Olomouc, Czech Republic

Palacky University

Olomouc, Czech Republic

Palacký University, Olomouc is the oldest university in Moravia and the second-oldest in the Czech Republic. It was established in 1573 as a public university led by the Jesuit order in Olomouc, which was at that time the capital of Moravia and the seat of the episcopacy. At first it taught only theology, but soon the fields of philosophy, law and medicine were added.After the Bohemian King Joseph II's reforms in the 1770s the university became increasingly state-directed, while today it is a public university. During the Revolution of 1848 university students and professors played a very active role on the side of democratisation. The conservative king Francis Joseph I closed most of its faculties during the 1850s, but they were reopened by an act of the Interim National Assembly passed on 21 February 1946. This act also extended the name from University of Olomouc to Palacký University, Olomouc, naming it for František Palacký, a 19th-century Moravian historian and politician.Today the university is an example of an old university in a small town, like Yale University in New Haven and the University of Tübingen in Tübingen. The town of Olomouc has 100,000 inhabitants , and some 25,000 university students , which is the highest density of university students in Central Europe. The town itself is very old and picturesque and it is surrounded by sports facilities and nature.Many distinguished figures have taught, worked and studied here including Albrecht von Wallenstein and Gregor Mendel. Wikipedia.

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Azoles antifungals are widespread used drugs for various medicinal indications. These drugs are well known for their numerous drug-drug interactions, which are believed to occur via inhibition of CYP3A4 enzymatic activity and consequently altering pharmacokinetic of co-administered drugs. In the current communication a complex view on the molecular interactions between azoles antimycotics and CYP3A4 is presented. Beside inhibition of CYP3A4 catalytic activity, azoles influence transcriptional activity of pregnane X receptor (PXR) and consequently expression of drug-metabolizing enzymes, including CYP3A4. Interactions between azoles and PXR occur by multiple mechanisms, including modulation of ligand-dependent activation of PXR (agonism, antagonism) or affecting recruitment of PXR co-activators SRC-1 (steroid receptor co-activator 1) and HNF4α (hepatocyte nuclear factor 4α). Miconazole and ketoconazole are antagonists of glucocorticoid receptor (GR), therefore these drugs inhibit GR-mediated expression of PXR and drug metabolizing cytochromes P450. In addition, PXR and GR are key regulators of intermediary metabolism (e.g. carbohydrate, lipids or bile acids homeostasis) and many other cellular functions (e.g. immune response), hence, the interactions between azoles and PXR/GR are of broader physiological importance. In conclusion, while inhibition of CYP3A4 enzymatic activity by azoles is considered as primary cause of azoles drug-drug interactions, the effects of azoles on PXR and GR should be taken in account. Apart from CYP3A4, azoles influence the expression and activity of others drug-metabolizing cytochromes P450. © 2011.

The effort to repurpose old drugs for new uses is not sufficient; even drugs that have been used clinically for decades must undergo expensive clinical trials. This process requires the pharmaceutical industry to fund the repatenting of old drugs. Because inexpensive drugs are necessary for people around the world, attempts should be made to develop nonprofit drugs through clinical trials of generic drugs that are funded by governments and charities. Evidence supports the use the old anti-alcoholic drug Antabuse as a new nonprofit drug for cancer. © 2011 Elsevier Ltd. All rights reserved.

Cvek B.,Palacky University
Current Cancer Drug Targets | Year: 2011

An old drug, Antabuse (disulfiram), used for decades in alcohol aversion therapy, and its metabolite Ditiocarb were shown from 1970s to suppress cancer growth in vivo and even in human patients. The drug targets multidrug resistance, angiogenesis, invasion, and proteasome. Today, there are ongoing clinical trials of Antabuse as an adjuvant therapy against lung cancer and as a monotherapy against cancers metastasizing to liver. The larger clinical trials, if appropriate, will need support from governments and charities to get the generic drug into the clinic as a "non-profit" drug. © 2011 Bentham Science Publishers Ltd.

Spichal L.,Palacky University
Functional Plant Biology | Year: 2012

Cytokinins (CKs) are evolutionally old and highly conserved low-mass molecules that have been identified in almost all known organisms. In plants, they evolved into an important group of plant hormones controlling many physiological and developmental processes throughout the whole lifespan of the plant. CKs and their functions are, however, not unique to plants. In this review, the strategies and mechanisms of plants and phylogenetically distinct plant-interacting organisms such as bacteria, fungi, nematodes and insects employing CKs or regulation of CK status in plants are described and put into their evolutionary context. The major breakthroughs made in the last decade in the fields of CK biosynthesis, degradation and signalling are also summarised. © 2012 CSIRO.

Pospisil P.,Palacky University
Biochimica et Biophysica Acta - Bioenergetics | Year: 2012

Photosystem II (PSII) is a multisubunit protein complex in cyanobacteria, algae and plants that use light energy for oxidation of water and reduction of plastoquinone. The conversion of excitation energy absorbed by chlorophylls into the energy of separated charges and subsequent water-plastoquinone oxidoreductase activity are inadvertently coupled with the formation of reactive oxygen species (ROS). Singlet oxygen is generated by the excitation energy transfer from triplet chlorophyll formed by the intersystem crossing from singlet chlorophyll and the charge recombination of separated charges in the PSII antenna complex and reaction center of PSII, respectively. Apart to the energy transfer, the electron transport associated with the reduction of plastoquinone and the oxidation of water is linked to the formation of superoxide anion radical, hydrogen peroxide and hydroxyl radical. To protect PSII pigments, proteins and lipids against the oxidative damage, PSII evolved a highly efficient antioxidant defense system comprising either a non-enzymatic (prenyllipids such as carotenoids and prenylquinols) or an enzymatic (superoxide dismutase and catalase) scavengers. It is pointed out here that both the formation and the scavenging of ROS are controlled by the energy level and the redox potential of the excitation energy transfer and the electron transport carries, respectively. The review is focused on the mechanistic aspects of ROS production and scavenging by PSII. This article is part of a Special Issue entitled: Photosystem II. © 2011 Elsevier B.V. All rights reserved.

Opatrny T.,Palacky University
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2015

A unified tensor description of quadratic spin squeezing interactions is proposed, covering the single- and two-axis twisting as special cases of a general scheme. A closed set of equations of motion of the first moments and variances is derived in Gaussian approximation, and their solutions are discussed from the prospect of fastest squeezing generation. It turns out that the optimum rate of squeezing generation is governed by the difference between the largest and the smallest eigenvalues of the twisting tensor. A cascaded optical interferometer with Kerr nonlinear media is proposed as one of possible realizations of the general scheme. © 2015 American Physical Society.

Bergougnoux V.,Palacky University
Biotechnology Advances | Year: 2014

Imported from the Andean region to Europe in the 16th century, today tomato is widespread throughout the world and represents the most economically important vegetable crop worldwide. Tomato is not only traded in the fresh market but is also used in the processing industry in soups, as paste, concentrate, juice, and ketchup. It is an incredible source of important nutrients such as lycopene, β-carotene and vitamin C, which all have positive impacts on human health. Its production and consumption is increasing with population growth. In this review, we report how tomato was already domesticated by the ancient Incan and Aztec civilizations, and how it came to Europe, where its breeding history started. The development of genetic, molecular biology and plant biotechnology have opened the doors towards the modern genetic engineering of tomato. The different goals of tomato genetic engineering are presented, as well as examples of successfully engineered tomatoes in terms of resistance to biotic and abiotic stresses, and fruit quality. The development of GM tomato for biopharming is also described. © 2013 Elsevier Inc.

The present invention provides a method for predicting the sensitivity of a patient suffering from a cancer disease to DNA methylation inhibitor therapy, which comprises determining in vitro in cancer cells taken from the patient and comparing with values for parent type of cells- the level of expression of at least one bromodomain containing gene,and/or- the level of expression of at least one bromodomain containing proteinand/or- the mutations involving the non-synonymous change in amino acid sequence of at least one bromodomain containing geneand/or- the half maximal inhibitory concentration (IC_(50)) of a DNA methylation inhibitor and/or a histone demethylase inhibitor, wherein the increase in the half maximal inhibitory concentration of the DNA methylation inhibitor and/or the histone demethylase inhibitor signifies cross-resistance,and/or- the half maximal inhibitory concentration (IC_(50)) of a selective BET bromodomain inhibitor, wherein the decrease in the half maximal inhibitory concentration of the selective BET bromodomain inhibitor signifies sensitivity. The invention further provides a combination therapy of cancers using bromodomain inhibitors in combination with DNA methylation inhibitors.

The invention provides a combination therapy of cancers using bromodomain inhibitors in combination with DNA methylation inhibitors.

The present invention provides a composite material containing nanoscale zerovalent iron particles, which comprises a fibrous host material and nanoscale zerovalent iron particles (NZVIs) comprising iron and optionally further one or more metals. The invention further provides a method of preparation of the material containing nanoscale zerovalent iron particles of any one of the preceding claims, wherein a fibrous material is impregnated with an aqueous or C1-C4-alcoholic iron salt solution, said solution optionally containing at least one further metal containing salt, and subsequently the impregnated fibrous material is subjected to reduction to convert in situ the metal ions to nanoscale zerovalent iron particles. The novel composite materials are useful as filters and/or catalysts.

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