \gt 99%. The described automated radiosynthesis allows the production of two different amino acid analogues with minor alternations to the parameter settings of the automated system, rendering this unit versatile for both research and clinical practice. Copyright © 2009 John Wiley & Sons, Ltd.
Protein–surface interactions: challenging experiments and computations
Authors: Cohavi Ori , Corni Stefano , De Rienzo Francesca , Di Felice Rosa , Gottschalk Kay E. , Hoefling Martin , Kokh Daria , Molinari Elisa , Schreiber Gideon , Vaskevich Alexander , Wade Rebecca C. 
Published: November 2009

AbstractProtein–surface interactions are fundamental in natural processes, and have great potential for applications ranging from nanotechnology to medicine. A recent workshop highlighted the current achievements and the main challenges in the field. Copyright © 2009 John Wiley & Sons, Ltd.
Viral infection in bone marrow transplants: Is JC virus involved?
Authors: Mischitelli Monica , Fioriti Daniela , Anzivino Elena , Bellizzi Anna , Barucca Valentina , Boldorini Renzo , Miglio Umberto , Sica Simona , Sorà Federica , De Matteis Silvia , Chiarini Fernanda , Pietropaolo Valeria 
Published: November 2009

AbstractHemorrhagic cystitis is characterized by hematuria due to inflammation of the bladder. In bone marrow transplants, this disease is linked to the infection by human polyomavirus BK, whereas the role of the human polyomavirus JC is unclear. The transcriptional control regions of both viruses contain important cellular transcription factor binding sites that undergo rearrangement process generating suitable variants that could be more active for viral replication and for the onset of hemorrhagic cystitis. In this study urine obtained from seven patients with bone marrow transplant were examined. Polyomavirus genomes were quantified by PCR and viral loads were compared. The transcriptional regions of both viruses were amplified and sequenced to determine the presence of variants. Subtypes of polyomaviruses were determined by amplification and sequencing of the viral protein 1 region. The results showed that four of seven patients were positive for BK DNA, two of seven patients had BK and JC DNA and one of seven had JC DNA. Positive samples were amplified and sequenced successively for transcriptional regions. The viral archetype was always found in both viruses. Finally, typing showed that BK virus subtype I infected patients with BK, whereas JC virus genotype IA and genotype 1B were found in patients infected with JC. The data suggest that new and different approaches are required to improve the morbidity and mortality caused by polyoma‐associated hemorrhagic cystitis, since it known that BK virus is involved in the onset of hemorrhagic cystitis, whereas the role of JC virus should be investigated further. J. Med. Virol. 82:138–145, 2010. © 2009 Wiley‐Liss, Inc.
Detection of a new yellow fever virus lineage within the South American genotype I in Brazil
Authors: de Souza Renato P. , Foster Peter G. , Sallum Maria Anice M. , Coimbra Terezinha L.M. , Maeda Adriana Y. , Silveira Vivian R. , Moreno Eduardo S. , da Silva Fernanda G. , Rocco Iray M. , Ferreira Ivani B. , Suzuki Akemi , Oshiro Fabíola M. , Petrella Selma M.C.N. , Pereira Luiz E. , Katz Giselda , Tengan Cilea H. , Siciliano Melissa M. , dos Santos Cecília L.S. 
Published: November 2009

AbstractNucleotide sequences of two regions of the genomes of 11 yellow fever virus (YFV) samples isolated from monkeys or humans with symptomatic yellow fever (YF) in Brazil in 2000, 2004, and 2008 were determined with the objective of establishing the genotypes and studying the genetic variation. Results of the Bayesian phylogenetic analysis showed that sequences generated from strains from 2004 and 2008 formed a new subclade within the clade 1 of the South American genotype I. The new subgroup is here designated as 1E. Sequences of YFV strains recovered in 2000 belong to the subclade 1D, which comprises previously characterized YFV strains from Brazil. Molecular dating analyses suggested that the new subclade 1E started diversifying from 1D about 1975 and that the most recent 2004–2008 isolates arose about 1985. J. Med. Virol. 82:175–185, 2010. © 2009 Wiley‐Liss, Inc.
Influence of amino‐acid polymorphism in the core protein on progression of liver disease in patients infected with hepatitis C virus genotype 1b
Authors: Kobayashi Mariko , Akuta Norio , Suzuki Fumitaka , Hosaka Tetsuya , Sezaki Hitomi , Kobayashi Masahiro , Suzuki Yoshiyuki , Arase Yasuji , Ikeda Kenji , Watahiki Sachiyo , Mineta Rie , Iwasaki Satomi , Miyakawa Yuzo , Kumada Hiromitsu 
Published: November 2009

AbstractThe substitution of amino acid (aa) 70 of arginine for glutamine and/or that of aa91 of leucine for methionine in the core protein in patients infected with hepatitis C virus (HCV) genotype 1b is associated with a poor response to pegylated interferon and ribavirin. Factors influencing these substitutions were sought in 1,097 patients infected with HCV‐1b who had not received antiviral treatment. HCV variants with Arg70 and Leu91 (wild‐type) decreased, while those with Gln70 and/or Met91 (mutant types) increased with age (P < 0.001). Of the 1,097 patients, 464 (42.3%) were infected with the Gln70 variant and the remaining 633 patients with the Arg70 variant. The proportion of patients with the Gln70 variant increased with the severity of liver disease (P < 0.001), elevated γ‐glutamyl transpeptidase (γ‐GTP) levels (P < 0.001) and a decrease in platelet count (P = 0.008). In univariate analysis patients with hepatocellular carcinoma, elevated aspartate aminotransferase (AST ≥ 58 IU/L) and γ‐GTP (≥61 IU/L), and decreased albumin levels (<3.9 g/dl) were more frequent in the patients with the Gln70 variant than the Arg70 variant (P = 0.003, 0.005, <0.001, and 0.031, respectively). In multivariate analysis HCC (odds ratio 1.829 [95% confidence interval 1.147–2.917]) and γ‐GTP ≥61 IU/L (1.647 [1.268–2.139]) increased the risk for the Gln70 variant. In conclusion, the substitution of amino aa70 of Arg for Gln in patients infected with HCV‐1b increases with age, and it is associated with severe liver disease accompanied by elevated AST and γ‐GTP levels, as well as the development of hepatocellular carinoma. J. Med. Virol. 82:41–48, 2010. © 2009 Wiley‐Liss, Inc.
Long‐term shedding of hepatitis E virus in the feces of pigs infected naturally, born to sows with and without maternal antibodies
Authors: Kanai Yuta , Tsujikawa Muneo , Yunoki Mikihiro , Nishiyama Shoko , Ikuta Kazuyoshi , Hagiwara Katsuro 
Published: November 2009

AbstractPigs are presumed reservoirs for hepatitis E virus (HEV) transmission to humans. To examine infection kinetics, two litters of domestic pigs (A and B, each containing 10 piglets) infected naturally with HEV were studied until pigs were 6 months old. Maternal IgG and IgA antibodies were detected in litter A piglets, but not in litter B ones. All pigs shed HEV in feces when they were 30–110 days old, and 17 developed viremia at 40–100 days of age. Phylogenetic analysis revealed a highly close sequence of HEV genotype 3 in all pigs. The serum levels of specific IgG and IgA were similar in all pigs, although IgA was not detected in the feces. Interestingly, the onset of both viremia and seroconversion was delayed significantly in litter A pigs. The kinetics of fecal virus shedding was similar in both litters; shedding was not detected after the pigs were 120 days old. The differences in the infection kinetics between litters A and B suggested that maternal antibodies delayed the onset of viremia and seroconversion. Quantitative real‐time reverse transcriptase‐polymerase chain reaction revealed that HEV RNA in feces peaked 10 days after initial shedding of approximately 106.0 copies/g. The viral load was much lower in the serum than in the feces. At 200 days of age, HEV RNA was found in the internal organs of 3 out of 13 pigs. These study findings improve the understanding of the dynamics of natural HEV transmission in pigs, which could help in controlling virus transmission from pigs to humans. J. Med. Virol. 82:69–76, 2010. © 2009 Wiley‐Liss, Inc.
Passage in egg culture is a major cause of apparent positive selection in influenza B hemagglutinin
Authors: Gatherer Derek 
Published: November 2009

AbstractSeveral studies have identified residues apparently under positive selection in influenza B virus hemagglutinin. Host immune evasion is the main mechanism proposed to exert this selection pressure. However, these reports have not considered the culture history of the strains used to calculate positive selection. This article shows that passage of influenza B virus through egg culture is a strong contributory factor to the strength and statistical significance of positive selection on hemagglutinin. Non‐synonymous mutations resulting in the loss of the N‐glycosylation site at positions 197–199 of hemagglutinin have been positively selected to a far greater degree in egg‐cultured strains than in other strains. Once egg‐cultured strains are removed from the analysis, positive selection is found to be far weaker, less statistically significant, and more diffusely localized along the protein. Caution should therefore be exercised both in claims for the existence of positive selection in influenza B hemagglutinin, and in attribution of host immune evasion as its cause. The major cause of molecular adaptation in influenza B hemagglutinin proteins may well be laboratory eggs rather than natural hosts. J. Med. Virol. 82:123–127, 2010. © 2009 Wiley‐Liss, Inc.
Detection of GII‐4/2006b variant and recombinant noroviruses in children with acute gastroenteritis, South Korea
Authors: Chung Ju‐Young , Han Tae‐Hee , Park Sang‐Hun , Kim Sang Woo , Hwang Eung‐Soo 
Published: November 2009

AbstractNorovirus (NoV), a single‐stranded, positive RNA virus, is an important etiologic agent of acute gastroenteritis in children worldwide. In this study, a total of 434 fecal samples collected from 434 children with acute gastroenteritis in Seoul, between September 2007 and July 2008 were tested to determine the molecular epidemiology of NoVs and characterize recombinant strains by using RT‐PCR followed by sequencing. Of the 434 specimens, NoV, rotavirus, and adenovirus were detected in 155 (35.8%), 72 (16.6%), and 19 specimens (4.3%), respectively. NoV GI was detected in 7 specimens (1.6%) and GII in 148 (34.1%) specimens. Phylogenetic analysis of capsid sequences in the GII‐positive specimens revealed the presence of the following strains: GII‐4, 111 (75.0%); GII‐3, 35 cases (23.6%); GII‐6b, 1 case; and GII‐16, 1 case. Most of the GII‐4 strains were grouped with the GII‐4/2006b variant with 98–100% nucleotide identity. Eleven strains were identified as recombinant (GII‐4/GII‐3 in 10 cases and GII‐b polymerase/GII‐16 capsid in 1 case) by sequencing based on the RdRP and capsid genes. The putative recombination point in the recombinant strains was the ORF‐1/ORF2 overlap, located at nucleotide 5,046 with reference to Lordsdale. In conclusion, GII‐4/2006b variants were detected predominantly and a new recombinant strain (GII‐4/GII‐3) was found in the Korean children with gastroenteritis. Continuous monitoring of the genetic diversity of NoVs is important to determine the trend of the predominant genotype and new recombinant strain. J. Med. Virol. 82:146–152, 2010. © 2009 Wiley‐Liss, Inc.
Proteomic analysis of cell lines expressing small hepatitis B surface antigen revealed decreased glucose‐regulated protein 78 kDa expression in association with higher susceptibility to apoptosis
Authors: Zhao Chao , Zhang Wei , Tian Xiaochen , Fang Caiyun , Lu Haojie , Yuan Zhenghong , Yang Pengyuan , Wen Yumei 
Published: November 2009

AbstractAccumulating evidence suggests a key role of hepatocyte apoptosis in the pathogenesis of viral hepatitis B. It was found in this study that stable expression of small hepatitis B surface antigen (SHBs) in HepG2 and Huh7 cells increased susceptibility to apoptosis. Proteomic analysis of SHBs expressing HepG2 cells revealed 43 down‐regulated and 38 up‐regulated proteins. Some have been implicated in apoptosis, including glucose‐regulated protein 78 kDa (GRP78), heterogeneous nuclear ribonucleoprotein H3 (hnRNP H), Rho GDP dissociation inhibitor (GDI), cystatin B, far upstream element‐binding protein (FUSEbp), and TNF receptor‐associated protein 1 (TRAP1). Differential expression of GRP78 and several other proteins was confirmed by Western blot analysis. Replenishing GRP78 improved cellular resistance to apoptosis, whereas reduction of GRP78 by siRNA increased susceptibility even in the absence of SHBs. Taken together, these results suggest that HBsAg plays a pro‐apoptotic role through down‐regulation of GRP78. J. Med. Virol. 82:14–22, 2010. © 2009 Wiley‐Liss, Inc.