bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of the HLA-DRB1 alleles with characteristic MRI features of Asian multiple sclerosis
Authors: Matsuoka T , Matsushita T , Osoegawa M , Kawano Y , Minohara M , Mihara F , Nishimura Y , Ohyagi Y , Kira J 
Published: October 2008

Background In Asian patients with multiple sclerosis (MS), a paucity of brain lesions and longitudinally extensive spinal cord lesions (LESCLs) extending three or more vertebral segments are characteristic findings on magnetic resonance imaging (MRI). We aimed to disclose possible factors contributing to the development of such MRI features. Method Genotyping of HLA-DRB1 and -DPB1 alleles was performed in 121 consecutive Japanese patients with clinically definite MS based on the Poser criteria and 125 healthy controls. Possible factors associated with MRI features were determined by multiple logistic analysis. Patients with MS were classified based on the presence or absence of brain lesions fulfilling the Barkhof criteria (Barkhof brain lesions) and LESCLs. Barkhof brain lesion–negative (−) patients had a markedly lower frequency of HLA-DRB1*0901 than controls ( Pcorr < 0.05), whereas the frequency of DRB1*1501 was increased in the Barkhof brain lesion–positive (+) group, although this increase was not significant after correction. No Barkhof(−)LESCL(+) patients carried DRB1*0901 ( Pcorr < 0.05), despite this being the most common allele in Japanese. The Barkhof(−)LESCL(−) group showed a significant increase in the frequency of DRB1*0405 compared with controls ( Pcorr < 0.05). None of the DPB1 alleles were significantly different among the groups. Using multiple logistic analysis, the absence of oligoclonal bands was positively associated with an absence of Barkhof brain lesions, whereas a higher EDSS score was positively associated with the presence of LESCLs; however, the presence of anti-aquaporin-4 antibodies was not associated with either feature. Conclusion The characteristic MRI features in Asians are partly related to distinct HLA-DRB1 gene alleles and an absence of oligoclonal bands.
A retroviral mutagenesis screen reveals strong cooperation between Bcl11a overexpression and loss of the Nf1 tumor suppressor gene
Authors: Yin Bin , Delwel Ruud , Valk Peter J. , Wallace Margaret R. , Loh Mignon L. , Shannon Kevin M. , Largaespada David A. 
Published: October 2008

AbstractNF1 inactivation occurs in specific human cancers, including juvenile myelomonocytic leukemia, an aggressive myeloproliferative disorder of childhood. However, evidence suggests that Nf1 loss alone does not cause leukemia. We therefore hypothesized that inactivation of the Nf1 tumor suppressor gene requires cooperating mutations to cause acute leukemia. To search for candidate genes that cooperate with Nf1 deficiency in leukemogenesis, we performed a forward genetic screen using retroviral insertion mutagenesis in Nf1 mutant mice. We identified 43 common proviral insertion sites that contain candidate genes involved in leukemogenesis. One of these genes, Bcl11a, confers a growth advantage in cultured Nf1 mutant hematopoietic cells and causes early onset of leukemia of either myeloid or lymphoid lineage in mice when expressed in Nf1-deficient bone marrow. Bcl11a-expressing cells display compromised p21Cip1 induction, suggesting that Bcl11a's oncogenic effects are mediated, in part, through suppression of p21Cip1. Importantly, Bcl11a is expressed in human chronic myelomonocytic leukemia and juvenile myelomonocytic leukemia samples. A subset of AML patients, who had poor outcomes, of 16 clusters, displayed high levels of BCL11A in leukemic cells. These findings suggest that deregulated Bcl11a cooperates with Nf1 in leukemogenesis, and a therapeutic strategy targeting the BCL11A pathway may prove beneficial in the treatment of leukemia.
Urokinase mediates endothelial cell survival via induction of the X-linked inhibitor of apoptosis protein
Authors: Prager Gerald W. , Mihaly Judit , Brunner Patrick M. , Koshelnick Yuri , Hoyer-Hansen Gunilla , Binder Bernd R. 
Published: October 2008

AbstractUrokinase-type plasminogen activator (uPA) additionally elicits a whole array of pro-angiogenic responses, such as differentiation, proliferation, and migration. In this study, we demonstrate that in endothelial cells uPA also protects against apoptosis by transcriptional up-regulation and partially by mRNA stabilization of inhibitor of apoptosis proteins, most prominently the X-linked inhibitor of apoptosis protein (XIAP). The antiapoptotic activity of uPA was dependent on its protease activity, the presence of uPA receptor (uPAR) and low-density lipoprotein receptor-related protein (LRP), but independent of the phosphatidylinositol 3 (PI3) kinase pathway, whereas vascular endothelial growth factor (VEGF)–induced antiapoptosis was PI3 kinase dependent. uPA-induced cell survival involved phosphorylation of p21-activated kinase 1 (Pak1) and the IκB kinase α that leads to nuclear factor κB (NF-κB) p52 activation. Indeed, blocking NF-κB activation by using specific NF-κB inhibitors abolished uPA-induced cell survival as it blocked uPA-induced XIAP up-regulation. Furthermore, down-regulating XIAP expression by small interfering RNA (siRNA) significantly reduced uPA-dependent endothelial cell survival. This mechanism is also important for VEGF-induced antiapoptosis because VEGF-dependent up-regulation of XIAP was found defective in uPA−/− endothelial cells. This led us to conclude that uPA is part of a novel NF-κB–dependent cell survival pathway.
Evidence for the significant role of immunoglobulin light chains in antigen recognition and selection in chronic lymphocytic leukemia
Authors: Hadzidimitriou Anastasia , Darzentas Nikos , Murray Fiona , Smilevska Tanja , Arvaniti Eleni , Tresoldi Cristina , Tsaftaris Athanasios , Laoutaris Nikolaos , Anagnostopoulos Achilles , Davi Frederic , Ghia Paolo , Rosenquist Richard , Stamatopoulos Kostas , Belessi Chrysoula 
Published: October 2008

AbstractWe analyzed somatic hypermutation (SHM) patterns and secondary rearrangements involving the immunoglobulin (IG) light chain (LC) gene loci in 725 patients with chronic lymphocytic leukemia (CLL). Important differences regarding mutational load and targeting were identified in groups of sequences defined by IGKV/IGLV gene usage and/or K/LCDR3 features. Recurrent amino acid (AA) changes in the IGKV/IGLV sequences were observed in subsets of CLL cases with stereotyped B-cell receptors (BCRs), especially those expressing IGHV3-21/IGLV3-21 and IGHV4-34/IGKV2-30 BCRs. Comparison with CLL LC sequences carrying heterogeneous K/LCDR3s or non-CLL LC sequences revealed that distinct amino acid changes appear to be “CLL-biased.” Finally, a significant proportion of CLL cases with monotypic LC expression were found to carry multiple potentially functional LC rearrangements, alluding to active, (auto)antigen-driven receptor editing. In conclusion, SHM targeting in CLL LCs is just as precise and, likely, functionally driven as in heavy chains. Secondary LC gene rearrangements and subset-biased mutations in CLL LC genes are strong indications that LCs are crucial in shaping the specificity of leukemic BCRs, in association with defined heavy chains. Therefore, CLL is characterized not only by stereotyped HCDR3 and heavy chains but, rather, by stereotyped BCRs involving both chains, which generate distinctive antigen-binding grooves.
Notch signaling is required for proliferation but not for differentiation at a well-defined β-selection checkpoint during human T-cell development
Authors: Taghon Tom , Van de Walle Inge , De Smet Greet , De Smedt Magda , Leclercq Georges , Vandekerckhove Bart , Plum Jean 
Published: October 2008

AbstractNotch signaling is absolutely required for β-selection during mouse T-cell development, both for differentiation and proliferation. In this report, we investigated whether Notch has an equally important role during human T-cell development. We show that human CD34+ thymocytes can differentiate into CD4+CD8β+ double positive (DP) thymocytes in the absence of Notch signaling. While these DP cells phenotypically resemble human β-selected cells, they lack a T-cell receptor (TCR)–β chain. Therefore, we characterized the β-selection checkpoint in human T-cell development, using CD28 as a differential marker at the immature single positive CD4+CD3−CD8α− stage. Through intracellular TCR-β staining and gene expression analysis, we show that CD4+CD3−CD8α−CD28+ thymocytes have passed the β-selection checkpoint, in contrast to CD4+CD3−CD8α−CD28− cells. These CD4+CD3−CD8α−CD28+ thymocytes can efficiently differentiate into CD3+TCRαβ+ human T cells in the absence of Notch signaling. Importantly, preselection CD4+CD3−CD8α−CD28− thymocytes can also differentiate into CD3+TCRαβ+ human T cells without Notch activation when provided with a rearranged TCR-β chain. Proliferation of human thymocytes, however, is clearly Notch-dependent. Thus, we have characterized the β-selection checkpoint during human T-cell development and show that human thymocytes require Notch signaling for proliferation but not for differentiation at this stage of development.
Quinine-dependent, platelet-reactive monoclonals mimic antibodies found in patients with quinine-induced immune thrombocytopenia
Authors: Bougie Daniel W. , Birenbaum Jessica , Rasmussen Mark , Poncz Mortimer , Aster Richard H. 
Published: October 2008

AbstractDrug-induced immune thrombocytopenia (DITP) is caused by drug-dependent antibodies (DDAbs) that are nonreactive in themselves but bind tightly to specific platelet membrane glycoproteins (GP) when soluble drug is present at pharmacologic concentrations. This reaction takes place without covalent linkage of drug to the target, indicating that drug does not function as a classical hapten to promote antibody binding. Studies to define other mechanism(s) responsible for this interaction have been frustrated by the polyclonal nature of human DDAbs and limited quantities of antibody usually available. We produced 2 monoclonal antibodies (mAbs), 314.1 and 314.3, from a mouse immunized with purified human GPIIb/IIIa and quinine that recognize the N terminus of the GPIIb β propeller domain only when soluble quinine is present. Both monoclonals closely mimic the behavior of antibodies from patients with quinine-induced immune thrombo-cytopenia in their reactions at various concentrations of quinine and quinine congeners. Sequencing studies showed that the 2 mAbs are closely related structurally and that mAb 314.3 probably evolved from mAb 314.1 in the course of the immune response. These monoclonal reagents are the first of their kind and should facilitate studies to define the molecular basis for drug-dependent antibody binding and platelet destruction in DITP.
Normalization of Illumina Infinium whole-genome SNP data improves copy number estimates and allelic intensity ratios
Authors: Staaf Johan , Vallon-Christersson Johan , Lindgren David , Juliusson Gunnar , Rosenquist Richard , Höglund Mattias , Borg Åke , Ringnér Markus 
Published: October 2008

Abstract

Background
Illumina Infinium whole genome genotyping (WGG) arrays are increasingly being applied in cancer genomics to study gene copy number alterations and allele-specific aberrations such as loss-of-heterozygosity (LOH). Methods developed for normalization of WGG arrays have mostly focused on diploid, normal samples. However, for cancer samples genomic aberrations may confound normalization and data interpretation. Therefore, we examined the effects of the conventionally used normalization method for Illumina Infinium arrays when applied to cancer samples.

Results
We demonstrate an asymmetry in the detection of the two alleles for each SNP, which deleteriously influences both allelic proportions and copy number estimates. The asymmetry is caused by a remaining bias between the two dyes used in the Infinium II assay after using the normalization method in Illumina's proprietary software (BeadStudio). We propose a quantile normalization strategy for correction of this dye bias. We tested the normalization strategy using 535 individual hybridizations from 10 data sets from the analysis of cancer genomes and normal blood samples generated on Illumina Infinium II 300 k version 1 and 2, 370 k and 550 k BeadChips. We show that the proposed normalization strategy successfully removes asymmetry in estimates of both allelic proportions and copy numbers. Additionally, the normalization strategy reduces the technical variation for copy number estimates while retaining the response to copy number alterations.

Conclusion
The proposed normalization strategy represents a valuable tool that improves the quality of data obtained from Illumina Infinium arrays, in particular when used for LOH and copy number variation studies.
Domain-specific regulation of foxP2 CNS expression by lef1
Authors: Bonkowsky Joshua L , Wang Xu , Fujimoto Esther , Lee Ji Eun , Chien Chi-Bin , Dorsky Richard I 
Published: October 2008

Abstract
Background
FOXP2 is a forkhead transcription factor critical for normal development of language in humans, but little is known of its broader function and regulation during central nervous system (CNS) development. We report here that lef1, a member of the Lef/Tcf family of transcription factors activated by Wnt signaling, regulates foxP2 during embryogenesis, and we isolate novel foxP2 enhancers which are lef1-dependent.

Results
Loss, knock down, or inhibition of lef1 led to loss of foxP2 expression. We isolated DNA fragments from the foxP2 genomic region that function as enhancers to drive GFP expression in the CNS during development, including in the telencephalon, diencephalon, eye, tectum, and hindbrain. Three of these enhancers, foxP2-enhancerA.1, foxP2-enhancerB, and foxP2-enhancerD, contain putative Lef1 binding sites, and are regulated by lef1. However, two other genomic fragments containing Lef1 sites failed to function in vivo as enhancers. Chromatin immunoprecipitation confirmed that Lef1 binds to sites in foxP2-enhancerA.1 and foxP2-enhancerB.

Conclusion
This work shows that lef1 is necessary for expression of foxP2 in the tectum, mid-hindbrain boundary, and hindbrain during CNS development, and is the first insight into the upstream regulation of foxP2 during development. We also demonstrate that in silico prediction of potential lef1 binding sites poorly predicts their ability to function in vivo as enhancers. The foxP2 enhancers we identified will allow dissection of foxP2's role during CNS development.
Matching curated genome databases: a non trivial task
Authors: Descorps-Declère Stéphane , Barba Matthieu , Labedan Bernard 
Published: October 2008

Abstract

Background
Curated databases of completely sequenced genomes have been designed independently at the NCBI (RefSeq) and EBI (Genome Reviews) to cope with non-standard annotation found in the version of the sequenced genome that has been published by databanks GenBank/EMBL/DDBJ. These curation attempts were expected to review the annotations and to improve their pertinence when using them to annotate newly released genome sequences by homology to previously annotated genomes. However, we observed that such an uncoordinated effort has two unwanted consequences. First, it is not trivial to map the protein identifiers of the same sequence in both databases. Secondly, the two reannotated versions of the same genome differ at the level of their structural annotation.

Results
Here, we propose CorBank, a program devised to provide cross-referencing protein identifiers no matter what the level of identity is found between their matching sequences. Approximately 98% of the 1,983,258 amino acid sequences are matching, allowing instantaneous retrieval of their respective cross-references. CorBank further allows detecting any differences between the independently curated versions of the same genome. We found that the RefSeq and Genome Reviews versions are perfectly matching for only 50 of the 641 complete genomes we have analyzed. In all other cases there are differences occurring at the level of the coding sequence (CDS), and/or in the total number of CDS in the respective version of the same genome.
CorBank is freely accessible at http://www.corbank.u-psud.fr. The CorBank site contains also updated publication of the exhaustive results obtained by comparing RefSeq and Genome Reviews versions of each genome. Accordingly, this web site allows easy search of cross-references between RefSeq, Genome Reviews, and UniProt, for either a single CDS or a whole replicon.

Conclusion
CorBank is very efficient in rapid detection of the numerous differences existing between RefSeq and Genome Reviews versions of the same curated genome. Although such differences are acceptable as reflecting different views, we suggest that curators of both genome databases could help reducing further divergence by agreeing on a minimal dialogue and attempting to publish the point of view of the other database whenever it is technically possible.
Nitric oxide production in the exhaled air of patients with pulmonary tuberculosis in relation to HIV co-infection
Authors: Idh Jonna , Westman Anna , Elias Daniel , Moges Feleke , Getachew Assefa , Gelaw Aschalew , Sundqvist Tommy , Forslund Tony , Alemu Addis , Ayele Belete , Diro Ermias , Melese Endalkachew , Wondmikun Yared , Britton Sven , Stendahl Olle , Schön Thomas 
Published: October 2008

Abstract

Background
Nitric oxide (NO) is essential for host defense in rodents, but the role of NO during tuberculosis (TB) in man remains controversial. However, earlier observations that arginine supplementation facilitates anti-TB treatment, supports the hypothesis that NO is important in the host defense against TB. Local production of NO measured in fractional exhaled air (FeNO) in TB patients with and without HIV co-infection has not been reported previously. Thus, our aim was to investigate levels of FeNO in relation to clinical symptoms and urinary NO metabolites (uNO).

Methods
In a cross sectional study, FeNO and uNO were measured and clinical symptoms, chest x-ray, together with serum levels of arginine, tumor necrosis factor alpha (TNF-alpha) and interleukin 12 (IL-12) were evaluated in sputum smear positive TB patients (HIV+/TB, n = 36, HIV-/TB, n = 59), their household contacts (n = 17) and blood donors (n = 46) from Gondar University Hospital, Ethiopia.

Results
The proportion of HIV-/TB patients with an increased FeNO level (> 25 ppb) was significantly higher as compared to HIV+/TB patients, but HIV+/TB patients had significantly higher uNO than HIV-/TB patients. HIV+ and HIV-/TB patients both had lower levels of FeNO compared to blood donors and household contacts. The highest levels of both uNO and FeNO were found in household contacts. Less advanced findings on chest x-ray, as well as higher sedimentation rate were observed in HIV+/TB patients as compared to HIV-/TB patients. However, no significant correlation was found between FeNO and uNO, chest x-ray grading, clinical symptoms, TNF-alpha, IL-12, arginine levels or sedimentation rate.

Conclusion
In both HIV negative and HIV co infected TB patients, low levels of exhaled NO compared to blood donors and household were observed. Future studies are needed to confirm whether low levels of exhaled NO could be a risk factor in acquiring TB and the relative importance of NO in human TB.
The clinicopathological and prognostic impact of 14-3-3 sigma expression on vulvar squamous cell carcinomas
Authors: Wang Zhihui , Tropè Claes G , Suo Zhenhe , Trøen Gunhild , Yang Guanrui , Nesland Jahn M , Holm Ruth 
Published: October 2008

Abstract

Background
14-3-3 sigma (σ) promotes G2/M cell cycle arrest by sequestering cyclin B1-CDC2 complex in cytoplasm. Down-regulation of 14-3-3σ, which has been demonstrated in various carcinomas, may contribute to malignant transformation. However, the exact role of 14-3-3σ in the pathogenesis of vulvar carcinoma is not fully characterized, and the prognostic impact of 14-3-3σ protein expression is still unknown.

Methods
We investigated the 14-3-3σ expression in a series of 302 vulvar squamous cell carcinomas using immunohistochemistry and its associations with clinicopathological factors and clinical outcome.

Results
In cytoplasm, nucleus and cytoplasm/nucleus of vulvar carcinomas high 14-3-3σ protein expression was found in 72%, 59% and 75% of the carcinomas, respectively, and low levels in 28%, 41% and 25% of the cases, respectively. High level of 14-3-3σ in cytoplasm, nucleus and cytoplasm/nucleus was significantly correlated to large tumor diameter (p = 0.001, p = 0.002 and p = 0.001, respectively) and deep invasion (p = 0.01, p = 0.001 and p = 0.007, respectively). Variations of 14-3-3σ protein expression were not associated to disease-specific survival.

Conclusion
Our results indicate that 14-3-3σ may be involved in the development of a subset of vulvar squamous cell carcinomas by down-regulation of 14-3-3σ protein. Neither cytoplasmic nor nuclear level of 14-3-3σ expression was associated with prognosis.
Design of a randomised controlled trial on immune effects of acidic and neutral oligosaccharides in the nutrition of preterm infants: carrot study
Authors: Westerbeek Elisabeth AM , van Elburg Ruurd M , Berg Anemone van den , Berg Jolice van den , Twisk Jos WR , Fetter Willem PF , Lafeber Harrie N 
Published: October 2008

AbstractBackgroundPrevention of serious infections in preterm infants is a challenge, since prematurity and low birth weight often requires many interventions and high utility of devices. Furthermore, the possibility to administer enteral nutrition is limited due to immaturity of the gastrointestinal tract in the presence of a developing immune system. In combination with delayed intestinal bacterial colonisation compared with term infants, this may increase the risk for serious infections. Acidic and neutral oligosaccharides play an important role in the development of the immune system, intestinal bacterial colonisation and functional integrity of the gut. This trial aims to determine the effect of enteral supplementation of acidic and neutral oligosaccharides on infectious morbidity (primary outcome), immune response to immunizations, feeding tolerance and short-term and long-term outcome in preterm infants. In addition, an attempt is made to elucidate the role of acidic and neutral oligosaccharides in postnatal modulation of the immune response and postnatal adaptation of the gut.Methods/DesignIn a double-blind placebo controlled randomised trial, 120 preterm infants (gestational age <32 weeks and/or birth weight <1500 gram) are randomly allocated to receive enteral acidic and neutral oligosaccharides supplementation (20%/80%) or placebo supplementation (maltodextrin) between day 3 and 30 of life. Primary outcome is infectious morbidity (defined as the incidence of serious infections). The role of acidic and neutral oligosaccharides in modulation of the immune response is investigated by determining the immune response to DTaP-IPV-Hib(-HBV)+PCV7 immunizations, plasma cytokine concentrations, faecal Calprotectin and IL-8. The effect of enteral acidic and neutral oligosaccharides supplementation on postnatal adaptation of the gut is investigated by measuring feeding tolerance, intestinal permeability, intestinal viscosity, and determining intestinal microflora. Furthermore, short-term and long-term outcome are evaluated.DiscussionEspecially preterm infants, who are at increased risk for serious infections, may benefit from supplementation of prebiotics. Most studies with prebiotics only focus on the colonisation of the intestinal microflora. However, the pathways how prebiotics may influence the immune system are not yet fully understood. Studying the immune modulatory effects is complex because of the multicausal risk of infections in preterm infants. The combination of neutral oligosaccharides with acidic oligosaccharides may have an increased beneficial effect on the immune system. Increased insight in the effects of prebiotics on the developing immune system may help to decrease the (infectious) morbidity and mortality in preterm infants.Trial registrationCurrent Controlled Trials ISRCTN16211826.