Resistance to vitamin D has been known for decades as vitamin D resistant rickets, caused by mutations of the gene encoding for vitamin D receptor (VDR). Findings of extra-skeletal effects of vitamin D and learning of the molecular mechanisms used by its biologically active metabolite calcitriol revealed other ways leading to its impaired sensitivity. Calcitriol takes advantage of both genomic and non-genomic mechanisms through its binding to vitamin D receptor, located not only in the cell nuclei but also in a perinuclear space. On the genomic level the complex of calcitriol bound to VDR binds to the DNA responsive elements of the controlled gene in concert with another nuclear receptor, retinoid X receptor, and expression of the VDR itself is controlled by its own ligand. These elements were found not only in the promotor region, but are scattered over the gene DNA. The gene expression includes a number of nuclear transcription factors which interact with the responsive elements and with each other and learning how they operate would further contribute to revealing causes of the impaired vitamin D sensitivity. Finally, the examples of major disorders are provided, associated with impairment of the vitamin D function and its receptor., L. Máčová, M. Bičíková, R. Hampl., and Obsahuje bibliografii
Fatty liver disease associated with obesity is an important medical problem and the mechanisms for lipid accumulation in hepatocytes are not fully elucidated yet. Recent findings indicate that mitochondria play an importan t role in this process. Our data on hepatocytes in which mitochondria are in contact with other cytosolic structures importan t for their function, extend observations obtained on isolated mitochondria and confirm inhibition of Complex I activity in hepatocytes isolated from rats fed by high fat diet (HFD) compared with controls fed by standard diet (STD). Furthermore we have found that HFD- hepatocytes are more sensitive to the peroxidative stress because under these conditions also Complex II activity is disturbed. Therefore in HFD animals decrease of Complex I activity cannot be compensated by Complex II substrates as in STD hepatocytes. Our data thus indicates that combination of HFD and peroxidative stress potentiates HFD damaging effect of mitochondria because both branches of the respiratory chain (NADH- and flavoprotein-dependent) are disturbed., T. Garnol ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The electrical properties of the supported lipid bilayer membrane (s-BLM) of egg phosphatidylcholine (PC) selfassembled on agar surface were examined. To characterize the insulating properties of s-BLMs, electrochemical impedance spectroscopy (EIS) was used. The analysis of impedance spectra in terms of an equivalent circuit of agar/electrolyte and agar/s-BLM/electrolyte in the frequency range of 0.1 Hz-10 kHz was performed. The high-density lipoproteins (HDL)/s-BLM interaction in the concentration range from 20 μg/ml to 80 μg/ml of HDL was investigated. It is evident that treatment of s-BLM with HDL resulted in an increase of the lipid film resistance and a decrease of membrane capacitance., M. Legiň, G. Laputková, J. Sabo, L. Vojčíková., and Obsahuje bibliografii
Four space geodesy techniques, namely VLBI, GPS, SLR and Doris, produce Earth orientation parameters (EOP) and station coordinates independently of each other. A method to combine them in a non-rigorous way (as described elsewhere) was modified by implementing Vondrak’s smoothing. It replaces a simple constraint to tie EOP at adjacent epochs by a more general expression defining smoothness of the resulting curves. This gives the method better stability of derived EOP. The new method was tested on GPS, VLBI and SLR data covering a one-year interval. The results were compared with the results of the original method and with the IERS c04 solution. The former indicates the effect of modification while the latter shows differences of this particular solution from the official IERS series, Vojtěch Štefka and Ivan Pešek., and Obsahuje bibliografické odkazy
Animals, including human beings, tend to respond more strongly to stimuli that are associated with the highest relative rewards. This applies not only to food rewards but also to reproductive success. In the present review article this issue is discussed for insects in connection with intersexual communication and flower-visiting behaviour. Implications of the preference for supernormal visual releasing stimuli are examined from a sensory and evolutionary perspective, including a consideration of the choice of potential mates and recognition of the most rewarding flowers., Karl Kral., and Obsahuje bibliografii
The objective of this study was to find out the implication of QRS duration in dogs with rapid pacing-induced heart failure. Sixteen Beagle dogs were implanted with transvenous cardiac pacemakers and underwent rapid right ventricular pacing for 3 weeks at 260 bpm to induce hear t failure. Dogs were divided into two groups according to the QRS duration: 9 with normal QRS duration (<100 ms) and 7 wi th prolonged QRS duration (≥100 ms). Cardiac systolic functi on and size was analyzed by real time 3-dimensional echocardiography and left ventricular dyssynchrony was assessed by speckle tracking strain imaging. Congestive heart failure developed 3 weeks after rapid right ventricular pacing. Dogs with prolonged QRS duration showed more extensive radial strain and circumferential strain dyssynchrony than dogs with norm al QRS duration. At the end of 4-week recovery, greater improvemen t of left ventricular ejection fraction and left ventricular end-systolic volume was detected in dogs with normal QRS duration. The findings suggested that left ventricular dyssynchrony, indicated by a prolonged QRS duration, predicted an unsatisfying recovery in dogs with rapid pacing- induced heart failure. QRS duration had the potential to be a prognostic indicator for dogs with heart failure., Y. Wang ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Článek se zabývá analýzou jazykových prostředků v dialogickém diskurzu literárního díla. Studuje propojení tří paralelně strukturovaných vrstev dialogu v úryvku z románu Penelopy Lively Heat Wave, a to explicitního dialogu mezi postavami románu, vnitřního vzájemného dialogu mezi hrdinkou a postavami románu, a vnitřního dialogu hrdinky románu. Autorka se zároveň snaží popsat a zhodnotit jazykové prostředky, kterými tvůrce literárního díla dosahuje v dialogu autentičnosti, a konfrontuje je s prostředky ozvláštnění významu.
There are five subtypes of muscarinic receptors that serve various important physiological functions in the central nervous system and the periphery. Mental functions like attention, learning, and memory are attributed to the muscarinic M1 subtype. These functions decline during natural aging and an early deficit is typical for Alzheimer´s disease. In addition, stimulation of the M1 receptor increases non-amyloidogenic processing of the amyloid precursor protein and thus prevents accumulation of noxious β-amyloid fragments. The selectivity of classical muscarinic agonists among receptor subtypes is very low due to the highly conserved nature of the orthosteric binding site among receptor subtypes. Herein we summarize some recent studies with the functionally-selective M1 agonist xanomeline that indicate complex pharmacological profile of this drug that includes interactions with and activation of receptor from both orthosteric and ectopic binding sites, and the time-dependent changes of ligand binding and receptor activation. These findings point to potential profitability of exploitation of ectopic ligands in the search for truly selectiev muscarinic receptor agonists., J. Jakubík, P. Michal, E. Machová, V. Doležal., and Obsahuje bibliografii a bibliografické odkazy
There is a growing interest for the beneficial effect of magnesium (Mg) in cardiovascular disorders. A number of cardiovascular disorders including myocardial infarction, arrhythmias and congestive heart failure have been associated with low extracellular or intracellular concentrations of Mg. The efficiency of the preconditioning effect of Mg on cardiac function and infarct size in the globally ischemic-reperfused isolated rat heart was studied together with the role of ATP-sensitive potassium (KATP) channels in protection induced by Mg. Rat hearts were Langendorff perfused, subjected to 30 min of global ischemia and 90 min of reperfusion, including treatment groups which focused on different times of Mg (8 mmol/l) use. Infarct size was measured by triphenyltetrazolium chloride (TTC) method. The left ventricular function was assessed by left ventricular developed pressure (LVDP), heart rate (HR) and coronary flow (CF). The administration of Mg before ischemia had an anti-infarct effect in rat hearts and improved cardiac function. The protective effects of magnesium was abolished by the blocking of KATP channels and suggests that K-ATP channel has an important role in the heart protection effect of Mg as a preconditioning agent., M. Bazargan, M. Faghihi, M. Chitsaz., and Obsahuje bibliografii a bibliografické odkazy