Biochemical requirements for the maturation of mitochondrial c-type cytochromes

AbstractCytochromes c are metalloproteins that function in electron transfer reactions and contain a heme moiety covalently attached via thioether linkages between the co-factor and a CXXCH motif in the protein. Covalent attachment of the heme group occurs on the positive side of all energy-transducing membranes (bacterial periplasm, mitochondrial intermembrane space and thylakoid lumen) and requires minimally: 1) synthesis and translocation of the apocytochromes c and heme across at least one biological membrane, 2) reduction of apocytochromes c and heme and maintenance under a reduced form prior to 3) catalysis of the heme attachment reaction. Surprisingly, the conversion of apoforms of cytochromes c to their respective holoforms occurs through at least three different pathways (systems I, II and III). In this review, we detail the assembly process of soluble cytochrome c and membrane-bound cytochrome c1, the only two mitochondrial c-type cytochromes that function in respiration. Mitochondrial c-type cytochromes are matured in the intermembrane space via the system I or system III pathway, an intriguing finding considering that the biochemical requirements for cytochrome c maturation are believed to be common regardless of the energy-transducing membrane under study

Retrospective space-time analysis of H5N1 Avian Influenza emergence in Thailand

<p>Abstract</p> <p>Background</p> <p>The highly pathogenic avian influenza (HPAI) H5N1 virus remains a worldwide threat to human and animal health, while the mechanisms explaining its epizootic emergence and re-emergence in poultry are largely unknown. Data from Thailand, a country that experienced significant epidemics in poultry and has recorded suspicious cases of HPAI on a daily basis since 2004, are used here to study the process of emergence. A spatial approach is employed to describe all HPAI H5N1 virus epizootics from 2004 to 2008 and to characterize the pattern of emergence: multiple independent introductions of the virus followed by moderate local spread vs. very rare emergences followed by strong local spread and rare long range diffusion jumps. Sites where epizootics originate (by foreign introduction, local persistence, or long range jump) were selected from those to which the disease subsequently spreads using a filter based on relative date and position. The spatial distribution of these selected foci was statistically analyzed, and to differentiate environmental factors from long range diffusion, we investigate the relationship of these foci with environmental exposure factors and with rearing characteristics.</p> <p>Results</p> <p>During each wave of epizootics, the temporal occurrence of cases did not show a temporal interruption of more than a week. All foci were globally clustered; i.e., more than 90% of cases had a previous case within a 10 km range and a 21 day period of time, showing a strong local spread. We were able to estimate 60 km as the maximum distance for the local farm to farm dissemination process. The remaining "emergent" cases have occurred randomly over Thailand and did not show specific location, clusters, or trends. We found that these foci are not statistically related to specific environmental conditions or land cover characteristics, and most of them may be interpreted as long range diffusion jumps due to commercial practices.</p> <p>Conclusion</p> <p>We conclude that only a few foci appear to have been at the origin of each HPAI epidemic wave, leading to the practical action that surveillance and control must focus on farm to farm transmission rather than on emergence or wild fauna.</p

CDC-42 and RAC-1 regulate opposite chemotropisms in Neurospora crassa

Cell polarization and fusion are crucial developmental processes that occur in response to intracellular and extracellular signals. Asexual spores (conidia) of the mold Neurospora crassa differentiate two types of polarized cell protrusions, germ tubes and conidial anastomosis tubes (CATs), which exhibit negative and positive chemotropism, respectively. We provide the first evidence that shared and separate functions of the Rho-type GTPases CDC-42 and RAC-1 regulate these opposite chemotropisms. We demonstrate that RAC-1 is essential for CAT formation and cell fusion, whereas CDC-42 is necessary and sufficient for normal germ tube development. Cdc42-Rac-interactive-binding (CRIB) reporters were constructed to exclusively label locally activated GTP-bound GTPases. Time course analyses showed that repositioning of these activated GTPase clusters within germ tube and CAT tip apices controls directional growth in the absence of a tip-localized vesicle supply center (Spitzenkörper). We propose a model in which the local assembly of a plasma-membrane-associated GTPase-PAK-MAPK signaling platform regulates chemoattractant perception and secretion in order to synchronize oscillatory cell-cell communication and directional CAT tip growth

BAG3 promotes pancreatic ductal adenocarcinoma growth by activating stromal macrophages

The incidence and death rate of pancreatic ductal adenocarcinoma (PDAC) have increased in recent years, therefore the identification of novel targets for treatment is extremely important. Interactions between cancer and stromal cells are critically involved in tumour formation and development of metastasis. Here we report that PDAC cells secrete BAG3, which binds and activates macrophages, inducing their activation and the secretion of PDAC supporting factors. We also identify IFITM-2 as a BAG3 receptor and show that it signals through PI3K and the p38 MAPK pathways. Finally, we show that the use of an anti-BAG3 antibody results in reduced tumour growth and prevents metastasis formation in three different mouse models. In conclusion, we identify a paracrine loop involved in PDAC growth and metastatic spreading, and show that an anti-BAG3 antibody has therapeutic potential

Měření společenské odpovědnosti: komparativní žánrová analýza jako metoda kontrastu výkonu CSR mezi dvěma firmami

Tato průzkumná studie představuje žánrovou analýzu jako lingvistický nástroj pro zkoumání zpráv o CSR se zaměřením na výkonnost ESG společností Southwest Airlines a Delta Air Lines. S využitím komparativní žánrové analýzy zkoumá analýzu pohybové struktury, tematickou analýzu, analýzu textu a vizuální žánrovou analýzu, aby odhalila vzorce a rétorické strategie v jejich CSR narativech. Tato studie odhaluje odlišné strategie CSR mezi firmami, zejména pokud jde o využití témat, snižování emisí a letecké palivo. Jsou také identifikovány odlišné příběhy, přičemž Southwest Airlines používá přístup shora dolů. Zjištění poskytují strategickou hodnotu pro zlepšení výkonu CSR a reportingu, nabízejí praktické obchodní důsledky pro strategické řízení, jako je benchmarking, analýza konkurence, identifikace trendů a rozpoznávání osvědčených postupů.This exploratory study introduces genre analysis as a linguistic tool for examining CSR reports, focusing on the ESG performance of Southwest Airlines and Delta Air Lines. Utilising comparative genre analysis, it investigates move-structure analysis, thematic analysis, text analysis, and visual genre analysis to reveal patterns and rhetorical strategies in their CSR narratives. This study uncovers distinct CSR strategies between the firms, particularly regarding topic utilisation, emission reduction and aviation fuel. Differing narratives are also identified, with Southwest Airlines adopting a top-down approach. The findings provide strategic value for enhancing CSR performance and reporting, offering practical business implications for strategic management, such as benchmarking, competitor analysis, identifying trends, and recognising best practices

Mécanisme de régulation de l'ATP synthase mitochondriale de la levure Saccharomyces cerevisiae par son peptide inhibiteur endogène IF1

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Devenir à 1 an en fonction du lieu de rééducation de patients âgés ayant eu une fracture de l'extrémité supérieure du fémur (à propos de 184 cas)

BORDEAUX2-BU Santé (330632101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Insight into the Bind-Lock Mechanism of the Yeast Mitochondrial ATP Synthase Inhibitory Peptide

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