bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cysteine Scanning Mutagenesis and Topological Mapping of the
Escherichia coli
Twin-Arginine Translocase TatC Component
Authors: Punginelli Claire , Maldonado Bárbara , Grahl Sabine , Jack Rachael , Alami Meriem , Schröder Juliane , Berks Ben C. , Palmer Tracy 
Published: June 2007

ABSTRACT

The TatC protein is an essential component of the
Escherichia coli
twin-arginine (Tat) protein translocation pathway. It is a polytopic membrane protein that forms a complex with TatB, together acting as the receptor for Tat substrates. In this study we have constructed 57 individual cysteine substitutions throughout the protein. Each of the substitutions resulted in a TatC protein that was competent to support Tat-dependent protein translocation. Accessibility studies with membrane-permeant and -impermeant thiol-reactive reagents demonstrated that TatC has six transmembrane helices, rather than the four suggested by a previous study (K. Gouffi, C.-L. Santini, and L.-F. Wu, FEBS Lett. 525:65-70, 2002). Disulfide cross-linking experiments with TatC proteins containing single cysteine residues showed that each transmembrane domain of TatC was able to interact with the same domain from a neighboring TatC protein. Surprisingly, only three of these cysteine variants retained the ability to cross-link at low temperatures. These results are consistent with the likelihood that most of the disulfide cross-links are between TatC proteins in separate TatBC complexes, suggesting that TatC is located on the periphery of the complex.
Antinuclear antibody is associated with a more advanced fibrosis and lower RNA levels of hepatitis C virus in patients with chronic hepatitis C
Authors: Hsieh M-Y , Dai C-Y , Lee L-P , Huang J-F , Tsai W-C , Hou N-J , Lin Z-Y , Chen S-C , Wang L-Y , Chang W-Y , Chuang W-L , Yu M-L 
Published: June 2007

Aims:Positive serum antinuclear antibody (ANA) is present in a number of patients with chronic hepatitis C virus (HCV) infection. This study aimed to evaluate the prevalence of ANA in patients with chronic hepatitis C (CHC) and to elucidate its clinical implications in virological and histological characteristics of CHC infection.Methods:A total of 614 CHC patients were enrolled in this prospective, hospital-based study. The serum levels of aspartate aminotransferase, alanine aminotransferase and ANA, and HCV genotype, HCV RNA level, and histological activity index scores for liver histopathology, were determined.Results:The prevalence of positive ANA (titre >1:40) was 35.0%. Women had a significantly higher prevalence than men (41.2 vs 31.0%; p = 0.012). Patients positive for ANA were significantly older (mean (SD), 53.7 (10.5) vs 49.7 (11.3) years; p<0.001) and had higher mean (SD) alanine aminotransferase levels (186.9 (178.8) vs 155.50 (113.5) IU/l; p<0.001) and lower mean (SD) HCV RNA levels (5.2 (0.9) vs 5.4 (1.0) log IU/ml; p = 0.048) than those without ANA. Among 447 patients undergoing liver biopsy, those positive for ANA had a significantly higher mean (SD) fibrosis score (2.0 (1.3) vs 1.5 (1.1); p<0.001) and a higher frequency of F3–4 (69/187, 36.9% vs 50/260, 19.2%; p<0.001) than those negative for ANA. Multivariate logistic regression analyses showed that advanced fibrosis, lower HCV RNA levels and age were significant factors related to positive ANA.Conclusion:ANA is associated with a more advanced liver fibrosis and lower serum HCV RNA level in patients with CHC.
Platelet particle formation by anti–GPIIIa49-66 Ab, Ca2+ ionophore A23187, and phorbol myristate acetate is induced by reactive oxygen species and inhibited by dexamethasone blockade of platelet phospholipase A2, 12-lipoxygenase, and NADPH oxidase
Authors: Nardi Michael A. , Gor Yelena , Feinmark Steven J. , Xu Fang , Karpatkin Simon 
Published: June 2007

AbstractAn HIV antibody (Ab) against platelet integrin GPIIIa49-66 induces complement-independent platelet particle formation by the elaboration of reactive oxygen species (ROS) downstream of the activation of the platelet NADPH oxidase by the 12-lipoxygenase (12-LO) product 12(S)-HETE. To determine whether other inducers of platelet particle formation also function via the induction of ROS, we examined the effects of the Ca2+ ionophore A23187 and phorbol myristate acetate (PMA). Both agents induced oxidative platelet particle formation in an identical fashion as Ab, requiring Ca2+ flux and 12(S)-HETE production as well as intact NADPH oxidase and 12-LO pathways. Since HIV-ITP patients with this Ab correct their platelet counts with dexamethasone (Dex), we examined the role of this steroid in this unique autoimmune disorder. Dex at therapeutic concentrations inhibited Ab-, A23187-, or PMA-induced platelet particle formation by inhibiting platelet PLA2, 12-LO, and NADPH oxidase. The operational requirement of translocation of PLA2, 12-LO, and NADPH oxidase components (p67 phox) from cytosol to membrane for induction of ROS was both inhibited and partially reversed by Dex in platelets. We conclude that (1) platelet particle formation can be induced by the generation of ROS; and (2) platelet PLA2, 12-LO, NADPH oxidase, and cytosol membrane translocation, requirements for ROS production, are inhibited by Dex.
BCL6 programs lymphoma cells for survival and differentiation through distinct biochemical mechanisms
Authors: Parekh Samir , Polo Jose M. , Shaknovich Rita , Juszczynski Przemyslaw , Lev Paola , Ranuncolo Stella M. , Yin Yingnan , Klein Ulf , Cattoretti Giorgio , Favera Riccardo Dalla , Shipp Margaret A. , Melnick Ari 
Published: June 2007

AbstractThe BCL6 transcriptional repressor is the most commonly involved oncogene in diffuse large B-cell lymphomas (DLBCLs). Constitutive expression of BCL6 mediates lymphomagenesis through aberrant proliferation, survival, and differentiation blockade. Binding of BCL6 to the SMRT/N-CoR corepressors mediates the BCL6 survival effect in DLBCL. Although the basis for differentiation blockade is unknown in DLBCL, recent data suggest that BCL6 binding to the MTA3 corepressor might be involved. We report that BCL6 and MTA3 are coexpressed in normal germinal center B cells and DLBCL. Depletion of MTA3 in DLBCL cells induced a differentiation-related BCL6 target gene (PRDM1), but not target genes involved in survival. Accordingly, MTA3 and PRDM1 expression are mutually exclusive in germinal center B cells. We performed chromatin immunoprecipitation (ChIP)–on-chip mapping of the PRDM1 locus, identifying a novel BCL6 binding site on intron 3 of the PRDM1 gene, and show that BCL6 recruits MTA3 to this site. In DLBCL cells, MTA3 depletion induced plasmacytic differentiation but did not decrease viability of DLBCL cells. However, MTA3 depletion synergized with a specific BCL6 inhibitor that blocks SMRT/N-CoR binding to decrease DLBCL viability. Taken together, these results show that BCL6 regulates distinct transcriptional programs through the SMRT/N-CoR and MTA3 corepressors, respectively, and provides a basis for combinatorial therapeutic targeting of BCL6.
The role of jak2a in zebrafish hematopoiesis
Authors: Ma Alvin C. H. , Ward Alister C. , Liang Raymond , Leung Anskar Y. H. 
Published: June 2007

AbstractJanus kinase 2 (Jak2) transduces signals from hematopoietic cytokines, and a gain-of-function mutation (Jak2617V>F) is associated with myeloproliferative diseases, particularly polycythemia vera. In this study, we examined the role of jak2a in zebrafish embryos in knock-down and overexpression studies using morpholinos (MOs) targeting the 5′ untranslated region (UTR) (jak2aUTR-MO) and splice-site junction (jak2aSS-MO) of jak2a, a Jak inhibitor AG490 and a constitutive-active form of jak2a (jak2aca). At 18 and 24 hours after fertilization (hpf), jak2a is expressed predominantly in the intermediate cell mass (ICM; site of primitive hematopoiesis) of wild-type and chordin morphant embryos (characterized by expansion of ICM). Both jak2a MOs and AG490 reduced gata1+ (erythroid) cells in Tg(gata1:GFP) embryos, signal transducer and activation of transcription 5 (stat5) phosphorylation, and gene expression associated with early progenitors (scl and lmo2) and erythroid (gata1, αhe1 and βhe1) and myeloid (spi1 [early] and mpo [late]) lineages. The chordin morphant is associated with increased stat5 phosphorylation, and both jak2a MOs and treatment with AG490 significantly ameliorated ICM expansion and hematopoietic gene up-regulation in these embryos. Injection of plasmid encoding jak2aca significantly increased erythropoiesis and expression of gata1, αhe1 and βhe1, spi1, mpo, and l-plastin. In conclusion, zebrafish jak2a is involved in primitive hematopoiesis under normal and deregulated conditions.
Functional genomics of the pregnant uterus: from expectations to reality, a compilation of studies in the myometrium
Authors: Breuiller-Fouche Michèle , Charpigny Gilles , Germain Guy 
Published: June 2007

Abstract

Background
Studies on the human myometrium have reported on different microarrays containing different sets of genes or ESTs. However each study profiled only a small number of patients due to various constraints. More profiling information would be an addition to our knowledge base of parturition.

Methods
We compiled from five human studies, transcriptional differences between the non pregnant myometrium (NP), preterm myometrium (PTNIL), term myometrium not in labor (TNIL) and term myometrium in labor (TIL). Software modules developed by the Draghici's group at Wayne State University (Detroit, MI, USA) were used to propose a hierarchical list of several KEGG pathways most likely adjusted to changes observed in microarray experiments.

Results
The differential expression of 118 genes could be dispatched in 14 main KEGG pathways that were the most representative of the changes seen in NP and PTNIL, versus TNIL or TIL. Despite the potential of multiple pitfalls inherent to the use of the microarray technology, gene module analysis of the myometrial transcriptome reveals the activation of precise signaling pathways, some of which may have been under evaluated.

Conclusion
The remodelling and maturation processes that the uterus undergoes in pregnancy appear clearly as phenomena which last during the full course of gestation. It is attested by the nature of the main signaling pathways represented, in the comparison of the PTNIL versus TNIL uterus. Comparatively, the onset of labor is a phenomenon which remains less well characterized by these methods of analysis, possibly because it is a phenomenon occurring in too short a window to have been grasped by the studies carried out up to now.
Malarial pigment haemozoin, IFN-gamma, TNF-alpha, IL-1beta and LPS do not stimulate expression of inducible nitric oxide synthase and production of nitric oxide in immuno-purified human monocytes
Authors: Skorokhod Oleksii A , Schwarzer Evelin , Ceretto Monica , Arese Paolo 
Published: June 2007

AbstractBackgroundEnhanced production of nitric oxide (NO) following upmodulation of the inducible isoform of NO synthase (iNOS) by haemozoin (HZ), inflammatory cytokines and LPS may provide protection againstPlasmodium falciparummalaria by killing hepatic and blood forms of parasites and inhibiting the cytoadherence of parasitized erythrocytes (RBC) to endothelial cells. Monocytes and macrophages are considered to contribute importantly to protective upregulation of iNOS and production of NO. Data obtained with murine phagocytes fed with human HZ and synthetic HZ (sHZ) indicate that supplemental treatment of those cells with IFN-gamma elicited significant increases in protein and mRNA expression of iNOS and NO production, providing a potential mechanism linking HZ phagocytosis and increased production of NO. Purpose of this study was to analyse the effect ofP. falciparumHZ and sHZ supplemental to treatment with IFN-gamma and/or a stimulatory cytokine-LPS mix on iNOS protein and mRNA expression in immuno-purified human monocytes.MethodsAdherent immunopurified human monocytes (purity >85%), and murine phagocytic cell lines RAW 264.7, N11 and ANA1 were fed or not withP. falciparumHZ or sHZ and treated or not with IFN-gamma or a stimulatory cytokine-LPS mix. Production of NO was quantified in supernatants, iNOS protein and mRNA expression were measured after immunoprecipitation and Western blotting and quantitative RT-PCT, respectively.ResultsPhagocytosis of HZ/sHZ by human monocytes did not increase iNOS protein and mRNA expression and NO production either after stimulation by IFN-gamma or the cytokine-LPS mix. By contrast, in HZ/sHZ-laden murine macrophages, identical treatment with IFN-gamma and the cytokine-LPS mix elicited significant increases in protein and mRNA expression of iNOS and NOS metabolites production, in agreement with literature data.ConclusionResults indicate that human monocytes fed or not with HZ/sHZ were constantly unable to express iNOS and generate NOS metabolites even after stimulation with IFN-gamma or a cytokine-LSP mix that were very active on HZ-fed murine phagocytic lines. Present data do not support the hypothesis that monocytes are mediators of anti-parasitic defence in clinical malaria via activation of iNOS and production of NO, and suggest caution in extrapolating data obtained with murine or hybrid systems to human malaria.
Bilateral male breast cancer with male potential hypogonadism
Authors: Hirose Yukiko , Sasa Mitsunori , Bando Yoshimi , Hirose Toshiyuki , Morimoto Tadaoki , Kurokawa Yasushi , Nagao Taeko , Tangoku Akira 
Published: June 2007

AbstractBackgroundMale breast cancer is a comparatively rare disease, and simultaneous bilateral male breast cancer is considered to be an extremely rare event. Risk factors are said to be genetic factors and hormonal abnormalities due to obesity or testicular diseases.Case presentationThe patient was a 47-year-old Japanese male. His family had no history of female breast cancer. This patient also had hypospadias and hormonal examination indicated the presence of primary testicular potential hypogonadism, and these hormonal abnormalities seemed to be present since childhood or the fetal period. The bilateral breast cancer developed in this man at a comparatively young age, and histopathological studies of multiple sections showed that there was almost no normal epithelial cell in the ducts, while the ducts were almost completely filled with breast cancer cells.ConclusionIt is thought that male breast cancer is caused by an imbalance between estrogen and testosterone. We cannot rule out the possibility that the breast cancer developed due to the effect of the slight elevation of estrogen over a long period of time, but the actual causative factors in this patient were unable to be definitively identified. In the future, we hope to further elucidate the causes of male breast cancer.
Giant scrotal elephantiasis of inflammatory etiology: a case report
Authors: Denzinger Stefan , Watzlawek Elke , Burger Maximilian , Wieland Wolf F , Otto Wolfgang 
Published: June 2007

Abstract

Background
Scrotal lymphedema is rare outside endemic filariasis regions in Africa and Asia. It is of variable origin in the western world.

Case presentation
We present a case of a 40-year-old European man with massive elephantiasis of the scrotum attributed to chronic inflammation of the lower urinary tract caused by urinary outlet obstruction and diabetes mellitus. The patient underwent subtotal scrotectomy saving penis, testes and spermatic cords and followed by scrotal reconstruction with adequate cosmetic and functional outcome.

Conclusion
In this report we discuss a rare case of scrotal elephantiasis in an European patient, reflect on the etiology and the diagnostic and therapeutic approaches. Surgery can be successful even in giant scrotal elephantiasis.
Computational and transcriptional evidence for microRNAs in the honey bee genome
Authors: Weaver Daniel B , Anzola Juan M , Evans Jay D , Reid Jeffrey G , Reese Justin T , Childs Kevin L , Zdobnov Evgeny M , Samanta Manoj P , Miller Jonathan , Elsik Christine G 
Published: June 2007

Abstract
Background
Non-coding microRNAs (miRNAs) are key regulators of gene expression in eukaryotes. Insect miRNAs help regulate the levels of proteins involved with development, metabolism, and other life history traits. The recently sequenced honey bee genome provides an opportunity to detect novel miRNAs in both this species and others, and to begin to infer the roles of miRNAs in honey bee development.

Results
Three independent computational surveys of the assembled honey bee genome identified a total of 65 non-redundant candidate miRNAs, several of which appear to have previously unrecognized orthologs in the Drosophila genome. A subset of these candidate miRNAs were screened for expression by quantitative RT-PCR and/or genome tiling arrays and most predicted miRNAs were confirmed as being expressed in at least one honey bee tissue. Interestingly, the transcript abundance for several known and novel miRNAs displayed caste or age-related differences in honey bees. Genes in proximity to miRNAs in the bee genome are disproportionately associated with the Gene Ontology terms 'physiological process', 'nucleus' and 'response to stress'.

Conclusion
Computational approaches successfully identified miRNAs in the honey bee and indicated previously unrecognized miRNAs in the well-studied Drosophila melanogaster genome despite the 280 million year distance between these insects. Differentially transcribed miRNAs are likely to be involved in regulating honey bee development, and arguably in the extreme developmental switch between sterile worker bees and highly fertile queens.
Hodgkin’s Reed-Sternberg cell line (KM-H2) promotes a bidirectional differentiation of CD4+CD25+Foxp3+ T cells and CD4+ cytotoxic T lymphocytes from CD4+ naive T cells
Authors: Tanijiri Tsutomu , Shimizu Toshiki , Uehira Kazutaka , Yokoi Takashi , Amuro Hideki , Sugimoto Hiroyuki , Torii Yoshitaro , Tajima Kenichirou , Ito Tomoki , Amakawa Ryuichi , Fukuhara Shirou 
Published: June 2007

AbstractA recent report revealed that a large population of Hodgkin’s lymphoma-infiltrating lymphocytes (HLILs) consisted of regulatory T cells. In this study, we cocultured CD4+ naive T cells with KM-H2, which was established as a Hodgkin’s Reed-Sternberg cell line, to clarify their ability to induce CD25+Forkhead box P3+ (Foxp3+) T cells. The characteristic analyses of T cells cocultured with KM-H2 revealed the presence of CD4+CD25+ T cells. They expressed CTLA-4, glucocorticoid-induced TNFR family-related gene, and Foxp3 and could produce large amounts of IL-10. Conversely, KM-H2 also generated CD4+ CTLs, which expressed Granzyme B and T cell intracellular antigen-1 in addition to Foxp3+ T cells. They exhibit a strong cytotoxic effect against the parental KM-H2. In conclusion, KM-H2 promotes a bidirectional differentiation of CD4+ naive T cells toward Foxp3+ T cells and CD4+ CTLs. In addition to KM-H2, several cell lines that exhibit the APC function were able to generate Foxp3+ T cells and CD4+ CTLs. Conversely, the APC nonfunctioning cell lines examined did not induce both types of cells. Our findings suggest that the APC function of tumor cells is essential for the differentiation of CD4+ naive T cells into CD25+Foxp3+ T cells and CD4+ CTLs and at least partly explains the predominance of CD25+Foxp3+ T cells in HLILs and their contribution to a better prognosis. Therefore, in APC-functioning tumors, including classical Hodgkin lymphomas, which generate Foxp3+ T cells and CD4+ CTLs, these T cell repertories play a beneficial role synergistically in disease stability.
Midazolam vs. Diphenhydramine for the Treatment of Metoclopramide‐induced Akathisia: A Randomized Controlled Trial
Authors: Parlak Ismet , Erdur Bulent , Parlak Mine , Ergin Ahmet , Ayrik Cuneyt , Tomruk Onder , Turkcuer Ibrahim , Ergin Nesrin 
Published: June 2007

ObjectivesTo compare the effects of midazolam, which is a fast and short‐acting benzodiazepine, and diphenhydramine, which is a widely used anticholinergic agent, in clinical practice for the treatment of metoclopramide‐induced akathisia. MethodsAll adults older than 17 years given metoclopramide for nausea and vomiting or for headache and who had akathisia were eligible for this clinical, randomized, double‐blind trial. Patients were randomized to receive diphenhydramine or midazolam. Subjective, objective, and total akathisia scores and modified Ramsay Sedation Scale scores were recorded. Repeated‐measures analysis of variance was used to compare the efficacy and side effects of the medications. ResultsForty‐one (73.3%) of the 56 enrolled patients were women. The mean (±SD) age was 39.9 (±15.7) years in the diphenhydramine group and 40.9 (±16.2) years in the midazolam group. Mean subjective, objective, and total akathisia scores in the first 5 minutes declined considerably in the midazolam group compared with the diphenhydramine group (p < 0.001). However, the mean Ramsay Sedation Scale score in the first 15 minutes increased significantly in the midazolam group compared with the diphenhydramine group (p < 0.001). ConclusionsMidazolam can correct the symptoms of metoclopramide‐induced akathisia faster than diphenhydramine, but it causes more sedation.
Symptoms of Anxiety and Depression in Young Adults: Genetic and Environmental Influences on Stability and Change
Authors: Nes Ragnhild B. , Røysamb Espen , Reichborn-Kjennerud Ted , Harris Jennifer R. , Tambs Kristian 
Published: June 2007

AbstractEtiological factors for stability and change in symptoms of anxiety and depression, including sex differences, are largely unexplored in young adults. Using biometric modeling and two-wave longitudinal data from 4393 Norwegian twins aged 18 to 31 we explored (i) heritabilities of symptoms of anxiety and depression, (ii) effects of genetic and environmental factors on the stability and change of such symptoms, and (iii) sex-specific effects. The phenotypic cross-time correlations for symptoms of anxiety and depression were estimated to .54 and .49 for males and females, respectively. The best fitting longitudinal model specified additive genetic and individual environmental influences and emerging effects from the shared environment for females only. For both males and females, long-term stability was mainly attributable to stable additive genetic factors, whereas change was essentially related to environmental influences. Minor time-specific genetic effects were indicated, and some stable variance was due to the individual environment. Additive genetic risk factors explained 87% and 68% of the phenotypic cross-time correlation for males and females, with the unique environment accounting for the remaining covariance. The results provide strong evidence for the temporal stability of genetic risk factors for symptoms of anxiety and depression in young adults, and substantial sex-specific influences on heritability, stability and change.