1,720,986 research outputs found
Bone marrow mononuclear cells are recruited to the sites of VEGF-induced neovascularization but are not incorporated into the newly formed vessels
No full textVascular endothelial growth factor (VEGF)
is a key regulator of blood vessel formation
during both vasculogenesis and angiogenesis.
The prolonged expression of
VEGF in the normoperfused skeletal
muscles of adult rodents after gene transfer
using AAV vectors induces the formation
of a large set of new capillaries and
small arteries. Notably, this process is
accompanied by the massive infiltration
by mononuclear cells. This observation
raises the possibility that these cellsmight
represent circulating progenitors that are
eventually incorporated in the newly
formed vessels. Here we explore this possibility
by exploiting 4 different experimental
models based on (a) the transplantation
of male bone marrow into female
recipients; (b) the transplantation of Tie2-
GFP transgenic bone marrow; (c) the
transplantation of bone marrow in the
presence of erythropoietin (EPO), a mobilizer
of endothelial progenitor cells
(EPCs); and (d) the reimplantation of ex
vivo–expanded EPCs. In all 4 models,
VEGF acted as a powerful attractor of
bone marrow–derived mononuclear cells,
bearing different myeloid and endothelial
markers proper of the EPCs to the sites of
neovascularization. In no case, however,
were the attracted cells incorporated in
the newly formed vasculature. These observations
indicate that new blood vessel
formation induced by VEGF occurs
through bona fide sprouting angiogenesis;
the contribution of the infiltrating
bone marrow–derived cells to this process
still remains enigmatic
"Functional blood vessels formation by combined VEGF and angiopoietin-1 gene transfer usina AAV vectors"
No full textA novel myogenic cell line with phenotypic properties of muscle progenitors
No full textSkeletal myogenesis is a multistep process starting
with progenitor cell proliferation, followed by their exit
from the cell cycle, differentiation, alignment, and fusion to
form multinucleated myotubes, typical of the differentiated
muscle tissue. While the molecular players involved in
early myogenesis have been extensively characterized,
information about the later steps of the process is scanty.
Here, we describe a novel myogenic cell line (MYOP7),
composed of highly proliferating Sca-1+ muscle precursor
cells, which can be induced to terminally differentiate into
spontaneously contracting multinucleated myotubes. By
performing high-density microarray analysis on these cells,
we identified a series of genes, differentially expressed in
proliferating vs differentiating conditions, which are candidates
to play a major role in the later phase of myogenesis.
In addition, we confirmed that the late stages of muscle
differentiation are characterized by a marked upregulation
of the cellular receptors for the vascular endothelial growth
factor
Potent inhibition of arterial intimal hyperplasia by TIMP1 gene transfer using AAV vectors.
No full textSeminal to the process of arterial restenosis after balloon angioplasty is extracellular matrix
degradation by metalloproteinases (MMPs); activity of these proteins is strongly inhibited by the
tissue inhibitors of MMPs (TIMPs). Here we exploit gene transfer using an adeno-associated virus
(AAV) for TIMP1 gene delivery in a rat model of intimal hyperplasia. High-titer AAV-Timp1
efficiently transduced human coronary artery smooth muscle cells (SMCs) in vitro and inhibited
the capacity of these cells to migrate through a Matrigel barrier. In injured rat carotid arteries,
AAV vectors were found to transduce SMCs efficiently and to maintain transgene expression for
several weeks in vivo. In AAV-Timp1-transduced animals, the intima:media ratio of injured
carotids was significantly reduced by 70.5% after 2 weeks, by 58.5% after 1 month, and by 52.4%
after 2 months from treatment. The decrease in intimal hyperplasia was paralleled by a significant
inhibition of collagen accumulation and by increased elastin deposition in the neointima, two
findings that relate to the inhibition of MMP activity. These results indicate that AAV vectors are
efficient tools for delivering genes to the arterial wall and emphasize the importance of MMPs for
the generation of intimal hyperplasia. Local TIMP1 gene transfer might thus represent an efficient
strategy to prevent restenosis
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
EFFETTI DEL TRASFERIMENTO INTRAMUSCOLARE DEL GENE VEGF165 MEDIANTE VETTORI VIRALI ADENO-ASSOCIATI (AAV) SU LEMBI ADDOMINALI PERFORANTI DEL RATTO
No full textInduction of functional neovascularization by combined VEGF and angiopoietin-1 gene transfer using AAV vectors
No full textVectors based on the adeno-associated virus (AAV) deliver therapeutic genes to muscle and heart
at high efficiency and maintain transgene expression for long periods of time. Here we report
about the synergistic effect on blood vessel formation of AAV vectors expressing the 165 aa
isoform of vascular endothelial growth factor (VEGF165), a powerful activator of endothelial cells,
and of angiopoietin-1 (Ang-1), which is required for vessel maturation. High titer AAV-VEGF165
and AAV-Ang-1 vector preparations were injected either alone or in combination in the normoperfused
tibialis anterior muscle of rats. Long term expression of VEGF165 determined massive
cellular infiltration of the muscle tissues over time, with the formation of a large set of new vessels.
Strikingly, some of the cells infiltrating the treated muscles were found positive for markers of
activated endothelial precursors (VEGFR-2/KDR and Tie-2) and for c-kit, an antigen expressed by
pluripotent bone marrow stem cells. Expression of VEGF165 eventually resulted in the formation
of structured vessels surrounded by a layer of smooth muscle cells. Presence of these arteriolae
correlated with significantly increased blood perfusion in the injected areas. Co-expression of
VEGF165 with angiopoietin-1-which did not display angiogenic effect per se-remarkably reduced
leakage of vessels produced by VEGF165 alone
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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