Phosphoproteomics data classify hematological cancer cell lines according to tumor type and sensitivity to kinase inhibitors

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Osteotomía de Weil percutánea en el tratamiento de las metatarsalgias: correlación clínico-radiológica

El objetivo del presente trabajo fue evaluar los resultados de la osteotomía de Weil percutánea para el tratamiento de la metatarsalgia de origen mecánico. Para ello, se revisaron de forma retrospectiva los primeros 28 casos consecutivos intervenidos mediante osteotomía de Weil percutánea en pacientes con metatarsalgia mecánica por sobrecarga de los metatarsianos centrales. Se entrevistó a la totalidad de los pacientes, evaluando los resultados radiológicos, estéticos y funcionales, utilizando para ello la Escala de Valoración funcional AOFAS (American Orthopaedic Foot and Ankle Society) para el antepié. Los resultados fueron considerados como buenos o excelentes desde el punto de vista funcional en 81% de los pies intervenidos y en el 89% desde el punto de vista estético. La puntuación final media en la escala AOFAS fue de 78,3. Tuvimos 3 casos de infección por estafilococo aureus que se resolvieron con tratamiento antibiótico específico. No se observaron pseudoartrosis. Por todo ello, consideramos que la osteotomía de Weil es una técnica adecuada y segura para tratar las metatarsalgias de causa mecánica.The aim of this retrospective study was to evaluate the short-term results after percutaneous Weil osteotomy for the treatment secondary metatarsalgia related to repetitive high-pressure loading under the metatarsal heads. We analyzed retrospectively clinical and radiological outcome of 28 consecutive patients who were treated with percutaneous, subcapital osteotomy for metatarsalgia with overload etiology. Analysis of the esthetic, functional and radiologic results was performed using AOFAS forefoot score. Good to excellent functional results were achieved in 81% of the feet, cosmetic in 89% with average score 78,3 points. Three patients developed a superficial wound infections, which responded to antibiotics. Union occurred in all cases. Percutaneous Weil osteotomy is safe and effective technique for treatment of secondary metatarsalgia with mechanic etiology

Prediction of Signed Protein Kinase Regulatory Circuits.

Complex networks of regulatory relationships between protein kinases comprise a major component of intracellular signaling. Although many kinase-kinase regulatory relationships have been described in detail, these tend to be limited to well-studied kinases whereas the majority of possible relationships remains unexplored. Here, we implement a data-driven, supervised machine learning method to predict human kinase-kinase regulatory relationships and whether they have activating or inhibiting effects. We incorporate high-throughput data, kinase specificity profiles, and structural information to produce our predictions. The results successfully recapitulate previously annotated regulatory relationships and can reconstruct known signaling pathways from the ground up. The full network of predictions is relatively sparse, with the vast majority of relationships assigned low probabilities. However, it nevertheless suggests denser modes of inter-kinase regulation than normally considered in intracellular signaling research. A record of this paper's transparent peer review process is included in the Supplemental Information

Report of the Workshop on Age estimation of European anchovy (Engraulis encrasicolus)

Based on the results of a full-scale otolith exchange held in 2014, the Working Group on Biological Parameters (WGBIOP 2015) identified the need for an age reading workshop on European Anchovy otoliths (WKARA2). This workshop (chaired by Andres Uriarte, Spain, Begoña Villamor, Spain and Gualtiero Basilone, Italy), was held in Pasaia, Gui-puzcoa (Spain) from the 28 November to 2 December 2016. Five countries took part in this workshop (Spain, Italy, Croatia, Greece and Tunisia), with a total of 16 participants from 9 laboratories. In total 17 areas/stocks were analysed (4 from the Atlantic area and 13 from Mediterranean Sea) The aim of this workshop was to review the information on age determination, discuss the results of the previous exchange (2014), review the validation methods existing on these species, clarify the interpretation of annual rings and update the age reading pro-tocol and a reference collection of well-defined otoliths. Age validation studies, in the Bay of Biscay and preliminary validation studies in Divi-sion 9a, Alboran Sea and Strait of Sicily areas were presented, including a compilation of age validation studies of this species as well in the literature. There are several ar-eas/stocks in which validations of the anchovy annual age determination have not been done yet. Due to the poor percentage of agreement achieved in the 2014 Exchange (mean agree-ment of 66%; mean CV of 58%), the workshop proceeded with a detailed and joint dis-cussion on the growth patterns shown by otoliths from the different areas to find out the major reasons for discrepancies in age determination among readers. At the same time, the joint discussion allowed a better understanding of the pattern of otolith growth in-crements by areas to improve the guidelines for their interpretation. The discussions on examples among otoliths which generated discrepancies in the age determination led to conclude that there were two major sources of disagreements: a) Divergent otolith inter-pretation: different interpretations of the marks, growth bands and edges in terms of their conformity with the expected growth pattern of the anchovies, seasonal formation of the otolith by ages and most common checks. and b) wrong application of the age allocation Rules: it was evidenced during the workshop that for the birthdate first July (or first June) in some cases the age determination rule was not being correctly applied during the first half of the year (from January to June). Following the workshop discussions there has been a progressive change in the percep-tion of the growth pattern applicable to these anchovy otoliths in many areas which led to some revisions of the otolith interpretation and assigned ages, by which growth at ages 0 and 1 are far prominent than at older ages and the occurrence of checks became more frequently admitted. Furthermore, there have been evidences that the age determination rules have in some instances been inconsistently applied. All these evidences led to con-clude on the need to review past age determinations. Although this task should be de-layed until running an exchange in 2018 to be sure that all the readers apply the protocol and the current criteria of this workshop coherently, since current criteria would change the otoliths interpretation and the age determination in many areas. In addition, for the Mediterranean regions the convenience of midyear birthdates was put in question in comparison with the simplicity of the conventional birthdates at first of January (as these anchovies are in the northern hemisphere). As a corollary of the former statements, intercalibration exercises by areas, for the differ-ent countries taking part in the age reading of the same exploited stock, are still required. Finally, this Workshop adopted a common protocol for all areas in order to standardize the anchovy age assignments and to improve the coherence of the age estimates. An agreed collection of otoliths by areas were produced and upload to the Age Readers Fo-rum

Issues related to the MEDITS reference list of species

The MEDITS survey programme started in 1994 and adopted the basic protocols by the four first partners, just before the first survey. These protocols included the design of the survey, the sampling gear, the information collected, and the management of the data as far as the production of common standardized analyses of the data (Bertrand et al., 2002). The last updating of protocols has been done in 2007 (MEDITS, 2007). According to it, for each species the total weight and number of individuals is recorded. For a reference list of 38 species of fish, crustaceans and cephalopods, the length frequency by sex must be reported, as well as the maturity stage of the gonads. However, two different things should be taken into account. On one hand, for most works performed using MEDITS data (including assessments), the length frequency distributions are used, without taking into account the sex. On the other hand, the period of the surveys is not always coincident with the spawning season for all the species in the MEDITS reference list. This document attempts to be a practical exercise in relation to these topics, using both surveys and commercial data, and gives some proposals to the reference list of specie

Current challenges in software solutions for mass spectrometry-based quantitative proteomics

This work was in part supported by the PRIME-XS project, grant agreement number 262067, funded by the European Union seventh Framework Programme; The Netherlands Proteomics Centre, embedded in The Netherlands Genomics Initiative; The Netherlands Bioinformatics Centre; and the Centre for Biomedical Genetics (to S.C., B.B. and A.J.R.H); by NIH grants NCRR RR001614 and RR019934 (to the UCSF Mass Spectrometry Facility, director: A.L. Burlingame, P.B.); and by grants from the MRC, CR-UK, BBSRC and Barts and the London Charity (to P.C.

Evaluation of the zucker diabetic fatty (ZDF) rat as a model for human disease based on urinary peptidomic profiles

Representative animal models for diabetes-associated vascular complications are extremely relevant in assessing potential therapeutic drugs. While several rodent models for type 2 diabetes (T2D) are available, their relevance in recapitulating renal and cardiovascular features of diabetes in man is not entirely clear. Here we evaluate at the molecular level the similarity between Zucker diabetic fatty (ZDF) rats, as a model of T2D-associated vascular complications, and human disease by urinary proteome analysis. Urine analysis of ZDF rats at early and late stages of disease compared to age- matched LEAN rats identified 180 peptides as potentially associated with diabetes complications. Overlaps with human chronic kidney disease (CKD) and cardiovascular disease (CVD) biomarkers were observed, corresponding to proteins marking kidney damage (eg albumin, alpha-1 antitrypsin) or related to disease development (collagen). Concordance in regulation of these peptides in rats versus humans was more pronounced in the CVD compared to the CKD panels. In addition, disease-associated predicted protease activities in ZDF rats showed higher similarities to the predicted activities in human CVD. Based on urinary peptidomic analysis, the ZDF rat model displays similarity to human CVD but might not be the most appropriate model to display human CKD on a molecular level

Spatial and temporal variability of discards indicators and fishery factors affecting otter-trawl fishery in the spanish Mediterranean sea

A set of diversity indices were studied from data of observers on board two Mediterranean trawlers from 2001 to 2009. These diversity indices comprise relationships between total catch, landing and discard fractions to explore the accuracy of the estimates and to analyse the series trends using different methods, such as ARIMA. The hypothesis tested was that diversity indicators give a good representation of the changes produced in impacted bottom‐trawl areas, providing a reasonable fit of the data. ARIMA models are useful because they handle time-correlated modelling and forecasting. These techniques can also reveal changes in total catch as well changes in catch composition, probably induced by changes in effort fishery, seasonal (time) fluctuations, and environmental or climatic processes. Contrasted trends were also compared with survey data by MEDITS Mediterranean trawl survey time‐series indicator

Adipocytes disrupt the translational programme of acute lymphoblastic leukaemia to favour tumour survival and persistence

The specific niche adaptations that facilitate primary disease and Acute Lymphoblastic Leukaemia (ALL) survival after induction chemotherapy remain unclear. Here, we show that Bone Marrow (BM) adipocytes dynamically evolve during ALL pathogenesis and therapy, transitioning from cellular depletion in the primary leukaemia niche to a fully reconstituted state upon remission induction. Functionally, adipocyte niches elicit a fate switch in ALL cells towards slow-proliferation and cellular quiescence, highlighting the critical contribution of the adipocyte dynamic to disease establishment and chemotherapy resistance. Mechanistically, adipocyte niche interaction targets posttranscriptional networks and suppresses protein biosynthesis in ALL cells. Treatment with general control nonderepressible 2 inhibitor (GCN2ib) alleviates adipocyte-mediated translational repression and rescues ALL cell quiescence thereby significantly reducing the cytoprotective effect of adipocytes against chemotherapy and other extrinsic stressors. These data establish how adipocyte driven restrictions of the ALL proteome benefit ALL tumours, preventing their elimination, and suggest ways to manipulate adipocyte-mediated ALL resistance

Perineural invasion in pancreatic cancer: proteomic analysis and in vitro modelling.

Perineural invasion (PNI) is a common and characteristic feature of pancreatic ductal adenocarcinoma (PDAC) that is associated with poor prognosis, tumor recurrence, and generation of pain. However, the molecular alterations in cancer cells and nerves within PNI have not previously been comprehensively analysed. Here, we describe our proteomic analysis of the molecular changes underlying neuro-epithelial interactions in PNI using liquid chromatography-mass spectrometry (LC-MS/MS) in microdissected PNI and non-PNI cancer, as well as invaded and non-invaded nerves from formalin-fixed, paraffin-embedded PDAC tissues. In addition, an in vitro model of PNI was developed using a co-culture system comprising PDAC cell lines and PC12 cells as the neuronal element. The overall proteomic profiles of PNI and non-PNI cancer appeared largely similar. In contrast, upon invasion by cancer cells, nerves demonstrated widespread plasticity with a pattern consistent with neuronal injury. The upregulation of SCG2 (secretogranin II) and neurosecretory protein VGF (non-acronymic) in invaded nerves in PDAC tissues was further validated using immunohistochemistry. The tested PDAC cell lines were found to be able to induce neuronal plasticity in PC12 cells in our in vitro established co-culture model. Changes in expression levels of VGF, as well as of two additional proteins previously reported to be overexpressed in PNI, Nestin and Neuromodulin (GAP43), closely recapitulated our proteomic findings in PDAC tissues. Furthermore, induction of VGF, while not necessary for PC12 survival, mediated neurite extension induced by PDAC cell lines. In summary, here we report the proteomic alterations underlying PNI in PDAC and confirm that PDAC cells are able to induce neuronal plasticity. In addition, we describe a novel, simple, and easily adaptable co-culture model for in vitro study of neuro-epithelial interactions