Cysteine and Folate metabolism are targetable vulnerabilities of metastatic colorectal cancer

With most cancer-related deaths resulting from metastasis, the development of new therapeutic approaches against metastatic colorectal cancer (mCRC) is essential to increasing patient survival. The metabolic adaptations that support mCRC remain undefined and their elucidation is crucial to identify potential therapeutic targets. Here, we employed a strategy for the rational identification of targetable metabolic vulnerabilities. This strategy involved first a thorough metabolic characterisation of same-patient-derived cell lines from primary colon adenocarcinoma (SW480), its lymph node metastasis (SW620) and a liver metastatic derivative (SW620-LiM2), and second, using a novel multi-omics integration workflow, identification of metabolic vulnerabilities specific to the metastatic cell lines. We discovered that the metastatic cell lines are selectively vulnerable to the inhibition of cystine import and folate metabolism, two key pathways in redox homeostasis. Specifically, we identified the system xCT and MTHFD1 genes as potential therapeutic targets, both individually and combined, for combating mCRC

Impacto antrópico en el Manto Acuífero Barva (Heredia, Costa Rica) con énfasis en el uso del suelo (1992-2006)

The advance of urbanization in the Central Valley of Costa Rica is having negative impacts on land use and stresses the environment with a high demand of natural resources, particularly water resources. One example is the Barva Water Table, one of the main water suppliers of semi-urban areas of the Greater Metropolitan Area of Costa Rica, which leads to conflicts between social actors involved with this resource. Comparing land use maps of the area defined by Act LXV of 1888, as well as the literature, we found that forest cover is decreasing while area covered by crops and pastures has increased from 1992 and 2006. At the same time, the forest area has undergone a process of fragmentation, and the increasing number of forest patches has an edge effect in all classes of land use. We recommend sustainable governance of water resources in the protected area’s buffer zone, with the participation of the local government, development associations, and other related public and private institutions.El gran avance de la urbanización en el Valle Central de Costa Rica está generando impactos negativos sobre el uso del suelo y está sometiendo al ambiente a intensas presiones debido a la gran demanda de los recursos naturales, particularmente del hídrico. El Manto Acuífero Barva, una de las principales fuentes de agua que abastece zonas urbanas y semiurbanas de la Gran Área Metropolitana, actualmente se encuentra bajo una fuerte presión de cambio de uso en el suelo, lo que a su vez genera conflictos entre diferentes actores sociales involucrados con este recurso. Comparando los mapas de uso de suelo de 1992 y 2006 referentes a la zona delimitada por la Ley LXV de 1888, así como diversas fuentes bibliográficas, se observa que el área boscosa está disminuyendo mientras que la zona de cultivos y pasturas ha aumentado. Asimismo, la región ha sufrido un proceso de fragmentación, lo que se refleja en el aumento de parches, así como del efecto de borde en todas las clases de uso de suelo. Se recomienda iniciar un proceso de gestión participativa y de gobernabilidad sostenible del recurso hídrico en la zona de amortiguamiento del área protegida y así desarrollar acciones de manera conjunta con las comunidades ubicadas en la zona de influencia, con los gobiernos locales, asociaciones de desarrollo, instituciones públicas y privadas interesadas o directamente relacionadas con la protección, conservación y manejo sostenible de los recursos hídricos.

Workforce preparation: the Biohealth computing model for Master and PhD students

The article addresses the strategic role of workforce preparation in the process of adoption of Systems Medicine as a driver of biomedical research in the new health paradigm. It reports on relevant initiatives, like CASyM, fostering Systems Medicine at EU level. The chapter focuses on the BioHealth Computing Program as a reference for multidisciplinary training of future systems-oriented researchers describing the productive interactions with the Synergy-COPD project

TFG 2015/2016

Amb aquesta publicació, EINA, Centre universitari de Disseny i Art adscrit a la Universitat Autònoma de Barcelona, dóna a conèixer el recull dels Treballs de Fi de Grau presentats durant el curs 2015-2016. Voldríem que un recull com aquest donés una idea més precisa de la tasca que es realitza a EINA per tal de formar nous dissenyadors amb capacitat de respondre professionalment i intel·lectualment a les necessitats i exigències de la nostra societat. El treball formatiu s’orienta a oferir resultats que responguin tant a paràmetres de rigor acadèmic i capacitat d’anàlisi del context com a l’experimentació i la creació de nous llenguatges, tot fomentant el potencial innovador del disseny.Con esta publicación, EINA, Centro universitario de diseño y arte adscrito a la Universidad Autónoma de Barcelona, da a conocer la recopilación de los Trabajos de Fin de Grado presentados durante el curso 2015-2016. Querríamos que una recopilación como ésta diera una idea más precisa del trabajo que se realiza en EINA para formar nuevos diseñadores con capacidad de responder profesional e intelectualmente a las necesidades y exigencias de nuestra sociedad. El trabajo formativo se orienta a ofrecer resultados que respondan tanto a parámetros de rigor académico y capacidad de análisis, como a la experimentación y la creación de nuevos lenguajes, al tiempo que se fomenta el potencial innovador del diseño.With this publication, EINA, University School of Design and Art, affiliated to the Autonomous University of Barcelona, brings to the public eye the Final Degree Projects presented during the 2015-2016 academic year. Our hope is that this volume might offer a more precise idea of the task performed by EINA in training new designers, able to speak both professionally and intellectually to the needs and demands of our society. The educational task is oriented towards results that might respond to the parameters of academic rigour and the capacity for contextual analysis, as well as to considerations of experimentation and the creation of new languages, all the while reinforcing design’s innovative potential

Preparation of a mesoporous silica-based nano-vehicle for dual DOX/CPT pH-triggered delivery

A dual doxorubicin/camptothecin (DOX/CPT) pH-triggered drug delivery mesoporous silica nanoparticle (MSN)-based nano-vehicle has been prepared. In this drug-delivery system (DDS), CPT is loaded inside the pores of the MSNs, while DOX is covalently attached to the surface of an aldehyde-functionalized MSN through a dihydrazide–polyethylene glycol chain. Thus, DOX and the linker act as pH-sensitive gatekeeper. The system is versatile and easy to assemble, not requiring the chemical modification of the drugs. While at physiological conditions the release of the drugs is negligible, at acidic pH a burst release of DOX and a gradual release of CPT take place. In vitro cytotoxicity tests have demonstrated that this DDS can deliver efficiently DOX and CPT for combination therapy

Biogenic Amine Levels Markedly Increase in the Aqueous Humor of Individuals with Controlled Type 2 Diabetes.

The composition of the aqueous humor of patients with type 2 diabetes is relevant to understanding the underlying causes of eye-related comorbidities. Information on the composition of aqueous humor in healthy subjects is limited due to the lack of adequate controls. To carry out a metabolomics study, 31 samples of aqueous humor from healthy subjects without ocular pathology, submitted to refractive surgery and seven samples from patients with type 2 diabetes without signs of ocular pathology related to diabetes were used. The level of 25 molecules was significantly (p < 0.001) altered in the aqueous humor of the patient group. The concentration of a single molecule, N-acetylornithine, makes it possible to discriminate between control and diabetes (sensitivity and specificity equal to 1). In addition, receptor operating characteristic curve and principal component analysis for the above-mentioned six molecules yielded significantly (p < 0.001) altered in the aqueous humor of the patient group. In addition, receptor operating characteristic curve and principal component analysis for six compounds yielded cut-off values and remarkable sensitivity, specificity, and segregation ability. The altered level of N-acetylornithine may be due to an increased amount of acetate in diabetes. It is of interest to further investigate whether this alteration is related to the pathogenesis of the disease. The increase in the amino form of pyruvate, alanine, in diabetes is also relevant because it could be a means of reducing the formation of lactate from pyruvate

Noninvasive prediction models of intra-amniotic infection in women with preterm labor

Among women with preterm labor, those with intraamniotic infection present the highest risk of early delivery and the most adverse outcomes. The identification of intra-amniotic infection requires amniocentesis, perceived as too invasive by women and physicians. Noninvasive methods for identifying intra-amniotic infection and/or early delivery are crucial to focus early efforts on high-risk preterm labor women while avoiding unnecessary interventions in low-risk preterm labor women