Contribution to van der Waerden's conjecture

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

PAISAJES DE ESPAÑA [Material gráfico]

Copia digital. Madrid : Ministerio de Educación, Cultura y Deporte, 201

Caveolin-1-Enhanced Motility and Focal Adhesion Turnover Require Tyrosine-14 but Not Accumulation to the Rear in Metastatic Cancer Cells

Caveolin-1 is known to promote cell migration, and increased caveolin-1 expression is associated with tumor progression and metastasis. In fibroblasts, caveolin-1 polarization and phosphorylation of tyrosine-14 are essential to promote migration. However, the role of caveolin-1 in migration of metastatic cells remains poorly defined. Here, caveolin-1 participation in metastatic cell migration was evaluated by shRNA targeting of endogenous caveolin-1 in MDA-MB-231 human breast cancer cells and ectopic expression in B16-F10 mouse melanoma cells. Depletion of caveolin-1 in MDA-MB-231 cells reduced, while expression in B16-F10 cells promoted migration, polarization and focal adhesion turnover in a sequence of events that involved phosphorylation of tyrosine-14 and Rac-1 activation. In B16-F10 cells, expression of a non-phosphorylatable tyrosine-14 to phenylalanine mutant failed to recapitulate the effects observed with wild-type caveolin-1. Alternatively, treatment of MDA-MB-231 cells with the Src family kinase inhibitor PP2 reduced caveolin-1 phosphorylation on tyrosine-14 and cell migration. Surprisingly, unlike for fibroblasts, caveolin-1 polarization and re-localization to the trailing edge were not observed in migrating metastatic cells. Thus, expression and phosphorylation, but not polarization of caveolin-1 favor the highly mobile phenotype of metastatic cells

Astrocytic αVβ3 Integrin Inhibits Neurite Outgrowth and Promotes Retraction of Neuronal Processes by Clustering Thy-1

Thy-1 is a membrane glycoprotein suggested to stabilize or inhibit growth of neuronal processes. However, its precise function has remained obscure, because its endogenous ligand is unknown. We previously showed that Thy-1 binds directly to αVβ3 integrin in trans eliciting responses in astrocytes. Nonetheless, whether αVβ3 integrin might also serve as a Thy-1-ligand triggering a neuronal response has not been explored. Thus, utilizing primary neurons and a neuron-derived cell line CAD, Thy-1-mediated effects of αVβ3 integrin on growth and retraction of neuronal processes were tested. In astrocyte-neuron co-cultures, endogenous αVβ3 integrin restricted neurite outgrowth. Likewise, αVβ3-Fc was sufficient to suppress neurite extension in Thy-1(+), but not in Thy-1(−) CAD cells. In differentiating primary neurons exposed to αVβ3-Fc, fewer and shorter dendrites were detected. This effect was abolished by cleavage of Thy-1 from the neuronal surface using phosphoinositide-specific phospholipase C (PI-PLC). Moreover, αVβ3-Fc also induced retraction of already extended Thy-1(+)-axon-like neurites in differentiated CAD cells as well as of axonal terminals in differentiated primary neurons. Axonal retraction occurred when redistribution and clustering of Thy-1 molecules in the plasma membrane was induced by αVβ3 integrin. Binding of αVβ3-Fc was detected in Thy-1 clusters during axon retraction of primary neurons. Moreover, αVβ3-Fc-induced Thy-1 clustering correlated in time and space with redistribution and inactivation of Src kinase. Thus, our data indicates that αVβ3 integrin is a ligand for Thy-1 that upon binding not only restricts the growth of neurites, but also induces retraction of already existing processes by inducing Thy-1 clustering. We propose that these events participate in bi-directional astrocyte-neuron communication relevant to axonal repair after neuronal damage

Biomimetic, Mild Chemical Synthesis of CdTe-GSH Quantum Dots with Improved Biocompatibility

Multiple applications of nanotechnology, especially those involving highly fluorescent nanoparticles (NPs) or quantum dots (QDs) have stimulated the research to develop simple, rapid and environmentally friendly protocols for synthesizing NPs exhibiting novel properties and increased biocompatibility

Cellular signaling

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"

Introduction to supramolecular complex formation in cell signaling and disease

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

Helicobacter pylori and Gastric Cancer: Adaptive Cellular Mechanisms Involved in Disease Progression

Helicobacter pylori (H. pylori) infection is the major risk factor associated with the development of gastric cancer. The transition from normal mucosa to non-atrophic gastritis, triggered primarily by H. pylori infection, initiates precancerous lesions which may then progress to atrophic gastritis and intestinal metaplasia. Further progression to dysplasia and gastric cancer is generally believed to be attributable to processes that no longer require the presence of H. pylori. The responses that develop upon H. pylori infection are directly mediated through the action of bacterial virulence factors, which drive the initial events associated with transformation of infected gastric cells. Besides genetic and to date poorly defined environmental factors, alterations in gastric cell stress-adaptive mechanisms due to H. pylori appear to be crucial during chronic infection and gastric disease progression. Firstly, H. pylori infection promotes gastric cell death and reduced epithelial cell turnover in the majority of infected cells, resulting in primary tissue lesions associated with an initial inflammatory response. However, in the remaining gastric cell population, adaptive responses are induced that increase cell survival and proliferation, resulting in the acquisition of potentially malignant characteristics that may lead to precancerous gastric lesions. Thus, deregulation of these intrinsic survival-related responses to H. pylori infection emerge as potential culprits in promoting disease progression. This review will highlight the most relevant cellular adaptive mechanisms triggered upon H. pylori infection, including endoplasmic reticulum stress and the unfolded protein response, autophagy, oxidative stress, and inflammation, together with a subsequent discussion on how these factors may participate in the progression of a precancerous lesion. Finally, this review will shed light on how these mechanisms may be exploited as pharmacological targets, in the perspective of opening up new therapeutic alternatives for non-invasive risk control in gastric cancer

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

CONICYT-FONDAP 15130011 FONDECYT 1090071 1130250 Anillo ACT 111