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  • 1
    Electronic Resource
    Electronic Resource
    Chronicity rate of hepatitis B virus infection in the families of 60 hepatitis B surface antigen positive chronic carrier children: Role of horizontal transmission (1992)
    Springer
    European journal of pediatrics 151 (1992), S. 188-191 
    Details
    ISSN: 1432-1076
    Keywords: Chronic hepatitis B ; Familial clustering ; Horizontal transmission ; Age of infection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It is known that the 5%–10% of adults infected with hepatitis B virus (HBV) develop a chronic infection and that HBV infection acquired at birth by an hepatitis B surface antigen (HBsAg)/hepatitis B “e” antigen (HBeAg)-positive mother almost invariably leads to chronic infection. Little information is, however, available about the risk of HBV infection acquired in childhood becoming chronic. We have, therefore, studied the chronicity rate of HBV infection in the families of 60 consecutive HBsAg-positive chronic carrier children. Of parents 81.5% and 78.6% of children showed serological evidence of past or ongoing HBV infection. The chronicity rate was significantly higher among children (73.4%) than parents (35.6%). Such a high chronicity rate in these children was not correlated with vertical transmission, since this was reported in only 1.7% of them. It is noteworthy that the chronicity rate of HBV infection was not significantly different between children of HBsAg-positive mothers and those in whom infection must have been horizontally transmitted because their mothers were HBsAg-negative. Although the families studied represent a selected sample and the role of genetic factors could not be excluded, our results seem to show that the most important factor in determining the outcome of infection is the acquisition of hepatitis B during childhood.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01954381
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    Paper (German National Licenses)
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  • 2
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    Pax5 loss imposes a reversible differentiation block in B-progenitor acute lymphoblastic leukemia [Research Papers] (2014)
    Cold Spring Harbor Laboratory Press
    Details
    Publication Date: 2014-06-18
    Description: Loss-of-function mutations in hematopoietic transcription factors including PAX5 occur in most cases of B-progenitor acute lymphoblastic leukemia (B-ALL), a disease characterized by the accumulation of undifferentiated lymphoblasts. Although PAX5 mutation is a critical driver of B-ALL development in mice and humans, it remains unclear how its loss contributes to leukemogenesis and whether ongoing PAX5 deficiency is required for B-ALL maintenance. Here we used transgenic RNAi to reversibly suppress endogenous Pax5 expression in the hematopoietic compartment of mice, which cooperates with activated signal transducer and activator of transcription 5 (STAT5) to induce B-ALL. In this model, restoring endogenous Pax5 expression in established B-ALL triggers immunophenotypic maturation and durable disease remission by engaging a transcriptional program reminiscent of normal B-cell differentiation. Notably, even brief Pax5 restoration in B-ALL cells causes rapid cell cycle exit and disables their leukemia-initiating capacity. These and similar findings in human B-ALL cell lines establish that Pax5 hypomorphism promotes B-ALL self-renewal by impairing a differentiation program that can be re-engaged despite the presence of additional oncogenic lesions. Our results establish a causal relationship between the hallmark genetic and phenotypic features of B-ALL and suggest that engaging the latent differentiation potential of B-ALL cells may provide new therapeutic entry points.
    Print ISSN: 0890-9369
    Topics: Biology
    Published by Cold Spring Harbor Laboratory Press
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  • 3
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    Notch pathway activation targets AML-initiating cell homeostasis and differentiation (2013)
    Rockefeller University Press
    Details
    Publication Date: 2013-02-12
    Description: Notch signaling pathway activation is known to contribute to the pathogenesis of a spectrum of human malignancies, including T cell leukemia. However, recent studies have implicated the Notch pathway as a tumor suppressor in myeloproliferative neoplasms and several solid tumors. Here we report a novel tumor suppressor role for Notch signaling in acute myeloid leukemia (AML) and demonstrate that Notch pathway activation could represent a therapeutic strategy in this disease. We show that Notch signaling is silenced in human AML samples, as well as in AML-initiating cells in an animal model of the disease. In vivo activation of Notch signaling using genetic Notch gain of function models or in vitro using synthetic Notch ligand induces rapid cell cycle arrest, differentiation, and apoptosis of AML-initiating cells. Moreover, we demonstrate that Notch inactivation cooperates in vivo with loss of the myeloid tumor suppressor Tet2 to induce AML-like disease. These data demonstrate a novel tumor suppressor role for Notch signaling in AML and elucidate the potential therapeutic use of Notch receptor agonists in the treatment of this devastating leukemia.
    Print ISSN: 0022-1007
    Electronic ISSN: 1540-9538
    Topics: Medicine
    Published by Rockefeller University Press
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  • 4
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    Cohesin loss alters adult hematopoietic stem cell homeostasis, leading to myeloproliferative neoplasms (2015)
    Rockefeller University Press
    Details
    Publication Date: 2015-10-13
    Electronic ISSN: 1540-8140
    Topics: Biology
    Published by Rockefeller University Press
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  • 5
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    Cohesin loss alters adult hematopoietic stem cell homeostasis, leading to myeloproliferative neoplasms (2015)
    Rockefeller University Press
    Details
    Publication Date: 2015-10-20
    Description: The cohesin complex (consisting of Rad21, Smc1a, Smc3, and Stag2 proteins) is critically important for proper sister chromatid separation during mitosis. Mutations in the cohesin complex were recently identified in a variety of human malignancies including acute myeloid leukemia (AML). To address the potential tumor-suppressive function of cohesin in vivo, we generated a series of shRNA mouse models in which endogenous cohesin can be silenced inducibly. Notably, silencing of cohesin complex members did not have a deleterious effect on cell viability. Furthermore, knockdown of cohesin led to gain of replating capacity of mouse hematopoietic progenitor cells. However, cohesin silencing in vivo rapidly altered stem cells homeostasis and myelopoiesis. Likewise, we found widespread changes in chromatin accessibility and expression of genes involved in myelomonocytic maturation and differentiation. Finally, aged cohesin knockdown mice developed a clinical picture closely resembling myeloproliferative disorders/neoplasms (MPNs), including varying degrees of extramedullary hematopoiesis (myeloid metaplasia) and splenomegaly. Our results represent the first successful demonstration of a tumor suppressor function for the cohesin complex, while also confirming that cohesin mutations occur as an early event in leukemogenesis, facilitating the potential development of a myeloid malignancy.
    Print ISSN: 0022-1007
    Electronic ISSN: 1540-9538
    Topics: Medicine
    Published by Rockefeller University Press
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  • 6
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    miR-29a maintains mouse hematopoietic stem cell self-renewal by regulating Dnmt3a (2015)
    American Society of Hematology (ASH)
    In: Blood
    Details
    Publication Date: 2015-04-03
    Description: Hematopoietic stem cells (HSCs) possess the ability to generate all hematopoietic cell types and to self-renew over long periods, but the mechanisms that regulate their unique properties are incompletely understood. Herein, we show that homozygous deletion of the miR-29a/b-1 bicistron results in decreased numbers of hematopoietic stem and progenitor cells (HSPCs), decreased HSC self-renewal, and increased HSC cell cycling and apoptosis. The HSPC phenotype is specifically due to loss of miR-29a , because miR-29b expression is unaltered in miR-29a/b-1 -null HSCs, and only ectopic expression of miR-29a restores HSPC function both in vitro and in vivo. HSCs lacking miR-29a/b - 1 exhibit widespread transcriptional dysregulation and adopt gene expression patterns similar to normal committed progenitors. A number of predicted miR-29 target genes, including Dnmt3a , are significantly upregulated in miR-29a/b-1 -null HSCs. The loss of negative regulation of Dnmt3a by miR-29a is a major contributor to the miR-29a/b-1 -null HSPC phenotype, as both in vitro Dnmt3a short hairpin RNA knockdown assays and a genetic haploinsufficiency model of Dnmt3a restored the frequency and long-term reconstitution capacity of HSCs from miR-29a/b - 1 -deficient mice. Overall, these data demonstrate that miR - 29a is critical for maintaining HSC function through its negative regulation of Dnmt3a .
    Keywords: Hematopoiesis and Stem Cells
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology (ASH)
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  • 7
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    Conserved IKAROS-regulated genes associated with B-progenitor acute lymphoblastic leukemia outcome (2017)
    Rockefeller University Press
    Details
    Publication Date: 2017-03-07
    Description: Genetic alterations disrupting the transcription factor IKZF1 (encoding IKAROS) are associated with poor outcome in B lineage acute lymphoblastic leukemia (B-ALL) and occur in 〉70% of the high-risk BCR-ABL1 + (Ph + ) and Ph-like disease subtypes. To examine IKAROS function in this context, we have developed novel mouse models allowing reversible RNAi-based control of Ikaros expression in established B-ALL in vivo. Notably, leukemias driven by combined BCR-ABL1 expression and Ikaros suppression rapidly regress when endogenous Ikaros is restored, causing sustained disease remission or ablation. Comparison of transcriptional profiles accompanying dynamic Ikaros perturbation in murine B-ALL in vivo with two independent human B-ALL cohorts identified nine evolutionarily conserved IKAROS-repressed genes. Notably, high expression of six of these genes is associated with inferior event–free survival in both patient cohorts. Among them are EMP1 , which was recently implicated in B-ALL proliferation and prednisolone resistance, and the novel target CTNND1 , encoding P120-catenin. We demonstrate that elevated Ctnnd1 expression contributes to maintenance of murine B-ALL cells with compromised Ikaros function. These results suggest that IKZF1 alterations in B-ALL leads to induction of multiple genes associated with proliferation and treatment resistance, identifying potential new therapeutic targets for high-risk disease.
    Keywords: Leukemia & Lymphoma
    Print ISSN: 0022-1007
    Electronic ISSN: 1540-9538
    Topics: Medicine
    Published by Rockefeller University Press
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  • 8
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    Volcanoes in Italy and the role of muon radiography (2019)
    The Royal Society publishing
    Details
    Publication Date: 2023-01-25
    Description: Cosmic-ray muon radiography (muography), an imaging technique that can provide measurements of rock densities within the top few 100m of a volcanic cone, has now achieved a spatial resolution of the order of 10m in optimal detection conditions. Muography provides images of the top region of a volcano edifice with a resolution that is considerably better than that typically achieved with other conventional methods (i.e. gravimetric). We expect such precise measurements, to provide us with information on anomalies in the rock density distribution, which can be affected by dense lava conduits, low-density magma supply paths or the compression with the depth of the overlying soil. The MUon RAdiography of VESuvius (MURAVES) project is now in its final phase of construction and deployment. Up to four muon hodoscopes, each with a surface of roughly 1m2, will be installed on the slope of Vesuvius and take data for at least 12 months. We will use the muographic profiles, combined with data from gravimetric and seismic measurement campaigns, to determine the stratigraphy of the lava plug at the bottom of the Vesuvius crater, in order to infer potential eruption pathways. While the MURAVES project unfolds, others are using emulsion detectors on Stromboli to study the lava conduits at the top of the volcano. These measurements are ongoing: they have completed two measurement campaigns and are now performing the first data analysis. This article is part of the Theo Murphy meeting issue ‘Cosmic-ray muography’.
    Description: Published
    Description: id 20180050
    Description: Newport Pagnell, Buckinghamshire
    Description: 2V. Struttura e sistema di alimentazione dei vulcani
    Description: JCR Journal
    Keywords: muons, volcanoes, muography, particle detector, scintillators
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 9
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    The MU-RAY detector for muon radiography of volcanoes (2016)
    Elsevier Science Limited
    Details
    Publication Date: 2023-01-25
    Description: The MU-RAY detector has been designed to perform muon radiography of volcanoes. The possible use on the field introduces several constraints. First the electric power consumption must be reduced to the minimum, so that the detector can be solar-powered. Moreover it must be robust and transportable, for what concerns the front-end electronics and data acquisition. A 1m2 prototype has been constructed and is taking data at Mt.Vesuvius. The detector consists of modules of 32 scintillator bars with wavelength shifting fibers and silicon photomultiplier read-out. A dedicated front-end electronics has been developed, based on the SPIROC ASIC. An introduction to muon radiography principles, the MU-RAY detector description and results obtained in laboratory will be presented.
    Description: We acknowledge the support provided by the Istituto Nazionale di Fisica Nucleare(INFN). We wish to thank A.Brosfor the scintillator bars provided by FERMILAB-NICADD. We are grateful to Aldo Orlandi of the Laboratori Nazionali di Frascati of INFN for polishing and mirroring the fibers.
    Description: Published
    Description: 423-426
    Description: 1V. Storia e struttura dei sistemi vulcanici
    Description: JCR Journal
    Description: restricted
    Keywords: Muon radiography ; Muon detector ; SiPM ; Volcanoes ; Muography ; 04. Solid Earth::04.08. Volcanology::04.08.99. General or miscellaneous
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 10
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    The MU-RAY project: detector technology and first data from Mt. Vesuvius (2016)
    Details
    Publication Date: 2023-01-25
    Description: Muon Radiography allows to map the density of a volcanic cone. It is based on the measurement of the attenuation of the flux of muons present in the cosmic radiation on the ground. The MU-RAY project has developed an innovative detector designed for the muon radiography. The main features are the low electric power consumption, robustness and transportability, good spatial resolution and muon time of flight measurement. A 1 m2 detector prototype has been constructed. and collected data at Mt. Vesuvius for approximately 1 month in spring 2013. A second campaign of measurement has been performed at the Puy de Dˆome, France, in the last four months of 2013. In this article the principles of muon radiography, the MU-RAY detector and the first results from the collected data will be described.
    Description: Published
    Description: C02029
    Description: 1V. Storia e struttura dei sistemi vulcanici
    Description: JCR Journal
    Description: restricted
    Keywords: Particle tracking detectors ; Scintillators ; scintillation and light emission processes (solid, gas and liquid scintillators) ; 04. Solid Earth::04.08. Volcanology::04.08.99. General or miscellaneous
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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