bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impaired Quality of the Hepatitis B Virus (HBV)-Specific T-Cell Response in Human Immunodeficiency Virus Type 1-HBV Coinfection
Authors: Chang J. Judy , Sirivichayakul Sunee , Avihingsanon Anchalee , Thompson Alex J. V. , Revill Peter , Iser David , Slavin John , Buranapraditkun Supranee , Marks Pip , Matthews Gail , Cooper David A. , Kent Stephen J. , Cameron Paul U. , Sasadeusz Joe , Desmond Paul , Locarnini Stephen , Dore Gregory J. , Ruxrungtham Kiat , Lewin Sharon R. 
Published: May 2009

ABSTRACTHepatits B virus (HBV)-specific T cells play a key role both in the control of HBV replication and in the pathogenesis of liver disease. Human immunodeficiency virus type 1 (HIV-1) coinfection and the presence or absence of HBV e (precore) antigen (HBeAg) significantly alter the natural history of chronic HBV infection. We examined the HBV-specific T-cell responses in treatment-naïve HBeAg-positive and HBeAg-negative HIV-1-HBV-coinfected (n= 24) and HBV-monoinfected (n= 39) Asian patients. Peripheral blood was stimulated with an overlapping peptide library for the whole HBV genome, and tumor necrosis factor alpha and gamma interferon cytokine expression in CD8+T cells was measured by intracellular cytokine staining and flow cytometry. There was no difference in the overall magnitude of the HBV-specific T-cell responses, but the quality of the response was significantly impaired in HIV-1-HBV-coinfected patients compared with monoinfected patients. In coinfected patients, HBV-specific T cells rarely produced more than one cytokine and responded to fewer HBV proteins than in monoinfected patients. Overall, the frequency and quality of the HBV-specific T-cell responses increased with a higher CD4+T-cell count (P= 0.018 and 0.032, respectively). There was no relationship between circulating HBV-specific T cells and liver damage as measured by activity and fibrosis scores, and the HBV-specific T-cell responses were not significantly different in patients with either HBeAg-positive or HBeAg-negative disease. The quality of the HBV-specific T-cell response is impaired in the setting of HIV-1-HBV coinfection and is related to the CD4+T-cell count.
Functional Analysis of Glycoprotein L (gL) from Rhesus Lymphocryptovirus in Epstein-Barr Virus-Mediated Cell Fusion Indicates a Direct Role of gL in gB-Induced Membrane Fusion
Authors: Plate Aileen E. , Smajlović Jasmina , Jardetzky Theodore S. , Longnecker Richard 
Published: May 2009

ABSTRACTGlycoprotein L (gL), which complexes with gH, is a conserved herpesvirus protein that is essential for Epstein-Barr virus (EBV) entry into host cells. The gH/gL complex has a conserved role in entry among herpesviruses, yet the mechanism is not clear. To gain a better understanding of the role of gL in EBV-mediated fusion, chimeric proteins were made using rhesus lymphocryptovirus (Rh-LCV) gL (Rh gL), which shares a high sequence homology with EBV gL but does not complement EBV gL in mediating fusion with B cells. A reduction in fusion activity was observed with chimeric gL proteins that contained the amino terminus of Rh gL, although they retained their ability to process and transport gH/gL to the cell surface. Amino acids not conserved within this region in EBV gL when compared to Rh gL were further analyzed, with the results mapping residues 54 and 94 as being functionally important for EBV-mediated fusion. All chimeras and mutants displayed levels of cell surface expression similar to that of wild-type gL and interacted with gH and gp42. Our data also suggest that the role of gL involves the activation or recruitment of gB with the gH/gL complex, as we found that reduced fusion of Rh gL, EBV/Rh-LCV chimeras, and gL point mutants could be restored by replacing EBV gB with Rh gB. These observations demonstrate a distinction between the role of gL in the processing and trafficking of gH to the cell surface and a posttrafficking role in cell-cell fusion.
Effect of the Human Immunodeficiency Virus Type 1 Reverse Transcriptase Polymorphism Leu-214 on Replication Capacity and Drug Susceptibility
Authors: Puertas Maria Carmen , Buzón Maria Jose , Artese Anna , Alcaro Stefano , Menendez-Arias Luis , Perno Carlo Federico , Clotet Bonaventura , Ceccherini-Silberstein Francesca , Martinez-Picado Javier 
Published: May 2009

ABSTRACTA negative association between polymorphism Leu-214 and type-1 thymidine analogue mutations (TAM1) and a positive association with a clinically favorable virological response to thymidine analogue-based combination antiretroviral therapy have been described. In this study, the impact of Leu-214 on replication capacity and resistance to zidovudine (ZDV) of viruses containing TAM1 or TAM2 was determined. Leu-214 decreased the growth rate of viruses bearing Tyr-215, as well as their resistance to ZDV. This observation was confirmed by structural and molecular modeling data, suggesting a regulatory role for Leu-214 in the emergence and phenotypic resistance of TAM1.
Pharmacovirological Impact of an Integrase Inhibitor on Human Immunodeficiency Virus Type 1 cDNA Species In Vivo
Authors: Goffinet Christine , Allespach Ina , Oberbremer Lena , Golden Pamela L. , Foster Scott A. , Johns Brian A. , Weatherhead Jason G. , Novick Steven J. , Chiswell Karen E. , Garvey Edward P. , Keppler Oliver T. 
Published: May 2009

ABSTRACT
Clinical trials of the first approved integrase inhibitor (INI), raltegravir, have demonstrated a drop in the human immunodeficiency virus type 1 (HIV-1) RNA loads of infected patients that was unexpectedly more rapid than that with a potent reverse transcriptase inhibitor, and apparently dose independent. These clinical outcomes are not understood. In tissue culture, although their inhibition of integration is well documented, the effects of INIs on levels of unintegrated HIV-1 cDNAs have been variable. Furthermore, there has been no report to date on an INI's effect on these episomal species in vivo. Here, we show that prophylactic treatment of transgenic rats with the strand transfer INI GSK501015 reduced levels of viral integrants in the spleen by up to 99.7%. Episomal two-long-terminal-repeat (LTR) circles accumulated up to sevenfold in this secondary lymphoid organ, and this inversely correlated with the impact on the proviral burden. Contrasting raltegravir's dose-ranging study with HIV patients, titration of GSK501015 in HIV-infected animals demonstrated dependence of the INI's antiviral effect on its serum concentration. Furthermore, the in vivo 50% effective concentration calculated from these data best matched GSK501015's in vitro potency when serum protein binding was accounted for. Collectively, this study demonstrates a titratable, antipodal impact of an INI on integrated and episomal HIV-1 cDNAs in vivo. Based on these findings and known biological characteristics of viral episomes, we discuss how integrase inhibition may result in additional indirect antiviral effects that contribute to more rapid HIV-1 decay in HIV/AIDS patients.
Mineralogical and chemical characterization of some vermiculites from the Mozambique Belt of Tanzania for agricultural use
Authors: Marwa E. M. M. , Hillier S. , Rice C. M. , Meharg A. A. 
Published: May 2009

AbstractVermiculite minerals are locally available in the Mozambique Belt of Tanzania but are not currently commercially exploited. In part this may be due to lack of any precise characterization. This study was carried out as a first step to assess the suitability of these vermiculites for crop production by characterization of their mineralogical and chemical compositions. X-ray diffraction and scanning electron microscopy combined with an energy-dispersive X-ray system were used to establish the mineralogy. Electron microprobe analysis and inductively coupled plasma-mass spectrometry were used to study the chemical compositions and to identify any possible issues related to chemical composition that might affect their use if applied as soil conditioners. The samples were characterized as vermiculites and hydrobiotites with a wide variety of accessory minerals. Accessory minerals that might be of some concern are galena, fibrous amphiboles and sepiolite. The total levels of Ni in all vermiculites, and Cr in some, were also found to be high relative to common European standards and this might limit their potential as soil conditioners. It is clear that a field assessment of the bioavailability of various elements would be necessary before decisions relating to potential agricultural use could be made.
Allophane and imogolite: role in soil biogeochemical processes
Authors: Parfitt R. L. 
Published: May 2009

AbstractThe literature on the formation, structure and properties of allophane and imogolite is reviewed, with particular emphasis on the seminal contributions by Colin Farmer. Allophane and imogolite occur not only in volcanic-ash soils but also in other environments. The conditions required for the precipitation of allophane and imogolite are discussed. These include pH, availability of Al and Si, rainfall, leaching regime, and reactions with organic matter. Because of their excellent water storage and physical properties, allophanic soils can accumulate large amounts of biomass. In areas of high rainfall, these soils often occur under rain forest, and the soil organic matter derived from the forest biomass is stabilized by allophane and aluminium ions. Thus the turnover of soil organicmatter in allophanicsoils is slower than that in non-allophanicsoils. The organic matter appears to be derived from the microbial by-products of the plant material rather than from the plant material itself. The growth of young forests may be limited by nitrogen supply but growth of older forests tends to be P limited. Phosphorus is recycled through both inorganic and organic pathways, but it is also strongly sorbed by Al compounds including allophane. When crops are grown in allophanic soils, large amounts of labile P are required and, accordingly, these soils have to be managed to counteract the large P sorption capacity of allophane and other Al compounds, and to ensure an adequate supply of labile P. Because of their physical and chemical properties, allophanic soils are excellent filters of heavy metals and pathogens.
Electrical conductivity of montmorillonite as a function of relative humidity: La-montmorillonite
Authors: García N. J. , Bazán J. C. 
Published: May 2009

AbstractThe conductivity of La-montmorillonite was measured in the domain of water relative pressures (p/p0) of <1, and compared with the conductivites of Li- and Na-montmorillonite. La-montmorillonite shows smaller conductivity over the whole range of p/p0 studied. To explain this, theoretical considerations of the polarizing power and of the local stacking order induced by the exchangeable cation were addressed.
Protein synthesis is resistant to rapamycin and constitutes a promising therapeutic target in acute myeloid leukemia
Authors: Tamburini Jerome , Green Alexa S. , Bardet Valerie , Chapuis Nicolas , Park Sophie , Willems Lise , Uzunov Madalina , Ifrah Norbert , Dreyfus François , Lacombe Catherine , Mayeux Patrick , Bouscary Didier 
Published: May 2009

AbstractThe deregulation of translation markedly contributes to the malignant phenotype in cancers, and the assembly of the translation initiating complex eIF4F is the limiting step of this process. The mammalian Target of Rapamycin Complex 1 (mTORC1) is thought to positively regulate eIF4F assembly and subsequent oncogenic protein synthesis through 4E-BP1 phosphorylation. We showed here that the translation inhibitor 4EGI-1 decreased the clonogenic growth of leukemic progenitors and induced apoptosis of blast cells, with limited toxicity against normal hematopoiesis, which emphasize the importance of translation deregulation in acute myeloid leukemia (AML) biology. However, the mTORC1 inhibitor RAD001 (a rapamycin derivate) did not induce AML blast cell apoptosis. We herein demonstrated that mTORC1 disruption using raptor siRNA or RAD001 failed to inhibit 4E-BP1 phosphorylation in AML. Moreover, RAD001 failed to inhibit eIF4F assembly, to decrease the proportion of polysome-bound c-Myc mRNA, and to reduce the translation-dependent accumulation of oncogenic proteins. We identified the Pim-2 serine/threonine kinase as mainly responsible for 4E-BP1 phosphorylation on the S65 residue and subsequent translation control in AML. Our results strongly implicate an mTORC1-independent deregulation of oncogenic proteins synthesis in human myeloid leukemogenesis. Direct inhibition of the translation initiating complex thus represents an attractive option for the development of new therapies in AML.
High frequency of PTEN, PI3K, and AKT abnormalities in T-cell acute lymphoblastic leukemia
Authors: Gutierrez Alejandro , Sanda Takaomi , Grebliunaite Ruta , Carracedo Arkaitz , Salmena Leonardo , Ahn Yebin , Dahlberg Suzanne , Neuberg Donna , Moreau Lisa A. , Winter Stuart S. , Larson Richard , Zhang Jianhua , Protopopov Alexei , Chin Lynda , Pandolfi Pier Paolo , Silverman Lewis B. , Hunger Stephen P. , Sallan Stephen E. , Look A. Thomas 
Published: May 2009

Abstract
To more comprehensively assess the pathogenic contribution of the PTEN-PI3K-AKT pathway to T-cell acute lymphoblastic leukemia (T-ALL), we examined diagnostic DNA samples from children with T-ALL using array comparative genomic hybridization and sequence analysis. Alterations of PTEN, PI3K, or AKT were identified in 47.7% of 44 cases. There was a striking clustering of PTEN mutations in exon 7 in 12 cases, all of which were predicted to truncate the C2 domain without disrupting the phosphatase domain of PTEN. Induction chemotherapy failed to induce remission in 3 of the 4 patients whose lymphoblasts harbored PTEN deletions at the time of diagnosis, compared with none of the 12 patients with mutations of PTEN exon 7 (P = .007), suggesting that PTEN deletion has more adverse therapeutic consequences than mutational disruptions that preserve the phosphatase domain. These findings add significant support to the rationale for the development of therapies targeting the PTEN-PI3K-AKT pathway in T-ALL.
Analysis of the role of COP9 Signalosome (CSN) subunits in K562; the first link between CSN and autophagy
Authors: Pearce Claire , Hayden Rachel E , Bunce Christopher M , Khanim Farhat L 
Published: May 2009

Abstract

Background
The COP9/signalosome (CSN) is a highly conserved eight subunit complex that, by deneddylating cullins in cullin-based E3 ubiquitin ligases, regulates protein degradation. Although studied in model human cell lines such as HeLa, very little is known about the role of the CSN in haemopoietic cells.

Results
Greater than 95% knockdown of the non-catalytic subunit CSN2 and the deneddylating subunit CSN5 of the CSN was achieved in the human myeloid progenitor cell line K562. CSN2 knockdown led to a reduction of both CSN5 protein and mRNA whilst CSN5 knockdown had little effect on CSN2. Both knockdowns inhibited CSN deneddylase function as demonstrated by accumulation of neddylated Cul1. Furthermore, both knockdowns resulted in the sequential loss of Skp2, Cdc4 and β-TrCP F-box proteins. These proteins were rescued by the proteasome inhibitor MG132, indicating the autocatalytic degradation of F-box proteins upon loss of CSN2 or CSN5. Interestingly, altered F-box protein gene expression was also observed in CSN2 and CSN5 knockdowns, suggesting a potential role of the CSN in regulating F-box protein transcription.
Loss of either CSN subunit dramatically reduced cell growth but resulted in distinct patterns of cell death. CSN5 knockdown caused mitotic defects, G2/M arrest and apoptotic cell death. CSN2 knockdown resulted in non-apoptotic cell death associated with accumulation of both the autophagy marker LC3-II and autophagic vacuoles. Treatment of vector control K562 cells with the autophagy inhibitors 3-methyladenine and bafilomycin A1 recapitulated the growth kinetics, vacuolar morphology and LC3-II accumulation of CSN2 knockdown cells indicating that the cellular phenotype of CSN2 cells arises from autophagy inhibition. Finally, loss of CSN2 was associated with the formation of a CSN5 containing subcomplex.

Conclusion
We conclude that CSN2 is required for CSN integrity and the stability of individual CSN subunits, and postulate that CSN2 loss results in a phenotype distinct from that of cells lacking CSN5 possibly as a consequence of altered CSN5 activity within a resultant CSN subcomplex. Our data present the first evidence for the sequential loss of F-box proteins upon CSN manipulation and are the first to identify a potential link between CSN function and autophagy.
Recent dermatophyte divergence revealed by comparative and phylogenetic analysis of mitochondrial genomes
Authors: Wu Yuan , Yang Jian , Yang Fan , Liu Tao , Leng Wenchuan , Chu Yonglie , Jin Qi 
Published: May 2009

Abstract

Background
Dermatophytes are fungi that cause superficial infections of the skin, hair, and nails. They are the most common agents of fungal infections worldwide. Dermatophytic fungi constitute three genera, Trichophyton, Epidermophyton, and Microsporum, and the evolutionary relationships between these genera are epidemiologically important. Mitochondria are considered to be of monophyletic origin and mitochondrial sequences offer many advantages for phylogenetic studies. However, only one complete dermatophyte mitochondrial genome (E. floccosum) has previously been determined.

Results
The complete mitochondrial DNA sequences of five dermatophyte species, T. rubrum (26,985 bp), T. mentagrophytes (24,297 bp), T. ajelloi (28,530 bp), M. canis (23,943 bp) and M. nanum (24,105 bp) were determined. These were compared to the E. floccosum sequence. Mitochondrial genomes of all 6 species were found to harbor the same set of genes arranged identical order indicating that these dermatophytes are closely related. Genome size differences were largely due to variable lengths of non-coding intergenic regions and the presence/absence of introns. Phylogenetic analyses based on complete mitochondrial genomes reveals that the divergence of the dermatophyte clade was later than of other groups of pathogenic fungi.

Conclusion
This is the first systematic comparative genomic study on dermatophytes, a highly conserved and recently-diverged lineage of ascomycota fungi. The data reported here provide a basis for further exploration of interrelationships between dermatophytes and will contribute to the study of mitochondrial evolution in higher fungi.
A kinase-dead knock-in mutation in mTOR leads to early embryonic lethality and is dispensable for the immune system in heterozygous mice
Authors: Shor Boris , Cavender Druie , Harris Crafford 
Published: May 2009

AbstractBackgroundThe mammalian target of rapamycin protein (mTOR) is an evolutionarily conserved kinase that regulates protein synthesis, cell cycle progression and proliferation in response to various environmental cues. As a critical downstream mediator of PI3K signaling, mTOR is important for lymphocyte development and function of mature T and B-cells. Most studies of mTOR in immune responses have relied on the use of pharmacological inhibitors, such as rapamycin. Rapamycin-FKBP12 complex exerts its immunosuppressive and anti-proliferative effect by binding outside the kinase domain of mTOR, and subsequently inhibiting downstream mTOR signaling.ResultsTo determine the requirement for mTOR kinase activity in the immune system function, we generated knock-in mice carrying a mutation (D2338) in the catalytic domain of mTOR. While homozygous mTOR kd/kd embryos died before embryonic day 6.5, heterozygous mTOR+/kd mice appeared entirely normal and are fertile. mTOR +/kd mice exhibited normal T and B cell development and unaltered proliferative responses of splenocytes to IL-2 and TCR/CD28. In addition, heterozygousity for the mTOR kinase-dead allele did not sensitize T cells to rapamycin in a CD3-mediated proliferation assay. Unexpectedly, mTOR kinase activity towards its substrate 4E-BP1 was not decreased in hearts and livers from heterozygous animals.ConclusionAltogether, our findings indicate that mTOR kinase activity is indispensable for the early development of mouse embryos. Moreover, a single wild type mTOR allele is sufficient to maintain normal postnatal growth and lymphocyte development and proliferation.
Outcomes and factors influencing survival in cirrhotic cases with spontaneous rupture of hepatocellular carcinoma: a multicenter study
Authors: Kirikoshi Hiroyuki , Saito Satoru , Yoneda Masato , Fujita Koji , Mawatari Hironori , Uchiyama Takashi , Higurashi Takuma , Imajo Kento , Sakaguchi Takashi , Atsukawa Kazuhiro , Sawabe Aya , Kanesaki Akira , Takahashi Hirokazu , Abe Yasunobu , Inamori Masahiko , Kobayashi Noritoshi , Kubota Kensuke , Ueno Norio , Nakajima Atsushi 
Published: May 2009

Abstract

Background
Spontaneous rupture is rare complication of hepatocellular carcinoma (HCC) with high mortality rate in cirrhotic cases. The aim of this study was to determine the factors influencing prognosis in cases of spontaneously ruptured HCC and to investigate the outcomes of the treatments employed, especially transcatheter arterial embolization (TAE).

Methods
A retrospective multicenter study was conducted in 48 cirrhotic patients with spontaneous rupture of HCC. Conservative treatment was employed in 32 patients (ConT group) and TAE was performed in 16 patients (TAE group).

Results
The median survival time (MST) in the ConT group was only 13.1 days and the survival rate was extremely poor: 59.4% at 7 days, 37.5% at 14 days, and 6.3% at 30 days. On the other hand, the MST in the TAE group was 244.8 days and the survival rate was 87.5% at 1 month, 56.3% at 3 months, 23.4% at 12 months, and 15.6% at 24 months. According to the results of univariate analyses, factors associated with poor hepatic function and poor suitability for TAE was important determinants of short-term death (less than 3 weeks) among the patients (p < 0.05). On the other hand, among the patients in whom initial TAE was successfully performed (n = 15), a multivariate analysis showed that a maximum tumor size not exceeding 7 cm was the only independent factor determining long-term survival (p = 0.0130).

Conclusion
Despite the inherent limitations of this retrospective study, TAE appears to be a useful treatment strategy for cirrhotic patients with spontaneous HCC rupture, as it yielded a longer survival period compared with conservative treatment in patients with ruptured HCC. Among the patients with ruptured HCC in whom initial TAE was successfully performed, the maximum tumor size was an important factor influencing survival.