bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non‐CLL‐like monoclonal B‐cell lymphocytosis in the general population: Prevalence and phenotypic/genetic characteristics
Authors: Nieto Wendy G. , Teodosio Cristina , López Antonio , Rodríguez‐Caballero Arancha , Romero Alfonso , Bárcena Paloma , Gutierrez Maria Laura , Langerak Anton W. , Fernandez‐Navarro Paulino , Orfao Alberto , Almeida Julia ,   the Primary Health Care Group of Salamanca for the Study of MBL
Published: September 2010

AbstractBackground:Monoclonal B‐cell lymphocytosis (MBL) indicates <5 × 109 peripheral blood (PB) clonal B‐cells/L in healthy individuals. In most cases, MBL cells show similar phenotypic/genetic features to chronic lymphocytic leukemia cells—CLL‐like MBL—but little is known about non‐CLL‐like MBL.Methods:PB samples from 639 healthy individuals (46% men/54% women) >40 years old (62 ± 13years) with normal lymphocyte counts (2.1 ± 0.7 × 109/L) were immunophenotyped using high‐sensitive flow cytometry, based on 8‐color stainings and the screening for >5 × 106 total PB leukocytes.Results:Thirteen subjects (2.0%; 9 males/4 females, aged 73 ± 10 years; absolute lymphocyte count: 2.4 ± 0.8 × 109/L) showed a non‐CLL‐like clonal B‐cell population, whose frequency clearly increased with age: 0.4%, 3%, and 5.4% of subjects aged 40–59, 60–79, and ≥80 years, respectively. One single B‐cell clone was detected in 9/13 cases, while two B‐cell clones were found in 4/13 (n = 17 MBL populations). Nine MBL cell populations showed a CD5− phenotype (usually overlapping with marginal zone‐derived (MZL) or lymphoplasmacytic (LPL) non‐Hodgkin lymphoma (NHL) B‐cells, or an unclassifiable NHL), but CD5−/+d (n = 3) and CD5+ (n = 3 non‐CLL‐like MBL, consistent with a mantle‐cell lymphoma (MCL)‐like phenotype, and n = 2 CLL‐like) MBL were also identified; iFISH supported the diagnosis in most cases. No preferential IGHV usage of B‐cell receptor could be found. Twelve cases reevaluated at month +12 showed circulating clonal B‐cells, at mean levels significantly higher than those initially detected.Conclusions:Non‐CLL‐like MBL cases frequently show biclonality, in association with MZL‐, LPL‐, MCL‐like, or unclassifiable phenotypic profiles. As with CLL‐like MBL, the frequency of non‐CLL‐like MBL increases with age, with a clear predominance of males. © 2010 International Clinical Cytometry Society
Early induction of GAD65‐reactive Th2 response in type 1 diabetic children treated with alum‐formulated GAD65
Authors: Axelsson Stina , Hjorth Maria , Åkerman Linda , Ludvigsson Johnny , Casas Rosaura 
Published: September 2010

AbstractBackgroundWe have previously shown that two injections of 20 µg alum‐formulated glutamic acid decarboxylase 65 (GAD65) (GAD‐alum; Diamyd®) in children with recent‐onset type 1 diabetes lead to preservation of residual insulin secretion. In vitro cytokine production at the 15 months' follow‐up indicated immunomodulation. In the present study, we took advantage of peripheral blood mononuclear cells, cryopreserved during early follow‐ups, to investigate whether the immunomodulatory effect of GAD‐alum was apparent earlier after treatment, preceding the changes previously reported at 15 months.MethodsPeripheral blood mononuclear cells from 70 type 1 diabetic children, randomly assigned GAD‐alum (n = 35) or placebo (n = 35), that had been frozen at baseline (n = 27) and after 1 (n = 58), 3 (n = 67) and 9 (n = 66) months, were stimulated in vitro with GAD65, tyrosine phosphatase‐like protein IA‐2 peptide, insulin peptide, GAD‐alum, alum formulation or phytohaemagglutinin. Interleukin (IL)‐5, ‐6, ‐10, ‐12, ‐13, ‐17, tumour necrosis factor and interferon‐γ were measured in cell supernatants and serum samples using Luminex. Expression of FOXP3 and transforming growth factor‐β was determined by real‐time reverse transcription polymerase chain reaction.ResultsAlready 1 month after the first injection, GAD65‐induced IL‐5 and IL‐13 together with FOXP3 were enhanced in GAD‐alum‐treated patients compared to those with placebo. The in vitro response at 3 and 9 months was characterized by a broader range of cytokines in the treated group. Notably, only the T‐helper 2‐associated cytokines IL‐5 and IL‐13 together with FOXP3 increased continuously over time.ConclusionsTreatment with GAD‐alum in type 1 diabetic children induced an early T‐helper 2 immune enhanced response to GAD65, followed by a wider spectrum of cytokines at 3 and 9 months. Copyright © 2010 John Wiley & Sons, Ltd.
HIF‐1α inhibition ameliorates an allergic airway disease via VEGF suppression in bronchial epithelium
Authors: Kim So Ri , Lee Kyung Sun , Park Hee Sun , Park Seoung Ju , Min Kyung Hoon , Moon Hee , Puri Kamal D. , Lee Yong Chul 
Published: September 2010

AbstractHypoxia‐inducible factor‐1α (HIF‐1α) plays a critical role in immune and inflammatory responses. One of the HIF‐1α target genes is vascular endothelial growth factor (VEGF), which is a potent stimulator of inflammation, airway remodeling, and physiologic dysregulation in allergic airway diseases. Using OVA‐treated mice and murine tracheal epithelial cells, the signaling networks involved in HIF‐1α activation and the role of HIF‐1α in the pathogenesis of allergic airway disease were investigated. Transfection of airway epithelial cells with HIF‐1α siRNA suppressed VEGF expression. In addition, the increased levels of HIF‐1α and VEGF in lung tissues after OVA inhalation were substantially decreased by an HIF‐1α inhibitor, 2‐methoxyestradiol. Our data also show that the increased numbers of inflammatory cells, increased airway hyperresponsiveness, levels of IL‐4, IL‐5, IL‐13, and vascular permeability in the lungs after OVA inhalation were significantly reduced by 2‐methoxyestradiol or a VEGF inhibitor, CBO‐P11. Moreover, we found that inhibition of the PI3K p110δ isoform (PI3K‐δ) or HIF‐1α reduced OVA‐induced HIF‐1α activation in airway epithelial cells. These findings indicate that HIF‐1α inhibition may attenuate antigen‐induced airway inflammation and hyperresponsiveness through the modulation of vascular leakage mediated by VEGF, and that PI3K‐δ signaling may be involved in the allergen‐induced HIF‐1α activation.
TLR3‐mediated IFN‐β gene induction is negatively regulated by the TLR adaptor MyD88 adaptor‐like
Authors: Siednienko Jakub , Halle Annett , Nagpal Kamalpreet , Golenbock Douglas T. , Miggin Sinéad M. 
Published: September 2010

AbstractThere is limited insight into the mechanisms involved in the counterregulation of TLR. Given the important role of TLR3/TIR domain‐containing adaptor‐inducing IFN‐β (TRIF)‐dependent signalling in innate immunity, novel insights into its modulation is of significance in the context of many physiological and pathological processes. Herein, we sought to perform analysis to definitively assign a mechanistic role for MyD88 adaptor‐like (Mal), an activator of TLR2/4 signalling, in the negative regulation of TLR3/TRIF signalling. Biochemical and functional analysis demonstrates that Mal negatively regulates TLR3, but not TLR4, mediated IFN‐β production. Co‐immunoprecipitation experiments demonstrate that Mal associates with IRF7 (IRF, IFN regulatory factor), not IRF3, and Mal specifically blocks IRF7 activation. In doing so, Mal impedes TLR3 ligand‐induced IFN‐β induction. Interestingly, Mal does not affect the induction of IL‐6 and TNF‐α upon TLR3 ligand engagement. Together, these data show that the TLR adaptor Mal interacts with IRF7 and, in doing so, impairs IFN‐β induction through the positive regulatory domains I‐III enhancer element of the IFN‐β gene following poly(I:C) stimulation. Our findings offer a new mechanistic insight into TLR3/TRIF signalling through a hitherto unknown mechanism whereby Mal inhibits poly(I:C)‐induced IRF7 activation and concomitant IFN‐β production. Thus, Mal is essential in restricting TLR3 signalling thereby protecting the host from unwanted immunopathologies associated with excessive IFN‐β production.
The biology of myeloid‐derived suppressor cells: The blessing and the curse of morphological and functional heterogeneity
Authors: Youn Je‐In , Gabrilovich Dmitry I. 
Published: September 2010

AbstractMyeloid‐derived suppressor cells (MDSC) play an important role in the cellular network regulating immune responses in cancer, chronic infectious diseases, autoimmunity, and in other pathological conditions. Morphological, phenotypic and functional heterogeneity is a hallmark of MDSC. This heterogeneity demonstrates the plasticity of this immune suppressive myeloid compartment, and shows how various tumors and infectious agents can have similar biological effects on myeloid cells despite the differences in the factors that they produce to influence the immune system; however, such a heterogeneity creates ambiguity in the definition of MDSC as well as confusion regarding the origin and fate of these cells. In this review, we will discuss recent findings that help to better clarify these issues and to determine the place of MDSC within the myeloid cell lineage.
Antioxidant activity of blackcurrant seeds extract and rosemary extracts in soybean oil
Authors: Samotyja Urszula , Małecka Maria 
Published: September 2010

AbstractThe objective of this research was to investigate the antioxidative properties of extract from blackcurrant seeds (BCSs) and commercially available rosemary extracts (Stabiloton OS, oil‐soluble and WS, water soluble) in soybean oil (SO). The antioxidant activity of plant extracts was compared with those of α‐tocopherol and butylated hydroxytoluene (BHT). The results of present research reveal differentiation of action of investigated extracts toward primary (peroxide value (PV), conjugated dienes (CDs)) and secondary (measured as anisidine value (AV), hexanal) oxidation products in SO. WS and OS rosemary extracts show high efficiency in delaying primary and secondary oxidative changes. BCSs extract markedly retards oxidation, nevertheless its activity falls down with formation and succeeding deterioration of primary products. Although the use of BCSs, residues of fruit processing, as a source of antioxidants would be reasonable because of economic and environmental reasons, it may be limited by low activity toward secondary oxidation products in certain lipid substrates. Taking primary oxidative changes into consideration, all extracts studied perform better than used standard antioxidants – BHT and α‐tocopherol.
Solid‐Phase Synthesis of Phosphoramidate‐Linked Glycopeptides (Eur. J. Org. Chem. 26/2010)
Authors: Jaradat Da'san M. M. , Hamouda Houda , Hackenberger Christian P. R. 
Published: September 2010

AbstractThe cover picture shows the synthesis of a novel class of carbohydrate–peptide conjugates, which proceeds by a Staudinger‐phosphite reaction of glycosyl azides with phosphitylated peptides. The synthetic protocol is easy to perform, as the carbohydrate has to be added to the solid‐supported peptide before the resulting glycoconjugate is cleaved from the resin by TFA treatment. The obtained phosphoramidate‐linked glycopeptides derived from the dimethyl phosphitylated peptides are stable under acidic and physiological conditions. Details are discussed in the article by C. P. R. Hackenberger et al. on p. 5004 ff. The authors thank Nico Zapke and the “cowema.com medienlabor” for their contribution in designing the cover picture.
Late Mesozoic‐Cenozoic exhumation history of the Lesser Hinggan Mountains, NE China, revealed by fission track thermochronology
Authors: Li Xiao‐Ming , Gong Gui‐Lun 
Published: September 2010

AbstractThis study uses zircon and apatite fission‐track (FT) analyses to reveal the exhumation history of the granitoid samples collected from the Lesser Hinggan Mountains, northeast China. A southeast to northwest transect across the Lesser Hinggan Mountains yielded zircon FT ages between 89.8 ± 5.7 and 100.4 ± 8.6 Ma, and apatite FT ages between 50.6 ± 13.8 and 74.3 ± 4.5 Ma with mean track lengths between 11.7 ± 2.0 and 12.8 ± 1.7 µm. FT results and modelling identify three stages in sample cooling history spanning the late Mesozoic and Cenozoic eras. Stage one records rapid cooling from the closure temperature of zircon FT to the high temperature part of the apatite FT partial annealing zone (∼210–110 °C) during ca. 95 to 65 Ma. Stage two records a period of relative slow cooling (∼110–60 °C) taking place between ca. 65 and 20 Ma, suggesting that the granitoids had been exhumed to the depth of ∼1−2 km. Final stage cooling (60–20 °C) occurred since the Miocene at an accelerated rate bringing the sampled rocks to the Earth's surface. The maximum exhumation is more than 5 km under a steady‐state geothermal gradient of 35 °C/km. Integrated with the tectonic setting, this exhumation is possibly led by the Pacific Plate subduction combined with intracontinental orogeny associated with asthenospheric upwelling. Copyright © 2010 John Wiley & Sons, Ltd.
Collagen XXVIII is a distinctive component of the peripheral nervous system nodes of ranvier and surrounds nonmyelinating glial cells
Authors: Grimal Sophie , Puech Sylvie , Wagener Raimund , Ventéo Stéphanie , Carroll Patrick , Fichard‐Carroll Agnès 
Published: September 2010

AbstractGrowing evidence indicates that collagens perform crucial functions during the development and organization of the nervous system. Collagen XXVIII is a recently discovered collagen almost exclusively expressed in the peripheral nervous system (PNS). In this study, we show that this collagen is associated with nonmyelinated regions of the PNS. With the notable exception of type II terminal Schwann cell in the hairy skin, collagen XXVIII surrounds all nonmyelinating glial cells studied. This includes satellite glial cells of the dorsal root ganglia, terminal Schwann cells type I around mechanoceptors in the skin, terminal Schwann cells around proprioceptors in the muscle spindle or at the neuromuscular junction and olfactory ensheathing cells. Collagen XXVIII is also detected at nodes of Ranvier where the myelin sheath of myelinated fibers is interrupted and is thus a distinctive component of the PNS nodal gap. The correlation between the absence of myelin and the presence of collagen XXVIII is confirmed in a mouse model of Charcot‐Marie‐Tooth characterized by dysmyelinated nerve fibers, in which enhancement of collagen XXVIII labeling is observed. © 2010 Wiley‐Liss, Inc.
BCL6 gene rearrangement and protein expression are associated with large cell presentation of extranodal marginal zone B‐cell lymphoma of mucosa‐associated lymphoid tissue
Authors: Flossbach Lucia , Antoneag Elias , Buck Michaela , Siebert Reiner , Mattfeldt Torsten , Möller Peter , Barth Thomas F.E. 
Published: September 2010

AbstractExtranodal marginal zone B‐cell lymphoma of mucosa‐associated lymphoid tissue (MALT lymphoma) is an indolent B‐cell lymphoma, which is often localized in the stomach. It is characterized by typical morphology, immunology, cytogenetics and expression profile. The coexistence of a large B‐cell lymphoma and a MALT lymphoma in the gastrointestinal tract is defined as a composite lymphoma (ComL) and, as we have previously shown, is almost always the consequence of secondary transformation of MALT lymphoma. Here, we have analyzed a panel of seven MALT lymphomas, seven ComL and thirteen large cell variants of marginal zone B‐cell lymphomas (MZBL) using FISH for the detection of rearrangements of IGH, MALT1, BCL6, BCL10 and FOXP1 and immunohistochemistry for Bcl6, Bcl10 and FoxP1. Translocations involving IGH were found in 10/27 lymphomas including two cases with IGH‐BCL6 fusion and one with IGH‐BCL10 fusion; in 7/10 cases, the translocation partner was not identified. Bcl10 and FoxP1 protein expression was heterogeneous throughout the series. Genetic rearrangements of BCL6 and Bcl6 protein expression were found almost exclusively in the large cell components of the ComL and the large cell extranodal MZBL (p = 0.2093 and p = 0.0261, respectively). These findings suggest Bcl6 as a marker for transformation of MALT lymphoma.
Overexpression of eIF5A‐2 is an adverse prognostic marker of survival in stage I non–small cell lung cancer patients
Authors: He Li‐Ru , Zhao Hong‐Yun , Li Bin‐Kui , Liu Yan‐Hui , Liu Meng‐Zhong , Guan Xin‐Yuan , Bian Xiu‐Wu , Zeng Yi‐Xin , Xie Dan 
Published: September 2010

AbstractWe have previously isolated an oncogene EIF5A2 (eukaryotic initiation factor 5A2) from a frequently amplified region at 3q of a primary ovarian cancer cell line, and demonstrated its impact on prognosis in human ovarian cancer. Amplification of chromosome 3q has also been detected frequently in non–small cell lung cancer (NSCLC), however, abnormalities of EIF5A2 and its clinicopathologic significance in NSCLC haven't been studied. In our study, the methods of immunohistochemistry and fluorescence in situ hybridization were utilized to examine protein expression and amplification of EIF5A2 in 248 surgically resected NSCLCs (learning cohort) and another validation cohort of 120 stage I NSCLC patients. Overexpression and amplification of EIF5A2 was detected informatively in 48.7% and 13.7% of NSCLCs in learning cohort, 33.3% and 6.0% of NSCLCs in validation cohort. Overexpression of eIF5A‐2 was found to correlate with gene amplification, increased cell proliferation and advanced T stage. In learning cohort, eIF5A‐2 expression was evaluated as a strong prognostic factor on disease‐specific survival, but in subgroup analyses, it only retained its stratified significance in stage I set (Hazards ratio = 2.799, p = 0.001). In validation cohort, the impact of eIF5A‐2 expression on survival in stage I NSCLC patients was also observed (Hazard ratio = 2.097, p = 0.014). Our findings suggested that overexpression of eIF5A‐2 correlates with local invasion of NSCLC, and might serve as an adverse prognostic marker of survival for stage I NSCLC patients.
Flashing light signaling circuit in sponges: Endogenous light generation after tissue ablation in Suberites domuncula
Authors: Wiens Matthias , Wang Xiaohong , Unger Andreas , Schröder Heinz C. , Grebenjuk Vladislav A. , Pisignano Dario , Jochum Klaus P. , Müller Werner E.G. 
Published: September 2010

AbstractThe skeleton of siliceous sponges (phylum Porifera: classes Demospongiae and Hexactinellida), composed of tightly interacting spicules that assemble to a genetically fixed scaffold, is formed of bio‐silica. This inorganic framework with the quality of quartz glass has been shown to operate as light waveguide in vitro and very likely has a similar function in vivo. Furthermore, the molecular toolkit for endogenous light generation (luciferase) and light/photon harvesting (cryptochrome) has been identified in the demosponge Suberites domuncula. These three components of a light signaling system, spicules—luciferase—cryptochrome, are concentrated in the surface layers (cortex) of the poriferan body. Specimens from which this cortex has been removed/ablated do not emit light. However, with regeneration and reconstitution of the cortex the animals re‐gain the capacity to flash light. This newly discovered characteristic of sponges to generate light prompted us to investigate the genetic basis for the endogenous light signaling system. As a potential transcription factor involved in the expression of luciferase and cryptochrome, a SOX‐related protein has been identified. In dark‐adapted animals or in tissue from below the cortex region, the medulla, no gene or protein expression of SOX‐related protein, luciferase, and cryptochrome could be detected. However, during the regeneration of the cortex, a stage‐specific expression pattern was recorded: SOX‐related protein > luciferase > cryptochrome. We conclude that a flashing light signaling circuit exists, which might control the retinoic acid‐induced differentiation of stem cells into pulsating and contracting sponge cells, that is, pinacocytes and myocytes. J. Cell. Biochem. 111: 1377–1389, 2010. © 2010 Wiley‐Liss, Inc.
PTEN suppression promotes neurite development exclusively in differentiating PC12 cells via PI3‐kinase and MAP kinase signaling
Authors: Jia Lintao , Ji Shaoping , Maillet Jean‐Christian , Zhang Xia 
Published: September 2010

AbstractAs a dual‐specificity phosphatase catalyzing the dephosphorylation of phosphatidylinositols and protein substrates, PTEN is critically involved in the nervous system development. However, the regulatory role of PTEN in neurite outgrowth is still controversial, and the downstream signaling events remain elusive. Here, we show that PTEN knockdown promoted the proliferation and survival but not the neurite outgrowth of rat pheochromocytoma PC12 cells when exposed to nerve growth factor (NGF). In contrast, selective PTEN silencing in differentiating PC12 cells that express nestin significantly facilitated neurite elongation. Elevated Akt and Erk1/2 phosphorylation was involved in accelerated NGF‐induced neurite development of PC12 cells following PTEN knockdown. Discriminated roles of the lipid phosphatase and protein phosphatase activities of PTEN in neurite development, as well as the detailed molecular profiles affected by these phosphatase activities, were defined by restored expression of a lipid phosphatase‐deficient PTEN mutant following endogenous PTEN silencing in PC12 cells. Our study suggests an overall inhibitory effect of PTEN in neurite development reconciled by a probably indispensable role of this phosphatase in the initiation of PC12 cell differentiation. J. Cell. Biochem. 111: 1390–1400, 2010. © 2010 Wiley‐Liss, Inc.
Changes in cell adhesivity and cytoskeleton‐related proteins during imatinib‐induced apoptosis of leukemic JURL‐MK1 cells
Authors: Kuželová K. , Pluskalová M. , Grebeňová D. , Pavlásková K. , Halada P. , Hrkal Z. 
Published: September 2010

AbstractThe fusion protein Bcr–Abl, which is the molecular cause of chronic myelogenous leukemia (CML) interacts in multiple points with signaling pathways regulating the cellular adhesivity and cytoskeleton architecture and dynamics. We explored the effects of imatinib mesylate, an inhibitor of Bcr–Abl protein used in front‐line CML therapy, on the adhesivity of JURL‐MK1 cells to fibronectin and searched for underlying changes in the cell proteome. As imatinib induces apoptosis of JURL‐MK1 cells, we used three different caspase inhibitors to discriminate between direct consequences of Bcr–Abl inhibition and secondary changes related to the apoptosis. Imatinib treatment caused a transient increase in JURL‐MK1 cell adhesivity to fibronectin, possibly due to the switch off of Bcr–Abl activity. Subsequently, we observed a number of changes including a decrease in cell adhesivity, F‐actin decomposition, reduction of integrin β1, CD44, and paxillin expression levels and a marked increase in cofilin phophorylation at Ser3. These events were generally related to the proceeding apoptosis but they differed in their sensitivity to the individual caspase inhibitors. J. Cell. Biochem. 111: 1413–1425, 2010. © 2010 Wiley‐Liss, Inc.
Identification of new modulators and protein alterations in non‐apoptotic programmed cell death
Authors: Sperandio Sabina , Poksay Karen S. , Schilling Birgit , Crippen Danielle , Gibson Bradford W. , Bredesen Dale E. 
Published: September 2010

AbstractThis study describes the first proteomic analysis of paraptosis—a non‐apoptotic form of programmed cell death. As with apoptosis, the first description of paraptosis was based on morphological criteria. Since there are no known markers for paraptosis, the purpose of this study was to dissect changes in the proteome profile occurring during paraptosis. Using one‐ and two‐dimensional SDS–PAGE, Western analysis, and mass spectrometry, we show that during paraptosis, alterations occur mainly in cytoskeletal proteins, signal transduction proteins, mitochondrial proteins, and some metabolic proteins. We also report the identification of: (1) a paraptosis inhibitor, phosphatidylethanolamine binding protein (PEBP‐1), and (2) a candidate mediator of paraptosis, prohibitin. Identification of specific paraptotic changes will ultimately lead to tools to detect this type of programmed cell death in in vivo systems and allow for its further characterization. J. Cell. Biochem. 111: 1401–1412, 2010. © 2010 Wiley‐Liss, Inc.