Interactomics and targeted protein degradation for kinase substrate discovery

Reversible phosphorylation is one of the most important post translational modifications that has allowed us as a species to quickly adapt to changing molecular environments due to external stimulation. This process is only capable through the activity of kinases to carry out the targeting of specific substrates defined by their recognition motif allowing for selective phosphorylation and activation and inactivation of distinct pathways as well as other changes that permit cell survival. By being so important for the maintenance of the cells disruption often leads to worsening of the cells, leading to various diseases like cancer, immunological and neurodegenerative disorders. This is why the comprehension of kinases, and their substrates is so important for making progress in the medical care of the patients. For this exact purpose we chose Polo like kinase 2 (Plk2) as the target of study. Even though a great deal of knowledge exists about it, like the fact that it plays roles during the cell cycle, cell differentiation, ontogenesis, stress response, tumorigenesis, neurodegenerative diseases, and inflammation. The mechanisms at play i.e the specific interactions that permits its function in all these systems is not entirely known. As such, we employed the use CRISPR/Cas9 as the method of genetic modification for the endogenous tagging of Plk2 with the auxin inducible degron (AID) for the selective degradation of our target. After having observed through LC/MS the limitations of being a low abundant protein, we combined proximity labeling through Turbo-ID and targeted degradation as a method of accomplishing this task. We were successful in the identification of novel substrates of Plk2 in the cell cycle, and capable of study the interactome of Plk2 in asynchronous and G1/S arrested cells. Providing a sundry of new insight into Plk2 biology and the diversification of its interactions. AID technology in combination with proximity labeling provides the next steps in the ability of study for any type of protein. Capable of gathering information about the context of the protein in regard to its environment, the interactions, and what the absence of that protein would have for specific pathways, while minimizing off-target effects

Taxonomía de la red de la élite capitular de Buenos Aires, 1776-1810

We analyze structural properties and visualization of a historical-data-constructed social network of the families with members in the Cabildo (city council) of colonial Buenos Aires. The data was obtained through the review of birth, marriage, and death records kept in various institutions and expanded from online genealogical sources. We find structural properties and visual presentations and also a link centrality analysis that shows that ritual relationship represents an important glue that held together with the network.Analizamos las propiedades estructurales y la visualización de una red social construida por datos históricos de las familias con miembros en el Cabildo (ayuntamiento) de la Buenos Aires colonial. Los datos se obtuvieron a través de la revisión de registros de nacimientos, matrimonios y defunciones mantenidos en varias instituciones y ampliados de fuentes genealógicas en línea. Encontramos propiedades estructurales y presentaciones visuales y también un análisis de centralidad de enlace que muestra que las relaciones rituales representan un pegamento importante que mantuvo unida la red

Teaching the science in neuroscience to protect from neuromyths: from courses to fieldwork

In recent decades, Cognitive Neuroscience has evolved from a rather arcane field trying to understand how the brain supports mental activities, to one that contributes to public policies. In this article, we focus on the contributions from Cognitive Neuroscience to Education. This line of research has produced a great deal of information that can potentially help in the transformation of Education, promoting interventions that help in several domains including literacy and math learning, social skills and science. The growth of the Neurosciences has also created a public demand for knowledge and a market for neuro-products to fulfill these demands, through books, booklets, courses, apps and websites. These products are not always based on scientific findings and coupled to the complexities of the scientific theories and evidence, have led to the propagation of misconceptions and the perpetuation of neuromyths. This is particularly harmful for educators because these misconceptions might make them abandon useful practices in favor of others not sustained by evidence. In order to bridge the gap between Education and Neuroscience, we have been conducting, since 2013, a set of activities that put educators and scientists to work together in research projects. The participation goes from discussing the research results of our projects to being part and deciding aspects of the field interventions. Another strategy consists of a course centered around the applications of Neuroscience to Education and their empirical and theoretical bases. These two strategies have to be compared to popularization efforts that just present Neuroscientific results. We show that the more the educators are involved in the discussion of the methodological bases of Neuroscientific knowledge, be it in the course or as part of a stay, the better they manage the underlying concepts. We argue that this is due to the understanding of scientific principles, which leads to a more profound comprehension of what the evidence can and cannot support, thus shielding teachers from the false allure of some commercial neuro-products. We discuss the three approaches and present our efforts to determine whether they lead to a strong understanding of the conceptual and empirical base of Neuroscience.ANII: FSED-2- 13882

Detecting order-disorder transitions in discourse : implications for schizophrenia

Abstract Several psychiatric and neurological conditions affect the semantic organization and content of a patient's speech. Specifically, the discourse of patients with schizophrenia is frequently characterized as lacking coherence. The evaluation of disturbances in discourse is often used in diagnosis and in assessing treatment efficacy, and is an important factor in prognosis. Measuring these deviations, such as “loss of meaning” and incoherence, is difficult and requires substantial human effort. Computational procedures can be employed to characterize the nature of the anomalies in discourse. We present a set of new tools derived from network theory and information science that may assist in empirical and clinical studies of communication patterns in patients, and provide the foundation for future automatic procedures. First we review information science and complex network approaches to measuring semantic coherence, and then we introduce a representation of discourse that allows for the computation of measures of disorganization. Finally we apply these tools to speech transcriptions from patients and a healthy participant, illustrating the implications and potential of this novel framework

Lexiland: A Tablet-based Universal Screener for Reading Difficulties in the School Context

First published online January 27, 2022Massive and timely screening of the student population for early signs of reading difficulties is needed to implement timely effective remediation of these difficulties. However, traditional approaches are costly and hard to apply. Here, we present Lexiland, a tablet-based reading assessment tool for kindergarten and primary school children developed to be applied in school settings with minimal personnel intervention. Following a story line, players help a character of the game perform several tasks that measure different predictors of reading outcomes. Most of the tasks that usually involve a verbal response were switched to receptive tasks to demand a touch-screen response only. The tablet application was administered to a sample of N = 616 5-yo kindergarten children and to a sub-sample of these children twice during the following two years (First and Second Grades). Applying logistic regression and cross-validation, we selected a reduced subset of tasks that can predict with great sensitivity and specificity, whether a five-year-old child will have reading difficulties by the end of first grade (sensitivity 90% and specificity 76%) and two years later (sensitivity 90% and specificity 61%). Importantly, Lexiland is a scalable tool to implement universal screening, given the increasing availability of devices able to run android and iOS applications.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project was funded by ANII FSED_2_2015_1_120741 and ANII FSED_2_2016_1_131230 grants to Juan Valle-Lisboa and Manuel Carreiras. Camila Zugarramurdi received a PhD Scholarship from Fundación Carolin

Glosario de términos en Acuicultura

175 páginas[ES] Este glosario recoge los principales términos del idioma castellano utilizados en Acuicultura con su correspondencia en inglés, francés, italiano y alemán y el nombre científico latino, cuando corresponde. Constituye por tanto una parte importante de la terminología científica utilizada en Acuicultura en relación con la reproducción, genética, patología, cultivo, nutrición, etc. tanto de especies acuícolas cultivables como de especies auxiliares.[EN] This glossary contains the main terms of the Spanish language used in Aquaculture with its correspondence in English, French, Italian and German and Latin scientific name, where it’s applicable. Is therefore an important part of the scientific terminology used in Aquaculture in relation to reproduction, genetics, pathology, crop, nutrition, etc. as arable aquaculture species as auxiliary species.Peer reviewe

Osteoartritis luética de rodilla

Se presenta el caso de un varón de 59 años, con antecedente de contacto sexual sospechoso entre 3 y 5 años antes, que desarrolló episodios de derrame articular indoloro en rodilla izquierda con una lesión osteítica destructiva en meseta tibial interna. Tras descartar otras patologías, el diagnóstico se efectuó por la intensa actividad treponéndca demostrada en la serología específica y la buena respuesta al tratamiento antibiótico. Los derrames desaparecieron, persistiendo únicamente la deformidad residual. No conseguimos identificar espiroquetas en el material obtenido por biopsia osteoarticular.We report a 59 years old man with a suspicious sexual contact between 3-5 years ago, who developed repeated painless swelling in his left knee, and a progressive destructive osteitis in his tibia. After rejecting other pathologies, the diagnosis arrived by the high treponemic activity proved by specific serology and the clinical recovery with antibiotic treatment. The swelling disappeared and only the residual deformity persisted. We didn't find any treponema in the biopsy

Conditioned increase of locomotor activity induced by haloperidol

Dopamine antagonist drugs have profound effects on locomotor activity. In particular, the administration of the D2 antagonist haloperidol produces a state that is similar to catalepsy. In order to confirm whether the modulation of the dopaminergic activity produced by haloperidol was repeatedly paired with the presence of distinctive contextual cues that served as a Conditioned Stimulus. Paradoxically, the results revealed a dose-dependent increase n locomotor activity following conditioning with dopamine antagonist (Experiments 1) that was susceptible of extinction when the conditioned stimulus was presented repeatedly by itself after conditioning (Experiment 2). These data are interpreted from an associative perspective, considering them as a result of a classical conditioning process.Ministerio de Economía, Industria y Competitividad PSI2015-64 965-

Effects of oral capsaicinoids and capsinoids supplementation on resistance and high intensity interval training: A systematic review of randomized controlled trials

Oral capsaicinoids and capsinoids supplementation has been studied recently for a plausible ergogenic impact on sports performance. However, non-aggregated literature has focused on the impact of this substances in healthy humans’ performance. The aim of the present systematic review was to explore the effects of capsaicinoids and capsinoids on resistance training (RT) and HIIT exercise. Studies searches were performed in the PubMed/MEDLINE, Scopus and Web of Science electronic databases. Studies where healthy subjects consumed capsaicinoids or capsinoids acutely or chronically compared to placebo before a RT or HIIT intervention were included. The methodological quality of the included studies was assessed with PEDro checklist. A total of 7 excellent-good quality placebo-controlled trials (i.e., 5 RT and 2 HIIT experiments) were included. The most prevalent protocol used capsaicin (i.e., 6 capsacin and 1 capsiate studies) and acute (i.e., 5 of 7 interventions) supplementation designs. Positive effects were only noted for capsaicin in repetitions until failure (+14.4 to +21.7%), total weight lifted (+13.0 to +23.3%), perceived effort (-6.4%), fatigue index (+15.0%) and peak torque (+6.1%) compared to placebo. Neuromuscular HIIT variables (e.g., total and medium sprint time) were not highly affected by capsaicin except the time to reach 90% VO2 peak (+61.2%) and the number of efforts performed (+14.7%). Collectively, our findings suggest a positive effect of 12 mg of capsaicin on strength endurance, total weight lifted and perceived effort variables in healthy males after acute (i.e., 45 minutes pre-exercise) supplementation