Structure Function Relationship in Hexacoordinate Heme Proteins: Mechanism of Globin X Interactions with Exogenous Ligands and Ligand Accessiblity in Cytoglobin and Neuroglobin

Cytoglobin (Cygb), neuroglobin (Ngb), and globin X (GbX) belongs to recently discovered members of the vertebrate globin family, they carry a heme prosthetic group that can reversibly bind exogenous ligands such as CO, NO and O2. Although the physiological functions of Cygb, Ngb and GbX are still under debate, several possible physiological functions for these proteins were proposed. Cytoglobin was reported to participate in lipid-based signaling and to stabilize the tumor suppressor p53 upon DNA damage, which imply its anti-cancer role. Neuroglobin was shown to interact with α-subunit of the heterotrimeric G protein as well as cytochrome c which indicates a role in cell apoptosis. Both proteins were also proposed to participate in NO metabolism. Compared to the well-known vertebrate globin, hemoglobin and myoglobin, the new members have several distinct structural characteristics. First, unlike Hb and Mb, the distal histidine coordinates with the heme iron at the sixth axial position in Cygb, Ngb and GbX, forming a hexa-coordinated heme iron and thus regulating kinetics and equilibrium constants for exogenous ligand binding to heme. Second, an oxidation/reduction of an intramolecular disulfide bridge which is found in all three hexa-coordinated globins, also modulates affinity for diatomic ligands such as O2 and CO. Additionally, both Cygb and GbX are found to have extended N- and C- terminals with unclear function, although the N-terminal in GbX proposed to be involved in the protein binding to the membrane. The work presented in this dissertation focuses on investigation of the role of internal ligand (distal histidine) and disulfide bridge on structure-function relationships in GbX, in terms of regulating affinity and kinetics for small diatomic ligands. Indeed, we shown a very weak ligand binding to heme iron in GbX, suggesting its district role among heaxa-coordiante vertebrate globins. In addition, the study of conformation dynamics that affect the heme cavity accessibility of Cygb and Ngb by incorporate heme fluorescent analogy ZnPPIX into the protein is also performed. These data shown a high conformational heterogeneity of the distal pocket in hexa-coordiante globins as well as increased accessibility of the heme pocket in Ngb

Macrophages Phenotype Regulated by IL-6 Are Associated with the Prognosis of Platinum-Resistant Serous Ovarian Cancer: Integrated Analysis of Clinical Trial and Omics

Background. The treatment of platinum-resistant recurrent ovarian cancer (PROC) is a clinical challenge and a hot topic. Tumor microenvironment (TME) as a key factor promoting ovarian cancer progression. Macrophage is a component of TME, and it has been reported that macrophage phenotype is related to the development of PROC. However, the mechanism underlying macrophage polarization and whether macrophage phenotype can be used as a prognostic indicator of PROC remains unclear. Methods. We used ESTIMATE to calculate the number of immune and stromal components in high-grade serous ovarian cancer (HGSOC) cases from The Cancer Genome Atlas database. The differential expression genes (DEGs) were analyzed via protein–protein interaction network, Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analysis to reveal major pathways of DEGs. CD80 was selected for survival analysis. IL-6 was selected for gene set enrichment analysis (GSEA). A subsequent cohort study was performed to confirm the correlation of IL-6 expression with macrophage phenotype in peripheral blood and to explore the clinical utility of macrophage phenotype for the prognosis of PROC patients. Results. A total of 993 intersecting genes were identified as candidates for further survival analysis. Further analysis revealed that CD80 expression was positively correlated with the survival of HGSOC patients. The results of GO and KEGG analysis suggested that macrophage polarization could be regulated via chemokine pathway and cytokine–cytokine receptor interaction. GSEA showed that the genes were mainly enriched in IL-6-STAT-3. Correlation analysis for the proportion of tumor infiltration macrophages revealed that M2 was correlated with IL-6. The results of a cohort study demonstrated that the regulation of macrophage phenotype by IL-6 is bidirectional. The high M1% was a protective factor for progression-free survival. Conclusion. Thus, the macrophage phenotype is a prognostic indicator in PROC patients, possibly via a hyperactive IL-6-related pathway, providing an additional clue for the therapeutic intervention of PROC

Simulator for Virtual Instrumentation Courses

Import 05/08/2014Tato bakalářská práce se zabývá návrhem a realizací simulátoru pro výuku virtuální instrumentace. Tento simulátor je zkonstruován na bázi mikrokontroléru, který obstarává hlavní funkčnost celého zařízení a je naprogramován tak, aby uměl vykonávat funkce napětím řízeného oscilátoru, napětím řízeného PWM, simulátoru servomotoru a generátoru impulzů. Částí této práce je i vytvoření řídícího programu, který komunikuje s mikrokontrolérem pomocí sériové linky a umožňuje parametrizaci a nastavení funkce simulátoru.This bechelor thesis describes the design and implementation of simulator for the teaching of virtual instrumentation courses. This simulator is based on microcontroller, which performs the main functionality of the device and is programmed to be able to perform the functions of a voltage-controlled oscillator, voltage controlled PWM, the simulator of servo motor and a pulse generator. Part of this work is the creation of a application that communicates with a microcontroller via a serial line and allows the configuration and settings of the simulator.450 - Katedra kybernetiky a biomedicínského inženýrstvívelmi dobř

Desafios e respostas baseadas em princípios à proteção da privacidade da tecnologia biométrica na China

Biometric technology has transformed human biological characteristics into a new form of privacy, and the misuse of this technology poses challenges to protecting this new privacy. This article initially defines biometric technology and biometric characteristics, further demonstrating why biometric characteristics belong to personal privacy and how biometric technology poses challenges to its protection. Through analysis, this article argues that the essence of these challenges is the conflicts between the ethical principle of privacy protection and the ethical principle of maximizing social benefits. In order to address these challenges, it is necessary first to weigh the fundamental ethical principles. The two basic principles of privacy protection and maximizing social benefits are not mutual antagonism but hierarchy, and this hierarchy should be based on the principle of practical feasibility. That is, applying biometric technology should first meet the principle of practical feasibility and, on this premise, realize the principle of maximizing social benefits based on not infringing on the principle of privacy protection.La tecnología biométrica ha transformado las características biológicas humanas en una nueva forma de privacidad, y el uso indebido de esta tecnología plantea desafíos a su protección. En este artículo se define inicialmente la tecnología biométrica y las características biométricas; se demuestra además por qué las características biométricas pertenecen a la privacidad personal y cómo la tecnología biométrica plantea retos para su protección. Este artículo argumenta que la esencia de estos retos es el conflicto entre el principio ético de protección de la privacidad y el de maximización de los beneficios sociales. Para abordar estos retos es necesario sopesar primero los principios éticos fundamentales. Los dos principios básicos de protección de la privacidad y maximización de los beneficios sociales no son antagónicos, sino jerárquicos, y esta jerarquía debe basarse en el principio de viabilidad práctica. Es decir, la aplicación de la tecnología biométrica debe cumplir primero el principio de viabilidad práctica y, a partir de esta premisa, realizar el principio de maximización de los beneficios sociales sobre la base de no infringir el principio de protección de la intimidad.A tecnologia biométrica transformou as características biológicas humanas em uma nova forma de privacidade, e o mal uso dessa tecnologia apresenta desafios para proteger essa nova privacidade. Esse artigo inicialmente define tecnologia biométrica e características biométricas, demonstrando posteriormente por que características biométricas pertencem à privacidade pessoal e como tecnologia biométrica coloca desafios à sua proteção. Através de análise, esse artigo discute que a essência desses desafios é o conflito entre o princípio ético da proteção da privacidade e o princípio ético de maximizar benefícios sociais. De forma a visar esses desafios é necessário primeiro ponderar os princípios éticos fundamentais. Os dois princípios básicos de proteção da privacidade e de maximizar benefícios sociais não são mutuamente antagônicos mas hierárquicos, e essa hierarquia deve ser baseada no princípio da viabilidade prática. Isso é, aplicar tecnologia biométrica deve primeiro atender ao princípio da viabilidade prática e, nessa premissa, compreender o princípio de maximizar benefícios sociais com base em não infringir o princípio de proteção da privacidade