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

Some remarks on the argument appealing to nature against synthetic biology

This paper will focus on analyzing the argument with appealing to nature against synthetic biology and provide a counter-argument against it through demonstrating the ambiguity of the concept of nature, denying the existence of a morally significant line between natural and non/unnatural, and disproving the allegations against synthetic biology raised by the argument appealing to nature. The paper consists of two parts following a brief introduction. The first part will describe the argument appealing to nature against synthetic biology, and identify the deficiencies of the argument per se, e.g., the ambiguity of the concept ‘nature’; and the problems in the morally significant line between the natural and the non/unnatural. The second part will discuss the allegations to synthetic biology stemming from this argument, e.g., committing metaphysical and ethical mistakes, and doing possible harms to the environment

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