Two mitochondrial DNA polymorphisms modulate cardiolipin binding and lead to synthetic lethality

Genetic screens have been used extensively to probe interactions betweennuclear genes and their impact on phenotypes. Probing interactions betweenmitochondrial genes and their phenotypic outcome, however, has not beenpossible due to a lack of tools to map the responsible polymorphisms. Here,using a toolkit we previously established in Drosophila, we isolate over 300recombinant mitochondrial genomes and map a naturally occurring polymorphism at the cytochrome c oxidase III residue 109 (CoIII109) that fully rescues the lethality and other defects associated with a point mutation incytochrome c oxidase I (CoIT300I). Through lipidomics profiling, biochemicalassays and phenotypic analyses, we show that the CoIII109 polymorphismmodulates cardiolipin binding to prevent complex IV instability caused by theCoIT300I mutation. This study demonstrates the feasibility of genetic interactionscreens in animal mitochondrial DNA. It unwraps the complex intra-genomicinterplays underlying disorders linked to mitochondrial DNA and how theyinfluence disease expression

Adolescents' perspectives on traditional, nontraditional, and direct political activities: The role of identity-processing styles and political beliefs

The study examined whether adolescents’ tendency to employ informational, or normative identity-processing style predicts their perceived effectiveness of different political activities. Data were taken from the broader longitudinal study conducted in the Czech Republic, and included reports from 179 participants (Time 1 = age 17; Time 2 = age 19). Path analyses suggested that adolescents who sought information tended to perceive non-traditional political activity (e.g., in civic organizations) as effective, while participants’ normative conformism predicted disbelief in direct activity (e.g., petitions). Perceived effectiveness of traditional activity (e.g., voting) reflected adolescents’ actual political trust rather than their identity-processing styles. These results complement previous findings on the correlates of identity-processing styles and adolescents’ political thinking

Workflow Designer – Webová aplikace na vizuální návrh pracovních postupů zpracování EEG signálu

This paper describes the Workflow Designer — a prototype web-based application allowing drag-and-drop creating, editing, and running workflows from a predefined library of methods. Adding a new method requires a minimal effort from users. Moreover, any workflow can be exported or imported in JSON format to ensure reusability and local execution of exported JSON configurations. The Workflow Designer can be applied to any general computation if the custom method library is available. The application has been successfully tested using electroencephalographic signal processing workflows. Článek popisuje Workflow Designer - prototypovou webovou aplikaci, která umožňuje snadné vytváření, úpravy a spouštění pracovních postupů z předdefinované knihovny metod. Přidání nové metody vyžaduje od uživatelů minimální úsilí. Kromě toho lze libovolný pracovní postup exportovat nebo importovat ve formátu JSON, aby se zajistilo opětovné použití a lokální vykonání exportovaných konfigurací JSON. Workflow designer lze použít na jakýkoli obecný výpočet, pokud je k dispozici knihovna vlastních metod. Aplikace byla úspěšně otestována pomocí workflow na zpracování elektroencefalografických signálů

Fish Tank Granuloma Caused by Mycobacterium marinum in Two Aquarists: Two Case Reports

Mycobacterium marinum, the cause of chronic systemic infections in fish, occasionally causes granulomatous skin and soft tissue lesions in humans. Cutaneous mycobacterial infection in two patients owing to unusual circumstances is presented in this report. The first patient was infected through improper hygienic behavior, while infection in the second patient was previously misdiagnosed as rheumatoid arthritis and treated with methylprednisolone for a period of three months, which resulted in a rare systemic spread of M. marinum into the bones of the hand, testis, and epididymis. Simultaneously, screening for possible sources of M. marinum infection in patients' aquaria revealed positive fish harboring VNTR profiles identical to those obtained for clinical isolates from patients

Bioénergétique des tumeurs (impact de l'hypoxie et de l'aglycémie sur le métabolisme énergétique du cancer du sein)

Non-canonical bioenergetics concerns with those physiological and pathophysiological situations under which ATP synthesis is suppressed. This thesis brings an outcome of three types of studies within the field of the non-canonical bioenergetics, investigating specific bioenergetic phenotypes of cancer cells, on one hand; and a role of mitochondrial uncoupling proteins as deduced from their transcript distribution in various tissues and organs; plus a role of a novel and likely pro-apoptotic factor CIDEa in mitochondria. Cancer cells generally present abnormal bioenergetic properties including an elevated glucose uptake, a high glycolysis and a poorly efficient oxidative phosphorylation system. However, the determinants of cancer cells metabolic reprogramming remain unknown. The main question in this project was how environmental conditions in vivo can influence functioning of mitochondrial OXPHOS, because details of mitochondrial bioenergetics of cancer cells is poorly documented. We have combined two conditions, namely glucose and oxygen deprivation, to measure their potential interaction. We examined the impact of glucose deprivation and oxygen deprivation on cell survival, overall bioenergetics and OXPHOS protein expression. As a model, we have chosen a human breast carcinoma (HTB-126) and appropriate control (HTB-125) cultured cells, as large fraction of breast malignancies exhibit hypoxic tumor regions with low oxygen concentrations and poor glucose delivery. The results demonstrate that glucose presence or absence largely influence functioning of mitochochondrial oxidative phosphorylation. The level of mitochondrial respiration capacity is regulated by glucose; by Crabtree effect, by energy substrate channeling towards anabolic pathways that support cell growth and by mitochondrial biogenesis pathways. Both oxygen deprivation and glucose deprivation can remodel the OXPHOS system, albeit in opposite directions. As an adaptative response to hypoxia, glucose inhibits mitochondrial oxidative phosphorylation to the larger extent than in normoxia. We concluded that the energy profile of cancer cells can be determined by specific balance between two main environmental stresses, glucose and oxygen deprivation. Thus, variability of intratumoral environment might explain the variability of cancer cells bioenergetic profile. Mitochondrial uncoupling proteins are proteins of inner mitochondrial membrane that uncouple respiration from ATP synthesis by their protonophoric activity. Originally determined tissue distribution seems to be invalid, since novel findings show that UCP1 is not restricted exclusively to brown fat and that originally considered brain-specific isoforms UCP4 and UCP5 might have wider tissue distribution. Hence, in second part of this thesis, I discuss consequences of findings of UCPn transcripts in the studied mouse and rat tissues. We have shown that mRNA of UCPn varies up to four orders of magnitude in rat and mouse tissues with highest expression in rat spleen, rat and mouse lung, and rat heart. Levels of the same order of magnitude were found for UCP3 mRNA in rat 100 and mouse skeletal muscle, for UCP4 and UCP5 mRNA in mouse brain, and for UCP2 and UCP5 mRNA in mouse white adipose tissue. Further, we have shown that expression pattern of UCPn varies between animal species, rat versus mouse, such as the dominance of UCP3/UCP5 vs. UCP2 transcript in mouse heart and vice versa in rat heart; or UCP2 (UCP5) dominance in rat brain contrary to 10-fold higher UCP4 and UCP5 dominance in mouse brain. spontaneous apoptosis due to CIDEa overexpression in HeLa cells, adapted for a tetracycline-inducible CIDEa expression, a portion of mitochondria-localized CIDEa molecules migrates to cytosol or nucleus.Résumé non disponibleBORDEAUX2-Bib. électronique (335229905) / SudocSudocFranceF

Mitochondrialni odprahujici proteiny, aniontove prenasece a iontove kanaly.

Mitochondrial uncoupling proteins and anion carriers which form the common gene family ensure various basic bioenergetic and physiological functions in organisms. Many of these functions are still unknown. For each carrier one can describe a central function (such as ADP/ATP antiport for the ADP/ATP carrier or thermogenesis for UCP1), but also a side function of the carrier, which is related to the carrier interaction with other substrates, ligands or cofactors, or with its participation in protein complexes with other proteins. These protein complexes might ensure a completely different function. As examples the following can serve: the interaction of fatty acids with the phosphate carrier and the ADP/ATP carrier that leads to uniport of fatty acid anions and to a concomitant mild uncoupling sensitive to the carrier substrates; moreover, the ADP/ATP carrier together with hexokinase and porin form a complex called permeability transition pore which possesses an indispensible role in signalling during initiation of apoptosis. Uncoupling proteins exhibit their basic functions in the mode of a mild uncoupling that leads to acceleration of metabolism, decreasing formation of reactive oxygen species and concomitant mild thermogenesis. Their physiological roles (with exception of UCP1) at higher uncoupling are yet to be proved in vivo.Text also in English.Available from STL Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

Meritev izkoristka reduktorjev električnih gospodarskih vozil med posebnimi voznimi cikli

This paper presents the results and the procedure for measuring the efficiency of a single-speed reduction gearbox developed for an autonomous electric utility vehicle. The resulting efficiency of the gearbox was investigated on three different driving cycles, which were selected because their speed profiles most closely matched the expected use of the autonomous vehicle. The required torque for each cycle was obtained from simulations of the vehicle’s driving behaviour including its predicted mass and dimensional parameters after a given driving cycle. The results of this research represent the achieved efficiency and average power loss of the gearbox on each driving cycle. The resulting gearbox efficiency was around 50 % in the predominant areas of driving cycles