Myeloid derived suppressor cells and autoimmunity

K

lemmingA encodes the Apc11 subunit of the APC/C in Drosophila melanogaster that forms a ternary complex with the E2-C type ubiquitin conjugating enzyme, Vihar and Morula/Apc2

<p>Abstract</p> <p>Background</p> <p>Ubiquitin-dependent protein degradation is a critical step in key cell cycle events, such as metaphase-anaphase transition and mitotic exit. The anaphase promoting complex/cyclosome (APC/C) plays a pivotal role in these transitions by recognizing and marking regulatory proteins for proteasomal degradation. Its overall structure and function has been elucidated mostly in yeasts and mammalian cell lines. The APC/C is, however, a multisubunit assembly with at least 13 subunits and their function and interaction within the complex is still relatively uncharacterized, particularly in metazoan systems. Here, <it>lemming </it>(<it>lmg</it>) mutants were used to study the APC/C subunit, Apc11, and its interaction partners in <it>Drosophila melanogaster</it>.</p> <p>Results</p> <p>The <it>lmg </it>gene was initially identified through a pharate adult lethal P element insertion mutation expressing developmental abnormalities and widespread apoptosis in larval imaginal discs and pupal abdominal histoblasts. Larval neuroblasts were observed to arrest mitosis in a metaphase-like state with highly condensed, scattered chromosomes and frequent polyploidy. These neuroblasts contain high levels of both cyclin A and cyclin B. The <it>lmg </it>gene was cloned by virtue of the <it>lmg⁰³⁴²⁴</it>P element insertion which is located in the 5' untranslated region. The <it>lemming </it>locus is transcribed to give a 2.0 kb mRNA that contains two ORFs, <it>lmgA </it>and <it>lmgB</it>. The <it>lmgA </it>ORF codes for a putative protein with more than 80% sequence homology to the APC11 subunit of the human APC/C. The 85 amino acid protein also contains a RING-finger motif characteristic of known APC11 subunits. The <it>lmgA </it>ORF alone was sufficient to rescue the lethal and mitotic phenotypes of the <it>lmg¹³⁸</it>null allele and to complement the temperature sensitive lethal phenotype of the <it>APC11-myc9 </it>budding yeast mutant. The LmgA protein interacts with Mr/Apc2, and they together form a binding site for Vihar, the E2-C type ubiquitin conjugating enzyme. Despite being conserved among <it>Drosophila </it>species, the LmgB protein is not required for viability or fertility.</p> <p>Conclusions</p> <p>Our work provides insight into the subunit structure of the <it>Drosophila </it>APC/C with implications for its function. Based on the presented data, we suggest that the Lmg/Apc11 subunit recruits the E2-C type ubiquitin conjugating enzyme, Vihar, to the APC/C together with Mr/Apc2 by forming a ternary complex.</p

Studia Litteraria

Juhász Géza (1894-1968), 3-6. Baranyi Imre (1935-1968), 7-10. Balogh István, Debreceniség, Egy irodalmi fogalom története és társadalmi háttere, 11-54. Kovács József László, Egy magyar humanista író portréjának kialakulása, Írások Lackner Kristófról 1631-1944, 55-74. Juhász Géza - J. Gulyás Margit, Csokonai latin zsengéi, 75-92. Boros Dezső, adalékok Csokonai csurgói tanárságához, 93-108. Baffy Dezső, Montesquieu hatása a fiatal Kemény gondolkodására, 109-120. Baranyi Imre, A fiatal Madách Pesten, 121-136

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INST: L_08

Microcirculatory consequences of osteoporosis

Introduction. The etiology of senile osteoporosis syndrome is multifactorial, but the reduced estrogen levels in peri-menopausal women are clearly associated with an accelerated bone loss. In our experimental studies, the consequences of osteoporosis and chronic estrogen supplementation were investigated on the periosteal microcirculatory inflammatory reactions and estrogen receptor expressions. Material and method. Six months after the initiation of estrogen replacement therapy with 17β-estradiol (E2, 20 µg-1kg-1day-1) in ovariectomized (OVX) Sprague-Dawley rats, the microcirculatory inflammatory consequences of 60-min total hindlimb ischemia followed by 180-min reperfusion were examined. Leukocyte estrogen receptor expression changes were also assessed 1 month after OVX plus E2 treatment. Results. Apart from reversing the osteopenic effects of OVX, E2 treatment significantly ameliorated the ischemia-reperfusion-induced elevation of neutrophil leukocyte adherence to the postcapillary venules of the periosteum (visualized by means of intravital fluorescence microscopy). This effect was not associated with a reduction of CD11b expression of the neutrophil leukocytes (FACS analysis). OVX caused a moderate decrease in leukocyte estrogen receptor (ER)-beta protein expression which tended to be reversed by E2. Leukocyte ER-alpha and ER-beta mRNA levels (RT-PCR) and the ER-alpha protein expression (Western blotting) were below the detection limit. Conclusions. Chronic estrogen supplementation efficiently ameliorates osteoporosis and the inflammatory microcirculatory consequences of transient limb ischemia. It appears that this effect is not mediated by leukocyte CD11b, or estrogen receptor expression changes