Eksperto liudytojo išvada apie parašų sudarytų iš simbolių (inicialų, pavienių ženklų) autentiškumą

This work is intended to address identification issues and present the problem of using initials from the handwriting expert point of view. Beginning the analysis of the main problems in examination of the signature composed from initials the author discusses the understanding of the initial (its definition) and leads reader to the more complicated problems related to the possibilities of such examinations, forming of the opinion and etc

SKIP is required for TGF-beta 1-induced epithelial mesenchymal transition and migration in transformed keratinocytes

Transforming growth factor-beta 1 (TGF-beta 1) potently induces the epithelial-mesenchymal transition (EMT) during tumoral progression. Although Sky-interacting protein (SKIP) regulates TGF-beta 1-induced Smad activation, its role in the induction of cell malignance remains uncertain. We found that TGF-beta 1 increases SKIP expression in PDV cells. In cells stably transfected with SKIP antisense, AS-S, Smad3 activation decreased, along with an inhibition of TGF-beta 1-induced EMT, and the cells were sensitized to the TGF-beta 1-dependent inhibition of proliferation. Also, AS-S cells showed a weaker migration and invasion response. Moreover, TGF-beta 1-induced urokinase-type plasminogen activator expression was inhibited, concomitantly with a TGF-beta 1-independent increment of the plasminogen-activator inhibitor-1 expression. Thus, these results suggest that SKIP is required for EMT and invasiveness induced by TGF-beta 1 in transformed cells

Combination of Sleeping Beauty transposition and chemically induced dimerization selection for robust production of engineered cells

The main methods for producing genetically engineered cells use viral vectors for which safety issues and manufacturing costs remain a concern. In addition, selection of desired cells typically relies on the use of cytotoxic drugs with long culture times. Here, we introduce an efficient non-viral approach combining the Sleeping Beauty (SB) Transposon System with selective proliferation of engineered cells by chemically induced dimerization (CID) of growth factor receptors. Minicircles carrying a SB transposon cassette containing a reporter transgene and a gene for the F36VFGFR1 fusion protein were delivered to the hematopoietic cell line Ba/F3. Stably-transduced Ba/F3 cell populations with >98% purity were obtained within 1 week using this positive selection strategy. Copy number analysis by quantitative PCR (qPCR) revealed that CID-selected cells contain on average higher copy numbers of transgenes than flow cytometry-selected cells, demonstrating selective advantage for cells with multiple transposon insertions. A diverse population of cells is present both before and after culture in CID media, although site-specific qPCR of transposon junctions show that population diversity is significantly reduced after selection due to preferential expansion of clones with multiple integration events. This non-viral, positive selection approach is an attractive alternative for producing engineered cells

Stroma Regulates Increased Epithelial Lateral Cell Adhesion in 3D Culture: A Role for Actin/Cadherin Dynamics

Cell shape and tissue architecture are controlled by changes to junctional proteins and the cytoskeleton. How tissues control the dynamics of adhesion and cytoskeletal tension is unclear. We have studied epithelial tissue architecture using 3D culture models and found that adult primary prostate epithelial cells grow into hollow acinus-like spheroids. Importantly, when co-cultured with stroma the epithelia show increased lateral cell adhesions. To investigate this mechanism further we aimed to: identify a cell line model to allow repeatable and robust experiments; determine whether or not epithelial adhesion molecules were affected by stromal culture; and determine which stromal signalling molecules may influence cell adhesion in 3D epithelial cell cultures.The prostate cell line, BPH-1, showed increased lateral cell adhesion in response to stroma, when grown as 3D spheroids. Electron microscopy showed that 9.4% of lateral membranes were within 20 nm of each other and that this increased to 54% in the presence of stroma, after 7 days in culture. Stromal signalling did not influence E-cadherin or desmosome RNA or protein expression, but increased E-cadherin/actin co-localisation on the basolateral membranes, and decreased paracellular permeability. Microarray analysis identified several growth factors and pathways that were differentially expressed in stroma in response to 3D epithelial culture. The upregulated growth factors TGFβ2, CXCL12 and FGF10 were selected for further analysis because of previous associations with morphology. Small molecule inhibition of TGFβ2 signalling but not of CXCL12 and FGF10 signalling led to a decrease in actin and E-cadherin co-localisation and increased paracellular permeability.In 3D culture models, paracrine stromal signals increase epithelial cell adhesion via adhesion/cytoskeleton interactions and TGFβ2-dependent mechanisms may play a key role. These findings indicate a role for stroma in maintaining adult epithelial tissue morphology and integrity

Pharmacological characterization of a novel 5-hydroxybenzothiazolone-derived b2-adrenoceptor agonist with functional selectivity for anabolic effects on skeletal muscle resulting in a wider cardiovascular safety window in preclinical studies

Copyright ª 2019 by The Author(s) The anabolic effects of b2-adrenoceptor (b2-AR) agonists on skeletal muscle have been demonstrated in various species. However, the clinical use of b2-AR agonists for skeletal muscle wasting conditions has been limited by their undesired cardiovascular effects. Here, we describe the preclinical pharmacological profile of a novel 5-hydroxybenzothiazolone (5-HOB) derived b2-AR agonist in comparison with formoterol as a representative b2-AR agonist that have been well characterized. In vitro, 5-HOB has nanomolar affinity for the human b2-AR and selectivity over the b1-AR and b3-AR. 5-HOB also shows potent agonistic activity at the b2-AR in primary skeletal muscle myotubes and induces hypertrophy of skeletal muscle myotubes. Compared with formoterol, 5-HOB demonstrates comparable full-agonist activity on cAMP production in skeletal muscle cells and skeletal muscle tissue–derived membranes. In contrast, a greatly reduced intrinsic activity was determined in cardiomyocytes and cell membranes prepared from the rat heart. In addition, 5-HOB shows weak effects on chronotropy, inotropy, and vascular relaxation compared with formoterol. In vivo, 5-HOB significantly increases hind limb muscle weight in rats with attenuated effects on heart weight and ejection fraction, unlike formoterol. Furthermore, changes in cardiovascular parameters after bolus subcutaneous treatment in rats and rhesus monkeys are significantly lower with 5-HOB compared with formoterol. In conclusion, the pharmacological profile of 5-HOB indicates superior tissue selectivity compared with the conventional b2-AR agonist formoterol in preclinical studies and supports the notion that such tissue-selective agonists should be investigated for the safe treatment of muscle-wasting conditions without cardiovascular limiting effects

Signatures as an object of autoforgery (self-forgery) = Podpisy jako obiekt autofałszerstwa

Praca prezentuje wyniki badań, których celem było wyodrębnienie cech graficznych najczęściej i najrzadziej modyfikowanych przez osoby dokonujące autofałszerstwa podpisów w sytuacjach, gdy wygląd naturalnych podpisów danej osoby nie jest odbiorcy znany. Badaniami objęto łącznie ponad 12.000 podpisów pochodzących od 200 osób, do ostatecznej oceny wybierając najbardziej udane próby autofałszerstwa podpisów czytelnych i nieczytelnych każdego probanta. Ustalono, że zmiany autofałszerskie skoncentrowane są zwykle na najbardziej rzucających się w oczy cechach podpisów, takich jak konstrukcja liter w początkowej części podpisu, wielkość, czytelność, impuls, nachylenie. Cechy drugoplanowe, trudniej niezauważalne albo takie, z których istnienia piszący nie zdają sobie sprawy (jak obecność lub brak uzupełnień, układ znaków względem siebie, kształt i kierunek linii podpisów, format w podpisach czytelnych) są zwykle w działaniach autofałszerskich pomijane. Wykrycie autofałszerstwa bywa dla biegłych dużym wyzwaniem, ponieważ wszelkie istotne różnice między podpisem kwestionowanym a podpisami porównawczymi są często błędnie uważane za skutek fałszerstwa. Dlatego aby wykryć autofałszerstwo należy przeanalizować strukturę cech łatwo zauważalnych, najbardziej wpływających na tzw. efekt obrazkowy podpisu, w zestawieniu z cechami mało efektownymi, które w większości przypadków autofałszerstwa pozostają niezmienione. Im bardziej charakterystyczne są te ostatnie, tym bardziej ich zgodność w materiale kwestionowanym i porównawczym przemawia za autofałszerstwem – bez względu na odmienność cech pierwszoplanowych. W przypadku podrobienia (fałszerstwa) podpisu jest odwrotnie: naśladowaniu przez fałszerza podlegają przede wszystkim najłatwiej zauważalne cechy podpisu, a różnice występują głównie w obrębie cech drugorzędnych

Interleukin-1 receptor-associated kinase 4 links innate immunity to the pathogenesis of rheumatoid arthritis.

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