Renal involvement in mitochondrial cytopathies

Mitochondrial cytopathies constitute a group of rare diseases that are characterized by their frequent multisystemic involvement, extreme variability of phenotype and complex genetics. In children, renal involvement is frequent and probably underestimated. The most frequent renal symptom is a tubular defect that, in most severe forms, corresponds to a complete De Toni-Debré-Fanconi syndrome. Incomplete proximal tubular defects and other tubular diseases have also been reported. In rare cases, patients present with chronic tubulo-interstitial nephritis or cystic renal diseases. Finally, a group of patients develop primarily a glomerular disease. These patients correspond to sporadic case reports or can be classified into two major defects, namely 3243 A>G tRNALEU mutations and coenzyme Q10 biosynthesis defects. The latter group is particularly important because it represents the only treatable renal mitochondrial defect. In this Educational Review, the principal characteristics of these diseases and the main diagnostic approaches are summarized

The role of 'filth flies' in the spread of antimicrobial resistance

'Filth flies' feed and develop in excrement and decaying matter and can transmit enteric pathogens to humans and animals, leading to colonization and infection. Considering these characteristics, 'filth flies' are potential vectors for the spread of antimicrobial resistance (AMR). This review defines the role of flies in the spread of AMR and identifies knowledge gaps. The literature search (original articles, reviews indexed for PubMed) was restricted to the English language. References of identified studies were screened for additional sources. 'Filth flies' are colonized with antimicrobial-resistant bacteria of clinical relevance. This includes extended spectrum beta-lactamase-, carbapenemase-producing and colistin-resistant (mcr-1 positive) bacteria. Resistant bacteria in flies often share the same genotypes with bacteria from humans and animals when their habitat overlap. The risk of transmission is most likely highest for enteric bacteria as they are shed in high concentration in excrements and are easily picked up by flies. 'Filth flies' can 'bio-enhance' the transmission of AMR as bacteria multiply in the digestive tract, mouthparts and regurgitation spots. To better understand the medical importance of AMR in flies, quantitative risk assessment models should be refined and fed with additional data (e.g. vectorial capacity, colonization dose). This requires targeted ecological, epidemiological and in vivo experimental studie

Respiratory chain dysfunction and oxidative stress correlate with severity of primary CoQ10 deficiency

12 páginas, 8 figuras, 2 tablas.Coenzyme Q10 (CoQ10) is essential for electron transport in the mitochondrial respiratory chain and antioxidant defense. Last year, we reported the first mutations in CoQ10 biosynthetic genes, COQ2, which encodes 4-parahydroxybenzoate: polyprenyl transferase; and PDSS2, which encodes subunit 2 of decaprenyl diphosphate synthase. However, the pathogenic mechanisms of primary CoQ10 deficiency have not been well characterized. In this study, we investigated the consequence of severe CoQ10 deficiency on bioenergetics, oxidative stress, and antioxidant defenses in cultured skin fibroblasts harboring COQ2 and PDSS2 mutations. Defects in the first two committed steps of the CoQ10 biosynthetic pathway produce different biochemical alterations. PDSS2 mutant fibroblasts have 12% CoQ10 relative to control cells and markedly reduced ATP synthesis, but do not show increased reactive oxygen species (ROS) production, signs of oxidative stress, or increased antioxidant defense markers. In contrast, COQ2 mutant fibroblasts have 30% CoQ10 with partial defect in ATP synthesis, as well as significantly increased ROS production and oxidation of lipids and proteins. On the basis of a small number of cell lines, our results suggest that primary CoQ10 deficiencies cause variable defects of ATP synthesis and oxidative stress, which may explain the different clinical features and may lead to more rational therapeutic strategies.—Quinzii, C. M., López, L. C., Von-Moltke, J., Naini, A., Krishna, S., Schuelke, M., Salviati, L., Navas, P., DiMauro, S., Hirano, M. Respiratory chain dysfunction and oxidative stress correlate with severity of primary CoQ10 deficiency.This work was supported by U.S. National Institutes of Health (NIH) grants NS-11766 and HD-32062, by grants from the Muscular Dystrophy Association, and by the Marriott Mitochondrial Disorder Clinical Research Fund. L.C.L. is a postdoctoral fellow of the Ministerio de Educacion y Ciencia, Spain. C.M.Q. is supported by the Muscular Dystrophy Association.Peer reviewe

Efficiency improvement of DSSC photoanode by scandium doping of mesoporous titania beads

Solid solutions of scandium in anatase as semiconductor material for DSSC photoanodes were prepared by the controlled hydrolysis of titanium(IV) isopropoxide and scandium(III) isopropoxide in hydroalcoholic medium. The final powder was constituted by mesoporous anatase beads doped with Sc. A superstructure characterizes the beads, which are spherical at the microscopic level (?650 nm) and rice-grain-shaped at the nanoscopic level (?20 nm). The BJH pore size distribution and BET surface area of the powder beads were found depending from the Sc content ranging the peak of the former between 7 and 25 nm and between 65 and 128 m2 g–1 the latter. Data obtained by XRD and EXAFS confirm that we are dealing with real solid solutions with ScTi substitution defects. The electronic properties of the synthesized semiconductor material as a function of Sc doping were investigated by the measure of the flat band potential, band gap, and deep levels. In the range 0.0–1.0 at. % of Sc, the flat band energy changes from ?4.15 to ?4.07 eV, whereas the band gap height increases by 0.03 eV. The presence of Sc modifies heavily the cathodoluminescence spectrum of anatase at the lowest concentration too. Several DSSCs with photoanodes at different Sc doping were tested both under solar simulator and in the dark. The maximum efficiency of 9.6% was found at 0.2 at. % of Sc in anatase that is 6.7% higher with respect to the DSSCs with pure anatase