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Proteoglycan control of cell movement during wound healing and cancer spreading
By virtue of their multifunctional nature, proteoglycans (PGs) are thought to govern the process of cell movement in numerous physiological and pathological contexts, spanning from early embryonic development to tumour invasion and metastasis. The precise mode by which they influence this process is still fragmentary, but evidence is accruing that they may affect it in a multifaceted manner. PGs bound to the plasma membrane mediate the polyvalent interaction of the cell with matrix constituents and with molecules of the neighbouring cells' surfaces; they modulate the activity of receptors implicated in the recognition of these components; and they participate in the perception and convergence of growth- and motility-promoting cues contributed by soluble factors. Through some of these interactions several PGs transduce to pro-motile cells crucial intracellular signals that are likely to be essential for their mobility. A regulated shedding of certain membrane-intercalated PGs seems to provide an additional level of control of cell movement. Coincidentally, matrix-associated PGs may govern cell migration by structuring permissive and non-permissive migratory paths and, when directly secreted by the moving cells, may alternatively create favourable or hostile microenvironments. To exert this latter, indirect effect on cell movement, matrix PGs strongly rely upon their primary molecular partners, such as hyaluronan, link proteins, tenascins, collagens and low-affinity cell surface receptors, whereas a further finer control is provided by a highly regulated proteolytic processing of the PGs accounted by both the migrating cells themselves and cells of their surrounding tissues. Overall, PGs seem to play an important role in determining the migratory phenotype of a cell by initiating, directing and terminating cell movement in a spatio-temporally controlled fashion. This implies that the "anti-adhesive and/or "anti-migratory" properties that have previously been assigned to certain PGs may be re-interpreted as being a means by which these macromolecules elaborate haptotaxis-like mechanisms imposing directionality upon the moving cells. Since these conditions would allow cells to be led to given tissue locations and become immobilized at these sites, a primary function may be ascribed to PGs in the dictation of a "stop or go" choice of the migrating cells. © 2005 Elsevier B.V./International Society of Matrix Biology. All rights reserved
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
Tumour dormancy induced by overexpression of PG-M/versican G1 domain in soft tissue sarcomas
Overexpression of the G1 domain of PG-M/Versican induces overgrowth of human leiomyosarcoma cells by altering their proliferation-apoptosis equilibrium
Dominant role of the G1 domain of PG-M/Versican in the control of the proliferation-apoptosis balance and invasive capabilities of tumour cells.
ABSTRACT
To dissect the role of the globular domains of PGM/versican a large hyaluronan binding
proteoglycan (PG) enriched in tumor lesions we have stably transduced a human
leiomyosarcoma cell line with either the G1 or G3 domain of the PG and subsequently assayed
the effect of this manipulation on several cellular processes in vitro and in vivo. G1- and G3-
overexpressing cells were found to exhibit an enhanced growth that was more accentuated in the
absence of serum components and was seen both when cells were cultured on ECM substrates
and in the absence of ECM anchorage. Accordingly, if inoculated subcutaneously into nude
mice, G1 transfectants formed larger tumor masses than control cells at the site of implantation,
albeit after a certain latency period. Upon binding to cell surface CD44, proliferation of G1-, but
not G3-, overexpressing cells were dose dependently inhibited by exogenous hyaluronan (HA) or
HA fragments. G1- and G3-transduced cells did not differ in their intrinsic ability to adhere and
migrate on various purified ECM components, whereas G1-overproducing sarcoma cells were
more invasive than the corresponding G3 mutants, and their locomotion was perturbed by
exogenous HA. The augmented anchorage-independent growth exhibited solely by G1-
transduced was largely ascribable to a reduced apoptotic rate, thereby indicating a shift in the
proliferation−apoptosis equilibrium of the cells toward the former. In fact, G1-overexpressing
cells appeared resistant to both cytotoxic drug-induced and Fas-dependent programmed cell
death, and this resistance implicated mitochondrial apoptotic genes. The results indicate that the
terminal domains of versican may differentially control propagation of tumor cells and diversely
modulate their responses to environmental HA
Key words: soft tissue sarcoma hyaluronan G1 G
Variations on the Author
“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
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