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Това изследване съчетава науките международни отношения и психология с уникална перспектива, разглеждайки формирането на националната идентичност и след това нейното въздействие върху външната политика на съответната национална държава. Теорията на обектните отношения, която се счита за основен подход в психологията както и конструктивизма от дисциплината международни отношения са обединени под името „конструктивна психология“ и така с нея е анализирано формирането на националната идентичност, която се оценява в контекста на рефлексивната онтология. Беше проведено изследване на конкретен казус, за да се придобие положително знание, в този контекст българската нация беше разгледана в детайли от известната й история от VII век до началото на XX век – как нацията е изградила своята национална идентичност и от коя психологическа динамика е била засегната. След това са анализирани ефектите на българската национална идентичност върху външната политика на българската държава. В този контекст в периода от създаването на българската държава до Първата световна война се анализира способността на рефлексивната национална идентичност да насочва материалните елементи в българската външна политика. Установено е, че особено историческите взаимодействия на българската нация с османците осигуряват развитието на агресивна психология относно турците в българската национална идентичност. Посочва се, че тази агресивна национална психология е изключително ефективна и важна от гледна точка на способността на българската държава да води отношенията си с османската/турската държава от миналото до настоящето. В резултат на това се забелязва, че националните идентичности могат да се конструират с определена психологическа динамика, те не са априори (предварително дадени), а частите извън техните субективни структури постоянно се конструират в контекста на субект-обектните взаимодействия и са отворени за промяна и трансформация. Националните идентичности също така влияят на политическите действия според формирания им характер. В контекста на приноса на работата към научната литературата беше посочено, че различни подходи, освен основните теории, могат да имат тежест в дисциплината Международни отношения и че политическата психология трябва да заеме своето заслужено място в дисциплината. This study combines the sciences of International Relations and Psychology with a unique perspective, examining the general formation of a national identity and then its effects on the foreign policy of the relevant national state. Object Relations Theory, which is considered as the mainstream approach in Psychology and Constructivism from the science of International Relations, were combined under the name of Constructive Psychology and therefore was analysed the national identity formation which is evaluated in the context of reflexive ontology. A case study was conducted to provide positive knowledge, in this context, the Bulgarian nation was examined in details by its known history from VIIth Century until the beginning of the XXth Century, how the nation constructed its national identity and by which psychological dynamics it was affected. Then the effects of the Bulgarian national identity on the foreign policy of the Bulgarian state have been analysed. In this context, in the period from the establishment of the Bulgarian state to the First World War, the capacity of a reflexive national identity to direct material elements in Bulgarian foreign policy was analysed. It has been determined that especially the historical interactions of the Bulgarian nation with the Ottomans provided the development of an aggressive psychology about Turks in the Bulgarian national identity. It is stated that this aggressive national psychology is extremely effective and important in terms of the Bulgarian state's ability to conduct its relations with the Ottoman / Turkish State from past to present. As a result, it has been observed that national identities can be constructed with certain psychological dynamics, they are not a priori (pre-given), and the parts outside their subjective structures are constantly constructed in the context of subject-object interactions and are open to change and transformation. National identities also affect political action according to their formed nature. In the context of the work's contributions to the literature, it was stated that different approaches besides mainstream theories may have weight in the International Relations discipline and that Political Psychology should take its deserved place in the discipline.

The recent global pandemic of Coronavirus Disease 2019 (COVID-19) caused by the new coronavirus SARS-CoV-2 presents an urgent need for new therapeutic candidates. Many efforts have been devoted to screening existing drug libraries with the hope to repurpose approved drugs as potential treatments for COVID-19. However, the antiviral mechanisms of action for the drugs found active in these phenotypic screens are largely unknown. To deconvolute the viral targets for more effective anti-COVID-19 drug development, we mined our in-house database of approved drug screens against 994 assays and compared their activity profiles with the drug activity profile in a cytopathic effect (CPE) assay of SARS-CoV-2. We found that the autophagy and AP-1 signaling pathway activity profiles are significantly correlated with the anti-SARS-CoV-2 activity profile. In addition, a class of neurology/psychiatry drugs was found significantly enriched with anti-SARS-CoV-2 activity. Taken together, these results have provided new insights into SARS-CoV-2 infection and potential targets for COVID-19 therapeutics.

Supplemental material, Supplemental_Material-Asawa_et_al for A Comparative Study of Target Engagement Assays for HDAC1 Inhibitor Profiling by Rosita R. Asawa, Alexey Zakharov, Taylor Niehoff, Ata Chitsaz, Ajit Jadhav, Mark J. Henderson, Anton Simeonov and Natalia J. Martinez in SLAS Discovery

The Assay Guidance Manual (AGM) is an eBook of best practices for the design, development, and implementation of robust assays for early drug discovery. Initiated by pharmaceutical company scientists, the manual provides guidance for designing a “testing funnel” of assays to identify genuine hits using high‐throughput screening (HTS) and advancing them through preclinical development. Combined with a workshop/tutorial component, the overall goal of the AGM is to provide a valuable resource for training translational scientists.

The apurinic/apyrimidinic endonuclease 1 (APE1) is a protein central to the base excision DNA repair pathway and operates in the modulation of gene expression through redox-dependent and independent mechanisms. Aberrant expression and localization of APE1 in tumors are recurrent hallmarks of aggressiveness and resistance to therapy. We identified and characterized the molecular association between APE1 and nucleophosmin (NPM1), a multifunctional protein involved in the preservation of genome stability and rRNA maturation. This protein-protein interaction modulates subcellular localization and endonuclease activity of APE1. Moreover, we reported a correlation between APE1 and NPM1 expression levels in ovarian cancer, with NPM1 overexpression being a marker of poor prognosis. These observations suggest that tumors that display an augmented APE1/NPM1 association may exhibit increased aggressiveness and resistance. Therefore, targeting the APE1/NPM1 interaction might represent an innovative strategy for the development of anticancer drugs, as tumor cells relying on higher levels of APE1 and NPM1 for proliferation and survival may be more sensitive than untransformed cells. We set up a chemiluminescence-based high-throughput screening assay in order to find small molecules able to interfere with the APE1/NPM1 interaction. This screening led to the identification of a set of bioactive compounds that impair the APE1/NPM1 association in living cells. Interestingly, some of these molecules display anti-proliferative activity and sensitize cells to therapeutically relevant genotoxins. Given the prognostic significance of APE1 and NPM1, these compounds might prove effective in the treatment of tumors that show abundant levels of both proteins, such as ovarian or hepatic carcinomas.

BACKGROUND: Humans are exposed to tens of thousands of chemical substances that need to be assessed for their potential toxicity. Acute systemic toxicity testing serves as the basis for regulatory hazard classification, labeling, and risk management. However, it is cost- and time-prohibitive to evaluate all new and existing chemicals using traditional rodent acute toxicity tests. In silico models built using existing data facilitate rapid acute toxicity predictions without using animals. OBJECTIVES: The U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) Acute Toxicity Workgroup organized an international collaboration to develop in silico models for predicting acute oral toxicity based on five different end points: Lethal Dose 50 (LD50 value, U.S. Environmental Protection Agency hazard (four) categories, Globally Harmonized System for Classification and Labeling hazard (five) categories, very toxic chemicals [LD50 (LD50≤50mg/kg)], and nontoxic chemicals (LD50>2,000mg/kg). METHODS: An acute oral toxicity data inventory for 11,992 chemicals was compiled, split into training and evaluation sets, and made available to 35 participating international research groups that submitted a total of 139 predictive models. Predictions that fell within the applicability domains of the submitted models were evaluated using external validation sets. These were then combined into consensus models to leverage strengths of individual approaches. RESULTS: The resulting consensus predictions, which leverage the collective strengths of each individual model, form the Collaborative Acute Toxicity Modeling Suite (CATMoS). CATMoS demonstrated high performance in terms of accuracy and robustness when compared with in vivo results. DISCUSSION: CATMoS is being evaluated by regulatory agencies for its utility and applicability as a potential replacement for in vivo rat acute oral toxicity studies. CATMoS predictions for more than 800,000 chemicals have been made available via the National Toxicology Program's Integrated Chemical Environment tools and data sets (ice.ntp.niehs.nih.gov). The models are also implemented in a free, standalone, open-source tool, OPERA, which allows predictions of new and untested chemicals to be made. https://doi.org/10.1289/EHP8495.