99 resultados para endosome escape


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The K-means algorithm is one of the most popular techniques in clustering. Nevertheless, the performance of the K-means algorithm depends highly on initial cluster centers and converges to local minima. This paper proposes a hybrid evolutionary programming based clustering algorithm, called PSO-SA, by combining particle swarm optimization (PSO) and simulated annealing (SA). The basic idea is to search around the global solution by SA and to increase the information exchange among particles using a mutation operator to escape local optima. Three datasets, Iris, Wisconsin Breast Cancer, and Ripley’s Glass, have been considered to show the effectiveness of the proposed clustering algorithm in providing optimal clusters. The simulation results show that the PSO-SA clustering algorithm not only has a better response but also converges more quickly than the K-means, PSO, and SA algorithms.

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Preserving the integrity of the skin's outermost layer (the epidermis) is vital for humans to thrive in hostile surroundings. Covering the entire body, the epidermis forms a thin but impenetrable cellular cordon that repels external assaults and blocks escape of water and electrolytes from within. This structure exists in a perpetual state of regeneration where the production of new cellular subunits at the base of the epidermis is offset by the release of terminally differentiated corneocytes from the surface. It is becoming increasingly clear that proteases hold vital roles in assembling and maintaining the epidermal barrier. More than 30 proteases are expressed by keratinocytes or infiltrating immune cells and the activity of each must be maintained within narrow limits and confined to the correct time and place. Accordingly, over- or under-exertion of proteolytic activity is a common factor in a multitude of skin disorders that range in severity from relatively mild to life-threatening. This review explores the current state of knowledge on the involvement of proteases in skin diseases and the latest findings from proteomic and transcriptomic studies focused on uncovering novel (patho)physiological roles for these enzymes.

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Plant microRNAs (miRNAs) are a class of endogenous small RNAs that are essential for plant development and survival. They arise from larger precursor RNAs with a characteristic hairpin structure and regulate gene activity by targeting mRNA transcripts for cleavage or translational repression. Efficient and reliable detection and quantification of miRNA expression has become an essential step in understanding their specific roles. The expression levels of miRNAs can vary dramatically between samples and they often escape detection by conventional technologies such as cloning, northern hybridization and microarray analysis. The stem-loop RT-PCR method described here is designed to detect and quantify mature miRNAs in a fast, specific, accurate and reliable manner. First, a miRNA-specific stem-loop RT primer is hybridized to the miRNA and then reverse transcribed. Next, the RT product is amplified and monitored in real time using a miRNA-specific forward primer and the universal reverse primer. This method enables miRNA expression profiling from as little as 10 pg of total RNA and is suitable for high-throughput miRNA expression analysis.

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A travel article about southern German festivals. IT WAS Golden October, when a last wave of Italian warmth made it across the Alps into southern Germany. Outside, the final sunlight of the day found the tops of trees, and the town seemed cast entirely in autumn patterns. I followed the busy pedestrian traffic across the Neckar River into the old part of Tübingen.

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Epithelial-to-mesenchymal transition (EMT) increases cell migration and invasion, and facilitates metastasis in multiple carcinoma types, but belies epithelial similarities between primary and secondary tumors. This study addresses the importance of mesenchymal-to-epithelial transition (MET) in the formation of clinically significant metastasis. The previously described bladder carcinoma TSU-Pr1 (T24) progression series of cell lines selected in vivo for increasing metastatic ability following systemic seeding was used in this study. It was found that the more metastatic sublines had acquired epithelial characteristics. Epithelial and mesenchymal phenotypes were confirmed in the TSU-Pr1 series by cytoskeletal and morphologic analysis, and by performance in a panel of in vitro assays. Metastatic ability was examined following inoculation at various sites. Epithelial characteristics associated with dramatically increased bone and soft tissue colonization after intracardiac or intratibial injection. In contrast, the more epithelial sublines showed decreased lung metastases following orthotopic inoculation, supporting the concept that EMT is important for the escape of tumor cells from the primary tumor. We confirmed the overexpression of the IIIc subtype of multiple fibroblast growth factor receptors (FGFR) through the TSU-Pr1 series, and targeted abrogation of FGFR2IIIc reversed the MET and associated functionality in this system and increased survival following in vivo inoculation in severe combined immunodeficient mice. This model is the first to specifically model steps of the latter part of the metastatic cascade in isogenic cell lines, and confirms the suspected role of MET in secondary tumor growth.

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Carcinogenesis involves the accretion of unprogrammed genetic and epigenetic changes, which lead to dysregulation of the normal control of cell number. But a key clinical turning point in carcinoma progression is the establishment by emigrant cells of secondary growth sites (i.e., metastasis). The metastatic “cascade” comprises numerous steps, including escape from the primary tumor site, penetration of local stroma, entry of local vascular or lymphatic vessels (intravasation), aggregation with platelets, interaction with and adhesion to distant endothelia, extravasation, recolonization, and expansion ( 1), all the time avoiding effective immune clearance and being able to survive in these multiple contexts...

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The progression of a tumour from one of benign and delimited growth to one that is invasive and metastatic is the major cause of poor clinical outcome in cancer patients. The invasion and metastasis of tumours is a highly complex and multistep process that requires a tumour cell to modulate its ability to adhere, degrade the surrounding extracellular matrix, migrate, proliferate at a secondary site and stimulate angiogenesis. Knowledge of the process has greatly increased and this has resulted in the identification of a number of molecules that are fundamental to the process. The involvement of these molecules has been shown to relate not only to the survival and proliferation of the tumour cell but, also to the processes of tumour cell adhesion, migration, and the tumour cells ability to degrade and escape the primary site as well as play a role in angiogenesis. These molecules may provide important therapeutic targets that represent the ability to target specific steps in the process of invasion and metastasis and provide additional therapies. The review focuses on representative key targets in each of these processes and summarises the state of play in each case.

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Inhibition of cholesterol export from late endosomes causes cellular cholesterol imbalance, including cholesterol depletion in the trans-Golgi network (TGN). Here, using Chinese hamster ovary (CHO) Niemann-Pick type C1 (NPC1) mutant cell lines and human NPC1 mutant fibroblasts, we show that altered cholesterol levels at the TGN/endosome boundaries trigger Syntaxin 6 (Stx6) accumulation into VAMP3, transferrin, and Rab11-positive recycling endosomes (REs). This increases Stx6/VAMP3 interaction and interferes with the recycling of αVβ3 and α5β1 integrins and cell migration, possibly in a Stx6-dependent manner. In NPC1 mutant cells, restoration of cholesterol levels in the TGN, but not inhibition of VAMP3, restores the steady-state localization of Stx6 in the TGN. Furthermore, elevation of RE cholesterol is associated with increased amounts of Stx6 in RE. Hence, the fine-tuning of cholesterol levels at the TGN-RE boundaries together with a subset of cholesterol-sensitive SNARE proteins may play a regulatory role in cell migration and invasion.

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Composite polymer insulators provide many advantages over the traditional porcelain insulators and they are increasingly being used at both transmission and distribution levels. In the present paper, an epoxy resin/silica nanocomposite dielectric material (NDM) structure is proposed and fabricated. Hydrophobic fumed silica is incorporated in epoxy resin matrix and acetone is adopted as media agent to effectively achieve homogenous dispersion of the nano-scale silica filler. The acetone also acts as diluents to reduce viscosity before the curing phase of epoxy resin and enables bubbles to escape from being trapped. Through partial discharge (PD) and surface aging tests, it is illustrated that the inception of surface discharge of the proposed NDM is relatively higher than that of the non-filled counterpart, and a better PD resistivity was observed in the negative half cycle regarding to applied AC voltage. Results of surface aging test indicate that surface discharge activity is retarded over the test conducting time. By contrast, surface discharge developed to the opposite way on the non-filled sample. Therefore, the proposed NDM could provide better safety reliability and lower maintenance cost to industrial application compared with nonfilled conventional epoxy resin.

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Favel Parrett’s second novel, When the Night Comes, opens with its teenage protagonist Isla lying awake in her bunk on a night ferry to Tasmania in the mid-1980s, ‘waiting for the rough seas’. Her younger brother sleeps beside her, and her distracted, emotionally distant mother – the kind of woman who is ‘always sitting places by herself in the night’ – is smoking on deck. Together, the three are weathering the roiling overnight passage in order to escape a violent past and make a new life in Hobart. The rough seas the novel goes on to navigate are, as one might expect, both literal and metaphorical...

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A travel article about Helsinki exploring the city's design culture. I’M often told that I’m from Finland. Even those who’ve known me for years confuse it with my birthplace, which is, in fact, Iceland. I’m not sure why the two countries are mixed up in this way, but it might be that Iceland and Finland are, in a sense, the “other” Scandinavian nations – on different sides of the Nordic world, but in the mind joined as its outer borders...

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A travel article about the Aland Islands, Finland, that discusses the mix of Swedish, Finnish, and Russian cultural influences in the area. On the map, Finland seems to end in fragments. The gods have stomped their heels on the southwestern corner, and between the cities of Helsinki and Turku it is jagged, rocky islands that form the final landmarks...

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A travel article about the Tamar Valley, Tasmania. FROM Launceston to Low Head and the Tamar River’s entry into Bass Strait, big tides bring with them an atmosphere of a beach community, but also of a community a little stranded in time. Half the day the locals live by the sea, and for the other half along wide flats. It’s an old rhythm in a place where much has gone unchanged...

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A travel article about a journey to Reykholt in Western Iceland, once the farm of saga author Snorri Sturluson. A TRIP back into snowbound Iceland's past in search of a famed warrior-poet throws up some old memories and fresh revelations for Kari Gislason "The fish must sing." An odd idea, I know - one uttered by a merchant in a novel by Halldor Laxness. But it said no more than what every Icelander since the settlement had known. If you were going to live on the edge of the world, it paid to do something to remind the rest of the world you were still here...

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A travel article about Halifax, Nova Scotia. MOTORISTS in Nova Scotia are so polite it's almost a shame to leave, writes Kari Gislason. By the end of my second day in Halifax, I begin to develop deep concerns about the safety of the locals, or the Haligonians as they're known. I wonder how they ever leave their fair city or, perhaps more to the point, how they ever make it back...