Relocation
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Dual-specificity mitogen-activated protein kinases kinases (MAPKKs) are the immediate upstream activators of MAPKs. They simultaneously phosphorylate the TXY motif within the activation loop of MAPKs, allowing them to interact with and regulate multiple substrates. Often, the activation of MAPKs triggers their nuclear translocation. However, the spatiotemporal dynamics and the physiological consequences of the activation of MAPKs, particularly in plants, are still poorly understood. Here, we studied the activation and localization of the Medicago sativa stress-induced MAPKK (SIMKK)-SIMK module after salt stress. In the inactive state, SIMKK and SIMK co-localized in the cytoplasm and in the nucleus. Upon salt stress, however, a substantial part of the nuclear pool of both SIMKK and SIMK relocated to cytoplasmic compartments. The course of nucleocytoplasmic shuttling of SIMK correlated temporally with the dual phosphorylation of the pTEpY motif. SIMKK function was further studied in Arabidopsis plants overexpressing SIMKK-yellow fluorescent protein (YFP) fusions. SIMKK-YFP plants showed enhanced activation of Arabidopsis MPK3 and MPK6 kinases upon salt treatment and exhibited high sensitivity against salt stress at the seedling stage, although they were salt insensitive during seed germination. Proteomic analysis of SIMKK-YFP overexpressors indicated the differential regulation of proteins directly or indirectly involved in salt stress responses. These proteins included catalase, peroxiredoxin, glutathione S-transferase, nucleoside diphosphate kinase 1, endoplasmic reticulum luminal-binding protein 2, and finally plasma membrane aquaporins. In conclusion, Arabidopsis seedlings overexpressing SIMKK-YFP exhibited higher salt sensitivity consistent with their proteome composition and with the presumptive MPK3/MPK6 hijacking of the salt response pathway.
- MeSH
- aktivace enzymů MeSH
- Arabidopsis genetika růst a vývoj metabolismus MeSH
- exprese genu MeSH
- geneticky modifikované rostliny genetika růst a vývoj metabolismus MeSH
- Medicago sativa enzymologie genetika MeSH
- mitogenem aktivované proteinkinasy kinas genetika metabolismus MeSH
- rostlinné proteiny genetika metabolismus MeSH
- semenáček genetika růst a vývoj metabolismus MeSH
- soli metabolismus MeSH
- transport proteinů MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Krevní výron, jako důsledek intravitálního krvácení, je z forenzního hlediska považován za důležitou známku vitální reakce poranění. Ve zvláštních případech je však nutno připustit možnost, že hematom vznikl až postmortálně. Vznik supravitálních změn je zřejmý kupř. u dárců orgánů u nichž je po smrti mozku udržován krevní oběh a plicní ventilace. Posmrtný vznik krevních výronů ale pozorujeme i u dárců po enukleaci očních bulbů odebraných až před pitvou na Ústavu soudního lékařství a toxikologie; tyto krevní výrony se manifestují za několik hodin po odběru. Mimoto jsme ale zaznamenali vznik hematomu v očnici, který nebyl způsoben ani intravitálním ani postmortálním přímým násilím; jeho vznik nelze vysvětlit jinak než posmrtnou propagací výronu ze zlomeniny přední jámy lební do očnice. V dostupné literatuře jsme nezjistili údaj o posmrtném vzniku resp. přemístění hematomu takového rozsahu. Jde tedy, v rámci znalostí o supravitální reakci o poznatek obecného významu, ovšem i s forenzním dopadem. V konkrétním případě, dokumentace z místa činu umožnila korigovat posouzení mechanismu vzniku poranění resp. úrazového děje z hlediska podezření na cizí zavinění, které by v takovém případě přicházelo v úvahu (jako např. úder do očnice a pád pod projíždějící soupravu metra).
The hemorrhage as a result of intravital bleeding is considered, from forensic point of view, as important sign of vital reaction of injury. However, in special cases it must be accepted that hemorrhage occurred after the death. The formation of supravital changes is evident e.g. in organ donors whose blood circulation and pulmonary ventilation is kept after the brain death. The post-mortem origin of hemorrhages can also be seen in donors of eyeballs after enucleation made before the autopsy at Institute of Forensic Medicine and Toxicology. These hemorrhages are manifested after several hours when eyeballs were removed. Moreover, we observed the origin of hemorrhage in orbit which was caused nor by intravital bleeding neither by direct force. Its origin could not be explained nothing but postmortem propagation of the hemorrhage from the fracture of anterior fossa of the scull base. We did not find information about postmortem origin or relocation of hemorrhage of such extent in the literature. In the frame of knowledge about supravital reaction, this finding is of general importance with forensic impact. The documentation from the scene of death allowed correcting the appreciation of the mechanism of injury and traumatic process from the point of view of foreign culpability which should be considered in such case (e.g. a blow to the orbit with following fall under passing subway train).
- Klíčová slova
- forenzní význam, postmortální propagace hematomu, vitální a supravitální reakce,
- MeSH
- dospělí MeSH
- hematom diagnóza klasifikace MeSH
- kraniocerebrální traumata diagnóza klasifikace patologie MeSH
- lidé MeSH
- pitva metody MeSH
- polytrauma diagnóza klasifikace MeSH
- poranění elektrickým proudem diagnóza klasifikace MeSH
- posmrtné změny MeSH
- úrazy a nehody klasifikace MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Formins are evolutionarily conserved eukaryotic proteins engaged in actin nucleation and other aspects of cytoskeletal organization. Angiosperms have two formin clades with multiple paralogs; typical plant Class I formins are integral membrane proteins that can anchor cytoskeletal structures to membranes. For the main Arabidopsis housekeeping Class I formin, FH1 (At3g25500), plasmalemma localization was documented in heterologous expression and overexpression studies. We previously showed that loss of FH1 function increases cotyledon epidermal pavement cell shape complexity via modification of actin and microtubule organization and dynamics. Here, we employ transgenic Arabidopsis expressing green fluorescent protein-tagged FH1 (FH1-GFP) from its native promoter to investigate in vivo behavior of this formin using advanced microscopy techniques. The fusion protein is functional, since its expression complements the fh1 loss-of-function mutant phenotype. Accidental overexpression of FH1-GFP results in a decrease in trichome branch number, while fh1 mutation has the opposite effect, indicating a general role of this formin in controlling cell shape complexity. Consistent with previous reports, FH1-GFP associates with membranes. However, the protein exhibits surprising actin- and secretory pathway-dependent dynamic localization and relocates between cellular endomembranes and the plasmalemma during cell division and differentiation in root tissues, with transient tonoplast localization at the transition/elongation zones border. FH1-GFP also accumulates in actin-rich regions of cortical cytoplasm and associates with plasmodesmata in both the cotyledon epidermis and root tissues. Together with previous reports from metazoan systems, this suggests that formins might have a shared (ancestral or convergent) role at cell-cell junctions.
- MeSH
- 2. světová válka MeSH
- dějiny 20. století MeSH
- studium veterinárního lékařství * dějiny MeSH
- univerzity * dějiny organizace a řízení MeSH
- veterinární lékařství MeSH
- vytváření politiky MeSH
- Check Tag
- dějiny 20. století MeSH
- Publikační typ
- historické články MeSH
- Geografické názvy
- Československo MeSH
AIM: This study was designed to evaluate feasibility and effectiveness of hysteroscopic intervention in the management of symptoms related to the displaced levonorgestrel-releasing intrauterine system (LNG-IUS). MATERIAL AND METHODS: One hundred and thirteen patients with displaced LNG-IUS presenting with irregular uterine bleeding, pelvic pain or asymptomatic displacement were recruited for hysteroscopic examination. Displaced LNG-IUS was relocated by hysteroscopic intervention and the effect on symptoms and LNG-IUS position was followed. RESULTS: The displaced LNG-IUS was successfully relocated by hysteroscope in 112 (99.1%) of 113 cases. Following LNG-IUS relocation, 71 (79.8%) patients of 89 with preoperative irregular uterine bleeding had amenorrhea or vaginal spotting, and 14 of 15 (93.3%) patients with preoperative pelvic pain became asymptomatic. LNG-IUS expulsion was recorded in two patients 7 and 21 days after hysteroscopy. CONCLUSION: Displaced LNG-IUS can cause clinical symptoms (e.g. irregular bleeding, pain). Hysteroscopic relocation of displaced LNG-IUS is a feasible method in the management of these symptoms. Risk of spontaneous expulsion associated with hysteroscopy is low.
- MeSH
- dospělí MeSH
- hysteroskopie * MeSH
- kohortové studie MeSH
- levonorgestrel aplikace a dávkování MeSH
- lidé středního věku MeSH
- lidé MeSH
- metroragie etiologie prevence a kontrola MeSH
- migrace nitroděložního tělíska škodlivé účinky MeSH
- mladý dospělý MeSH
- následné studie MeSH
- nitroděložní tělíska hormonální škodlivé účinky MeSH
- odstranění implantátu škodlivé účinky metody MeSH
- pánevní bolest etiologie prevence a kontrola MeSH
- studie proveditelnosti MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is known for its multifunctionality in several pathogenic bacteria. Our previously reported data suggest that the GAPDH homologue of Francisella tularensis, GapA, might also be involved in other processes beyond metabolism. In the present study, we explored GapA's potential implication in pathogenic processes at the host cell level. Using immunoelectron microscopy, we demonstrated the localization of this bacterial protein inside infected macrophages and its peripheral distribution in bacterial cells increasing with infection time. A quantitative proteomic approach based on stable isotope labeling of amino acids in cell culture (SILAC) combined with pull-down assay enabled the identification of several of GapA's potential interacting partners within the host cell proteome. Two of these partners were further confirmed by alternative methods. We also investigated the impact of gapA deletion on the transcription of selected cytokine genes and the activation of the main signaling pathways. Our results show that ∆gapA-induced transcription of genes encoding several cytokines whose expressions were not affected in cells infected with a fully virulent wild-type strain. That might be caused, at least in part, by the detected differences in ERK/MAPK signaling activation. The experimental observations together demonstrate that the F. tularensis GAPDH homologue is directly implicated in multiple host cellular processes and, thereby, that it participates in several molecular mechanisms of pathogenesis.
Puwainaphycins F and G, moderate cytotoxins, which cause necrotic cell death to mammalian cells, were isolated from the soil cyanobacterium Cylindrospermum alatosporum C24/89. Both compounds have been shown to be cyclic decapeptides containing unusual β-amino fatty acid (2-hydroxy-3-amino-4methyl tetradecanoic acid). Described variants differ in the substitution of threonine by glutamine in the fourth position. Their structures differ from the known puwainaphycins in five amino acids positions as well as in the β-amino fatty acid unit. The rapid interaction of these compounds with the plasma membrane of the mammal cell leads to an elevation of the concentration of intracellular Ca(2+), with kinetics comparable to the well-established calcium ionophore ionomycin. Subsequently, the induction of tyrosine phosphorylation was observed to be followed by the unique transformation of the actin cytoskeleton into ring structures around the nuclei. All of these alterations in the cellular morphology and physiology result in necrotic cell death after ca. 10 h. The IC(50) values were determined to be 2.2 μM for both puwainaphycins. The present data demonstrate the interaction of cyanobacterial secondary metabolites with eukaryotic plasma membrane and point out the possible toxic effects of cyanobacterial lipopeptides for humans.
- MeSH
- aktiny chemie metabolismus MeSH
- buněčná smrt účinky léků MeSH
- HeLa buňky MeSH
- lidé MeSH
- lipopeptidy chemie izolace a purifikace farmakologie MeSH
- mikrofilamenta účinky léků metabolismus MeSH
- molekulární struktura MeSH
- nádorové buněčné linie MeSH
- permeabilita buněčné membrány účinky léků MeSH
- protinádorové látky chemie izolace a purifikace farmakologie MeSH
- screeningové testy protinádorových léčiv MeSH
- sinice chemie MeSH
- vápník metabolismus MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
... 8, To Move or Not to Move: ThgJJ&zards of Relocation 123 -- Chapter VI. ...
Science monographs - National Institute of Mental Health DHEW publication ; no. (ADM) 78-687
vi, 181 stran ; 24 cm
