Inhibition of fucosylation in human invasive ductal carcinoma reduces E-selectin ligand expression, cell proliferation, and ERK1/2 and p38 MAPK activation

Breast cancer tissue overexpresses fucosylated glycans, such as sialyl-Lewis X/A (sLeX/A), and a-1,3/4-fucosyltransferases (FUTs) in relation to increased disease progression and metastasis. These glycans in tumor circulating cells mediate binding to vascular E-selectin, initiating tumor extravasation. However, their role in breast carcinogenesis is still unknown. Here, we aimed to define the contribution of the fucosylated structures, including sLeX/A, to cell adhesion, cell signaling, and cell proliferation in invasive ductal carcinomas (IDC), the most frequent type of breast cancer. We first analyzed expression of E-selectin ligands in IDC tissue and established primary cell cultures from the tissue. We observed strong reactivity with E-selectin and anti-sLeX/A antibodies in both IDC tissue and cell lines, and expression of a-1,3/4 FUTs FUT4, FUT5, FUT6, FUT10, and FUT11. To further assess the role of fucosylation in IDC biology, we immortalized a primary IDC cell line with human telomerase reverse transcriptase to create the ‘CF1_T cell line’. Treatment with 2-fluorofucose (2-FF), a fucosylation inhibitor, completely abrogated its sLeX/A expression and dramatically reduced adherence of CF1_T cells to E-selectin under hemodynamic flow conditions. In addition, 2-FF-treated CF1_T cells showed a reduced migratory ability, as well as decreased cell proliferation rate. Notably, 2-FF treatment lowered the growth factor expression of CF1_T cells, prominently for FGF2, vascular endothelial growth factor, and transforming growth factor beta, and negatively affected activation of signal-regulating protein kinases 1 and 2 and p38 mitogen-activated protein kinase signaling pathways. These data indicate that fucosylation licenses several malignant features of IDC, such as cell adhesion, migration, proliferation, and growth factor expression, contributing to tumor progression.The authors acknowledge the financial support from the LPCC/Pfizer 2011 and Portuguese Foundation for Science and Technology (FCT)—SFRH/BD/100970/ 2014 (MAC), SFRH/BD/81860/2011 (MS), and the United States National Institutes of Health National Heart Blood Institute (NHLBI Grant HL107146, RS). We also thank Dr Nicole Okeley from Seattle Genetics for the valuable help and opinions

Autotraducción : La influencia del autor en la traducción de su propia obra

La autotraducción siempre ha sido una práctica muy controvertida, para la que existen diversas definiciones y argumentos tanto a su favor como en contra. En este trabajo, que toma como base la novela El pirata, la coleccionista y el huevo (escrita por mí misma), se realizará un estudio de cómo ser autor puede afectar al trabajo de traductor. También se realizará un análisis de los conceptos clave para la creación de la historia y su proceso de traducción, teniendo siempre en cuenta mi perspectiva como autora y cómo esta influye en mi labor como traductoraL'autotraducció sempre ha estat una pràctica molt controvertida, per a la qual hi ha diverses definicions i arguments tant a favor seu com en contra. En aquest treball, que pren com a base la novel·la El pirata, la col·leccionista i l'ou (escrita per mi mateixa), es farà un estudi de com ser l'autor pot afectar el treball del traductor. També es realitzarà una anàlisi dels conceptes clau per a la creació de la historia i el seu procés de traducció, tenint sempre en compte la meva perspectiva com a autora i com aquesta influeix en la meva tasca com a traductoraSelf-translation has always been a very controversial practice, for which there are various definitions and arguments both for and against it. This project, which has been developed working on the novel The Pirate, the Collector and the Egg (written by myself), will study how being the author can affect one's work as a translator. An analysis of the key concepts for the creation of the story and its translation will be carried out, always taking into account my own perspective as the author and how this influences my work as a translato

Does Day Length Affect Winter Bird Distribution? Testing the Role of an Elusive Variable

Differences in day length may act as a critical factor in bird biology by introducing time constraints in energy acquisition during winter. Thus, differences in day length might operate as a main determinant of bird abundance along latitudinal gradients. This work examines the influence of day length on the abundance of wintering crested tits (Lophophanes cristatus) in 26 localities of Spanish juniper (Juniperus thurifera) dwarf woodlands (average height of 5 m) located along a latitudinal gradient in the Spanish highlands, while controlling for the influence of food availability, minimum night temperature, habitat structure and landscape characteristics. Top regression models in the AIC framework explained 56% of variance in bird numbers. All models incorporated day length as the variable with the highest magnitude effect. Food availability also played an important role, although only the crop of ripe juniper fruits, but not arthropods, positively affected crested tit abundance. Differences in vegetation structure across localities had also a strong positive effect (average tree height and juniper tree density). Geographical variation in night temperature had no influence on crested tit distribution, despite the low winter temperatures reached in these dwarf forests. This paper demonstrates for the first time that winter bird abundance increases with day length after controlling for the effect of other environmental variables. Winter average difference in day length was only 10.5 minutes per day along the 1°47′ latitudinal interval (190 km) included in this study. This amount of time, which reaches 13.5 h accumulated throughout the winter season, appears to be large enough to affect the long-term energy budget of small passerines during winter and to shape the distribution of winter bird abundance under restrictive environmental conditions

Many-body effects on the thermodynamics of closed quantum systems

Thermodynamics of quantum systems out-of-equilibrium is very important for the progress of quantum technologies, however, the effects of many body interactions and their interplay with temperature, different drives and dynamical regimes is still largely unknown. Here we present a systematic study of these interplays: we consider a variety of interaction (from non-interacting to strongly correlated) and dynamical (from sudden quench to quasi-adiabatic) regimes, and draw some general conclusions in relation to work extraction and entropy production. As treatment of many-body interacting systems is highly challenging, we introduce a simple approximation which includes, for the average quantum work, many-body interactions only via the initial state, while the dynamics is fully non-interacting. We demonstrate that this simple approximation is surprisingly good for estimating both the average quantum work and the related entropy variation, even when many-body correlations are significant.Comment: 17 pages, 11 figure

Proteomic Analysis of Polypeptides Captured from Blood during Extracorporeal Albumin Dialysis in Patients with Cholestasis and Resistant Pruritus

Albumin dialysis using the molecular adsorbent recirculating system (MARS) is a new therapeutic approach for liver diseases. To gain insight into the mechanisms involved in albumin dialysis, we analyzed the peptides and proteins absorbed into the MARS strong anion exchange (SAX) cartridges as a result of the treatment of patients with cholestasis and resistant pruritus. Proteins extracted from the SAX MARS cartridges after patient treatment were digested with two enzymes. The resulting peptides were analyzed by multidimensional liquid chromatography coupled to tandem mass spectrometry. We identified over 1,500 peptide sequences corresponding to 144 proteins. In addition to the proteins that are present in control albumin-derived samples, this collection includes 60 proteins that were specific to samples obtained after patient treatment. Five of these proteins (neutrophil defensin 1 [HNP-1], secreted Ly-6/uPAR-related protein 1 [SLURP1], serum amyloid A, fibrinogen alpha chain and pancreatic prohormone) were confirmed to be removed by the dialysis procedure using targeted selected-reaction monitoring MS/MS. Furthermore, capture of HNP-1 and SLURP1 was also validated by Western blot. Interestingly, further analyses of SLURP1 in serum indicated that this protein was 3-fold higher in cholestatic patients than in controls. Proteins captured by MARS share certain structural and biological characteristics, and some of them have important biological functions. Therefore, their removal could be related either to therapeutic or possible adverse effects associated with albumin dialysis