Enzyme activation by alternating magnetic field: Importance of the bioconjugation methodology

Iron oxide nanoparticles (NPs) are attractive materials for enzyme immobilization and, thanks to their superparamagnetism, can be accessed by remote stimuli. This can be exploited to activate molecules that are not remotely actuable. Here, we demonstrate that thermophilic enzymes chemically linked to NPs can be activated in a \u201cwireless\u201d fashion by an external alternate magnetic field (AMF). To this aim, we have conjugated, with different binding strategies, the thermophilic enzymes \u3b1-amylase and L-aspartate oxidase to iron oxide NPs obtaining NP-enzyme systems with activities depending on the different orientations and stretching of the enzymes. Since enzyme activation occurs without a significant rise of the \u201coverall\u201d temperature of the systems, we have speculated a local NP-enzyme heating that does not immediately interest the rest of the solution that remains at relatively low temperature, low enough to allow non-thermophilic enzymes to work together with the NP-conjugated thermophilic enzymes. Nanoactuation of thermophilic enzymes by AMF has potential applications in different fields. Indeed, multi-enzymatic processes with enzymes with different temperature optima could be carried out in the same reaction pot and thermolabile products could be efficiently produced by thermophilic enzymes without suffering for the high temperatures. Moreover, our findings represent a proof of concept of the possibility to achieve a fine-tuning of the enzyme-NP system with the aim to intervene in cell metabolism

Remote activation of enzyme nanohybrids for cancer prodrug therapy controlled by magnetic heating

Herein, we have developed nanohybrids (nHs) to remotely activate a therapeutic enzyme for its use in Directed Enzyme Prodrug Therapy (DEPT). The coencapsulation of magnetic nanoparticles (MNPs) with horseradish peroxidase (HRP) using biomimetic silica as an entrapment matrix was optimized to obtain nanosized hybrids (∼150 nm) for remote activation of the therapeutic enzyme. HRP converts indole-3-acetic acid (3IAA) into peroxylated radicals, whereas MNPs respond to alternating magnetic fields (AMFs) becoming local hotspots. The AMF application triggered an increase in the bioconversion rate of HRP matching the activity displayed at the optimal temperature of the nHs (Topt = 50 °C) without altering the temperature of the reaction media. This showed that enzyme nanoactuation is possible with MNPs even if they are not covalently bound. After an extensive physicochemical/magnetic characterization, the spatial location of each component of the nH was deciphered, and an insulating role of the silica matrix was suggested as critical for introducing remote control over HRP. In vitro assays, using a human pancreatic cancer cell line (MIA PaCa-2), showed that only upon exposure to AMF and in the presence of the prodrug, the enzyme-loaded nHs triggered cell death. Moreover, in vivo experiments showed higher reductions in the tumor volume growth in those animals treated with nHs in the presence of 3IAA when exposed to AMF. Thus, this work demonstrates the feasibility of developing a spatiotemporally controlled DEPT strategy to overcome unwanted off-target effects

Game Based Learning on Urban Sustainability: The "Sustain" Project

SUSTAIN is an ERASMUS+ project with an innovative perspective on urban sustainability. Its target is to promote the importance of sustainability on the everyday problems of the cities among the students of higher education, which are the policy makers of tomorrow and the ones that will shape the future. In order to achieve its goals, the research team will develop a course that will be based on an interactive game with an analytical style of education. This game will allow students to learn about transportation sustainability and societal metabolism through playing. In addition, the research team will develop small and illustrative simulation models, which will make the definitions more concrete and allow students to experiment in a consequence-free environment. It is a quite innovative and hybrid perspective way of learning, in the sense that it will combine game-based learning with a cognitive and analytical style of education

Estudio e investigaciones realizadas en el LEMIT sobre materiales empleados en edificios históricos

Cuando se abordan problemas de restauración, reparación y conservación de edificios y construcciones de valor histórico se debe realizar, antes de iniciar las tareas de puesta en valor, un estudio integral de las causales que han provocado los deterioros. Esta situación es de primordial importancia, ya que si no se eliminan las causales, rápidamente reaparecen los signos externos de las alteraciones. Sin embargo, muchas de las alteraciones y/o deterioros de las construcciones de valor patrimonial y/o de los materiales que las constituyen se deben, con exclusividad, al pasaje del tiempo (vida en servicio de la construcción). Los materiales empleados en la construcción experimentan procesos de deterioro por reacciones físico, químicas o físico-químicas entre el material y los agentes agresivos o el originado por el crecimiento de microorganismos, en particular algas en sectores húmedos y sombríos y/o líquenes o plantas mayores como por ejemplo helechos. En este trabajo se presentan investigaciones y estudios de distintos materiales constituyentes de construcciones de valor patrimonial, en particular, se analizan ladrillos cerámicos comunes, mezclas de asiento, morteros internos y externos, tejas y materiales de revestimiento (cerámicos, pinturas y papel). Estos estudios fueron realizados para la caracterización de los materiales y/o para disponer de información técnica para su restauración o reemplazo. En todos los casos, se informan las técnicas de caracterización mecánica, física y química empleadas para su evaluación. En algunos casos, se realizan estudios de difracción de rayos X, microscopia electrónica de barrido (SEM), cortes petrográficos, análisis en lupa microscópica y microscopio petrográfico. Además, se han aplicado técnicas para determinar color y rugosidad

Impact of DNA damage repair alterations on prostate cancer progression and metastasis

Prostate cancer is among the most common diseases worldwide. Despite recent progress with treatments, patients with advanced prostate cancer have poor outcomes and there is a high unmet need in this population. Understanding molecular determinants underlying prostate cancer and the aggressive phenotype of disease can help with design of better clinical trials and improve treatments for these patients. One of the pathways often altered in advanced prostate cancer is DNA damage response (DDR), including alterations in BRCA1/2 and other homologous recombination repair (HRR) genes. Alterations in the DDR pathway are particularly prevalent in metastatic prostate cancer. In this review, we summarise the prevalence of DDR alterations in primary and advanced prostate cancer and discuss the impact of alterations in the DDR pathway on aggressive disease phenotype, prognosis and the association of germline pathogenic1 alterations in DDR genes with risk of developing prostate cancer

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Identifying priority healthcare trainings in frozen conflict situations: The case of Nagorno Karabagh

<p>Abstract</p> <p>Introduction</p> <p>Health care in post-war situations, where the system's human and fixed capital are depleted, is challenging. The addition of a frozen conflict situation, where international recognition of boundaries and authorities are lacking, introduces further complexities.</p> <p>Case description</p> <p>Nagorno Karabagh (NK) is an ethnically Armenian territory locked within post-Soviet Azerbaijan and one such frozen conflict situation. This article highlights the use of evidence-based practice and community engagement to determine priority areas for health care training in NK. Drawing on the precepts of APEXPH (Assessment Protocol for Excellence in Public Health) and MAPP (Mobilizing for Action through Planning and Partnerships), this first-of-its-kind assessment in NK relied on in-depth interviews and focus group discussions supplemented with expert assessments and field observations. Training options were evaluated against a series of ethical and pragmatic principles.</p> <p>Discussion and Evaluation</p> <p>A unique factor among the ethical and pragmatic considerations when prioritizing among alternatives was NK's ambiguous political status and consequent sponsor constraints. Training priorities differed across the region and by type of provider, but consensus prioritization emerged for first aid, clinical Integrated Management of Childhood Illnesses, and Adult Disease Management. These priorities were then incorporated into the training programs funded by the sponsor.</p> <p>Conclusions</p> <p>Programming responsive to both the evidence-base and stakeholder priorities is always desirable and provides a foundation for long-term planning and response. In frozen conflict, low resource settings, such an approach is critical to balancing the community's immediate humanitarian needs with sponsor concerns and constraints.</p