Protein tyrosine phosphatase-1B modulates pancreatic β-cell mass

Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of the insulin signalling pathway. It has been demonstrated that PTP1B deletion protects against the development of obesity and Type 2 Diabetes, mainly through its action on peripheral tissues. However, little attention has been paid to the role of PTP1B in β-cells. Therefore, our aim was to study the role of PTP1B in pancreatic β-cells. Silencing of PTP1B expression in a pancreatic β-cell line (MIN6 cells) reveals the significance of this endoplasmic reticulum bound phosphatase in the regulation of cell proliferation and apoptosis. Furthermore, the ablation of PTP1B is able to regulate key proteins involved in the proliferation and/or apoptosis pathways, such as STAT3, AKT, ERK1/2 and p53 in isolated islets from PTP1B knockout (PTP1B (-)/(-)) mice. Morphometric analysis of pancreatic islets from PTP1B (-)/(-) mice showed a higher β-cell area, concomitantly with higher β-cell proliferation and a lower β-cell apoptosis when compared to islets from their respective wild type (WT) littermates. At a functional level, isolated islets from 8 weeks old PTP1B (-)/(-) mice exhibit enhanced glucose-stimulated insulin secretion. Moreover, PTP1B (-)/(-) mice were able to partially reverse streptozotocin-induced β-cell loss. Together, our data highlight for the first time the involvement of PTP1B in β-cell physiology, reinforcing the potential of this phosphatase as a therapeutical target for the treatment of β-cell failure, a central aspect in the pathogenesis of Type 2 Diabete

ooi: OpenStack OCCI interface

In this document we present an implementation of the Open Grid Forum’s Open Cloud Computing Interface (OCCI) for OpenStack, namely ooi (Openstack occi interface, 2015). OCCI is an open standard for management tasks over cloud resources, focused on interoperability, portability and integration. ooi aims to implement this open interface for the OpenStack cloud middleware, promoting interoperability with other OCCI-enabled cloud management frameworks and infrastructures. ooi focuses on being non-invasive with a vanilla OpenStack installation, not tied to a particular OpenStack release version

Controllable production of Janus ligaments by AC fields in a flow-focusing junction

We report the production of bicomponent Janus filaments of miscible aqueous fluids in a micro- fluidic electro-flow focusing device under the action of an AC electric field. The production of liquid filaments can lead to the generation of microfibers by adding a subsequent process of polymerization. Janus microfi- bers are of paramount importance in biomedical appli- cations such as tissue production on crimped scaffolds. We show that the filament length is a function of the frequency signal, voltage amplitude and of the visco- sity and conductivity of the dispersed phase. In par- ticular, Janus filaments with diameters ∼ 10μm and longer than 1 mm are produced by AC voltages with frequencies below 150 kHz and a viscosity of the dis- persed phase ∼ 10 cP

Droplet group production in an AC electro-flow-focusing microdevice

We report the production of droplet groups with a controlled number of drops in a microfluidic electro-flow focusing device under the action of an AC electric field. This regime appears for moderate voltages (500-700 V peak-to-peak) and signal frequencies between 25 and 100 Hz, much smaller than the droplet production rate ( ≈500 Hz). For this experimental conditions the production frequency of a droplet package is twice the signal frequency. Since the continuous phase flow in the microchannel is a Hagen-Poiseuille flow, the smaller droplets of a group move faster than the bigger ones leading to droplet clustering downstream.Ministerio de Economía y Competitividad DPI2013-46485-C3-1-RMinisterio de Economía y Competitividad FIS2014-54539- PJunta de Andalucía P11-FQM-791

Evaluation of Feature Selection Techniques for Breast Cancer Risk Prediction

This study evaluates several feature ranking techniques together with some classifiers based on machine learning to identify relevant factors regarding the probability of contracting breast cancer and improve the performance of risk prediction models for breast cancer in a healthy population. The dataset with 919 cases and 946 controls comes from the MCC-Spain study and includes only environmental and genetic features. Breast cancer is a major public health problem. Our aim is to analyze which factors in the cancer risk prediction model are the most important for breast cancer prediction. Likewise, quantifying the stability of feature selection methods becomes essential before trying to gain insight into the data. This paper assesses several feature selection algorithms in terms of performance for a set of predictive models. Furthermore, their robustness is quantified to analyze both the similarity between the feature selection rankings and their own stability. The ranking provided by the SVM-RFE approach leads to the best performance in terms of the area under the ROC curve (AUC) metric. Top-47 ranked features obtained with this approach fed to the Logistic Regression classifier achieve an AUC = 0.616. This means an improvement of 5.8% in comparison with the full feature set. Furthermore, the SVM-RFE ranking technique turned out to be highly stable (as well as Random Forest), whereas relief and the wrapper approaches are quite unstable. This study demonstrates that the stability and performance of the model should be studied together as Random Forest and SVM-RFE turned out to be the most stable algorithms, but in terms of model performance SVM-RFE outperforms Random Forest.The study was partially funded by the “Accion Transversal del Cancer”, approved on the Spanish Ministry Council on the 11th October 2007, by the Instituto de Salud Carlos III-FEDER (PI08/1770, PI08/0533, PI08/1359, PS09/00773, PS09/01286, PS09/01903, PS09/02078, PS09/01662, PI11/01403, PI11/01889, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150), by the Fundación Marqués de Valdecilla (API 10/09), by the ICGC International Cancer Genome Consortium CLL, by the Junta de Castilla y León (LE22A10-2), by the Consejería de Salud of the Junta de Andalucía (PI-0571), by the Conselleria de Sanitat of the Generalitat Valenciana (AP 061/10), by the Recercaixa (2010ACUP 00310), by the Regional Government of the Basque Country by European Commission grants FOOD-CT- 2006-036224- HIWATE, by the Spanish Association Against Cancer (AECC) Scientific Foundation, by the The Catalan Government DURSI grant 2009SGR1489. Samples: Biological samples were stored at the Parc de Salut MAR Biobank (MARBiobanc; Barcelona) which is supported by Instituto de Salud Carlos III FEDER (RD09/0076/00036). Furthermore, at the Public Health Laboratory from Gipuzkoa and the Basque Biobank. Furthermore, sample collection was supported by the Xarxa de Bancs de Tumors de Catalunya sponsored by Pla Director d’Oncologia de Catalunya (XBTC). Biological samples were stored at the “Biobanco La Fe” which is supported by Instituto de Salud Carlos III (RD 09 0076/00021) and FISABIO biobanking, which is supported by Instituto de Salud Carlos III (RD09 0076/00058).S

Microarrays as Platform for Multiplex Assays in Biomarker and Drug Discovery

Despite the tremendous advances in the understanding of the molecular mechanisms and the complexity of the diseases is one of the present challenges for the scientific community; then, novel strategies are required to be designed and developed for effective strategies for early diagnosis and treatment. As many cellular alterations are observed at protein level, high-throughput assays are dramatically needed for biomarker discovery. Herein, we describe advantages and limitations of protein microarrays, as proteomics strategy useful for multiplex and high-throughput protein characterization in clinical samples. Finally, a few examples are discussed; mostly of them related to currently disease biomarkers already identified in proximal fluids by protein arrays are discussed

Extendiendo ABP con feedback ágil en la enseñanza de Ingeniería del Software

El Aprendizaje Basado en Proyectos (ABP) ha sido aplicado con éxito en diversas áreas de la docencia de la informática en el ámbito universitario. A su vez, a nivel industrial en el contexto de la ingeniería del software, las metodologías ágiles se han instaurado como la opción más utilizada para el desarrollo de proyectos gracias en parte a su promoción de un feedback temprano y continuo que ayuda a enfocar y adaptar el desarrollo a las necesidades del cliente. Este artículo presenta una experiencia piloto que aúna ambos conceptos, extendiendo el enfoque ABP para incorporar el ciclo de feedback rápido y continuo de las metodologías ágiles en la docencia de ingeniería del software. Dicho ciclo se incorpora mediante la aplicación de una evaluación continua de las tareas realizadas por el alumno, en base a un backlog de tareas semanales y a listas de verificación que permiten evaluar el trabajo realizado de manera objetiva. Los resultados obtenidos son prometedores, tanto en términos de la distribución de notas de los alumnos como en cuanto a la motivación de los alumnos con asignatura. Finalmente, se ha realizado un análisis pormenorizado de las numerosas métricas recolectadas de las distintas plataformas utilizadas que ha permitido un estudio de las tipologías de alumnos y la obtención de un conjunto de lecciones aprendidas que pueden ser aplicadas en el diseño de experiencias docentes similares.Project Based Learning (PBL) has been successfully applied in a number of scenarios as part of the Computer Science teaching. Alternatively, from the software industry point of view, agile methodologies represent a first class citizen being the most suitable choice in several cases as they boost an early customer feedback so it can be adapted to its needs. This paper presents a first experience combining PBL and Agile methodologies in Software Engineering course. Specifically, our approach combines the usage of a weekly backlog with a peer-reviewing process based on checklists that allow an accurate continuous evaluation of students performance. The results analysis of our experience shows an appropriate distribution of scores and a significant improvement in the student motivation. Additionally, we detail the analysis of a number of metrics in order to characterize some students patterns that support a list of lessons learned to potentially improve the teaching in similar courses

Enfermeiras Consultoras em feridas Crónicas

Em diferentes países à nossa volta foi criada a figura da enfermeira consultora ficando demonstrada a sua efetividade tanto a nível clínico sobre utentes com lesões de perna, úlceras por pressão ou recentemente o pé diabético, do mesmo modo sobre a satisfação dos utentes. Figura muito valorizada nos centros onde existem ou entre os próprios profissionais como líderes de opinião capazes de difundir informação adequada ao resto de profissionais de saúde relacionados com as feridas crónicas, o que representa um efeito importante sobre a prática clínica diária.info:eu-repo/semantics/publishedVersio

Amino modified metal-organic frameworks as pH-responsive nanoplatforms for safe delivery of camptothecin

[EN] MIL-100(Fe) and MIL-101(Fe) metal-organic frameworks (MOFs) are excellent vehicles for drug delivery systems (DDSs) due to their high biocompatibility and stability in physiological fluids, as well as their pore diameter in the mesoporous range. Although they are appropriate for the internal diffusion of 20-(S)-camptothecin (CPT), a strongly cytotoxic molecule with excellent antitumor activity, no stable delivery system has been proposed so far for this drug based in MOFs. We here present novel DDSs based in amine functionalized MIL-100(Fe) and MIL-101(Fe) nanoMOFs with covalently bonded CPT. These CPT nanoplatforms are able to incorporate almost 20% of this molecule and show high stability at physiological pH, with no non-specific release. Based on their surface charge, some of these CPT loaded nanoMOFs present improved cell internalization in in vitro experiments. Moreover, a strong response to acid pH is observed, with up to four fold drug discharge at pH 5, which boost intracellular release by endosomolytic activity. These novel DDSs will help to achieve safe delivery of the very cytotoxic CPT, allowing to reduce the therapeutic dose and minimizing drug secondary effects. (C) 2019 Elsevier Inc. All rights reserved.Financial support of the Spanish Ministry of Economy and Competitiveness (projects TEC2016-80976-R and SEV-2016-0683) is gratefully acknowledged. A.C.G. thanks the La Caixa Foundation for a Ph.D. scholarship. We fully appreciate the assistance of the Electron Microscopy Service of the Universitat Politecnica de Valencia.Cabrera-García, A.; Checa-Chavarria, E.; Rivero-Buceta, EM.; Moreno Manzano, V.; Fernandez Jover, E.; Botella Asuncion, P. (2019). Amino modified metal-organic frameworks as pH-responsive nanoplatforms for safe delivery of camptothecin. Journal of Colloid and Interface Science. 541:163-174. https://doi.org/10.1016/j.jcis.2019.01.042S16317454

Deterioro cognito disejecutivo en pacientes con enfermedad coronaria: asociación con variables clínicas

Las enfermedades cardiacas se asocian con un incremento del riesgo de deterioro cognitivo. Hemos estudiado en pacientes coronarios la presencia de deterioro cognitivo leve (DCL) disejecutivo y su asociación con variables sociodemográficas y clínicas. Se ha evaluado en 35 pacientes la función ejecutiva (Trail Making Test, TMT; puntuaciones ajustadas por edad y escolaridad, NEURONORMA). Los pacientes presentaron rendimiento normal o con DCL (percentil de distribución TMT<10%). Se compararon ambos grupos y se estudió la relación del TMT con variables sociodemográficas y clínicas (pruebas no paramétricas y estudio de regresión múltiple). Los pacientes (66 ± 9 años, 69,4% varones) se clasificaron en grupos con rendimiento normal (n=28, 80%) o con rendimiento ejecutivo deficitario (n=7, 20%). El grupo con DCL disejecutivo presentó mayor grado de angina (p=0.03, Canadian Cardiovascular Society), enfermedad de 3 vasos (p=0,04) e índice de masa corporal (p=0.03) y menor tensión arterial diastólica (p=0.02), hemoglobina (p=0.02) y hematocrito (p=0.0001); estas variables resultaron significativas del rendimiento en el TMT como variable dependiente (R2=0,62) Se muestra en pacientes con enfermedad coronaria una importante prevalencia de DCL disejecutivo asociado al nivel de angina y otros factores de riesgo cardiovascular. Se recomienda realizar evaluación neuropsicológica y seguimiento de pacientes con enfermedad coronaria severa por su mayor riesgo de deterioro cognitivo y funcionalUniversidad de Málaga. Campus de Excelencia Internacional Andalucía Tech