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Pirkanmaa, Finland

Pohjoismaki J.L.O.,Max Planck Institute for Heart and Lung Research | Pohjoismaki J.L.O.,University of Eastern Finland | Kruger M.,Max Planck Institute for Heart and Lung Research | Al-Furoukh N.,Max Planck Institute for Heart and Lung Research | And 3 more authors.
Molecular BioSystems

Fetal (fCM) and adult cardiomyocytes (aCM) significantly differ from each other both by structure and biochemical properties. aCM own a higher mitochondrial mass compared to fCM due to increased energy demand and show a greater density and higher degree of structural organization of myofibrils. The energy metabolism in aCM relies virtually completely on β-oxidation of fatty acids while fCM use carbohydrates. Rewinding of the aCM phenotype (de-differentiation) arises frequently in diseased hearts spurring questions about its functional relevance and the extent of de-differentiation. Yet, surprisingly little is known about the changes in the human proteome occurring during maturation of fCM to aCM. Here, we examined differences between human fetal and adult hearts resulting in the quantification of 3500 proteins. Moreover, we analyzed mitochondrial proteomes from both stages to obtain more detailed insight into underlying biochemical differences. We found that the majority of changes between fCM and aCM were attributed to growth and maturation of cardiomyocytes. As expected, adult hearts showed higher mitochondrial mass and expressed increased levels of proteins involved in energy metabolism but relatively lower copy numbers of mitochondrial DNA (mtDNA) per total cell volume. We uncovered that the TFAM/mtDNA ratio was kept constant during postnatal development despite a significant increase of mitochondrial protein per mtDNA in adult mitochondria, which revises previous concepts. © The Royal Society of Chemistry. Source

Kovanen S.M.,University of Helsinki | Kivisto R.I.,University of Helsinki | Rossi M.,University of Helsinki | Schott T.,Leibniz Institute for Baltic Sea Research | And 8 more authors.
Journal of Clinical Microbiology

A total of 95 human Campylobacter jejuni isolates acquired from domestic infections and collected from three districts in Finland during the seasonal peak (June to September) in 2012 were analyzed by PCR-based multilocus sequence typing (MLST) and by whole-genome sequencing (WGS). Four predominant sequence types (STs) were detected among the isolates: ST-45 (21%) and ST-230 (14%, ST-45 clonal complex [CC]), ST-267 (21%, ST-283 CC), and ST-677 (19%, ST-677 CC). In districts 1 and 3, most of the infections occurred from early July to the middle of August, with a peak at weeks 29 to 31, but in district 2, the infections were dispersed more evenly throughout 3 months (June to August). WGS data were used for further whole-genome MLST (wgMLST) analyses of the isolates representing the four common STs. Shared loci of the isolates within each ST were analyzed as distance matrices of allelic profiles by the neighbor-net algorithm. The highest allelic variations (>400 different alleles) were detected between different clusters of ST-45 isolates (1,121 shared loci), while ST-230 (1,264 shared loci), ST-677 (1,169 shared loci), and ST-267 isolates (1,217 shared loci) were less diverse with the clusters differing by<40 alleles. Closely related isolates showing no allelic variation (subclusters) were detected among all four major STs. In some cases, they originated from different districts, suggesting that isolates can be epidemiologically connected and may have the same infection source despite being originally identified as sporadic infections. Copyright © 2014, American Society for Microbiology. All Rights Reserved. Source

Syrjanen L.,University of Tampere | Vermelho A.B.,Federal University of Rio de Janeiro | De Almeida Rodrigues I.,Federal University of Rio de Janeiro | Corte-Real S.,Oswaldo Cruz Institute OCI Platform | And 7 more authors.
Journal of Medicinal Chemistry

Leishmaniasis is an infection provoked by protozoans belonging to the genus Leishmania. Among the many species and subsepecies of such protozoa, Leishmania donovani chagasi causes visceral leishmaniasis. A β-carbonic anhydrase (CA, EC was cloned and characterized from this organism, denominated here LdcCA. LdcCA possesses effective catalytic activity for the CO2 hydration reaction, with kcat of 9.35 × 105 s -1 and kcat/KM of 5.9 × 107 M-1 s-1. A large number of aromatic/heterocyclic sulfonamides and 5-mercapto-1,3,4-thiadiazoles were investigated as LdcCA inhibitors. The sulfonamides were medium potency to weak inhibitors (K I values of 50.2 nM-9.25 μM), whereas some heterocyclic thiols inhibited the enzyme with KIs in the range of 13.4-152 nM. Some of the investigated thiols efficiently inhibited the in vivo growth of Leishmania chagasi and Leishmania amazonensis promastigotes, by impairing the flagellar pocket and movement of the parasites and causing their death. The β-CA from Leishmania spp. is proposed here as a new antileishmanial drug target. © 2013 American Chemical Society. Source

Syrjanen L.,University of Tampere | Tolvanen M.E.E.,University of Tampere | Hilvo M.,VTT Technical Research Center of Finland | Vullo D.,University of Florence | And 4 more authors.
Bioorganic and Medicinal Chemistry

Carbonic anhydrases (CAs) are essential and ubiquitous enzymes. Thus far, there are no articles on characterization of Drosophila melanogaster α-CAs. Data from invertebrate CA studies may provide opportunities for anti-parasitic drug development because α-CAs are found in many parasite or parasite vector invertebrates. We have expressed and purified D. melanogaster CAH1 and CAH2 as proteins of molecular weights 30 kDa and 28 kDa. CAH1 is cytoplasmic whereas CAH2 is a membrane-attached protein. Both are highly active enzymes for the CO2 hydration reaction, being efficiently inhibited by acetazolamide. CAH2 in the eye of D. melanogaster may provide a new animal model for CA-related eye diseases. A series of dithiocarbamates were also screened as inhibitors of these enzymes, with some representatives showing inhibition in the low nanomolar range. © 2012 Elsevier Ltd. All rights reserved. Source

Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen in many hospitals and long-term care facilities as well as in the community. To limit the spread of MRSA, early detection and proper treatment are essential. Because conventional culture as gold standard is time consuming, new techniques such as PCR-based and hybridization assays have emerged for the rapid detection of MRSA. This review will focus on the currently available molecular-based assays and on their utility and performance for detection of S. aureus, of its virulence factors and of the markers for acquired resistance. © 2014 Future Medicine Ltd. Source

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