197,284 research outputs found

    Oxidative, multistep activation of the noncanonical NF-kappa B pathway via disulfide Bcl-3/p50 complex

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    Buthionine sulfoximine ( BSO) is a well-known inhibitor of glutathione synthesis, producing slow glutathione ( GSH) depletion and oxidative stress; some "responder" cells avoid BSO-induced death by trans-activating the prosurvival protein Bcl-2. Here we show that BSO activates a noncanonical, inhibitory NF-kappa B- and p65-independent NF-kappa B pathway via a multistep process leading to the up-regulation of Bcl-2. The slow BSO-induced GSH depletion allows separation of two redox-related phases, namely, early thiol disequilibrium and late frank oxidative stress; each phase contributes to the progressive activation of a p50-p50 homodimer. The early phase, coinciding with substantial thiol depletion, produces a cytosolic preparative complex, consisting of p50 and its interactor Bcl-3 linked by interprotein disulfide bridges. The late phase, coinciding with reactive oxygen species production, is responsible, probably via p38 activation, for nuclear targeting of the complex and trans-activation of Bcl-2. Cristofanon, S., Morceau, F., Scovassi, A. I., Dicato, M., Ghibelli, L., Diederich, M. Oxidative, multistep activation of the noncanonical NF-kappa B pathway via disulfide Bcl-3/p50 complex. FASEB J. 23, 45-57 ( 2009

    Auf der Suche nach der Latrine des Ackerbürgerhauses - Warum?

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    Die Ausgrabungen im Jahr 2019: Schnitt 5: Ausgrabung im Hinterhof des Ackerbürgerhauses Stadtbestands-Plan von 1839 mit Hervorhebung des Ackerbürgerhauses (Foto: E. Zwerenz) Planum 1 in Schnitt 5 mit Blicknach Süden (Foto: V. Diederich) Planum 2 (Foto: V. Diederich) Westprofil Schnitt 5 (Foto: M. Rühle) Pflasterung. Foto: V. Diederich Zum Ackerbürgerhaus in Bärnau gehört ein Hinterhof, dessen Form sich seit dem 19. Jh. kaum verändert hat (Abb. 1). Die Parzelle reichte trapezförmig bis ..

    Agonimia pacifica Diederich

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    Agonimia pacifica (Harada) Diederich Harada (1993) described this species and placed it in a new genus Agonimiella. Diederich however convincingly showed that the differences between the new genus and Agonimia are more minor than thought by Harada (Aptroot et al. 1997). Consequently he transferred the species to the genus Agonimia. Our own observations confirmed those of Diederich. Previously, Agonimia pacifica was known from Brazil, Costa Rica, Japan, Reunion and Taiwan (Aptroot 2002, Aptroot et al. 2008, v.d. Boom et al. 2011). This report is a new addition to the Chinese lichen biota. Specimens examined: — CHINA. Zhejiang Province: Mount Tianmushan near Lin’an city; trail from Longfengjian Parking Lot to Peak of Immortales, in a rainforest with Carpinus viminea, Cyclocarva paliurus, Castanea henryi, Quercus serrata, etc. 1200 m. 30°20’ N, 119°26’ E, 19 October 2010, K. Kalb & Z.F. Jia (hb. Kalb 38740).—Qingyuan County; Mount Baishanzu, Baishanzu National Nature Reserve below the Baishanzu Protection Station, in a mixed mountain rainforest, 1400 m. 27°45’ N, 119°11’ E, 11 October 2010, K. Kalb & Z.F. Jia (hb. Kalb 38621).Published as part of Kalb, Klaus, Buaruang, Kawinnat, Mongkolsuk, Pachara & Boonpragob, Kansri, 2012, New or otherwise interesting Lichens. VI, including a lichenicolous fungus, pp. 35-47 in Phytotaxa 42 on pages 35-36, DOI: 10.11646/phytotaxa.42.1.5, http://zenodo.org/record/489482

    Multistep and multitask Bax activation

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    Bax is a pro-apoptotic protein allowing apoptosis to occur through the intrinsic, damage-induced pathway, and amplifying that one occurring via the extrinsic, receptor mediated pathway. Bax is present in viable cells and activated by pro-apoptotic stimuli. Activation implies structural changes, consisting of exposure of the N terminus and hydrophobic domains; changes in localization, consisting in migration from cytosol to mitochondria and endoplasmic reticulum membranes; changes in the aggregation status, from monomer to dimer and multimer. Bax has multiple critical domains, namely the N terminus exposed after activation; two hydrophobic stretches exposed for membrane anchorage; two reactive cysteines allowing multimerization; the BH3 domain for interactions with the Bcl-2 family members; alpha helix 1 for t-Bid interaction. Bax has also multiple functions: it releases different mitochondrial factors such as cytochrome c, SMAC/diablo; it regulates mitochondrial fission, the mitochondrial permeability transition pore; it promotes Ca(2+) leakage through ER membrane. Altogether, Bax activation is a complex multi-step phenomenon. Here, we analyze these events as logically separable or alternative steps, attempting to assess their role, timing and reciprocal relation

    Marchandiobasidium aurantiacum (Lasch) Diederich & Schultheis – new for Ukraine lichenicolous fungus

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    Наумович, Г. О. Marchandiobasidium aurantiacum (Lasch) Diederich & Schultheis – Новий для України вид ліхенофільного гриба / Гавриленко Л.М., Ходосовцев О.Є., Наумович Г.О. // Чорноморськ. бот. ж.– 2009. – Т. 5, №4. – С. 609-611.Наводяться локалітети, екологічні особливості та загальне поширення нового для України ліхенофільного гриба Marchandiobasidium aurantiacum (Lasch) Diederich & Schultheis, який паразитує на сланях епіфітних лишайників з родів Physcia та Xanthoria. Приводяться местообитания, экологические особенности и общее распространение нового для Украины лихенофильного гриба Marchandiobasidium aurantiacum (Lasch) Diederich & Schultheis, который паразитирует на слоевищах эпифитных лишайников родов Physcia и Xanthoria. The locations, ecology and general distribution of the new for Ukraine lichenicolous fungus Marchandiobasidium aurantiacum (Lasch) Diederich & Schultheis are given in the article. The species is determined to be a parasite of the corticolous lichenes Physcia and Xanthoria

    The Dual Role of Calcium as Messenger and Stressor in Cell Damage, Death, and Survival

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    Ca2+ is an important second messenger participating in many cellular activities; when physicochemical insults deregulate its delicate homeostasis, it acts as an intrinsic stressor, producing/increasing cell damage. Damage elicits both repair and death responses; intriguingly, in those responses Ca2+ also participates as second messenger. This delineates a dual role for Ca2+ in cell stress, making difficult to separate the different and multiple mechanisms required for Ca2+-mediated control of cell survival and apoptosis. Here we attempt to disentangle the two scenarios, examining on the one side, the events implicated in deregulated Ca2+ toxicity and the mechanisms through which this elicits reparative or death pathways; on the other, reviewing the role of Ca2+ as a messenger in the transduction of these same signaling events

    Cell type-dependent ROS and mitophagy response leads to apoptosis or necroptosis in neuroblastoma

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    A limiting factor in the therapeutic outcome of children with high-risk neuroblastoma is the intrinsic and acquired resistance to common chemotherapeutic treatments. Here we investigated the molecular mechanisms by which the hemisynthetic cardiac glycoside UNBS1450 overcomes this limitation and induces differential cell death modalities in both neuroblastic and stromal neuroblastoma through stimulation of a cell-type-specific autophagic response eventually leading to apoptosis or necroptosis. In neuroblastic SH-SY5Y cells, we observed a time-dependent production of reactive oxygen species that affects lysosomal integrity inducing lysosome-associated membrane protein 2 degradation and cathepsin B and L activation. Subsequent mitochondrial membrane depolarization and accumulation of mitochondria in phagophores occurred after 8h of UNBS1450 treatment. Results were confirmed by mitochondrial mass analysis, electron microscopy and co-localization of mitochondria with GFP-LC3, suggesting the impaired clearance of damaged mitochondria. Thus, a stress-induced defective autophagic flux and the subsequent lack of clearance of damaged mitochondria sensitized SH-SY5Y cells to UNBS1450-induced apoptosis. Inhibition of autophagy with small inhibitory RNAs against ATG5, ATG7 and Beclin-1 protected SH-SY5Y cells against the cytotoxic effect of UNBS1450 by inhibiting apoptosis. In contrast, autophagy progression towards the catabolic state was observed in stromal SK-N-AS cells: here reactive oxygen species (ROS) generation remained undetectable preserving intact lysosomes and engulfing damaged mitochondria after UNBS1450 treatment. Moreover, autophagy inhibition determined sensitization of SK-N-AS to apoptosis. We identified efficient mitophagy as the key mechanism leading to failure of activation of the apoptotic pathway that increased resistance of SK-N-AS to UNBS1450, triggering rather necroptosis at higher doses. Altogether we characterize here the differential modulation of ROS and mitophagy as a main determinant of neuroblastoma resistance with potential relevance for personalized anticancer therapeutic approaches.N

    DNA damage response: the emerging role of c-Abl as a regulatory switch?

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    A complex regulatory network of signaling pathways safeguards genome integrity following DNA damage. When double strand breaks occur several enzymes and mediators are recruited to the sites of lesion to release a network of DNA repair processes referred to as DNA damage response (DDR). c-Abl interacts in the nucleus with several proteins implicated in distinct aspects of DNA repair. This suggests that c-Abl may be involved in the regulation of double strand break repair. The involvement of c-Abl in DNA repair mechanisms came into the spotlight in female germ cells under genotoxic stress. Recent findings have implicated c-Abl in a cisplatin-induced signaling pathway eliciting death of immature oocytes. Pharmacological inhibition of c-Abl by Imatinib (STI571) protects the ovarian reserve from the toxic effect of cisplatin. This implies that the extent of c-Abl catalytic outcomes may tip the balance between survival (likely through DNA repair) and activation of a death response. Many observations indicate that timely ubiquitin-modifications and signal decoding are implicated in regulating DNA repair. Here, we discuss some connections between phosphorylation- and ubiquitin-mediated signaling at the damaged sites. We speculate about multiple interactions that may occur between c-Abl (and 'sensor' kinases) with ubiquitin-related proteins involved in DDR. Additional work is required to understand the complexity of the physiological outcomes of c-Abl in DDR. However, a fine-tuning of nuclear outcomes, through pharmacological inhibition of c-Abl, may provide novel paradigms for DDR and, potentially, therapeutic strategies for cancer treatmen

    Marchandiobasidium aurantiacum (Lasch) Diederich & Schultheis – новый для Украини вид лихенофильного гриба

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    ГАВРИЛЕНКО Л.М., ХОДОСОВЦЕВ А.Е., НАУМОВИЧ Г.О. 2009: Marchandiobasidium aurantiacum (Lasch) Diederich & Schultheis – новий для України вид ліхенофільного гриба. Чорноморськ. бот. ж., т. 5, N 4: 609-611.Наводяться локалітети, екологічні особливості та загальне поширення нового для України ліхенофільного гриба Marchandiobasidium aurantiacum (Lasch) Diederich & Schultheis, який паразитує на сланях епіфітних лишайників з родів Physcia та Xanthoria. The locations, ecology and general distribution of the new for Ukraine lichenicolous fungus Marchandiobasidium aurantiacum (Lasch) Diederich & Schultheis are given in the article. The species is determined to be a parasite of the corticolous lichenes Physcia and Xanthoria. Приводяться местообитания, экологические особенности и общее распространение нового для Украины лихенофильного гриба Marchandiobasidium aurantiacum (Lasch) Diederich & Schultheis, который паразитирует на слоевищах эпифитных лишайников родов Physcia и Xanthoria
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