Článek pojednává o současných vztahově patologických projevech na pracovištích, s důrazem na oblast zdravotnictví. Autoři ve svém přehledu shrnují a popisují jednotlivé projevy agrese, šikany, jejich současných forem bossingu, mobbingu a dalších forem problémového chování ve zdravotnických kolektivech. Upozorňují na nebezpečnost tohoto chování ve společnosti, na narůstající výskyt těchto jevů, což stručně dokumentují na dvou kazuistikách. Zabývají se, kdo je označován za původce bossingu, kdo je obětí, jak tyto formy nevhodného chování probíhají a jak jim lze předcházet a jak tyto situace řešit. V závěru shrnují preventivní opatření a odkazují na kvalifikované zdroje pomoci.
The article talks about the manifestations of bossing, specific for contemporary society and health care settings. The authors summarize and describe various displays of violence, bossing, mobbing and other forms of probleatic behavior in the context of relations of coworkers. Authors point out the dangers of such behaviour and its growing occurence and providing three case studies. In the article, they provide a definition of the perpetrators of bossing, its victims, the way boosing is usually played out, and the ways to prevent and solve these types of situations. In the conclusion, they provide an enumeration of preventive means and qualified resources of help.
- MeSH
- interprofesionální vztahy MeSH
- lidé MeSH
- násilí na pracovišti MeSH
- pracovní stres * prevence a kontrola psychologie MeSH
- zdravotnická zařízení MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- kazuistiky MeSH
- přehledy MeSH
Achondroplasia is the most prevalent genetic form of dwarfism in humans and is caused by activating mutations in FGFR3 tyrosine kinase. The clinical need for a safe and effective inhibitor of FGFR3 is unmet, leaving achondroplasia currently incurable. Here, we evaluated RBM-007, an RNA aptamer previously developed to neutralize the FGFR3 ligand FGF2, for its activity against FGFR3. In cultured rat chondrocytes or mouse embryonal tibia organ culture, RBM-007 rescued the proliferation arrest, degradation of cartilaginous extracellular matrix, premature senescence, and impaired hypertrophic differentiation induced by FGFR3 signaling. In cartilage xenografts derived from induced pluripotent stem cells from individuals with achondroplasia, RBM-007 rescued impaired chondrocyte differentiation and maturation. When delivered by subcutaneous injection, RBM-007 restored defective skeletal growth in a mouse model of achondroplasia. We thus demonstrate a ligand-trap concept of targeting the cartilage FGFR3 and delineate a potential therapeutic approach for achondroplasia and other FGFR3-related skeletal dysplasias.
- MeSH
- achondroplazie * farmakoterapie genetika MeSH
- aptamery nukleotidové * MeSH
- buněčná diferenciace MeSH
- chondrocyty MeSH
- krysa rodu rattus MeSH
- myši MeSH
- receptor fibroblastových růstových faktorů, typ 3 genetika MeSH
- vývoj kostí MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Many patients with chronic myeloid leukemia in deep remission experience return of clinical disease after withdrawal of tyrosine kinase inhibitors (TKIs). This suggests signaling of inactive BCR-ABL, which allows the survival of cancer cells, and relapse. We show that TKI treatment inhibits catalytic activity of BCR-ABL, but does not dissolve BCR-ABL core signaling complex, consisting of CRKL, SHC1, GRB2, SOS1, cCBL, p85a-PI3K, STS1 and SHIP2. Peptide microarray and co-immunoprecipitation results demonstrate that CRKL binds to proline-rich regions located in C-terminal, intrinsically disordered region of BCR-ABL, that SHC1 requires pleckstrin homology, src homology and tyrosine kinase domains of BCR-ABL for binding, and that BCR-ABL sequence motif located in disordered region around phosphorylated tyrosine 177 mediates binding of three core complex members, i.e., GRB2, SOS1, and cCBL. Further, SHIP2 binds to the src homology and tyrosine kinase domains of BCR-ABL and its inositol phosphatase activity contributes to BCR-ABL-mediated phosphorylation of SHC1. Together, this study characterizes protein-protein interactions within the BCR-ABL core complex and determines the contribution of particular BCR-ABL domains to downstream signaling. Understanding the structure and dynamics of BCR-ABL interactome is critical for the development of drugs targeting integrity of the BCR-ABL core complex.
- MeSH
- adaptorové proteiny signální transdukční metabolismus MeSH
- aminokyselinové motivy MeSH
- bcr-abl fúzní proteiny chemie genetika metabolismus MeSH
- chronická myeloidní leukemie metabolismus patologie MeSH
- čipová analýza proteinů MeSH
- fosfatidylinositol-3,4,5-trisfosfát-5-fosfatasy metabolismus MeSH
- fosforylace MeSH
- HEK293 buňky MeSH
- inhibitory proteinkinas farmakologie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- pyrimidiny farmakologie MeSH
- signální transdukce * účinky léků MeSH
- src homologní domény MeSH
- transformující protein 1 obsahující src homologní doménu 2 metabolismus MeSH
- vazba proteinů účinky léků MeSH
- vazebná místa MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Many patients with chronic myeloid leukemia in deep remission experience return of clinical disease after withdrawal of tyrosine kinase inhibitors (TKIs). This suggests signaling of inactive BCR-ABL, which allows the survival of cancer cells, and relapse. We show that TKI treatment inhibits catalytic activity of BCR-ABL, but does not dissolve BCR-ABL core signaling complex, consisting of CRKL, SHC1, GRB2, SOS1, cCBL, p85a-PI3K, STS1 and SHIP2. Peptide microarray and co-immunoprecipitation results demonstrate that CRKL binds to proline-rich regions located in C-terminal, intrinsically disordered region of BCR-ABL, that SHC1 requires pleckstrin homology, src homology and tyrosine kinase domains of BCR-ABL for binding, and that BCR-ABL sequence motif located in disordered region around phosphorylated tyrosine 177 mediates binding of three core complex members, i.e., GRB2, SOS1, and cCBL. Further, SHIP2 binds to the src homology and tyrosine kinase domains of BCR-ABL and its inositol phosphatase activity contributes to BCR-ABL-mediated phosphorylation of SHC1. Together, this study characterizes protein-protein interactions within the BCR-ABL core complex and determines the contribution of particular BCR-ABL domains to downstream signaling. Understanding the structure and dynamics of BCR-ABL interactome is critical for the development of drugs targeting integrity of the BCR-ABL core complex.
- MeSH
- adaptorové proteiny signální transdukční metabolismus MeSH
- aminokyselinové motivy MeSH
- bcr-abl fúzní proteiny chemie genetika metabolismus MeSH
- chronická myeloidní leukemie metabolismus patologie MeSH
- čipová analýza proteinů MeSH
- fosfatidylinositol-3,4,5-trisfosfát-5-fosfatasy metabolismus MeSH
- fosforylace MeSH
- HEK293 buňky MeSH
- inhibitory proteinkinas farmakologie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- pyrimidiny farmakologie MeSH
- signální transdukce účinky léků MeSH
- vazba proteinů účinky léků MeSH
- vazebná místa MeSH
- Check Tag
- lidé MeSH
Vertebrate primary cilium is a Hedgehog signaling center but the extent of its involvement in other signaling systems is less well understood. This report delineates a mechanism by which fibroblast growth factor (FGF) controls primary cilia. Employing proteomic approaches to characterize proteins associated with the FGF-receptor, FGFR3, we identified the serine/threonine kinase intestinal cell kinase (ICK) as an FGFR interactor. ICK is involved in ciliogenesis and participates in control of ciliary length. FGF signaling partially abolished ICK's kinase activity, through FGFR-mediated ICK phosphorylation at conserved residue Tyr15, which interfered with optimal ATP binding. Activation of the FGF signaling pathway affected both primary cilia length and function in a manner consistent with cilia effects caused by inhibition of ICK activity. Moreover, knockdown and knockout of ICK rescued the FGF-mediated effect on cilia. We provide conclusive evidence that FGF signaling controls cilia via interaction with ICK.
- MeSH
- buňky NIH 3T3 MeSH
- cilie metabolismus MeSH
- CRISPR-Cas systémy MeSH
- fibroblastové růstové faktory metabolismus MeSH
- fosforylace MeSH
- HEK293 buňky MeSH
- interakční proteinové domény a motivy MeSH
- lidé MeSH
- modely u zvířat MeSH
- myši knockoutované MeSH
- myši MeSH
- protein-serin-threoninkinasy genetika metabolismus MeSH
- proteiny hedgehog metabolismus MeSH
- proteomika MeSH
- receptor fibroblastových růstových faktorů, typ 1 metabolismus MeSH
- receptor fibroblastových růstových faktorů, typ 3 genetika metabolismus MeSH
- receptor fibroblastových růstových faktorů, typ 4 metabolismus MeSH
- receptory fibroblastových růstových faktorů genetika metabolismus MeSH
- signální transdukce MeSH
- simulace molekulového dockingu MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
V príspevku sa zameriavame na postoje študentov FTVŠ UK na tetovanie. Na zistenie postojov sme použili nami zostrojený neštandardizovaný dotazník s otázkami ohľadom tetovaní. Výskumnú vzorku tvorilo 142 študentov (n=142), priemerný vek bol 20,26 roka. Zistili sme, že v našom výskumnom súbore je tetovaných 17,6 % respondentov a tetovanie sa páči až 83,8 % študentom. V budúcnosti by sa chcelo dať tetovať 39,4 % respondentov. Existuje signifikantne významný negatívny vzťah medzi tetováciou a užívaním alkoholu. Ďalším existujúcim významným vzťahom je negatívny vzťah medzi páčením tetovaní a námietkam voči tetovaniam u zdravotníckych pracovníkov.
In the research we focus on opinions of students from FTVŠ UK about tattoos. Tattoos are defined as kind of needling colorful elements into injured skin. Tattoos are very popular among young people, however in our society there are various opinions on them. Tattoos are a form of self-expression, a reference to some social group, a fashion accessory or simple a need to differ from others. There are some health risks according to tattoos such as AIDS, hepatitis C or tetanus but also allergies, cysts or bleeding. Prejudices toward tattoos are lower when a person has his own tattoo on body. Some researchers found out that people who wear tattoos are more liable to alcohol and drug usage and their sexual behavior is more risky compared to people who don’t wear tattoos. Another research focused on relationship between wearing a tattoo and self-confidence or wearing a tattoo and personality characteristics. They found out that women who wear four or more tattoos seemed to be more self-confident compared to women who don’t wear any tattoo or who wear three or less tattoos. Another finding was that people who wear tattoos are more conscientious, extroverted, sexually unattached and they were in more need of attention and uniqueness compared to people who don’t wear any tattoo. Another topic is prejudice to tattoos and tattooed people entirely. Considering another research, it seemed to be common that people who don’t have tattoo have more prejudices to tattooed people regarding to larger area tattooed. So, the larger area on body is tattooed the more prejudices from people without tattoos are coming. Tattooed people seemed to be more tolerant to other people tattoos. We used a non-standardized questionnaire made by us to find out the opinions of students. Research sample consisted of 142 students (n=142), average age was 20,26 years. Following our findings, we found out that in our research sample there were 17,6% of respondents who have tattoo and even 83,8% of respondents like tattoos. In future would like to have a tattoo 39,4% of respondents, 23,2% don’t want any and 37,3% don’t know yet. Majority of respondents (57%) think that tattoo is considered neutral in our society, 40,2% think that tattoos are acceptable and 2,8% think that tattoos are not acceptable in our society. Moreover 90,1% of respondents consider tattoos as a form of art. The most objections to tattoos in various professions had health workers when 18,4% of respondents present they have a problem with health workers wearing a tattoo. Next profession with the most objections to tattoos was government workers with 17,6% and teachers, trainers and workers on official positions (such as bank workers or driver in public transport) least objections to tattoos (9,2%). Our respondents were very satisfied with their tattoos (75%) or satisfied with their tattoos (25%). None of our respondents was unsatisfied with his or her tattoo. The strongest motive to get a tattoo was a personally important event or memory in 60% of respondents with tattoo. In our research sample there were 4,2% smokers, 19,7% occasional smokers, 4,2% past smokers and 71,8% nonsmokers. We found a significant negative relationship between having a tattoo and use of alcohol and significant relationship between having a tattoo and planning to get a tattoo in future. Another finding is that there is a significant negative relationship between liking tattoos and objections against tattoos among healthcare workers.
Sustained activation of extracellular signal-regulated kinase (ERK) drives pathologies caused by mutations in fibroblast growth factor receptors (FGFRs). We previously identified the inositol phosphatase SHIP2 (also known as INPPL1) as an FGFR-interacting protein and a target of the tyrosine kinase activities of FGFR1, FGFR3, and FGFR4. We report that loss of SHIP2 converted FGF-mediated sustained ERK activation into a transient signal and rescued cell phenotypes triggered by pathologic FGFR-ERK signaling. Mutant forms of SHIP2 lacking phosphoinositide phosphatase activity still associated with FGFRs and did not prevent FGF-induced sustained ERK activation, demonstrating that the adaptor rather than the catalytic activity of SHIP2 was required. SHIP2 recruited Src family kinases to the FGFRs, which promoted FGFR-mediated phosphorylation and assembly of protein complexes that relayed signaling to ERK. SHIP2 interacted with FGFRs, was phosphorylated by active FGFRs, and promoted FGFR-ERK signaling at the level of phosphorylation of the adaptor FRS2 and recruitment of the tyrosine phosphatase PTPN11. Thus, SHIP2 is an essential component of canonical FGF-FGFR signal transduction and a potential therapeutic target in FGFR-related disorders.
- MeSH
- adaptorové proteiny signální transdukční genetika metabolismus MeSH
- aktivace enzymů MeSH
- extracelulárním signálem regulované MAP kinasy genetika metabolismus MeSH
- fosfatidylinositol-3,4,5-trisfosfát-5-fosfatasy genetika metabolismus MeSH
- fosforylace MeSH
- HEK293 buňky MeSH
- lidé MeSH
- MAP kinasový signální systém * MeSH
- membránové proteiny genetika metabolismus MeSH
- nádorové buněčné linie MeSH
- receptory fibroblastových růstových faktorů genetika metabolismus MeSH
- skupina kinas odvozených od src-genu genetika metabolismus MeSH
- tyrosinfosfatasa nereceptorového typu 11 genetika metabolismus MeSH
- vazba proteinů MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- MeSH
- duševně nemocní * psychologie MeSH
- duševní poruchy ekonomika terapie MeSH
- duševní zdraví MeSH
- lidé MeSH
- pohybová aktivita * MeSH
- terapie cvičením klasifikace metody psychologie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
PURPOSE: Quantitative description of hepatic microvascular bed could contribute to understanding perfusion CT imaging. Micro-CT is a useful method for the visualization and quantification of capillary-passable vascular corrosion casts. Our aim was to develop and validate open-source software for the statistical description of the vascular networks in micro-CT scans. METHODS: Porcine hepatic microvessels were injected with Biodur E20 resin, and the resulting corrosion casts were scanned with 1.9-4.7 [Formula: see text] resolution. The microvascular network was quantified using newly developed QuantAn software both in randomly selected volume probes (n = 10) and in arbitrarily outlined hepatic lobules (n = 4). The volumes, surfaces, lengths, and numbers of microvessel segments were estimated and validated in the same data sets with manual stereological counting. Calculations of tortuosity, radius histograms, length histograms, exports of the skeletonized vascular network into open formats, and an assessment of the degree of their anisotropy were performed. RESULTS: Within hepatic lobules, the microvessels had a volume fraction of 0.13 [Formula: see text] 0.05, surface density of 21.0 [Formula: see text] 2.0 [Formula: see text], length density of 169.0 [Formula: see text] 40.2 [Formula: see text], and numerical density of 588.5 [Formula: see text] 283.1 [Formula: see text]. Sensitivity analysis of the automatic analysis to binary opening, closing, threshold offset, and aggregation radius of branching nodes was performed. CONCLUSION: The software QuantAn and its source code are openly available to researchers working in the field of stochastic geometry of microvessels in micro-CT scans or other three-dimensional imaging methods. The implemented methods comply with reproducible stereological techniques, and they were highly consistent with manual counting. Preliminary morphometrics of the classical hepatic lobules in pig were provided.
- MeSH
- interpretace obrazu počítačem metody MeSH
- játra krevní zásobení diagnostické zobrazování MeSH
- koroze MeSH
- mikrocévy diagnostické zobrazování MeSH
- prasata MeSH
- rentgenová mikrotomografie metody MeSH
- software MeSH
- zobrazování trojrozměrné metody MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
