305,242 research outputs found
Integrated analysis of microRNA and mRNA expression profiles in physiological myelopoieis: role of hsa-mir- 299-5p in CD34+ progenitor cells commitment
No full textHematopoiesis entails a series of hierarchically organized events that proceed throughout cell specification and terminates with cell differentiation. Commitment needs the transcription factors effort that, in concert with microRNAs, drives cell fate and responds to promiscuous patterns of gene expression by turning-on lineage-specific genes and repressing alternate lineage transcripts. We obtained microRNAs profiles from human CD34+ hematopoietic progenitor cells and in-vitro differentiated erythroblasts, megakaryoblasts, monoblasts and myeloblasts precursors, that we analyzed together with their gene expression profiles. The integrated analysis of microRNA-mRNA expression levels highlighted an inverse correlation between microRNAs specifically up-regulated in one single cell progeny and their putative target genes, which resulted down-regulated. Among the up-regulated lineage-enriched microRNAs, hsa-miR-299-5p emerged as having a role in controlling CD34+ progenitors fate, grown in multilineage culture conditions. Gain- and loss-of-function experiments revealed that hsa-miR-299-5p participates the regulation of hematopoietic progenitors fate, modulating megakaryocytic-granulocytic versus erythroid-monocytic differentiation
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Clinically relevant low-frequency Next Generation Sequencing variants in hereditary cancer patients: an operational multi-step algorithm for laboratory managing
No full textDispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Author, publisher and bookseller : a tripartite synergy in Nigerian book industry
No full textThis work is about the roles of Author, Publisher and Bookseller in Book development in
Nigeria. The paper started by delving into the history of Book Publishing in Nigeria after
which it proceeded by defining who an author, a publisher, and a bookseller is and
expatiated on the indispensable roles of these key actors in Nigerian Book Industry and in
the emerging Information Society. Furthermore, the various constraints to book
development were identified while the paper advised on how the Book Industry can be
further promoted in Nigeria. However, the paper concluded and made recommendations
on how the Book sector can help in enhancing scholarship in the country
c-Myb supports erythropoiesis by transactivating KLF1 and LMO2 expression
No full textThe c-Myb transcription factor is highly expressed in immature hematopoietic cells and down-regulated during
differentiation. c-myb is essential for the hematopoietic development, as c-myb-/- mice die at E15 due to failure of fetal
hepatic erythropoiesis. To gain further insights into the role of c-myb during the hematopoietic lineage commitment, we
studied the effects of c-Myb silencing in human CD34+ hematopoietic stem/progenitor cells. c-Myb silencing in CD34+
cells was performed by transfection of siRNAs using the Amaxa Nucleofector® Technology. In order to keep c-Myb
expression silenced for all the commitment phase of CD34+ cells, each sample was nucleofected 3 times, once a day.
Moreover, to exclude non-specific effects of siRNA nucleofection, for each experiment, together with the sample
transfected with the siRNAs targeting c-Myb, one sample electroporated without siRNAs and one transfected with a
non-targeting siRNA were performed. c-Myb silencing effects on CD34+ cells differentiation ability were studied by
methylcellulose and collagen-based clonogenic assays and by morphological and immunophenotypic analyses after
liquid culture. Furthermore, we investigated by microarray analysis the changes in gene expression induced by c-Myb
silencing. Methylcellulose assay revealed a remarkable increase of the percentage of monocyte (CFU-M) colonies and a
decrease of the erythroid ones (BFU-E) in c-Myb-silenced CD34+ cells. Moreover, collagen-based clonogenic assay
demonstrated that c-Myb silencing strongly enhances the megakaryocyte commitment of CD34+ cells. In agreement
with these data, flow cytometric analysis showed an increase in mono-macrophage and megakaryocyte fractions in cmyb-silenced
cells, while the erythroid population was strongly decreased. Morphological evaluation of May
Grunwald-Giemsa stained cytospins further supported the conclusion that c-myb silencing forces the CD34+ cells
commitment towards the macrophage and megakaryocyte lineages at the expense of the erythroid one. Gene expression
profiling of c-Myb silenced CD34+ cells enabled us to identify new putative targets which can account for c-Myb
knockdown effects. Indeed, Chromatin Immunoprecipitation and Luciferase reporter assay demonstrated that c-Myb
binds to KLF1 and LMO2 promoters and transactivates their expression. Functional rescue experiments showed that the
retroviral vector-mediated overexpression of KLF1 and LMO2 transcription factors in c-Myb silenced cells is able to
rescue, at least in part, the impaired erythroid differentiation. Our data collectively demonstrate that c-Myb plays a
pivotal role in human primary hematopoietic stem/progenitor cells lineage commitment, by enhancing erythropoiesis at
the expense of megakaryocyte diffentiation. In particular, we identified c-Myb-driven KLF1 and LMO2 transactivation
as the molecular mechanism through which c-Myb regulates erythroid versus megakaryocyte lineage fate decision
Expression profiling of FSHD-1 and FSHD-2 cells during myogenic differentiation evidences common and distinctive gene dysregulation patterns.
No full textBackgroundDetermine global gene dysregulation affecting 4q-linked (FSHD-1) and non 4q-linked (FSHD-2) cells during early stages of myogenic differentiation. This approach has been never applied to FSHD pathogenesis.Methodology/principal findingsBy in vitro differentiation of FSHD-1 and FSHD-2 myoblasts and gene chip analysis we derived that gene expression profile is altered only in FSHD-1 myoblasts and FSHD-2 myotubes. The changes seen in FSHD-1 regarded a general defect in cell cycle progression, probably due to the upregulation of myogenic markers PAX3 and MYOD1, and a deficit of factors (SUV39H1 and HMGB2) involved in D4Z4 chromatin conformation. On the other hand, FSHD-2 mytubes were characterized by a general defect in RNA metabolism, protein synthesis and degradation and, to a lesser extent, in cell cycle. Common dysregulations regarded genes involved in response to oxidative stress and in sterol biosynthetic process. Interestingly, our results also suggest that miRNAs might be implied in both FSHD-1 and FSHD-2 gene dysregulation. Finally, in both cell differentiation systems, we did not observe a gradient of altered gene expression throughout the 4q35 chromosome.Conclusions/significanceFSHD-1 and FSHD-2 cells showed, in different steps of myogenic differentiation, a global deregulation of gene expression rather than an alteration of expression of 4q35 specific genes. In general, FSHD-1 and FSHD-2 global gene deregulation interested common and distinctive biological processes. In this regard, defects of cell cycle progression (FSHD-1 and to a lesser extent FSHD-2), protein synthesis and degradation (FSHD-2), response to oxidative stress (FSHD-1 and FSHD-2), and cholesterol homeostasis (FSHD-1 and FSHD-2) may in general impair a correct myogenesis. Taken together our results recapitulate previously reported defects of FSHD-1, and add new insights into the gene deregulation characterizing both FSHD-1 and FSHD-2, in which miRNAs may play a role
Ivar, an interpretation‐oriented tool to manage the update and revision of variant annotation and classification
No full textThe rapid evolution of Next Generation Sequencing in clinical settings, and the resulting challenge of variant reinterpretation given the constantly updated information, require robust data management systems and organized approaches. In this paper, we present iVar: a freely available and highly customizable tool with a user‐friendly web interface. It represents a platform for the unified management of variants identified by different sequencing technologies. iVar accepts variant call format (VCF) files and text annotation files and elaborates them, optimizing data organization and avoiding redundancies. Updated annotations can be periodically re‐uploaded and associated with variants as historically tracked attributes, i.e., modifications can be recorded whenever an updated value is imported, thus keeping track of all changes. Data can be visualized through variant‐centered and sample‐centered interfaces. A customizable search function can be exploited to periodically check if pathogenicity‐related data of a variant has changed over time. Patient recontacting ensuing from variant reinterpretation is made easier by iVar through the effective identification of all patients present in the database carrying a specific variant. We tested iVar by uploading 4171 VCF files and 1463 annotation files, obtaining a database of 4166 samples and 22,569 unique variants. iVar has proven to be a useful tool with good performance in terms of collecting and managing data from a medium‐throughput laboratory
[Report to Chief J. E. Curry, by an unknown author #2]
No full textReport to Chief J. E. Curry, by an unknown author. The report contains a list of officers who gave depositions to the United States Attorney
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