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Mayer A.,Academy of Sciences of the Czech Republic | Baran V.,Academy of Sciences of the Czech Republic | Baran V.,Institute of Animal Physiology | Sakakibara Y.,RIKEN | And 6 more authors.
Cell Cycle | Year: 2016

Because low levels of DNA double strand breaks (DSBs) appear not to activate the ATM-mediated prophase I checkpoint in full-grown oocytes, there may exist mechanisms to protect chromosome integrity during meiotic maturation. Using live imaging we demonstrate that low levels of DSBs induced by the radiomimetic drug Neocarzinostatin (NCS) increase the incidence of chromosome fragments and lagging chromosomes but do not lead to APC/C activation and anaphase onset delay. The number of DSBs, represented by γH2AX foci, significantly decreases between prophase I and metaphase II in both control and NCS-treated oocytes. Transient treatment with NCS increases >2-fold the number of DSBs in prophase I oocytes, but less than 30% of these oocytes enter anaphase with segregation errors. MRE11, but not ATM, is essential to detect DSBs in prophase I and is involved in H2AX phosphorylation during metaphase I. Inhibiting MRE11 by mirin during meiotic maturation results in anaphase bridges and also increases the number of γH2AX foci in metaphase II.  Compromised DNA integrity in mirin-treated oocytes indicates a role for MRE11 in chromosome integrity during meiotic maturation. © 2016 Taylor & Francis Group, LLC. Source


Deeg C.A.,Institute of Animal Physiology
Investigative Ophthalmology and Visual Science | Year: 2014

PURPOSE. The pathogenesis of juvenile idiopathic arthritis-associated uveitis (JIAU) is undefined. This study intended to analyze the presence of antiocular autoantibodies in serum and their correlation with disease course. METHODS. Serum samples from children with JIAU (n=47); JIA without uveitis (n=67); idiopathic anterior uveitis (IAU; n=12); and healthy controls (n=52) were collected. The binding patterns of serum antibodies to ocular cryosections from swine eyes were analyzed by indirect immunohistochemistry, and were correlated to epidemiological, clinical, and laboratory test results. RESULTS. The patient groups differed with respect to their presence of antibody binding to the sections: JIAU (94%), JIA (75%), IAU (75%), and healthy controls (29%) to uveal and/or retinal structures. Serum antibodies of JIAU patients predominantly bound at iris (74%), and ciliary body (79%). Iris/ciliary body positive staining correlated with the presence of uveitis complications (P < 0.005) in JIAU patients, but not with positivity of serum antinuclear antibodies (ANA), rheumatoid factor (RF), or HLA-B27, and was independent from uveitis activity or type of anti-inflammatory therapy. CONCLUSIONS. In JIAU patients, antiocular serum antibodies can be detected more frequently than in control groups. Binding patterns to ocular tissue correlate with complicated uveitis course but not with uveitis activity and anti-inflammatory treatment. Antibody binding is not specific for this uveitis entity, and does not correlate with ANA positivity. © 2014 The Association for Research in Vision and Ophthalmology, Inc. Source


Solc P.,Institute of Animal Physiology and Genetics | Kitajima T.S.,Cell biology and biophysics unit | Kitajima T.S.,RIKEN | Yoshida S.,RIKEN | And 7 more authors.
PLoS ONE | Year: 2015

Polo-like kinase 1 (PLK1) orchestrates multiple events of cell division. Although PLK1 function has been intensively studied in centriole-containing and rapidly cycling somatic cells, much less is known about its function in the meiotic divisions of mammalian oocytes, which arrest for a long period of time in prophase before meiotic resumption and lack centrioles for spindle assembly. Here, using specific small molecule inhibition combined with live mouse oocyte imaging, we comprehensively characterize meiotic PLK1's functions. We show that PLK1 becomes activated at meiotic resumption on microtubule organizing centers (MTOCs) and later at kinetochores. PLK1 is required for efficient meiotic resumption by promoting nuclear envelope breakdown. PLK1 is also needed to recruit centrosomal proteins to acentriolar MTOCs to promote normal spindle formation, as well as for stable kinetochore- microtubule attachment. Consequently, PLK1 inhibition leads to metaphase I arrest with misaligned chromosomes activating the spindle assembly checkpoint (SAC). Unlike in mitosis, the metaphase I arrest is not bypassed by the inactivation of the SAC.We show that PLK1 is required for the full activation of the anaphase promoting complex/cyclosome (APC/C) by promoting the degradation of the APC/C inhibitor EMI1 and is therefore essential for entry into anaphase I. Moreover, our data suggest that PLK1 is required for proper chromosome segregation and the maintenance of chromosome condensation during the meiosis I-II transition, independently of the APC/C. Thus, our results define the meiotic roles of PLK1 in oocytes and reveal interesting differential requirements of PLK1 between mitosis and oocyte meiosis in mammals. © 2015 Solc et al. Source


Perbandt M.,University of Hamburg | Ndjonka D.,University of Ngaoundere | Liebau E.,Institute of Animal Physiology
Current Medicinal Chemistry | Year: 2014

Helminths that are the causative agents of numerous neglected tropical diseases continue to be a major problem for human global health. In the absence of vaccines, control relies solely on pharmacoprophylaxis and pharmacotherapy to reduce transmission and to relieve symptoms. There are only a few drugs available and resistance in helminths of lifestock has been observed to the same drugs that are also used to treat humans. Clearly there is an urgent need to find novel antiparasitic compounds. Not only are helminths confronted with their own metabolically derived toxic and redox-active byproducts but also with the production of reactive oxygen species (ROS) by the host immune system, adding to the overall oxidative burden of the parasite. Antioxidant enzymes of helminths have been identified as essential proteins, some of them biochemically distinct to their host counterpart and thus appealing drug targets. In this review we have selected a few enzymatic antioxidants of helminths that are thought to be druggable. ©2014 Bentham Science Publishers. Source


Jung M.Y.,Korea Research Institute of Bioscience and Biotechnology | Kim J.-S.,Korea Research Institute of Bioscience and Biotechnology | Paek W.K.,National Science Museum | Styrak I.,Institute of Animal Physiology | And 8 more authors.
International Journal of Systematic and Evolutionary Microbiology | Year: 2012

A Gram-positive, rod-shaped, endospore-forming bacterium, designated strain BLB-1T, was isolated from samples of tidal flat sediment from the Yellow Sea. 16S rRNA gene sequence analysis demonstrated that the isolate belonged to the Bacillus rRNA group 2 and was closely related to Bacillus massiliensis CIP 108446T (97.4 %), Bacillus odysseyi ATCC PTA-4993T (96.7 %), Lysinibacillus fusiformis DSM 2898T (96.2 %) and Lysinibacillus boronitolerans DSM 17140T (95.9 %). Sequence similarities with related species in other genera, including Caryophanon, Sporosarcina and Solibacillus, were,<96.1 %. Chemotaxonomic data supported the affiliation of strain BLB-1T with the genus Lysinibacillus. The major menaquinone was MK-7, the cell-wall sugars were glucose and xylose, the cell-wall peptidoglycan type was A4α (L-Lys-D-Asp), the major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and several unknown phospholipids, and the major fatty acids were anteiso-C15: 0 (35.6 %), iso-C15: 0 (25.6 %) and anteiso-C17: 0 (16.5 %). The most closely related species, Bacillus massiliensis and Bacillus odysseyi, were also assigned to this genus based on phylogenetic analysis and phenotypic data. The results of DNA-DNA hybridizations and phenotypic tests supported the differentiation of all three taxa from species of the genus Lysinibacillus with validly published names. Thus, strain BLB-1T (=KCTC 13296T=JCM 15800T) represents a novel species, for which the name Lysinibacillus sinduriensis sp. nov. is proposed. It is also proposed that Bacillus massiliensis CIP 108446T (=4400831T=CCUG49529T=KCTC 13178T) and Bacillus odysseyi NBRC 100172T (534hs-1T = ATCC PTA-4993T =NRRL B-30641T =DSM 18869T =CIP 108263T =KCTC 3961T) be transferred to the genus Lysinibacillus as Lysinibacillus massiliensis comb. nov. and Lysinibacillus odysseyi comb. nov., respectively.© G 2012 IUMS. Source

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