bluuebunny/crossref_metadata_2025_split huggingface dataset:
TheCoxiella burnetiiAnkyrin Repeat Domain-Containing Protein Family Is Heterogeneous, with C-Terminal Truncations That Influence Dot/Icm-Mediated Secretion
Authors: Voth Daniel E. , Howe Dale , Beare Paul A. , Vogel Joseph P. , Unsworth Nathan , Samuel James E. , Heinzen Robert A. 
Published: May 2009

ABSTRACTCoxiella burnetiiis an obligate intracellular bacterium that directs biogenesis of a parasitophorous vacuole (PV) for replication. Effectors of PV maturation are likely translocated into the host cytosol by a type IV secretion system (T4SS) with homology to the Dot/Icm apparatus ofLegionella pneumophila. Since secreted bacterial virulence factors often functionally mimic the activities of host proteins, prokaryotic proteins with eukaryotic features are considered candidate T4SS substrates. Genes encoding proteins with eukaryotic-type ankyrin repeat domains (Anks) were identified upon genome sequencing of theC. burnetiiNine Mile reference isolate, which is associated with a case of human acute Q fever. Interestingly, recent genome sequencing of the G and K isolates, derived from human chronic endocarditis patients, and of the Dugway rodent isolate revealed remarkable heterogeneity in the Ank gene family, with the Dugway isolate harboring the largest number of full-length Ank genes. UsingL. pneumophilaas a surrogate host, we identified 10 Dugway Anks and 1 Ank specific to the G and K endocarditis isolates translocated into the host cytosol in a Dot/Icm-dependent fashion. A 10-amino-acid C-terminal region appeared to be necessary for translocation, with some Anks also requiring the chaperone IcmS for secretion. Ectopically expressed Anks localized to a variety of subcellular regions in mammalian cells, including microtubules, mitochondria, and the PV membrane. Collectively, these data suggest thatC. burnetiiisolates translocate distinct subsets of the Ank protein family into the host cytosol, where they modulate diverse functions, some of which may be unique toC. burnetiipathotypes.
Fixed Points and Stability of the Cauchy Functional Equation in "Equation missing" -Algebras
Authors: Park Choonkil 
Published: May 2009

AbstractUsing the fixed point method, we prove the generalized Hyers-Ulam stability of homomorphisms in "Equation missing"-algebras and Lie "Equation missing"-algebras and of derivations on "Equation missing"-algebras and Lie "Equation missing"-algebras for the Cauchy functional equation.
Recombinant and plasma-derived factor VIII products induce distinct splenic cytokine microenvironments in hemophilia A mice
Authors: Qadura Mohammad , Waters Braden , Burnett Erin , Chegeni Rouzbeh , Bradshaw Scott , Hough Christine , Othman Maha , Lillicrap David 
Published: May 2009

Abstract
The use of plasma-derived factor VIII (pdFVIII) concentrates in hemophilia A has been reported to result in reduced anti-FVIII antibody formation. In this study, we have investigated whether the cytokine microenvironment induced by pdFVIII has an influence on reducing anti-FVIII antibody titers in hemophilic mice. Microarray and confirmatory quantitative reverse transcription polymerase chain reaction (RT-PCR) experiments show that pdFVIII infusion causes a different transcriptional profile in dendritic cells than recombinant FVIII (rFVIII). Both treatments caused up-regulation of proinflammatory gene expression, but rFVIII and pdFVIII treatments promote expression of genes that induce Th1 and Th2 responses, respectively. Moreover, administration of rFVIII or pdFVIII concentrates resulted in distinct T-cell splenic cytokine microenvironments. rFVIII induced the release of Th1 cytokines and IL-10, whereas pdFVIII induced the release of Th2 cytokines and transforming growth factor-β. We have also observed high titers of anti–human von Willebrand factor (VWF) antibodies in the pdFVIII-treated mice and propose that this results from antigenic competition. We further investigated the role of this phenomenon using infusions of FVIII and increasing concentrations of recombinant human factor IX (FIX). These studies show an inverse relationship between increasing concentrations of FIX and the production of anti-FVIII antibodies. In summary, these studies report new mechanisms that contribute to reduced anti-FVIII antibody development in hemophilia A after pdFVIII infusions.
GATA-1 associates with and inhibits p53
Authors: Trainor Cecelia D. , Mas Caroline , Archambault Patrick , Di Lello Paola , Omichinski James G. 
Published: May 2009

Abstract
In addition to orchestrating the expression of all erythroid-specific genes, GATA-1 controls the growth, differentiation, and survival of the erythroid lineage through the regulation of genes that manipulate the cell cycle and apoptosis. The stages of mammalian erythropoiesis include global gene inactivation, nuclear condensation, and enucleation to yield circulating erythrocytes, and some of the genes whose expression are altered by GATA-1 during this process are members of the p53 pathway. In this study, we demonstrate a specific in vitro interaction between the transactivation domain of p53 (p53TAD) and a segment of the GATA-1 DNA-binding domain that includes the carboxyl-terminal zinc-finger domain. We also show by immunoprecipitation that the native GATA-1 and p53 interact in erythroid cells and that activation of p53-responsive promoters in an erythroid cell line can be inhibited by the overexpression of GATA-1. Mutational analysis reveals that GATA-1 inhibition of p53 minimally requires the segment of the GATA-1 DNA-binding domain that interacts with p53TAD. This inhibition is reciprocal, as the activation of a GATA-1–responsive promoter can be inhibited by p53. Based on these findings, we conclude that inhibition of the p53 pathway by GATA-1 may be essential for erythroid cell development and survival.
Red cell genotyping and the future of pretransfusion testing
Authors: Anstee David J. 
Published: May 2009

AbstractOver the past 20 years the molecular bases of almost all the major blood group antigens have been determined. This research has enabled development of DNA-based methods for determining blood group genotype. The most notable application of these DNA-based methods has been for determining fetal blood group in pregnancies when the fetus is at risk for hemolytic disease of the fetus and newborn. The replacement of all conventional serologic methods for pretransfusion testing by molecular methods is not straightforward. For the majority of transfusion recipients matching beyond ABO and D type is unnecessary, and the minority of untransfused patients at risk of alloimmunization who would benefit from more extensively blood group–matched blood cannot be identified reliably. Even if a method to identify persons most likely to make alloantibodies were available, this would not of itself guarantee the provision of extensively phenotype-matched blood for these patients because this is determined by the size and racial composition of blood donations available for transfusion. However, routine use of DNA-based extended phenotyping to provide optimally matched donations for patients with preexisting antibodies or patients with a known predisposition to alloimmunization, such as those with sickle cell disease, is widely used.
EphrinB reverse signaling contributes to endothelial and mural cell assembly into vascular structures
Authors: Salvucci Ombretta , Maric Dragan , Economopoulou Matina , Sakakibara Shuhei , Merlin Simone , Follenzi Antonia , Tosato Giovanna 
Published: May 2009

AbstractEphrinB transmembrane ligands and their cognate EphB receptor tyrosine kinases regulate vascular development through bidirectional cell-to-cell signaling, but little is known about the role of EphrinB during postnatal vascular remodeling. We report that EphrinB is a critical mediator of postnatal pericyte-to-endothelial cell assembly into vascular structures. This function is dependent upon extracellular matrix-supported cell-to-cell contact, engagement of EphrinB by EphB receptors expressed on another cell, and Src-dependent phosphorylation of the intracytoplasmic domain of EphrinB. Phosphorylated EphrinB marks angiogenic blood vessels in the developing and hypoxic retina, the wounded skin, and tumor tissue, and is detected at contact points between endothelial cells and pericytes. Furthermore, inhibition ofEphrinB activity prevents proper assembly of pericytes and endothelial cells into vascular structures. These results reveal a role for EphrinB signaling in orchestrating pericyte/endothelial cell assembly, and suggest that therapeutic targeting of EphrinB may prove useful for disrupting angiogenesis when it contributes to disease.
Regulation of Th17 cell differentiation and EAE induction by MAP3K NIK
Authors: Jin Wei , Zhou Xiao-Fei , Yu Jiayi , Cheng Xuhong , Sun Shao-Cong 
Published: May 2009

AbstractTh17 cells play an important role in mediating autoimmune diseases, but the molecular mechanism underlying Th17 differentiation is incompletely understood. We show here that NF-κB–inducing kinase (NIK), which is known to regulate B-cell maturation and lymphoid organogenesis, is important for the induction of Th17 cells. NIK-deficient naive CD4 T cells are attenuated in the differentiation to Th17 cells, although they are competent in committing to the other effector lineages. Consistently, NIK knockout mice are resistant to experimental autoimmune encephalomyelitis, a disease model that involves the function of Th17 cells. This phenotype was also detected in Rag2 knockout mice reconstituted with NIK-deficient T cells, confirming a T-cell intrinsic defect. We further show that NIK mediates synergistic activation of STAT3 by T-cell receptor and IL-6 receptor signals. NIK deficiency attenuates activation of STAT3 and induction of STAT3 target genes involved in Th17-commitment program. These findings establish NIK as an important signaling factor that regulates Th17 differentiation and experimental autoimmune encephalitis induction.
Phase 2 study of the efficacy and safety of the combination of arsenic trioxide, interferon alpha, and zidovudine in newly diagnosed chronic adult T-cell leukemia/lymphoma (ATL)
Authors: Kchour Ghada , Tarhini Mahdi , Kooshyar Mohamad-Mehdi , El Hajj Hiba , Wattel Eric , Mahmoudi Mahmoud , Hatoum Hassan , Rahimi Hossein , Maleki Masoud , Rafatpanah Houshang , Rezaee S. A. Rahim , Yazdi Mojtaba Tabatabaei , Shirdel Abbas , de Thé Hugues , Hermine Olivier , Farid Reza , Bazarbachi Ali 
Published: May 2009

AbstractAdult T-cell leukemia/lymphoma (ATL) is resistant to chemotherapy and carries a dismal prognosis particularly for the acute and lymphoma subtypes. Promising results were obtained with the combination of zidovudine and interferon-alpha. Chronic ATL has a relatively better outcome, but poor long-term survival is noted when patients are managed with a watchful-waiting policy or with chemotherapy. In ATL cell lines, arsenic trioxide shuts off constitutive NF-κB activation and potentiates interferon-alpha apoptotic effects through proteasomal degradation of Tax. Clinically, arsenic/interferon therapy exhibits some efficacy in refractory aggressive ATL patients. These results prompted us to investigate the efficacy and safety of the combination of arsenic, interferon-alpha, and zidovudine in 10 newly diagnosed chronic ATL patients. An impressive 100% response rate was observed including 7 complete remissions, 2 complete remissions but with more than 5% circulating atypical lymphocytes, and 1 partial response. Responses were rapid and no relapse was noted. Side effects were moderate and mostly hematologic. In conclusion, treatment of chronic ATL with arsenic, interferon-alpha, and zidovudine is feasible and exhibits an impressive response rate with moderate toxicity. Long-term follow up will clarify whether this will translate to disease cure. Overall, these clinical results strengthen the concept of oncogene-targeted cancer therapy.
ESTPiper – a web-based analysis pipeline for expressed sequence tags
Authors: Tang Zuojian , Choi Jeong-Hyeon , Hemmerich Chris , Sarangi Ankita , Colbourne John K , Dong Qunfeng 
Published: May 2009

AbstractBackgroundEST sequencing projects are increasing in scale and scope as the genome sequencing technologies migrate from core sequencing centers to individual research laboratories. Effectively, generating EST data is no longer a bottleneck for investigators. However, processing large amounts of EST data remains a non-trivial challenge for many. Web-based EST analysis tools are proving to be the most convenient option for biologists when performing their analysis, so these tools must continuously improve on their utility to keep in step with the growing needs of research communities. We have developed a web-based EST analysis pipeline called ESTPiper, which streamlines typical large-scale EST analysis components.ResultsThe intuitive web interface guides users through each step of base calling, data cleaning, assembly, genome alignment, annotation, analysis of gene ontology (GO), and microarray oligonucleotide probe design. Each step is modularized. Therefore, a user can execute them separately or together in batch mode. In addition, the user has control over the parameters used by the underlying programs. Extensive documentation of ESTPiper's functionality is embedded throughout the web site to facilitate understanding of the required input and interpretation of the computational results. The user can also download intermediate results and port files to separate programs for further analysis. In addition, our server provides a time-stamped description of the run history for reproducibility. The pipeline can also be installed locally, allowing researchers to modify ESTPiper to suit their own needs.ConclusionESTPiper streamlines the typical process of EST analysis. The pipeline was initially designed in part to support theDaphnia pulexcDNA sequencing project. A web server hosting ESTPiper is provided athttp://estpiper.cgb.indiana.edu/to now support projects of all size. The software is also freely available from the authors for local installations.
Different atrophy-hypertrophy transcription pathways in muscles affected by severe and mild spinal muscular atrophy
Authors: Millino Caterina , Fanin Marina , Vettori Andrea , Laveder Paolo , Mostacciuolo Maria Luisa , Angelini Corrado , Lanfranchi Gerolamo 
Published: May 2009

Abstract

Background
Spinal muscular atrophy (SMA) is a neurodegenerative disorder associated with mutations of the survival motor neuron gene SMN and is characterized by muscle weakness and atrophy caused by degeneration of spinal motor neurons. SMN has a role in neurons but its deficiency may have a direct effect on muscle tissue.

Methods
We applied microarray and quantitative real-time PCR to study at transcriptional level the effects of a defective SMN gene in skeletal muscles affected by the two forms of SMA: the most severe type I and the mild type III.

Results
The two forms of SMA generated distinct expression signatures: the SMA III muscle transcriptome is close to that found under normal conditions, whereas in SMA I there is strong alteration of gene expression. Genes implicated in signal transduction were up-regulated in SMA III whereas those of energy metabolism and muscle contraction were consistently down-regulated in SMA I. The expression pattern of gene networks involved in atrophy signaling was completed by qRT-PCR, showing that specific pathways are involved, namely IGF/PI3K/Akt, TNF-α/p38 MAPK and Ras/ERK pathways.

Conclusion
Our study suggests a different picture of atrophy pathways in each of the two forms of SMA. In particular, p38 may be the regulator of protein synthesis in SMA I. The SMA III profile appears as the result of the concurrent presence of atrophic and hypertrophic fibers. This more favorable condition might be due to the over-expression of MTOR that, given its role in the activation of protein synthesis, could lead to compensatory hypertrophy in SMA III muscle fibers.
Are social norms associated with smoking in French university students? A survey report on smoking correlates
Authors: Riou França Lionel , Dautzenberg Bertrand , Falissard Bruno , Reynaud Michel 
Published: May 2009

AbstractBackgroundKnowledge of the correlates of smoking is a first step to successful prevention interventions. The social norms theory hypothesises that students' smoking behaviour is linked to their perception of norms for use of tobacco. This study was designed to test the theory that smoking is associated with perceived norms, controlling for other correlates of smoking.MethodsIn a pencil-and-paper questionnaire, 721 second-year students in sociology, medicine, foreign language or nursing studies estimated the number of cigarettes usually smoked in a month. 31 additional covariates were included as potential predictors of tobacco use. Multiple imputation was used to deal with missing values among covariates. The strength of the association of each variable with tobacco use was quantified by the inclusion frequencies of the variable in 1000 bootstrap sample backward selections. Being a smoker and the number of cigarettes smoked by smokers were modelled separately.ResultsWe retain 8 variables to predict the risk of smoking and 6 to predict the quantities smoked by smokers. The risk of being a smoker is increased by cannabis use, binge drinking, being unsupportive of smoke-free universities, perceived friends' approval of regular smoking, positive perceptions about tobacco, a high perceived prevalence of smoking among friends, reporting not being disturbed by people smoking in the university, and being female. The quantity of cigarettes smoked by smokers is greater for smokers reporting never being disturbed by smoke in the university, unsupportive of smoke-free universities, perceiving that their friends approve of regular smoking, having more negative beliefs about the tobacco industry, being sociology students and being among the older students.ConclusionOther substance use, injunctive norms (friends' approval) and descriptive norms (friends' smoking prevalence) are associated with tobacco use.University-based prevention campaigns should take multiple substance use into account and focus on the norms most likely to have an impact on student smoking.
Correlation of histopathological diagnosis with habits and clinical findings in oral submucous fibrosis
Authors: Pandya Shruti , Chaudhary Ajay Kumar , Singh Mamta , Singh Mangal , Mehrotra Ravi 
Published: May 2009

Abstract

Background
Oral submucous fibrosis is a common oral health problem in India. This study was conducted to correlate the histopathological diagnosis with habits and clinical findings in patients suffering from oral submucous fibrosis (OSF).

Methods
Patients suffering from oral submucous fibrosis from the Departments of Otorhinolayngology and Pathology, Moti Lal Nehru Medical College, Allahabad, India were studied from 2004–2008. Detailed information was gathered in a pretested proforma. Emphasis was given to the various addictions, clinical findings and histological examination was done.

Results
Two hundred and thirty nine patients were studied, yielding a male to female ratio of 6.8:1. Maximum patients were in the 21–30 years age group with a marked male predominance. Of these, 197 (82.4%) patients chewed areca nut/dohra, 14 (5.8%) were smokers and 2 (0.8%) patients were habituated to alcohol. 89(37.2%) patients reported difficulty in opening of the mouth (trismus). 51 (57.4%) patients were found to have stage II (2–3 cm) trismus while rest had stage I and III. The buccal mucosa was found to be the most commonly involved site. On the basis of histopathological examination, 52(21.7%) were classified as OSF grade I, 75(31.3%) patients as grade II and 112(46.8%) had grade III disease.

Conclusion
The widespread habit of chewing dohra/paan masala is a major risk factor of OSF, especially in the younger age group. In this study, an increase in histopathological grading was found with severity and duration of addiction habit. However no significant correlation was found between clinical staging and histopathological grading.
An Audit of Urology Two-Week Wait Referrals in a Large Teaching Hospital in England
Authors: Mathew Anup , Desai KM 
Published: May 2009

INTRODUCTION Two week wait referral guidelines have been published by the UK Department of Health for suspected urological cancers. Concordance to these guidelines is variable. Our objectives were to assess the incidence of urological malignancy and the proportion of inappropriate referrals in the two-week wait pathway. PATIENTS AND METHODS Retrospective audit of all two-week wait referrals to the urology department over 6 months. Inappropriate referrals were those not satisfying the referral criteria, but referred under the two-week wait system. Detection rates were calculated for each referral criterion based on diagnosis obtained from histology, imaging reports and clinic letters. RESULTS Incidence of cancer was 90 of 400 two-week wait referrals (23%). The cancer-detection rate based on reasons for referral ranged from 50 of 122 (41%) for elevated prostate-specific antigen levels to 2 of 56 (4%) for scrotal lumps; 42 (11%) referrals were inappropriate. CONCLUSIONS The overall cancer-detection rate is acceptable. Most inappropriate referrals were for long-standing symptoms and non-specific testicular/scrotal symptoms. The testicular cancer detection rate raises questions about the two-week wait guidelines. Providing general practitioners with fast-track scrotal ultrasound and revising the guideline may reduce the disproportionately high number of patients referred with suspected testicular cancer. Other inappropriate referrals are a cause for concern as they add to the workload of the ‘urgent-referral’ pathway. Urological cancers (those involving the prostate, testis, penis, urethra, bladder, ureters and kidneys) accounted for 15.4% of all new cancers in England, 1 and 12.1% of deaths from cancer, 2 in England and Wales, in 2004. The two-week wait referral guidelines published by the UK Department of Health for suspected urological cancers 3 are summarised in Table 1 . NHS trusts and SHAs are encouraged to carry out clinical audits of suspected cancer referrals to generate further information. 4 There is wide variation among various centres and regions in the concordance of general practitioner (GP) referrals based on these guidelines, and also the rate of cancers detected based on the two-week wait system. [Table: see text] The objectives of this audit were to calculate: (i) the rate of detection of cancers among the two-week wait referrals; (ii) the rate of detection of cancers based on the reason for referral; and (iii) the proportion of inappropriate referrals.