Regulation of mammalian mitochondrial translation by post-translational modifications

Mitochondria are responsible for the production of over 90% of the energy in eukaryotes through oxidative phosphorylation performed by electron transfer and ATP synthase complexes. Mitochondrial translation machinery is responsible for the synthesis of 13 essential proteins of these complexes encoded by the mitochondrial genome. Emerging data suggest that acetyl-CoA, NAD(+), and ATP are involved in regulation of this machinery through post-translational modifications of its protein components. Recent high-throughput proteomics analyses and mapping studies have provided further evidence for phosphorylation and acetylation of ribosomal proteins and translation factors. Here, we will review our current knowledge related to these modifications and their possible role(s) in the regulation of mitochondrial protein synthesis using the homology between mitochondrial and bacterial translation machineries. However, we have yet to determine the effects of phosphorylation and acetylation of translation components in mammalian mitochondrial biogenesis. This article is part of a Special Issue entitled: Mitochondrial Gene Expression.     

Comparative pollen morphology of sect. <Emphasis Type="Italic">Quinqueloculares</Emphasis> (Campanulaceae) in Turkey

The pollen morphology of Turkish species belonging to sect. Quinqueloculares (Boiss.) Phitos (Campanulaceae) were investigated with a light microscope (LM) and scanning electron microscope (SEM). All examined species are endemic, except Campanula crispa Lam. According to the results of this study, pollen grains of the examined taxa were triporate and spheroidal. Their sculpture was spinose and baculate (C. crispa Lam.); spinulose and microperforate (C. tomentosa Lam.); microperforate (C. vardariana Bocquet) or more commonly, microechinate (C. iconia Phitos, C. lyrata Lam. subsp. lyrata, C. hagielia Boiss., C. sorgerae Phitos, C. betonicifolia SM., C. karadjana Bocquet, C. telmessi Hub.-Mor. & Phitos, C. davisii Turrill).     

Rhabdosciadium urusakii sp. nov. (Apiaceae) from east Anatolia (Turkey)

Rhabdosciadium urusakii E. Akal?n sp. nov. (Apiaceae) is described and illustrated. It occurs very locally on scree slopes in Kemaliye (Erzincan), east Anatolia. This slender species is closely related to R. aucheri (Iran) and R. oligocarpum (south Anatolia). It is a very rare and critically endangered species. A key to all Rhabdosciadium species is given in this paper. The new species is characterized by dichotomous branched, long petiolate, pinnate and linear leaves, ovate‐lanceolate bracts, a brownish band and hairs on the dorsal side of the petals.     

Some benzoxazoles and benzimidazoles as DNA topoisomerase I and II inhibitors

Some novel fused heterocyclic compounds of 2, 5-disubstituted-benzoxazole and benzimidazole derivatives, which were previously synthesized by our group, were investigated for their inhibitory activity on both eukaryotic DNA topoisomerase I and II in a cell free system. 2-Phenoxymethylbenzimidazole (17), 5-amino-2-(p-fluorophenyl)benzoxazole (3), 5-amino-2-(p-bromophenyl)benzoxazole (5), 5-nitro-2-phenoxymethyl-benzimidazole (18), 2-(p-chlorobenzyl)benzoxazole (10) and 5-amino-2-phenylbenzoxazole (2) were found to be more potent as eukaryotic DNA topoisomerase I poisons than the reference drug camptothecin having IC(50) values of 14.1, 132.3, 134.1, 248, 443.5, and 495 microM, respectively. 5-Chloro-2-(p-methylphenyl)benzoxazole (4), 2-(p-nitrobenzyl)benzoxazole (6) and 5-nitro-2-(p-nitrobenzyl)benzoxazole (8) exhibited significant activity as eukaryotic DNA topoisomerase II inhibitors, having IC(50) values of 22.3, 17.4, 91.41 microM, respectively, showing higher potency than the reference drug etoposide.     

Can screening Chlamydia trachomatis by serological tests predict tubal damage in infertile patients?

Effectiveness of screening Chlamydia trachomatis (CT) antibody to predict tubal damage was assessed in this prospective study which was performed in a teaching hospital between September 2003 and September 2004. The study group consisted of 152 patients who underwent laparoscopy for infertility and the control group consisted of 80 fertile women who gave birth in the same hospital. CT antibody levels were measured by IFA (Indirect Fluorescence Assay for CT). Adhesions were defined by Gomel's classification system. Rate of seropositivity of CT was 34.6% in the study group and 22.5% in the control group (p>0.05). In the study group, the sensitivity, specifity, positive predictive and negative predictive values of CT positivity for tubal damage were 40%, 69.5%, 50% and 60.2% respectively. In the infertile group, the rate of tubal adhesion in the CT positive group was 50% and in the CT negative group it was 39.7% (p>0.05). However, there was a positive correlation between the severity of tubo-peritoneal adhesions and seropositivity for CT. In this study, we found out that tubo-peritoneal adhesions could not be predicted by the presence of CT inserum. There was a positive correlation between high CT seropositivity and high degree of adhesions.     

Ceruloplasmin, Copper, Selenium, Iron, Zinc, and Manganese Levels in Normal and Sulfite Oxidase Deficient Rat Plasma: Effects of Sulfite Exposure

A noticeable effect of sulfite treatment was observed on the plasma ceruloplasmin ferroxidase activity of rats with normal sulfite oxidase activity when compared to normal controls. The plasma levels of selenium, iron, and zinc were unaffected by sulfite in normal and sulfite oxidase (SOX)-deficient rats. While plasma level of Mn was decreasing, plasma Cu level increased in SOX-deficient rats. Treating SOX-deficient groups with sulfite did not alter plasma level of Mn but made plasma level of Cu back to its normal level. This is the first evidence that Cu and Mn status were affected in experimental sulfite oxidase deficiency induced by low molybdenum diet with tungsten addition deserving further research to determine the underlying mechanisms of these observations in experimental sulfite oxidase deficiency.     

Potential active-site residues in polyneuridine aldehyde esterase, a central enzyme of indole alkaloid biosynthesis, by modelling and site-directed mutagenesis.

In the biosynthesis of the antiarrhythmic alkaloid ajmaline, polyneuridine aldehyde esterase (PNAE) catalyses a central reaction by transforming polyneuridine aldehyde into epi-vellosimine, which is the immediate precursor for the synthesis of the ajmalane skeleton. The PNAE cDNA was previously heterologously expressed in E. coli. Sequence alignments indicated that PNAE has a 43% identity to a hydroxynitrile lyase from Hevea brasiliensis, which is a member of the alpha/beta hydrolase superfamily. The catalytic triad, which is typical for this family, is conserved. By site-directed mutagenesis, the members of the catalytic triad were identified. For further detection of the active residues, a model of PNAE was constructed based on the X-ray crystallographic structure of hydroxynitrile lyase. The potential active site residues were selected on this model, and were mutated in order to better understand the relationship of PNAE with the alpha/beta hydrolases, and as well its mechanism of action. The results showed that PNAE is a novel member of the alpha/beta hydrolase enzyme superfamily.     

Inhibition of carbonic anhydrase isoforms I,II, IX and XII with secondary sulfonamides incorporating benzothiazole scaffolds

Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze the fundamental reaction of CO₂ hydration in all living organisms, being actively involved in the regulation of a plethora of patho/physiological conditions. A series of benzothiazole-based sulfonamides were synthesized and tested as possible CA inhibitors. Their inhibitory activity was assessed against the cytosolic human isoforms hCA I and hCA II and the transmembrane hCA IX and hCA XII. Several of the investigated derivatives showed interesting inhibition activity and selectivities for inhibiting hCA IX and hCA XII over the off-target ones hCA I and hCA II. Furthermore, computational procedures were used to investigate the binding mode of this class of compounds, within the active site of hCA IX.     

Impact of Laboratory Test Use Strategies in a Turkish Hospital

ObjectivesEliminating unnecessary laboratory tests is a good way to reduce costs while maintain patient safety. The aim of this study was to define and process strategies to rationalize laboratory use in Ankara Numune Training and Research Hospital (ANH) and calculate potential savings in costs.MethodsA collaborative plan was defined by hospital managers; joint meetings with ANHTA and laboratory professors were set; the joint committee invited relevant staff for input, and a laboratory efficiency committee was created. Literature was reviewed systematically to identify strategies used to improve laboratory efficiency. Strategies that would be applicable in local settings were identified for implementation, processed, and the impact on clinical use and costs assessed for 12 months.ResultsLaboratory use in ANH differed enormously among clinics. Major use was identified in internal medicine. The mean number of tests per patient was 15.8. Unnecessary testing for chloride, folic acid, free prostate specific antigen, hepatitis and HIV testing were observed. Test panel use was pinpointed as the main cause of overuse of the laboratory and the Hospital Information System test ordering page was reorganized. A significant decrease (between 12.6–85.0%) was observed for the tests that were taken to an alternative page on the computer screen. The one year study saving was equivalent to 371,183 US dollars.ConclusionHospital-based committees including laboratory professionals and clinicians can define hospital based problems and led to a standardized approach to test use that can help clinicians reduce laboratory costs through appropriate use of laboratory tests.