An informatics training environment for the integrated study of major depressive disorder

[EN]The complex brain alterations in major depressive disorder are difficult to address in training contexts. The increase in available evidence obtained through medical imaging studies and the latest information and communication technology developments offer favorable conditions to face this challenge. The objective of this paper is to generate a computer application that allows us to integrate and present, visually and interactively, the relevant contents to this clinical condition in training contexts. The implications of this digital resource are discussed in the teaching and learning process within the framework of the cognitive load theory.Centro de Imagen y Tecnología del Conocimiento Biomédico (CITECB) (Spain

Desarrollos informáticos para la generación de entornos virtuales y personajes animados tridimensionales con fines docentes

[ES]La creación de entornos virtuales de aprendizaje y personajes animados, constituye una excelente alternativa de enseñanza-aprendizaje, en el que los estudiantes pueden aprender conceptos, ideas, y actitudes. Sin embargo, saber elegir un desarrollo informático adecuado para estos fines, no es tarea fácil, dado el gran número de software comercial existente. Presentamos unos procedimientos informáticos excelentes que permiten generar personajes animados en tres dimensiones, para crear escenas próximas a la realidad, simulando entornos de aprendizaje que optimice y mejoren la docencia universitaria. Destacamos cuatro herramientas informáticas: Poser, Maya, 3ds Max y ZBrush. No cabe duda que la utilización de estos recursos didácticos, suponen un método atractivo, de apoyo y refuerzo, para transmitir información a los alumnos. Las aportaciones informáticas, para la generación de entornos virtuales, traen consigo nuevas formas de enseñanza y de comunicación, más atractivos, dinámicos y amenos, lo que repercutirá, sin duda, en una mejora significativa del aprendizaje. Por tanto estos procedimientos tecnológicos constituyen un beneficio y un aporte didáctico muy útil en la acción educativa de enseñanza-aprendizaje de los alumnos

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

Restoring the Immunity in the Tumor Microenvironment: Insights into Immunogenic Cell Death in Onco-Therapies.

[EN]Immunogenic cell death (ICD) elicited by cancer therapy reshapes the tumor immune microenvironment. A long-term adaptative immune response can be initiated by modulating cell death by therapeutic approaches. Here, the major hallmarks of ICD, endoplasmic reticulum (ER) stress, and damage-associated molecular patterns (DAMPs) are correlated with ICD inducers used in clinical practice to enhance antitumoral activity by suppressing tumor immune evasion. Approaches to monitoring the ICD triggered by antitumoral therapeutics in the tumor microenvironment (TME) and novel perspective in this immune system strategy are also reviewed to give an overview of the relevance of ICD in cancer treatment

Autoimmune responses in oncology: Causes and significance

© 2021 by the authors.Specific anti-tumor immune responses have proven to be pivotal in shaping tumorigenesis and tumor progression in solid cancers. These responses can also be of an autoimmune nature, and autoantibodies can sometimes be present even before the onset of clinically overt disease. Autoantibodies can be generated due to mutated gene products, aberrant expression and post-transcriptional modification of proteins, a pro-immunogenic milieu, anti-cancer treatments, cross-reactivity of tumor-specific lymphocytes, epitope spreading, and microbiota-related and genetic factors. Understanding these responses has implications for both basic and clinical immunology. Autoantibodies in solid cancers can be used for early detection of cancer as well as for biomarkers of prognosis and treatment response. High-throughput techniques such as protein microarrays make parallel detection of multiple autoantibodies for increased specificity and sensitivity feasible, affordable, and quick. Cancer immunotherapy has revolutionized cancer treatments and has made a considerable impact on reducing cancer-associated morbidity and mortality. However, immunotherapeutic interventions such as immune checkpoint inhibition can induce immune-related toxicities, which can even be life-threatening. Uncovering the reasons for treatment-induced autoimmunity can lead to fine-tuning of cancer immunotherapy approaches to evade toxic events while inducing an effective anti-tumor immune response.We gratefully acknowledge financial support from the Spanish Health Institute Carlos III (ISCIII) for grants FIS PI14/01538, FIS PI17/01930, and CB16/12/00400. We also acknowledge Fondos FEDER (EU), Junta Castilla-León (COVID-19 grant COV20EDU/00187), and Fundación Solórzano FS/38-2017. The Proteomics Unit belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019/0023 of the PE I + D + I 2017–2020 and funded by ISCIII and FEDER. A. Landeira-Viñuela is supported by the VIII Centenario-USAL PhD Program. P. Juanes-Velasco is supported by the JCYL PhD Program ‘JCYL Nos Impulsa’ and scholarship JCYL-EDU/601/2020

Deciphering biomarkers for leptomeningeal metastasis in malignant hemopathies (Lymphoma/Leukemia) patients by comprehensive multipronged proteomics characterization of cerebrospinal fluid

In the present work, leptomeningeal disease, a very destructive form of systemic cancer, was characterized from several proteomics points of view. This pathology involves the invasion of the leptomeninges by malignant tumor cells. The tumor spreads to the central nervous system through the cerebrospinal fluid (CSF) and has a very grim prognosis; the average life expectancy of patients who suffer it does not exceed 3 months. The early diagnosis of leptomeningeal disease is a challenge because, in most of the cases, it is an asymptomatic pathology. When the symptoms are clear, the disease is already in the very advanced stages and life expectancy is low. Consequently, there is a pressing need to determine useful CSF proteins to help in the diagnosis and/or prognosis of this disease. For this purpose, a systematic and exhaustive proteomics characterization of CSF by multipronged proteomics approaches was performed to determine different protein profiles as potential biomarkers. Proteins such as PTPRC, SERPINC1, sCD44, sCD14, ANPEP, SPP1, FCGR1A, C9, sCD19, and sCD34, among others, and their functional analysis, reveals that most of them are linked to the pathology and are not detected on normal CSF. Finally, a panel of biomarkers was verified by a prediction model for leptomeningeal disease, showing new insights into the research for potential biomarkers that are easy to translate into the clinic for the diagnosis of this devastating disease.We gratefully acknowledge financial support from the Spanish Health Institute, Carlos III (ISCIII), for the grants: FIS PI14/01538, FIS PI17/01930 and CB16/12/00400. We also acknowledge Fondos FEDER (EU) and Junta Castilla-León (COVID-19 grant COV20EDU/00187). The Proteomics Unit belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019/0023 of the PE I + D + I2017-2020, funded by ISCIII and FEDER—Norma Galicia is supported by the CONACYT Program. P. Juanes-Velasco is supported by JCYL PhD Program “Nos Impulsa-JCYL” and scholarship JCYLEDU/601/2020

Systematic evaluation of plasma signaling cascades by functional proteomics approaches: SARS-CoV-2 infection as model

Purpose Acute phase reactants (APRs) play a critical role in inflammation. The difference in their physiological functions or the different dynamic ranges of these proteins in plasma makes it difficult to detect them simultaneously and to use several of these proteins as a tool in clinical practice. Experimental Design A novel multiplex assay has been designed and optimized to carry out a high-throughput and simultaneous screening of APRs, allowing the detection of each of them at the same time and in their corresponding dynamic range. Results Using Sars-CoV-2 infection as a model, it has been possible to profile different patterns of acute phase proteins that vary significantly between healthy and infected patients. In addition, severity profiles (acute respiratory distress syndrome and sepsis) have been established. Conclusions and Clinical Relevance Differential profiles in acute phase proteins can serve as a diagnostic and prognostic tool, among patient stratification. The design of this new platform for their simultaneous detection paves the way for them to be more extensive use in clinical practice.We gratefully acknowledge financial support from the Spanish Health Institute Carlos III (ISCIII) for the grants: FIS PI18/00682, FIS PI21/01545 and CB16/12/00400. We also acknowledge Fondos FEDER (EU) and Junta Castilla-León (COVID-19 grant COV20EDU/00187). The Proteomics Unit belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019/0023, of the PE I+D+I 2017–2020, funded by ISCIII and FEDER. This research work was funded by the European Commission -NextGenerationEU, through CSIC's Global Health Platform (PTI Salud Global). This research work was performed in the framework of the Nanomedicine CSIC HUB (ref. 202180E048). AL-V is supported by VIII Centenario-USAL PhD Program. PJ-V is supported by JCYL PhD Program “Nos Impulsa-JCYL” and scholarship JCYL-EDU/601/2020.Peer reviewe

Dynamic Intracellular Metabolic Cell Signaling Profiles During Ag-Dependent B-Cell Differentiation

© 2021 Díez, Pérez-Andrés, Bøgsted, Azkargorta, García-Valiente, Dégano, Blanco, Mateos-Gomez, Bárcena, Santa Cruz, Góngora, Elortza, Landeira-Viñuela, Juanes-Velasco, Segura, Manzano-Román, Almeida, Dybkaer, Orfao and Fuentes.Human B-cell differentiation has been extensively investigated on genomic and transcriptomic grounds; however, no studies have accomplished so far detailed analysis of antigen-dependent maturation-associated human B-cell populations from a proteomic perspective. Here, we investigate for the first time the quantitative proteomic profiles of B-cells undergoing antigen-dependent maturation using a label-free LC-MS/MS approach applied on 5 purified B-cell subpopulations (naive, centroblasts, centrocytes, memory and plasma B-cells) from human tonsils (data are available via ProteomeXchange with identifier PXD006191). Our results revealed that the actual differences among these B-cell subpopulations are a combination of expression of a few maturation stage-specific proteins within each B-cell subset and maturation-associated changes in relative protein expression levels, which are related with metabolic regulation. The considerable overlap of the proteome of the 5 studied B-cell subsets strengthens the key role of the regulation of the stoichiometry of molecules associated with metabolic regulation and programming, among other signaling cascades (such as antigen recognition and presentation and cell survival) crucial for the transition between each B-cell maturation stage.We gratefully acknowledge financial support from the Spanish Health Institute Carlos III (ISCIII) for the grants: FIS PI14/01538, FIS PI17/01930 and CB16/12/00400. We also acknowledge Fondos FEDER (EU) and Junta Castilla-León (COVID19 grant COV20EDU/00187). Fundación Solórzano FS/38-2017.The Proteomics Unit belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019/0023, of the PE I + D + I 2017-2020, funded by ISCIII and FEDER. AL-V is supported by VIII Centenario-USAL PhD Program. PJ-V is supported by JCYL PhD Program and scholarship JCYL-EDU/601/2020. PD and EB are supported by a JCYL-EDU/346/2013 Ph.D. scholarship

SARS-CoV-2 Infection Triggers Auto-Immune Response in ARDS

Acute respiratory distress syndrome (ARDS) is a severe pulmonary disease, which is one of the major complications in COVID-19 patients. Dysregulation of the immune system and imbalances in cytokine release and immune cell activation are involved in SARS-CoV-2 infection. Here, the inflammatory, antigen, and auto-immune profile of patients presenting COVID-19-associated severe ARDS has been analyzed using functional proteomics approaches. Both, innate and humoral responses have been characterized through acute-phase protein network and auto-antibody signature. Severity and sepsis by SARS-CoV-2 emerged to be correlated with auto-immune profiles of patients and define their clinical progression, which could provide novel perspectives in therapeutics development and biomarkers of COVID-19 patients. Humoral response in COVID-19 patients’ profile separates with significant differences patients with or without ARDS. Furthermore, we found that this profile can be correlated with COVID-19 severity and results more common in elderly patients.We gratefully acknowledge financial support from the Spanish Health Institute Carlos III (ISCIII) for the grants: FIS PI14/01538, FIS PI17/01930, and CB16/12/00400. This research work was also funded by the European Commission – NextGenerationEU, through CSIC's Global Health Platform (PTI Salud Global) We also acknowledge Fondos FEDER (EU) and Junta Castilla-León (COVID19 grant COV20EDU/00187). The Proteomics Unit belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019/0023, of the PE I + D + I 2017-2020, funded by ISCIII and FEDER. AL-V is supported by the VIII Centenario-USAL PhD Program. PJ-V is supported by the JCYL PhD Program “Nos Impulsa-JCYL” and scholarship JCYL-EDU/601/2020. EXOHEP-CM S2017/BMD3727 by Comunidad de Madrid and Fondos FEDER (to JL and RH) and PI19/01091 by ISCIII (to RH).Peer reviewe