23 research outputs found

    Contribution to van der Waerden's conjecture

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    AbstractIn this paper, we give two different elementary proofs for the inequality which states that the permanent of doubly stochastic matrices is greater than or equal to (n!/nn). This inequality was proved earlier by the author, and independently by Egorychev and Falikman

    Introduction to supramolecular complex formation in cell signaling and disease

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    In summary, formation of multi-protein complexes is an essential if not defining feature of eukaryotic signaling. Clearly, we now appreciate this fact and are beginning to grasp some of the underlying guiding principles. However, much remains yet to be accomplished. The hope is that insights to these mechanisms will not only further our understanding of fundamental processes in biology like signal transduction, but will also help in the development of new strategies to treat human disease

    Cellular signaling

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    Cellular signaling is an area of intense research that transcends all fields of experimental biology. As such, progress in this domain will continue to have an ever-increasing impact on society in general and health-related issues in particular. This Special Edition of Biological Research provides a glimpse at progress made in a few select areas with emphasis on linking such insights to disease. At the heart of the issue is "Cellular Communication," the ability of a cell to receive, interpret, and respond to cues provided by the environment. In a multi-cellular organism, alterations in this may threaten not only the viability of the cell or cell population involved, but often, if gone unchecked, that of the entire organism. For many years, research has focused on identifying new elements in "signaling cascades", the information super-highways of the cell. These cascades are predominantly depicted as linear pathways, akin in design to those described in earlier decades for cell metabolism, that frequently link changes perceived at the cell surface to responses in internal cellular compartments required to alter cell behavior in an appropriate fashion. Interestingly, some of the individual links in these chains of events are proteins that lack any clearly defined enzymatic activity. Instead, they serve to link consecutive components (adaptors) or bring together multiple proteins from the same or different pathways (scaffolding proteins). In the absence of such proteins, signaling in a pathway (or various pathways) ceases to proceed in an efficient manner. Such observations, in conjunction with the recognition that a considerable amount of sequence information in proteins is dedicated to elements (modules) required for correct cellular localization, rather than activity, underscore the importance of "positional" information for eukaryotic signaling. As a consequence, understanding the mechanisms that govern how multi-protein complexes coalesce during signaling to form not the linear pathways depicted in text books, but rather highly dynamic, integrated signaling networks that link the activity of receptors to, for instance, alterations in gene transcription and how such events may go array to promote disease is rapidly becoming one of the most challenging and exciting areas of biomedical research today. This international symposium brings together 21 researchers from Chile and abroad to discuss such issues. The choice of topics is timely and will be of interest to a broad spectrum of specialist and non-specialist scientists alike. This special edition contains articles written by each researcher presenting data at the symposium that summarize the specific area of interest. Together these should serve to guide the audience through what will hopefully become an intense and highly stimulating discussion of "Supramolecular complex formation in cellular signaling and disease"

    Sub cytotoxic doses of anti-neoplastic drugs increase caveolin-1-dependent migration, invasion and metastasis of cancer cells

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    CONICYT-FONDAP 15130011 FONDECYT 1090071 1130250 Anillo ACT 111

    Caveolin-1 function at the plasma membrane and in intracellular compartments in cancer

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    Caveolin-1 (CAV1) is commonly considered to function as a cell surface protein, for instance in the genesis of caveolae. Nonetheless, it is also present in many intracellular organelles and compartments. The contributions of these intracellular pools to CAV1 function are generally less well understood, and this is also the case in the context of cancer. This review will summarize literature available on the role of CAV1 in cancer, highlighting particularly our understanding of the canonical (CAV1 in the plasma membrane) and non-canonical pathways (CAV1 in organelles and exosomes) linked to the dual role of the protein as a tumor suppressor and promoter of metastasis. With this in mind, we will focus on recently emerging concepts linking CAV1 function to the regulation of intracellular organelle communication within the same cell where CAV1 is expressed. However, we now know that CAV1 can be released from cells in exosomes and generate systemic effects. Thus, we will also elaborate on how CAV1 participates in intracellular communication between organelles as well as signaling between cells (non-canonical pathways) in cancer.Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) CONICYT FONDECYT 1200836 3190330 1170925 Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) CONICYT FONDAP 1513001

    Signaling triggered by Thy-1 interaction with β3 integrin on astrocytes is an essential step towards unraveling neuronal Thy-1 function

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    Thy-1 is an abundant neuronal glycoprotein in mammals. Despite such prevalence, Thy-1 function remains largely obscure in the absence of a defined ligand. Recently described evidence that Thy-1 interacts with β3 integrin on astrocytes will be discussed. Thy-1 binding to β3 integrin triggers tyrosine phosphorylation of focal adhesion proteins in astrocytes, thereby promoting focal adhesion formation, cell attachment and spreading. Thy-1 has been reported to modulate neurite outgrowth by triggering a cellular response in neurons. However, our data indicate that Thy-1 can also initiate signaling events that promote adhesion of adjacent astrocytes to the underlying surface. Preliminary results suggest that morphological changes observed in the actin cytoskeleton of astrocytes as a consequence of Thy-1 binding is mediated by small GTPases from the Rho family. Our findings argue that Thy-1 functions in a bimodal fashion, as a receptor on neuronal cells and as a ligand for β3 integrin recept

    Caveolae and caveolae-like membrane domains in cellular signaling and disease: Identification of downstream targets for the tumor suppressor protein caveolin-1

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    Caveolae are small, flask-shaped invaginations of the plasma membrane present on a large number of mammalian cells. Recent results obtained with knock-out mice for the gene caveolin-1 demonstrate that expression of caveolin-1 protein is essential for caveolae formation in vivo. Caveolae are implicated in a wide variety of cellular events including transcytosis, cholesterol trafficking and as cellular centers important in coordinating signalling events. Caveolae share this role and the property of detergent insolubility with plasma membrane assemblies rich in glycosphingolipids and cholesterol, often called lipid rafts, but preferably referred to here as caveolae-like membrane domains. Due to such widespread presence and usage in cellular function, caveolae and related domains are implicated in human diseases, including cancer. In particular, the protein caveolin-1 is suggested to function as a tumor suppressor protein. Evidence demonstrating such a role for caveolin-1 in human colon c
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