46 research outputs found

    Importance of Plasma Membrane Nanodomains in Skeletal Muscle Regeneration

    Get PDF
    Numerous studies showed the importance of skeletal muscle plasma membrane (sarcolemma) in the control of skeletal muscle biology. The emphasis in this review is on the sarcolemmal bioactive lipids decisive for survival, proliferation, differentiation, and function of skeletal muscle cells with the particular concern on muscle stem cells (resident satellite cells, RSC) responsible for muscle regeneration. Nowadays, it is obvious that cholesterol (CHOL), basic component of the lipid rafts (LR) through the control of assembled dystrophin–glycoprotein complexes (DGC), directs muscle fiber contractile properties. Another phospholipid, phosphatidylserine (PS), is a component of the inner plasma membrane leaflet, even though it allows the fusion of myoblasts when exteriorized. Sphingolipids, such as ceramide, sphingosine, sphingosine-1-phosphate, and ganglioside GM3, are important signaling molecules in the charge of RSC activation, their motility, and commitment to particular lineage (myoblasts and myofibroblasts). Phosphoinositides and phosphatidylinositol-4,5-biphosphate (PIP2) specifically establish protoplasmic platforms for protein interactions essential for cell viability and mitochondrial activity. Additionally, both prenylation and palmitoylation of certain proteins (i.e., heterotrimeric G proteins) determine their biological activity in signal transduction from G-protein coupled receptors (GPCR). Isoprenoids are therefore crucial for the recruitment and metabolic responses of RSC to physiological and pathological stimuli. Finally, iatrogenic modifications of sarcolemma with hydroxylamines and their derivatives lead to increased resistance of muscle cells to apoptotic stimuli and slow progression of some skeletal muscle dystrophies

    Molecular basis of parthenolide-dependent proapoptotic activity in cancer cells.

    Get PDF
    This review outlines the molecular events that accompany the anti-tumor action of parthenolide (PN). Parthenolide (PN) is naturally derived compound, isolated from plant Tanacetum parthenium. PN has been previously shown to withdraw cells from cell cycle or to promote cell differentiation, and finally to induce programmed cell death. Recent advances in molecular biology indicate that this sesquiterpene lactone might evoke the above-mentioned effects by indirect action on genes. PN was shown to inhibit NF-kappaB- and STATs-mediated antiapoptotic gene transcription. On one hand, the proapoptotic activity of PN includes stimulation of intrinsic apoptotic pathway with the higher level of intracellular ROS and modifications of Bcl-2 family proteins (conformational changes of Bak and Bax, Bid cleavage). On the other hand, PN amplifies the apoptotic signal through the sensitization of cancer cells to extrinsic apoptosis, induced by TNF-alpha. These effects are specific to tumor cells. Unique properties of PN make this agent a promising metabolic inhibitor to retard tumorigenesis and to suppress tumor growth

    Variability of Some Physical Properties of Limnic Rendzinas in the Mazurian Lakeland (NE Poland)

    Get PDF
    The variability of some physical properties of limnic rendzinas in the Mazurian Lakeland are discussed in the paper. For the study, six sites (68 soil carbonate samples) in NE Poland were examined in terms of their physical properties: total porosity, specific density, wet and dry bulk densities, volumetric and gravimetric water content. Moreover, the content of organic matter, CaCO3 and non-calcareous fractions were also analysed to determine the type of soil calcareous sediments, and on this basis, three groups were isolated: calcareous gyttja, meadow limestone, lacustrine chalk. The highest values of specific and bulk densities were stated in lacustrine chalk, whereas the lowest ones – in calcareous gyttja. The highest total porosity was noted in calcareous gyttja, and the lowest one in meadow limestone. Lacustrine chalk and calcareous gyttja had the highest water content, and the differences between physical properties and soil calcareous materials were statistically significant. However, the differences between soil physical properties in surface soil horizons and calcareous materials were not statistically significant. Correlation coefficients showed that there were statistical dependencies between the examined soil properties, and the principal component analysis proved that soil physical properties were dependent mainly on organic matter

    Killing Me Softly: Connotations to Unfolded Protein Response and Oxidative Stress in Alzheimer’s Disease

    Get PDF
    This review is focused on the possible causes of mitochondrial dysfunction in AD, underlying molecular mechanisms of this malfunction, possible causes and known consequences of APP, Aβ, and hyperphosphorylated tau presence in mitochondria, and the contribution of altered lipid metabolism (nonsterol isoprenoids) to pathological processes leading to increased formation and accumulation of the aforementioned hallmarks of AD. Abnormal protein folding and unfolded protein response seem to be the outcomes of impaired glycosylation due to metabolic disturbances in geranylgeraniol intermediary metabolism. The origin and consecutive fate of APP, Aβ, and tau are emphasized on intracellular trafficking apparently influenced by inaccurate posttranslational modifications. We hypothesize that incorrect intracellular processing of APP determines protein translocation to mitochondria in AD. Similarly, without obvious reasons, the passage of Aβ and tau to mitochondria is observed. APP targeted to mitochondria blocks the activity of protein translocase complex resulting in poor import of proteins central to oxidative phosphorylation. Besides, APP, Aβ, and neurofibrillary tangles of tau directly or indirectly impair mitochondrial biochemistry and bioenergetics, with concomitant generation of oxidative/nitrosative stress. Limited protective mechanisms are inadequate to prevent the free radical-mediated lesions. Finally, neuronal loss is observed in AD-affected brains typically by pathologic apoptosis

    TNF- α

    Get PDF

    Vascular phenotypes in early hypertension

    Get PDF
    The study characterises vascular phenotypes of hypertensive patients utilising machine learning approaches. Newly diagnosed and treatment-naïve primary hypertensive patients without co-morbidities (aged 18–55, n = 73), and matched normotensive controls (n = 79) were recruited (NCT04015635). Blood pressure (BP) and BP variability were determined using 24 h ambulatory monitoring. Vascular phenotyping included SphygmoCor® measurement of pulse wave velocity (PWV), pulse wave analysis-derived augmentation index (PWA-AIx), and central BP; EndoPAT™-2000® provided reactive hyperaemia index (LnRHI) and augmentation index adjusted to heart rate of 75bpm. Ultrasound was used to analyse flow mediated dilatation and carotid intima-media thickness (CIMT). In addition to standard statistical methods to compare normotensive and hypertensive groups, machine learning techniques including biclustering explored hypertensive phenotypic subgroups. We report that arterial stiffness (PWV, PWA-AIx, EndoPAT-2000-derived AI@75) and central pressures were greater in incident hypertension than normotension. Endothelial function, percent nocturnal dip, and CIMT did not differ between groups. The vascular phenotype of white-coat hypertension imitated sustained hypertension with elevated arterial stiffness and central pressure; masked hypertension demonstrating values similar to normotension. Machine learning revealed three distinct hypertension clusters, representing ‘arterially stiffened’, ‘vaso-protected’, and ‘non-dipper’ patients. Key clustering features were nocturnal- and central-BP, percent dipping, and arterial stiffness measures. We conclude that untreated patients with primary hypertension demonstrate early arterial stiffening rather than endothelial dysfunction or CIMT alterations. Phenotypic heterogeneity in nocturnal and central BP, percent dipping, and arterial stiffness observed early in the course of disease may have implications for risk stratification

    Analiza zawartości informacyjnej dywidend na Giełdzie Papierów Wartościowych w Warszawie

    Get PDF
    The article analyzes efficiency of the Warsaw Stock Exchange with respectto dividends’ payments. The article presents possible causes of anomaly relatedto dividends, reviews the English language literature of the field and finally presents the results of empirical studies related to companies listed on the Warsaw StockExchange. The results indicate that it is possible to construct investment strategysystematically generating financial benefits which proves that the Polish capitalmarket is ineffective

    Can European-Style Options Be Priced Better Than in Carr-Madan Model. Review of Models Based on Fourier Transform

    No full text
    This document relates to the valuation of options using the Fourier transform. Topics covered in the document include both analysis of the traditional approaches and alternative concepts. The subject matter of particular interest is the speed and computational precision of the European-style option valuation methods

    ANALYSIS OF HULL – WHITE MODEL

    No full text
    W niniejszym artykule analizowany jest model J. Hulla i A. White’a. W ramach podejmowanej problematyki przedstawiane są aspekty teoretyczne rozpatrywanego podejścia oraz wykorzystywane są dane empiryczne do sprawdzenia precyzji wyceny w relacji do cen rynkowych generowanych przez model F. Blacka i M. Scholesa. Ponadto, przeprowadzana jest analiza wrażliwości wyceny opcji. Otrzymane wyniki wskazują, iż model J. Hulla i A. White’a, w swojej podstawowej postaci, pozwala wycenić opcje równie dobrze jak model F. Blacka i M. Scholesa, bez konieczności jednak wprowadzania założenia upraszczającego opis funkcjonowania rynku kapitałowego, tj. stałości wariancji stóp zwrotu z aktywów bazowych.In this article Hull – White model is analyzed. As a part of the subject matter theoretical aspects of the considered approach are presented. Then, empirical data is used to verify the accuracy of valuation with respect to the Black - Scholes model. In addition, the analysis of sensitivity of option pricing is performed. The results indicate that the Hull - White model allows to price options similarly to the Black – Scholes model but without imposing simplifying assumption which refers to description of the functioning of the capital market, i.e. constant variance of returns of the underlying assets
    corecore