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Glypican-3 (GPC-3) is a heparin sulfate proteoglycan located extracellularly and anchored to the cell membrane of transformed hepatocytes. GPC-3 is not expressed in normal or cirrhotic liver tissue but is overexpressed in hepatocellular carcinoma (HCC). Because of this, GPC-3 is one of the most important emerging immunotargets for treatment and as an early detection marker of HCC. To determine if GPC-3 domains associated with serum small extracellular vesicles (sEVs) could be used as an HCC diagnostic marker, we predicted in silico GPC-3 structural properties and tested for the presence of its full-length form and/or cleaved domains in serum sEVs isolated from patients with HCC. Structural analysis revealed that the Furin cleavage site of GPC-3 is exposed and readily accessible, suggesting the facilitation of GPC-3 cleavage events. Upon isolation of sEVs from both hepatocytes, culture media and serum of patients with HCC were studied for GPC-3 content. This data suggests that Furin-dependent GPC-3 cleaved domains could be a powerful tool for detection of initial stages of HCC and serve as a predictor for disease prognosis.

Bruno A, Alessi M, Soresi S, et al. J Inflamm Res. 2011;4:51–59. The Editor and Publisher of Journal of Inflammation Research wish to retract the published article. Concerns were raised regarding the duplication of images in Figure 3 describing leptin receptor expression with those from an article published by the authors several years previously describing muscarinic receptor expression. Specifically: Figure 3A, Leptin receptor expression, Smokers, appears to have been duplicated with Figure 2 panel M3 COPD, for the expression of muscarinic receptors. Figure 3D, Leptin expression, Smokers, appears to have been duplicated with Figure 2 panel M1 Smokers, for the expression of muscarinic receptors. Figure 3A, Leptin receptor expression, Smokers, appears to share duplicated elements with Figure 3D, Leptin expression, Smokers. The authors did not respond to our queries and the Editor advised for the article to be retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Andreina Bruno1, Marinella Alessi2, Simona Soresi2, Anna Bonanno1, Loredana Riccobono1, Angela Marina Montalbano1, Giusy Daniela Albano1, Mark Gjomarkaj1, Mirella Profita11Institute of Biomedicine and Molecular Immunology, Italian National Research Council, Palermo, Italy; 2Dipartimento Biomedico di Biomedicina Interna e Specialistica, University Palermo, ItalyBackground: Leptin, a hormone produced mainly by adipose tissue, regulates food intake and energy expenditure. It is involved in inflammatory diseases such as chronic obstructive pulmonary disease (COPD) and its deficiency is associated with increased susceptibility to the infection. The leptin receptor is expressed in the lung and in the neutrophils.Methods: We measured the levels of leptin, tumor necrosis factor alpha (TNF-a) and soluble form of intercellular adhesion molecule-1 (sICAM-1) in sputum and plasma from 27 smoker and former smoker patients with stable COPD using ELISA methods. Further we analyzed leptin and its receptor expression in sputum cells from 16 COPD patients using immunocytochemistry.Results: In plasma of COPD patients, leptin was inversely correlated with TNF-a and positively correlated with the patient weight, whereas the levels of sICAM-1 were positively correlated with TNF-a. In sputum of COPD patients leptin levels were correlated with forced expiratory volume in 1 second/forced vitality capacity. Additionally, increased levels of sputum leptin and TNF-a were observed in COPD former smokers rather than smokers. Further the expression of leptin receptor in sputum neutrophils was significantly higher in COPD former smokers than in smokers, and the expression of leptin and its receptor was positively correlated in neutrophils of COPD former smokers.Conclusion: Our findings suggest a role of leptin in the local and systemic inflammation of COPD and, taking into account the involvement of neutrophils in this inflammatory disease, describe a novel aspect of the leptin/leptin receptor pathway in the regulation of host defense after smoking cessation.Keywords: COPD, smokers, inflammation, leptin, neutrophils

Interactions in internet discussion forums provide data on a variety of social issues. Forums are often a meeting-place for people affected by a given problem; in fact, cyberspace has become a framework of reference in the study of such interaction. The ready availability of the participants’ discourse, and the textual nature of the forum's contents, facilitate the use of qualitative methodologies. The present article analyses harassment in internet forums in order to study its subjective implications, specially those aspects related to the formulation of participants' identities. The article also explores the organizational implications of harassment, focusing on its structural and functional dimensions.

This article focuses on the ways of generation of media discourse about management and labour organizations. This discourse plays a central role in the social construction of organizational criterions and practices as well as the definition of work health indicators for all the implicated social groups in the labour phenomenon. His common justification is the intention of educating and spreading mass knowledge. Both are conducting to produce a high homogenous view about how to do with persons in organizations. Our analysis uncovers a fundamental interpretative repertory: systemic conceptualization of organizations and the implications for the persons at work subjectivity in a time defined for a erased labour class. This article focusses on the ways in which work and management are discursively represented in the media. Media discourse plays an important part in the social construction, by various interested parties, of well-being at work. The basic rationale of the discourse is, it claims, educational. That leads, we argue, to a very undifferentiated understanding of how personnel should be managed. We identify a pervasive interpretative repertoire: the systematic view of organisations, and its implications for the subjectivity of employees, in an era defined by the diminishing certainty of working class identity in contemporary social structure.

The success of asteroseismology in characterising G-K giants has motivated the extension of the same techniques to stars after the central He-burning and M-giants. The latter have been usually studied only as radial pulsators; the presence, however, of fine-structure in the period-luminosity diagram of red variables in the Magellanic Clouds could result from the presence of non-radial oscillations, offering the potential of observational indexes based on non-radial oscillations also for luminous red giants. We present here the results of a first approach aiming to identify the origin of the sub-ridges in the sequence A of the LMC red variables.

The intrinsic variability of luminous red giants is an observable providing important information about stellar structure and evolution. Our aim is to provide a solid theoretical background to the wide amount of data coming from present and future variability surveys. We present here the first comparison between long period variables in the LMC (from OGLE-III) and our grid of pulsation models computed for a wide range of stellar parameters and input physics.

CoRoT and Kepler provided a precious by-product: a number of eclipsing binaries containing variable stars and, among these, non-radial pulsators. This providential occurrence allows combining independent information from two different phenomena whose synergy yields scientific results well beyond those from the single sources. In particular, the analysis of pulsations in eclipsing binary components throws light on the internal structure of the pulsating star, on the system evolution, and on the role of tidal forces in exciting the oscillations. The case study of the Kepler target KIC 3858884 is illustrative of the difficulties of analysis and of the achievements in this rapidly developing field.

The efficiency of convection in stars affects many aspects of their evolution and remains one of the key-open questions in stellar modelling. In particular, the size of the mixed core in core-He-burning low-mass stars is still uncertain and impacts the lifetime of this evolutionary phase and, e.g., the C/O profile in white dwarfs. One of the known observables related to the Horizontal Branch (HB) and Asymptotic Giant Branch (AGB) evolution is the AGB bump. Its luminosity depends on the position in mass of the helium-burning shell at its first ignition, that is affected by the extension of the central mixed region. In this preliminary work we show how various assumptions on near-core mixing and on the thermal stratification in the overshooting region affect the luminosity of the AGB bump, as well as the period spacing of gravity modes in core-He-burning models.

Clusters are excellent test benches for verification and improvement of stellar evolution theory. The recent detection of solar-like oscillations in G-K giants in the open cluster NGC6819 with Kepler provides us with independent constraints on the masses and radii of stars on the red giant branch, as well as on the distance to clusters and their ages. We present, for NGC6819, evolutionary models by considering rotation-induced mixing ; and the theoretical low-l frequencies of our stellar models.

A precise characterisation of the red giants in the seismology fields of the CoRoT satellite is a prerequisite for further in-depth seismic modelling. The optical spectra obtained for 19 targets have been used to accurately estimate their fundamental parameters and chemical composition. The extent of internal mixing is also investigated through the abundances of Li, CNO and Na (as well as 12C/13C in a few cases).

CoRoT and Kepler observations of red giants reveal rich spectra of non-radial solar-like oscillations allowing to probe their internal structure. We compare the theoretical spectrum of two red giants in the same region of the HR diagram but in different evolutionary phases. We present here our first results on the inertia, lifetimes and amplitudes of the oscillations and discuss the differences between the two stars.

The Liège International Astrophysical Colloquia (LIAC) started in 1949 at the initiative of Pol Swings, and they were continued with the efforts of Paul Ledoux and Marcel Migeotte. They were organized each year except for those when a General Assembly of the IAU took place. About sixty years after the first edition we are now at the 40th edition of the series.

Solar-like oscillating giants observed by the space-borne satellites CoRoT and Kepler can be used as key tracers of stellar populations in the Milky Way. When combined with additional photometric/spectroscopic constraints, the pulsation spectra of solar-like oscillating giant stars not only reveal their radii, and hence distances, but also provide well-constrained estimates of their masses, which can be used as proxies for the ages of these evolved stars. In this contribution we provide supplementary material to the comparison we presented in Miglio et al. (2013) between populations of giants observed by CoRoT in the fields designated LRc01 and LRa01.

Since the detection of non-radial solar-like oscillation modes in red giants with the CoRoT satellite, the interest in the asteroseismic properties of red giants and the link with their global properties and internal structure is increasing. Moreover, more and more precise data are being collected with the space-based telescopes CoRoT and Kepler. Particularly relevant has been the detection of mixed modes in a large number of G-K red giants. In this contribution we discuss the potential of these dipole mixed modes to provide information on core extra-mixing and transport of angular momentum.

Abstract Background Chromosome changes in the bone marrow (BM) of patients with persistent cytopenia are often considered diagnostic for a myelodysplastic syndrome (MDS). Comprehensive cytogenetic evaluations may give evidence of the real pathogenetic role of these changes in cases with cytopenia without morphological signs of MDS. Results Chromosome anomalies were found in the BM of three patients, without any morphological evidence of MDS: 1) an acquired complex rearrangement of chromosome 21 in a boy with severe aplastic anaemia (SAA); the rearrangement caused the loss of exons 2–8 of the RUNX1 gene with subsequent hypoexpression. 2) a constitutional complex rearrangement of chromosome 21 in a girl with congenital thrombocytopenia; the rearrangement led to RUNX1 disruption and hypoexpression. 3) an acquired paracentric inversion of chromosome 1, in which two regions at the breakpoints were shown to be lost, in a boy with aplastic anaemia; the MPL gene, localized in chromosome 1 short arms was not mutated neither disrupted, but its expression was severely reduced: we postulate that the aplastic anaemia was due to position effects acting both in cis and in trans, and causing Congenital Amegakaryocytic Thrombocytopenia (CAMT). Conclusions A clonal anomaly in BM does not imply per se a diagnosis of MDS: a subgroup of BM hypoplastic disorders is directly due to chromosome structural anomalies with effects on specific genes, as was the case of RUNX1 and MPL in the patients here reported with diagnosis of SAA, thrombocytopenia, and CAMT. The anomaly may be either acquired or constitutional, and it may act by deletion/disruption of the gene, or by position effects. Full cytogenetic investigations, including a-CGH, should always be part of the diagnostic evaluation of patients with BM aplasia/hypoplasia and peripheral cytopenias.

Abstract Background DNA vaccines represent promising therapeutic strategies in autoimmune disorders such as multiple sclerosis (MS). However, the precise mechanisms by which DNA vaccines induce immune regulation remain largely unknown. Here, we aimed to expand previous knowledge existing on the mechanisms of action of DNA vaccines in the animal model of MS, experimental autoimmune encephalomyelitis (EAE), by treating EAE mice with a DNA vaccine encoding the myelin oligodendrocyte glycoprotein (MOG), and exploring the therapeutic effects on the disease-induced inflammatory and neurodegenerative changes. Methods EAE was induced in C57BL6/J mice by immunization with MOG35-55 peptide. Mice were intramuscularly treated with a MOG-DNA vaccine or vehicle in prophylactic and therapeutic approaches. Histological studies were performed in central nervous system (CNS) tissue. Cytokine production and regulatory T cell (Treg) quantification were achieved by flow cytometry. Gene expression patterns were determined using microarrays, and the main findings were validated by real-time PCR. Results MOG-DNA treatment reduced the clinical and histopathological signs of EAE when administered in both prophylactic and therapeutic settings. Suppression of clinical EAE was associated with dampening of antigen (Ag)-specific proinflammatory Th1 and Th17 immune responses and, interestingly, expansion of Treg in the periphery and upregulation in the CNS of genes encoding neurotrophic factors and proteins involved in remyelination. Conclusions These results suggest for the first time that the beneficial effects of DNA vaccines in EAE are not limited to anti-inflammatory mechanisms, and DNA vaccines may also exert positive effects through hitherto unknown neuroprotective mechanisms.

The Asiago Red Clump Spectroscopic Survey (ARCS) is an ongoing survey that provides atmospheric parameters, distances and space velocities of a well selected sample of Red Clump stars distributed along the celestial equator. We used the ARCS catalog for a preliminary investigation of the Galactic disk in the Solar Neighborhood, in particular we focused on detection and characterization of moving groups.

The detection of radial and non-radial solar-like oscillations in thousands of G-K giants with CoRoT and Kepler is paving the road for detailed studies of stellar populations in the Galaxy. The available average seismic constraints allow a precise and largely model-independent determination of stellar radii (hence distances) and masses. We here briefly report on the distance determination of thousands of giants in the CoRoT and Kepler fields of view.

Abstract Background The results of cytogenetic investigations on unbalanced chromosome anomalies, both constitutional and acquired, were largely improved by comparative genomic hybridization on microarray (a-CGH), but in mosaicism the ability of a-CGH to reliably detect imbalances is not yet well established. This problem of sensitivity is even more relevant in acquired mosaicism in neoplastic diseases, where cells carrying acquired imbalances coexist with normal cells, in particular when the proportion of abnormal cells may be low. We constructed a synthetic mosaicism by mixing the DNA of three patients carrying altogether seven chromosome imbalances with normal sex-matched DNA. Dilutions were prepared mimicking 5%, 6%, 7%, 8%, 10% and 15% levels of mosaicism. Oligomer-based a-CGH (244 K whole-genome system) was applied on the patients' DNA and customized slides designed around the regions of imbalance were used for the synthetic mosaics. Results and conclusions The a-CGH on the synthetic mosaics proved to be able to detect as low as 8% abnormal cells in the tissue examined. Although in our experiment some regions of imbalances escaped to be revealed at this level, and were detected only at 10-15% level, it should be remarked that these ones were the smallest analyzed, and that the imbalances recurrent as clonal anomalies in cancer and leukaemia are similar in size to those revealed at 8% level.

We show that there is only one natural Turing-degree invariant, analytic equivalence relation with ℵ1 many equivalence classes: the equivalence X ≡ω1 Y ⇐⇒ ωX 1 = ωY 1 . More precisely, under PD + ¬CH, we show that every Turing-degree invariant, analytic equivalence relation with ℵ1 many equivalence classes is equal to ≡ω1 on a Turing cone. [ABSTRACT FROM AUTHOR]

This article shows how the travel accounts of three thirteenth-century Franciscan friars provide a window into intercultural communications of the medieval world. The three accounts were written by John of Plano Carpini (1245-47), William of Rubruck (1253-55), and John of Montecorvino (1289). Each of the friars traveled from Europe to the Mongol Empire. The article has two themes: first, how the friars' encounters with new lands, peoples, and cultures prompted them to reconsider, but ultimately not recast, their vocational identities; second, how their participation in long-distance networks reinforced their assumptions about Christianity and human nature. [ABSTRACT FROM AUTHOR]

Analysis of eclipsing binaries containing non-radial pulsators allows i) combining two different and independent sources of information on the internal structure and evolutionary status of the components and ii) studying the effects of tidal forces on pulsations. KIC 3858884 is a bright Kepler target whose light curve shows deep eclipses, complex pulsation patterns with pulsation frequencies typical of δ Sct, and a highly eccentric orbit. We present the result of the analysis of Kepler photometry and of high resolution phaseresolved spectroscopy. Spectroscopy yielded both the radial velocity curves and, after spectral disentangling, the primary-component effective temperature and metallicity, and line-of-sight projected rotational velocities. The Kepler light curve was analyzed with an iterative procedure that was devised to disentangle eclipses from pulsations and takes the visibility of the pulsating star into account during eclipses. The search for the best set of binary parameters was performed by combining the synthetic light curve models with a genetic minimization algorithm, which yielded a robust and accurate determination of the system parameters. The binary components have very similar masses (1.88 and 1.86 M☉) and effective temperatures (6800 and 6600 K), but different radii (3.45 and 3.05 R☉). The comparison with the theoretical models showed a somewhat different evolutionary status of the components and the need to introduce overshooting in the models. The pulsation analysis indicates the hybrid nature of the pulsating (secondary) component, where the corresponding high order g-modes might be excited by an intrinsic mechanism or by tidal forces. [ABSTRACT FROM AUTHOR]

BACKGROUND: The CD34+ cell content is a predictive factor for engraftment and survival after umbilical cord blood (UCB) transplantation. The high variability in the CD34 assay results in different recommended cell doses for infusion across transplant centers and also limits the clinical utility of the CD34+ cell counts provided by cord blood banks (CBBs). This bi-institutional study was intended to understand the sources of this variability. STUDY DESIGN AND METHODS: The level of CD34 agreement between the University of Minnesota (UM) and the Madrid CBB (MCBB) was evaluated on 50 UCB units before and after cryopreservation. Two cryopreserved vials per unit were thawed and processed at both laboratories. Dual-platform ISHAGE-based flow cytometry was used for CD34 enumeration. RESULTS: Postthaw nucleated cell recoveries were similar. However, whereas CD34+ cell enumeration before freezing was 0.35 ± 0.22 percent, the results after thawing were 0.98 ± 0.65 and 0.57 ± 0.39 percent at UM and MCBB, respectively. Bland-Altman plots analysis ruled out the interchangeability of MCBB and UM CD34 values. Differences in the initial cell acquisition settings accounted for most of the CD34 discrepancy, which was no longer present after normalization of the forward scatter threshold for cell acquisition. CONCLUSIONS: The standardization of CD34+ cell enumeration by flow cytometry is strongly reliant on a consistent initial cell acquisition procedure. The interlaboratory variation can be minimized by using frozen cell aliquots as reference samples. Both requisites should be considered for CD34 testing and UCB unit selection by regulatory institutions involved with cord blood banking and transplantation. [ABSTRACT FROM AUTHOR]