63 research outputs found
Regulation of mtDNA gene expression and the role of respiratory chain supercomplexes in mammalian mitochondria
No full textMitochondria are cellular organelles found in nearly all eukaryotic cells, where they fulfill a plethora of functions, including energy conversion. They harness energy from carbon sources to synthesize adenosine triphosphate (ATP) through the process of oxidative phosphorylation (OXPHOS). Mammalian mitochondria contain ~1200 proteins and only 13 of these are encoded by mitochondrial DNA (mtDNA). Despite the small contribution to the mitochondrial proteome, expression of mtDNA is nevertheless critically important for biogenesis and normal function of the OXPHOS system. The expression of mtDNA is dependent on ~200 nucleus-encoded proteins that are imported into mitochondria to control maintenance, replication, and transcription of mtDNA, as well as translation of the mtDNA-encoded messenger RNAs (mRNAs). Mitochondrial gene expression is thus controlled at many different levels. In the first part of this thesis, molecular mechanisms are reported for initiation and completion of mtDNA replication. Furthermore, mechanisms controlling the switch from transcription initiation to elongation, as well as a putative link between transcription elongation and RNA processing are reported. These results were based on extensive analysis of conditional knockout mouse models for RNase H1, TEFM, and mtSSB. In the second part of the thesis, the organization of the OXPHOS system is studied. It consists of the respiratory chain enzyme complexes, two electron shuttles and the ATP synthase. A wide range of studies have shown that the different respiratory chain enzyme complexes can interact with each other to form higher order assemblies, so called supercomplexes. The respirasome is a particularly interesting supercomplex as it consists of a complete respiratory chain. Results from multiple studies have suggested that the respirasome plays a crucial role in cellular bioenergetics by facilitating translocation and routing of electrons. To address this question, we extensively characterized a knockin mouse model engineered to have normal levels of respiratory chain complexes that cannot interact to form respirasomes. Surprisingly, mice with drastically reduced levels of respirasomes are healthy without any clear impact on bioenergetics or whole animal physiology. Our results thus challenge the multiple proposed roles for respirasomes in physiology and disease.List of scientific papersI. Jelena Misic, Dusanka Milenkovic, Ali Al-Behadili, Xie Xie, Min Jiang, Shan Jiang, Roberta Filograna, Camilla Koolmeister, Stefan J. Siira, Louise Jenninger, Aleksandra Filipovska, Anders R. Clausen, Leonardo Caporali, Maria Lucia Valentino, Chiara La Morgia, Valerio Carelli, Thomas J. Nicholls, Anna Wredenberg, Maria Falkenberg, Nils-Göran Larsson†. (2022). Mammalian RNase H1 directs RNA primer formation for mtDNA replication initiation and is also necessary for mtDNA replication completion. Nucleic Acids Res. 50, 8749–8766. †Corresponding author(s). https://doi.org/10.1093/nar/gkac661 II. Shan Jiang, Camilla Koolmeister, Jelena Misic, Stefan Siira, Inge Kühl, Eduardo Silva Ramos, Maria Miranda, Min Jiang, Viktor Posse, Oleksandr Lytovchenko, Ilian Atanassov, Florian A. Schober, Rolf Wibom, Kjell Hultenby, Dusanka Milenkovic, Claes M. Gustafsson, Aleksandra Filipovska, Nils-Göran Larsson†. (2019). TEFM regulates both transcription elongation and RNA processing in mitochondria. EMBO Rep. 20, 1–18. †Corresponding author(s). https://doi.org/10.15252/embr.201948101 III. Min Jiang*, Xie Xie*, Xuefeng Zhu*, Shan Jiang, Dusanka Milenkovic, Jelena Misic, Yonghong Shi, Nirwan Tandukar, Xinping Li, Ilian Atanassov, Louise Jenninger, Emily Hoberg, Sara Albarran-Gutierrez, Zsolt Szilagyi, Bertil Macao, Stefan J. Siira, Valerio Carelli, Jack D. Griffith, Claes M. Gustafsson, Thomas J. Nicholls, Aleksandra Filipovska, Nils-Göran Larsson†, Maria Falkenberg†. (2021). The mitochondrial single-stranded DNA binding protein is essential for initiation of mtDNA replication. Sci Adv. 7, eabf8631. *These authors contributed equally. †Corresponding author(s). https://doi.org/10.1126/sciadv.abf8631 IV. Dusanka Milenkovic, Jelena Misic, Johannes F. Hevler, Thibaut Molinié, Injae Chung, Ilian Atanassov, Xinping Li, Roberta Filograna, Andrea Mesaros, Arnaud Mourier, Albert J.R. Heck, Judy Hirst†, Nils-Göran Larsson†. (2023). Preserved respiratory chain capacity and physiology in mice with profoundly reduced levels of mitochondrial respirasomes. Cell Metab. 35, 1799-1813.e7. †Corresponding author(s). https://doi.org/10.1016/j.cmet.2023.07.015 </p
Photography as a process of staging the self
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Supercritical fluid and cocrystallization technologies for designing antimicrobial food packaging PLA nanocomposite foams loaded with eugenol cocrystals with prolonged release
No full textSearching for effective strategies to modify the release rate of essential oil derivatives is one of the main challenges in designing prolonged-release antimicrobial food packaging materials. Herein, supercritical fluid technology and cocrystallization engineering were used to develop novel eugenol (EU) prolonged-release poly (lactic acid) (PLA) nanocomposite foams. Eugenol-phenazine (EU-PHE) cocrystals, produced by a solvent-free mechanochemical method, were incorporated by supercritical solvent impregnation (SSI) inside PLA nanocomposite foams with different contents of Cloisite30B® (C30B). The effect of the cocrystallization process and C30B content on the EU release kinetics and its relation with their antimicrobial activity by direct contact (anti-attachment) and release in broth culture were studied. The deposition of isolated spherical-shaped micrometric EU-PHE cocrystal particles with 0.8 µm average diameter inside the pores of PLA foams was evidenced by XRD, SEM, DSC, and TGA analyses. The release mechanism of EU and its cocrystal was defined as a quasi-Fickian diffusion process successfully described by the Korsmeyer-Peppas model with release rate constants up to 3.6-fold lower than the release rate constant of pure EU. The impregnated foam samples completely inhibited the attachment of Listeria monocytogenes and Salmonella Enteritidis and provided prolonged antimicrobial activity in broth culture against both food-borne pathogens. This study suggests a new, environmentally friendly method for designing prolonged-release antimicrobial food packaging materials.M.J. Galotto and A. Rojas thank the support of Agencia Nacional de Investigación y Desarrollo through the Fondecyt regular Project N°1201301 and to the “Programa de Financiamiento Basal para Centros Científicos y Tecnológicos de Excelencia” (Project AFB220001). A. Rojas thanks the support of the University of Santiago de Chile through the Postdoctoral Fellowship DICYT Código 082371GL_Postdoc. C. López de Dicastillo acknowledges the “Ramon y Cajal” Fellowship RYC2020-029874-I/AEI/10.13039/501100011033 financed by the Spanish Ministry of Science and Innovation. D. Misic and I. Zizovic thank the support of Narodowe Centrum Nauki. (Poland), Grant number 2019/35/B/NZ9/02774.Peer reviewe
Unlocking the potential of eugenol-coformer co-amorphous pairs in active packaging designed for the controlled release and enhanced antibacterial activity
No full textThe occurrence of Bacillus cereus in food continues to be a worldwide issue for the food sector and public health due to its prevalence in post-food processing and its role in toxin-induced foodborne illnesses. Antibacterial packaging based on essential oil derivatives and biopolymers arises as an alternative for the elimination or reduction of Bacillus cereus concentration to a harmless level. In this study, the concepts of mechanochemistry to produce eugenol (EU)-phenazine (PHE) pairs and supercritical fluid technology to impregnate this pair in an environmentally friendly way into poly (lactic acid) (PLA) films were used to create a controlled-release antibacterial food packaging material whose biological properties were tested against B. cereus strains. The incorporation of EU-PHE co-amorphous pairs in PLA (10.81 wt%) was verified by XRD, DSC, and SEM. The EU-PHE co-amorphous pairs exhibited an effective diffusion coefficient (6.0 ×10−12 m2 s−1), which is around two orders of magnitude inferior to that of pure EU, thus providing the sustained release of the bioactive agent (EU). The antibacterial PLA films entirely prevented the adhesion of the tested B. cereus strains after 72 h and showed the strongest antibacterial action, with up to a 50 % decrease in the number of bacteria in the broth between 48 and 72 h
Specifics of the implementation of the security measures of medical nature in the Republic of Serbia
No full textThe medical security measures in the Republic of Serbia include:– mandatory psychiatric treatment and confinement in a medical institution;– mandatory psychiatric treatment at liberty;– mandatory treatment of alcoholics and;– compulsory Drug Addiction Treatment.The aim of this presentation is to explain how the medical security measures are implemented in the Republic of Serbia. The methods used in this study are analysis and synthesis of the implementation of security measures in the Republic of Serbia based on many years of practical work in forensic centre for the implementation of security measures. By duration of medical security, measures may be twofold:– of unlimited duration, when the offender is undergoing medical treatment and keeping in a medical institution, while there is a need for treatment, or until there is no threat to the environment (the length of time is difficult to determine, however, that the most common word on the permanent indefinite treatment and storage required special caution and detailed analysis of all the elements relevant for this decision).– limited duration, where the duration of treatment is determined by the court and to no longer than three years as provided in the current The Criminal Code of the Republic of Serbia.The basis of every civilized society make the legal and moral norms governing the relations within the community, and thus regulate and protect their most essential element – the man – his physical and psychological integrity.Disclosure of interestThe author has not supplied his/her declaration of competing interest.</jats:sec
Synthesis of Substituted 3‐Cyano‐2‐pyridones. Part 4. Influence of 3‐Alkyl‐2,4‐pentanedione and N‐Alkyl Cyanoacetamide Structure on the Enzyme Catalyzed Synthesis of Substituted 3‐Cyano‐2‐pyridones.
No full textPolymeric Microfiltration Membranes Modification by Supercritical Solvent Impregnation—Potential Application in Open Surgical Wound Ventilation
No full textThis study investigated supercritical solvent impregnation of polyamide microfiltration membranes with carvacrol and the potential application of the modified membranes in ventilation of open surgical wounds. The impregnation process was conducted in batch mode at a temperature of 40 °C under pressures of 10, 15, and 20 MPa for contact times from 1 to 6 h. FTIR was applied to confirm the presence of carvacrol on the membrane surface. In the next step, the impact of the modification on the membrane structure was studied using scanning electron and ion beam microscopy and cross-filtration tests. Further, the release of carvacrol in carbon dioxide was determined, and finally, an open thoracic cavity model was applied to evaluate the efficiency of carvacrol-loaded membranes in contamination prevention. Carvacrol loadings of up to 43 wt.% were obtained under the selected operating conditions. The swelling effect was detectable. However, its impact on membrane functionality was minor. An average of 18.3 µg of carvacrol was released from membranes per liter of carbon dioxide for the flow of interest. Membranes with 30–34 wt.% carvacrol were efficient in the open thoracic cavity model applied, reducing the contamination levels by 27% compared to insufflation with standard membranes
ChemInform Abstract: Modern Catalysis in the Synthesis of Some Pharmaceuticals and Fine Chemicals
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