Search

The anorexigenic neuropeptide prolactin-releasing peptide (PrRP) is involved in the regulation of food intake and energy expenditure. Lipidization of PrRP stabilizes the peptide, facilitates central effect after peripheral administration and increases its affinity for its receptor, GPR10, and for the neuropeptide FF (NPFF) receptor NPFF-R2. The two most potent palmitoylated analogs with anorectic effects in mice, palm11-PrRP31 and palm-PrRP31, were studied in vitro to determine their agonist/antagonist properties and mechanism of action on GPR10, NPFF-R2 and other potential off-target receptors related to energy homeostasis. Palmitoylation of both PrRP31 analogs increased the binding properties of PrRP31 to anorexigenic receptors GPR10 and NPFF-R2 and resulted in a high affinity for another NPFF receptor, NPFF-R1. Moreover, in CHO-K1 cells expressing GPR10, NPFF-R2 or NPFF-R1, palm11-PrRP and palm-PrRP significantly increased the phosphorylation of extracellular signal-regulated kinase (ERK), protein kinase B (Akt) and cAMP-responsive element-binding protein (CREB). Palm11-PrRP31, unlike palm-PrRP31, did not activate either c-Jun N-terminal kinase (JNK), p38, c-Jun, c-Fos or CREB pathways in cells expressing NPFF-1R. Palm-PrRP31 also has higher binding affinities for off-target receptors, namely, the ghrelin, opioid (KOR, MOR, DOR and OPR-L1) and neuropeptide Y (Y1, Y2 and Y5) receptors. Palm11-PrRP31 exhibited fewer off-target activities; therefore, it has a higher potential to be used as an anti-obesity drug with anorectic effects.

We measured the initial growth performance of a young plantation of European beech treated with a brassinosteroid compound prior to planting and compared it with a control treatment: we assessed heights, root collar diameters and mortality rate during the period 2012-2015. The trees showed posterior damage by ground frost after a substantial late frost event on the night of 4-5 May 2014. Therefore, we evaluated the post-stress vitality of trees, subsequent height increment from spring to August, and the height range of the damage. Mean height, root collar diameter, and mortality rate did not show any significantly better performance in the brassinosteroid treatment over the control treatment. Neither did the application treatment have a significant positive effect on the resistance of beech to late frosts. The severe frost damage was most intense at 30 cm above ground, and rapidly declined with increased height.

We tested the influence of a synthetically-produced brassinosteroid compound (2α,3α,17βtrihydroxy-5α-androstan-6-one) on seed germination in Norway spruce, Scots pine, Douglas fir and English oak. Before germination, 400 seeds of each species were steeped in a brassinosteroid solution and then placed for germination in a growth chamber under (i) optimal humidity and (ii) temporary drought stress (except for oak). Drought stress significantly reduced the germination capacity and germination rate in the control treatments of Norway spruce, Scots pine and Douglas fir. Nonetheless, the application of brassinosteroid significantly reduced the drought-stress effects in seeds of Norway spruce and Scots pine. The drought-stressed Douglas fir did not respond positively to the brassinosteroid application. English oak was germinated only under the optimal humidity regime and no differences in germination were detected between the control and brassinosteroid-treated acorns.

Until recently, Czech taxonomists often treated Betula carpatica as a distinct species. Several morphological traits for distinguishing B. carpatica from B. pubescens or other birches are described in literature; however, it has been proven impossible to reliably identify B. carpatica in the field. With the use of morphological and molecular approaches, we intended to assess the position of B. carpatica in the context of other birch taxa reported from the Bohemian Massif and to find more reliable morphological traits for their identification. In our dataset, we distinguished the following birch taxa referred to in the recent Czech literature: B. pendula, B. pubescens, B. carpatica, B. oycoviensis, B. nana, B. petraea and B. ×seideliana. We complemented them with triploids and several diploid and tetraploid "working units" into which we included intermediate individuals that in terms of morphology did not unambiguously match any of the abovementioned birch taxa. Holoploid genome size was measured to determine the ploidy level. To identify genetic relationships between selected taxa and "working units", microsatellite analyses were performed. Model-based STRUCTURE analysis together with principal coordinates analysis (PCoA) based on genetic distances was performed to identify the similarities in multilocus genotype data between groups distinguished in the dataset. The applied analyses were not able clearly to distinguish any group among tetraploid individuals. In this light, it was of no use to search for any more reliable morphological traits of B. carpatica and also B. petraea. Among diploids, B. nana was always distinguished, in contrast to B. oycoviensis, which was not genetically recognized despite being usually morphologically distinct. Based on our results and a literature review, we suggest that B. carpatica and also the closely similar B. petraea should not be considered separate species. A similar conclusion seems relevant also for B. oycoviensis; however, further verification is desirable in this case.

Two new minor Amaryllidaceae alkaloids were isolated from Hippeastrum × hybridum cv. Ferrari and Narcissus pseudonarcissus cv. Carlton. The chemical structures were identified by various spectroscopic (one- and two-dimensional (1D and 2D) NMR, circular dichroism (CD), high-resolution mass spectrometry (HRMS) and by comparison with literature data of similar compounds. Both isolated alkaloids were screened for their human acetylcholinesterase (hAChE) and butyrylcholinesterase (hBuChE) inhibition activity. One of the new compounds, a heterodimer alkaloid of narcikachnine-type, named narciabduliine (2), showed balanced inhibition potency for both studied enzymes, with IC50 values of 3.29 ± 0.73 µM for hAChE and 3.44 ± 0.02 µM for hBuChE. The accommodation of 2 into the active sites of respective enzymes was predicted using molecular modeling simulation.

Recent data suggest that the orexigenic peptide ghrelin and liverexpressed antimicrobial peptide 2 (LEAP2) have opposing effects on food intake regulation. Although circulating ghrelin is decreased in obesity, peripheral ghrelin administration does not induce food intake in obese mice. Limited information is available on ghrelin resistance in relation to LEAP2. In this study, the interplay between ghrelin and LEAP2 in obesity induced by a high-fat (HF) diet in mice was studied. First, the progression of obesity and intolerance to glucose together with plasma levels of active and total ghrelin, leptin, as well as liver LEAP2 mRNA expression at different time points of HF diet feeding was examined. In addition, the impact of switch from a HF diet to a standard diet on plasma ghrelin and LEAP2 production was studied. Second, sensitivity to the stable ghrelin analogue [Dpr3 ]Ghrelin or our novel LEAP2 analogue palm-LEAP2(1-14) during the progression of HF diet-induced obesity and after the switch for standard diet was investigated. Food intake was monitored after acute subcutaneous administration. HF diet feeding decreased both active and total plasma ghrelin and increased liver LEAP2 mRNA expression along with intolerance to glucose and the switch to a standard diet normalized liver LEAP2 mRNA expression and plasma level of active ghrelin, but not of total ghrelin. Additionally, our study demonstrates that a HF diet causes resistance to [Dpr³ ]Ghrelin, reversible by switch to St diet, followed by resistance to palm-LEAP2(1-14). Further studies are needed to determine the long-term effects of LEAP2 analogues on obesity-related ghrelin resistance. [ABSTRACT FROM AUTHOR]

Prolactin-releasing peptide (PrRP), a natural ligand for the GPR10 receptor, is a neuropeptide with anorexigenic and antidiabetic properties. Due to its role in the regulation of food intake, PrRP is a potential drug for obesity treatment and associated type 2 diabetes mellitus (T2DM). Recently, the neuroprotective effects of lipidized PrRP analogs have been proven. In this study, we focused on the molecular mechanisms of action of natural PrRP31 and its lipidized analog palm11-PrRP31 in the human neuroblastoma cell line SH-SY5Y to describe their cellular signaling and possible anti-apoptotic properties. PrRP31 significantly upregulated the phosphoinositide-3 kinase-protein kinase B/Akt (PI3K-PKB/Akt) and extracellular signal-regulated kinase/cAMP response element-binding protein (ERK-CREB) signaling pathways that promote metabolic cell survival and growth. In addition, we proved via protein kinase inhibitors that activation of signaling pathways is mediated specifically by PrRP31 and its palmitoylated analog. Furthermore, the potential neuroprotective properties were studied through activation of anti-apoptotic pathways of PrRP31 and palm11-PrRP31 using the SH-SY5Y cell line and rat primary neuronal culture stressed with toxic methylglyoxal (MG). The results indicate increased viability of the cells treated with PrRP and palm11-PrRP31 and a reduced degree of apoptosis induced by MG, suggesting their potential use in the treatment of neurological disorders.

We study ferromagnetic ordering and microscopic inhomogeneity in tensile strained LaCoO$_3$ using numerical simulations. We argue that both phenomena originate from effective superexchange interactions between atoms in the high-spin (HS) state mediated by the intermediate-spin excitations. We derive a model of the HS excitation as a bare atomic state dressed by electron and electron-hole fluctuations on the neighbor atoms. We construct a series of approximations to account for electron correlation effects responsible for HS fluctuations and magnetic exchange. The obtained amplitudes and directional dependence of magnetic couplings between the "dressed" HS states show a qualitative agreement with experimental observations and provide a new physical picture of LaCoO$_3$ films.

Thirteen known (1–12 and 16) and three previously undescribed Amaryllidaceae alkaloids of belladine structural type, named carltonine A-C (13–15), were isolated from bulbs of Narcissus pseudonarcissus cv. Carlton (Amaryllidaceae) by standard chromatographic methods. Compounds isolated in sufficient amounts, and not tested previously, were evaluated for their in vitro acetylcholinesterase (AChE; E.C. 3.1.1.7), butyrylcholinesterase (BuChE; E.C. 3.1.1.8) and prolyl oligopeptidase (POP; E.C. 3.4.21.26) inhibition activities. Significant human BuChE (hBUChE) inhibitory activity was demonstrated by newly described alkaloids carltonine A (13) and carltonine B (14) with IC50 values of 913 ± 20 nM and 31 ± 1 nM, respectively. Both compounds displayed a selective inhibition pattern for hBuChE with an outstanding selectivity profile over AChE inhibition, higher than 100. The in vitro data were further supported by in silico studies of the active alkaloids 13 and 14 in the active site of hBuChE.

Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (Mtb), each year causing millions of deaths. In this article, we present the synthesis and biological evaluations of new potential antimycobacterial compounds containing a fragment of the first-line antitubercular drug pyrazinamide (PZA), coupled with methyl or ethyl esters of selected amino acids. The antimicrobial activity was evaluated on a variety of (myco)bacterial strains, including Mtb H37Ra, M. smegmatis, M. aurum, Staphylococcus aureus, Pseudomonas aeruginosa, and fungal strains, including Candida albicans and Aspergillus flavus. Emphasis was placed on the comparison of enantiomer activities. None of the synthesized compounds showed any significant activity against fungal strains, and their antibacterial activities were also low, the best minimum inhibitory concentration (MIC) value was 31.25 µM. However, several compounds presented high activity against Mtb. Overall, higher activity was seen in derivatives containing l-amino acids. Similarly, the activity seems tied to the more lipophilic compounds. The most active derivative contained phenylglycine moiety (PC-d/l-Pgl-Me, MIC < 1.95 µg/mL). All active compounds possessed low cytotoxicity and good selectivity towards Mtb. To the best of our knowledge, this is the first study comparing the activities of the d- and l-amino acid derivatives of pyrazinamide as potential antimycobacterial compounds.

In this detailed phytochemical study of Narcissus cv. Professor Einstein, we isolated 23 previously known Amaryllidaceae alkaloids (1−23) of several structural types and one previously undescribed alkaloid, 7-oxonorpluviine. The chemical structures were identified by various spectroscopic methods (GC-MS, LC-MS, 1D, and 2D NMR spectroscopy) and were compared with literature data. Alkaloids which had not previously been isolated and studied for cytotoxicity before and which were obtained in sufficient amounts were assayed for their cytotoxic activity on a panel of human cancer cell lines of different histotype. Above that, MRC-5 human fibroblasts were used as a control noncancerous cell line to determine the general toxicity of the tested compounds. The cytotoxicity of the tested alkaloids was evaluated using the WST-1 metabolic activity assay. The growth of all studied cancer cell lines was inhibited by pancracine (montanine-type alkaloid), with IC50 values which were in the range of 2.20 to 5.15 µM.

Many-body calculations at the two-particle level require a compact representation of two-particle Green's functions. In this paper, we introduce a sparse sampling scheme in the Matsubara frequency domain as well as a tensor network representation for two-particle Green's functions. The sparse sampling is based on the intermediate representation basis and allows an accurate extraction of the generalized susceptibility from a reduced set of Matsubara frequencies. The tensor network representation provides a system independent way to compress the information carried by two-particle Green's functions. We demonstrate efficiency of the present scheme for calculations of static and dynamic susceptibilities in single- and two-band Hubbard models in the framework of dynamical mean-field theory.

In 1927, the first pollen diagram was published from the Bohemian/Bavarian Forest region of Central Europe, providing one of the first qualitative views of the long-term vegetation development in the region. Since then significant methodological advances in quantitative approaches such as pollen influx and pollen-based vegetation models (e.g., Landscape Reconstruction Algorithm, LRA) have contributed to enhance our understanding of temporal and spatial ecology. These types of quantitative reconstructions are fundamental for conservation and restoration ecology because they provide long-term perspectives on ecosystem functioning. In the Bohemian/Bavarian Forests, forest managers have a goal to restore the original forest composition at mid-elevation forests, yet they rely on natural potential vegetation maps that do not take into account long-term vegetation dynamics. Here we reconstruct the Holocene history of forest composition and discuss the implications the LRA has for regional forest management and conservation. Two newly analyzed pollen records from Prášilské jezero and Rachelsee were compared to 10 regional peat bogs/mires and two other regional lakes to reconstruct total land-cover abundance at both the regional- and local-scales. The results demonstrate that spruce has been the dominant canopy cover across the region for the past 9,000 years at both high- (>900 m) and mid-elevations (>700–900 m). At the regional-scale inferred from lake records, spruce has comprised an average of ~50% of the total forest canopy; whereas at the more local-scale at mid-elevations, spruce formed ~59%. Beech established ~6,000 cal. years BP while fir established later around 5,500 cal. years BP. Beech and fir growing at mid-elevations reached a maximum land-cover abundance of 24% and 13% roughly 1,000 years ago. Over the past 500 years spruce has comprised ~47% land-cover, while beech and fir comprised ~8% and

The worldwide increase in the incidence of obesity and cardiovascular and neurodegenerative diseases, e.g. Alzheimer's disease, is related to many factors, including an unhealthy lifestyle and aging populations. However, the interconnection between these diseases is not entirely clear, and it is unknown whether common mechanisms underlie these conditions. Moreover, there are currently no fully effective therapies for obesity and neurodegeneration. While there has been extensive research in preclinical models addressing these issues, the experimental findings have not been translated to the clinic. Another challenge relates to the time of onset of individual diseases, which may not be easily identified, since there are no specific indicators or biomarkers that define disease onset. Hence knowing when to commence preventive treatment is unclear. This is especially pertinent in neurodegenerative diseases, where the onset of the disease may be subtle and occur decades before the signs and symptoms manifest. In metabolic and cardiovascular disorders, the risk may occur in-utero, in line with the concept of fetal programming. This review provides a brief overview of the link between obesity, cardiovascular and neurodegenerative diseases and discusses potential common mechanisms including the role of the gut microbiome. [ABSTRACT FROM AUTHOR]

Analogs of anorexigenic neuropeptides, such as prolactin-releasing peptide (PrRP), have a potential as new anti-obesity drugs. In our previous study, palmitic acid attached to the N-terminus of PrRP enabled its central anorexigenic effects after peripheral administration. In this study, two linkers, γ-glutamic acid at Lys11 and a short, modified polyethylene glycol at the N-terminal Ser and/or Lys11, were applied for the palmitoylation of PrRP31 to improve its bioavailability. These analogs had a high affinity and activation ability to the PrRP receptor GPR10 and the neuropeptide FF2 receptor, as well as short-term anorexigenic effect similar to PrRP palmitoylated at the N-terminus. Two-week treatment with analogs that were palmitoylated through linkers to Lys11 (analogs 1 and 2), but not with analog modified both at the N-terminus and Lys11 (analog 3) decreased body and liver weights, insulin, leptin, triglyceride, cholesterol and free fatty acid plasma levels in a mouse model of diet-induced obesity. Moreover, the expression of uncoupling protein-1 was increased in brown fat suggesting an increase in energy expenditure. In addition, treatment with analogs 1 and 2 but not analog 3 significantly decreased urinary concentrations of 1-methylnicotinamide and its oxidation products N-methyl-2-pyridone-5-carboxamide and N-methyl-4-pyridone-3-carboxamide, as shown by NMR-based metabolomics. This observation confirmed the previously reported increase in nicotinamide derivatives in obesity and type 2 diabetes mellitus and the effectiveness of analogs 1 and 2 in the treatment of these disorders.

We tested the influence of exogenous application of brassinosteroids (BRs) on survival, growth and biomass production of Scots pine (Pinus sylvestris) seedlings. BRs are natural substances, supposedly having many positive effects on plants such as improving growth, stress tolerance, survival and biomass production. One part of the seedlings was treated with a low concentration of synthetically prepared BRs and the other part was designated as the control without any treatment. Mortality, height and root collar diameter were measured in two subsequent years, the root-to-shoot ratio of biomass volume was determined in autumn 2013. The application of BRs significantly slowed height and radial growth of pine. The height increment of the BRs-treated seedlings was lower by 11% between 2012 and 2013 compared to the control. The increment in root collar diameter (2012-2013) in the BRs-treated seedlings was lower by 13% than in the control. The BRs-treated pines also experienced a significantly higher mortality compared to the control. No significant influence of BRs on biomass production was found.

The aim of study: (1) to compare the survival rate, growth performance and nutrition of large and common-sized planting stock of rowan (Sorbus aucuparia L.) on a frost-exposed site and (2) to assess whether fertilizing had any effect on the plantations.Area of study: The Jizera Mts., an area heavily disturbed by air pollution situated on the Czech-Polish border close to GermanyMaterials and methods: Two types of planting stock were tested in a mountain frost hollow on an acidic mountain humic podsol: (a) the bare-rooted saplings 131–140 cm tall and (b) common-sized containerized transplants 26–35 cm. One half of the saplings and common-sized transplants were left untreated and the other half were fertilized with a low dose (30 g per tree) of a slow release fertilizer based on methylene urea and potassium magnesium phosphate. Growth performance and nutrition of plantations were investigated.Main results: Due to serious deformations and stem breakages inflicted by snow and frost, the prospects of common-sized transplants seem much worse than those of saplings. The height growth of saplings was significantly more rapid than that of common-sized transplants. As for growth, neither the saplings nor common-sized transplants did significantly respond to fertilizing. The effects of fertilizing on nutrition of rowans were unconvincing. The extreme temperature events during growth seasons and snow deformations in winters might be the decisive factors influencing growth performance of rowans under referred conditions.Research highlights: On the frost-exposed sites, the height of taller saplings might partly compensate for a missing shelter of forest stand since the terminal leaders are above ground-frost zone.Key words: mountain ash; sapling; common-sized transplants; nutritional status; temperature.Abbreviations: CS – Control Saplings; CT – Control Transplants; FS – Fertilized Saplings; FT – Fertilized Transplants

This study aims to evaluate the direct effects of anthropogenic deforestation on simulated climate at two contrasting periods in the Holocene, ~6 and ~0.2 k BP in Europe. We apply We apply the Rossby Centre regional climate model RCA3, a regional climate model with 50 km spatial resolution, for both time periods, considering three alternative descriptions of the past vegetation: (i) potential natural vegetation (V) simulated by the dynamic vegetation model LPJ-GUESS, (ii) potential vegetation with anthropogenic land use (deforestation) from the HYDE3.1 (History Database of the Global Environment) scenario (V + H3.1), and (iii) potential vegetation with anthropogenic land use from the KK10 scenario (V + KK10). The climate model results show that the simulated effects of deforestation depend on both local/regional climate and vegetation characteristics. At ~6 k BP the extent of simulated deforestation in Europe is generally small, but there are areas where deforestation is large enough to produce significant differences in summer temperatures of 0.5–1 °C. At ~0.2 k BP, extensive deforestation, particularly according to the KK10 model, leads to significant temperature differences in large parts of Europe in both winter and summer. In winter, deforestation leads to lower temperatures because of the differences in albedo between forested and unforested areas, particularly in the snow-covered regions. In summer, deforestation leads to higher temperatures in central and eastern Europe because evapotranspiration from unforested areas is lower than from forests. Summer evaporation is already limited in the southernmost parts of Europe under potential vegetation conditions and, therefore, cannot become much lower. Accordingly, the albedo effect dominates in southern Europe also in summer, which implies that deforestation causes a decrease in temperatures. Differences in summer temperature due to deforestation range from −1 °C in south-western Europe to +1 °C in eastern Europe. The choice of anthropogenic land-cover scenario has a significant influence on the simulated climate, but uncertainties in palaeoclimate proxy data for the two time periods do not allow for a definitive discrimination among climate model results.

The article assesses the effects of amphibolite applied to the planting holes of spruces on the soil chemistry. The sampling was conducted fourteen growth seasons after the establishment of the experimental spruce plantation. In both treatments (control and amphibolite) the soil samples were taken from the interior of the planting holes as well as from the intact area around the planting holes. Fourteen growth seasons after application the effects of the pulverised amphibolite were not marked despite being detectable. In comparison with the control the soil in the planting holes of the amphibolite treatment showed significantly higher soil reaction, concentration of available phosphorus and partially also concentration of exchangeable Ca. All the significant effects of amphibolite were confined to the soil inside the planting holes. As for the evaluated chemical properties no significant undesirable effects of the amphibolite on soil chemistry were recorded.

We have verified whether the temperatures in the zone of terminal leaders of saplings (+100 cm) were less extreme than the temperatures in the zone of terminal leaders of common-sized planting stock (+30 cm). In May and June of 2011 and 2012 we investigated the occurrence of late frosts at different levels above the ground. The number of days and amount of hourly frost records were counted and the sum of sub-zero temperatures was calculated. Our study confirmed that sub-zero temperatures mostly occur at levels near the ground. Therefore, on the sites exposed to late frosts, such as mountain frost hollows, in addition to common-sized planting stock we recommend to consider also the use of large-sized transplants (saplings), since their terminal buds are mostly above the zone near the ground most endangered by frost.

Prolactin-releasing peptide (PrRP) belongs to the large RF-amide neuropeptide family with a conserved Arg-Phe-amide motif at the C-terminus. PrRP plays a main role in the regulation of food intake and energy expenditure. This review focuses not only on the physiological functions of PrRP, but also on its pharmacological properties and the actions of its G-protein coupled receptor, GPR10. Special attention is paid to structure-activity relationship studies on PrRP and its analogs as well as to their effect on different physiological functions, mainly their anorexigenic and neuroprotective features and the regulation of the cardiovascular system, pain, and stress. Additionally, the therapeutic potential of this peptide and its analogs is explored.

We report the design, synthesis, and in vitro antimicrobial activity of a series of N-substituted 3-aminopyrazine-2-carboxamides with free amino groups in position 3 on the pyrazine ring. Based on various substituents on the carboxamidic moiety, the series is subdivided into benzyl, alkyl, and phenyl derivatives. The three-dimensional structures of the title compounds were predicted using energy minimization and low mode molecular dynamics under AMBER10:EHT forcefield. Compounds were evaluated for antimycobacterial, antibacterial, and antifungal activities in vitro. The most active compound against Mycobacterium tuberculosis H37Rv (Mtb) was 3-amino-N-(2,4-dimethoxyphenyl)pyrazine-2-carboxamide (17, MIC = 12.5 µg/mL, 46 µM). Antimycobacterial activity against Mtb and M. kansasii along with antibacterial activity increased among the alkyl derivatives with increasing the length of carbon side chain. Antibacterial activity was observed for phenyl and alkyl derivatives, but not for benzyl derivatives. Antifungal activity was observed in all structural subtypes, mainly against Trichophyton interdigitale and Candida albicans. The four most active compounds (compounds 10, 16, 17, 20) were evaluated for their in vitro cytotoxicity in HepG2 cancer cell line; only compound 20 was found to exert some level of cytotoxicity. Compounds belonging to the current series were compared to previously published, structurally related compounds in terms of antimicrobial activity to draw structure activity relationships conclusions.

5-Chloropyrazinamide (5-Cl-PZA) is an inhibitor of mycobacterial fatty acid synthase I with a broad spectrum of antimycobacterial activity in vitro. Some N-phenylpyrazine-2-carboxamides with different substituents on both the pyrazine and phenyl core possess significant in vitro activity against Mycobacterium tuberculosis. To test the activity of structures combining both the 5-Cl-PZA and anilide motifs a series of thirty 5-chloro-N-phenylpyrazine-2-carboxamides with various substituents R on the phenyl ring were synthesized and screened against M. tuberculosis H37Rv, M. kansasii and two strains of M. avium. Most of the compounds exerted activity against M. tuberculosis H37Rv in the range of MIC = 1.56–6.25 µg/mL and only three derivatives were inactive. The phenyl part of the molecule tolerated many different substituents while maintaining the activity. In vitro cytotoxicity was decreased in compounds with hydroxyl substituents, preferably combined with other hydrophilic substituents. 5-Chloro-N-(5-chloro-2-hydroxyphenyl)pyrazine-2-carboxamide (21) inhibited all of the tested strains (MIC = 1.56 µg/mL for M. tuberculosis; 12.5 µg/mL for other strains). 4-(5-Chloropyrazine-2-carboxamido)-2-hydroxybenzoic acid (30) preserved good activity (MIC = 3.13 µg/mL M. tuberculosis) and was rated as non-toxic in two in vitro models (Chinese hamster ovary and renal cell adenocarcinoma cell lines; SI = 47 and 35, respectively).

We evaluated the potential of crushed amphibolite and artificial slow-release N-P-K-Mg fertiliser to stimulate the survival, growth and nutrition of Norway spruce planted on an acidified air-polluted mountain site. Control plots and treatments with slow-release fertiliser (SRF) and amphibolite (AMT) were installed. In the SRF, forty grams of tabletted amendment were applied in the close vicinity of the trees. In the AMT, two kilograms of amendment were incorporated into the soil inside the planting hole of each tree at planting. The SRF application resulted in a significant growth stimulation of spruces. The growth stimulation by amphibolite was perceptible but not significant; this amendment, however, significantly reduced mortality. None of the amendments induced marked changes in foliar nutrient concentrations.

Deriving from the complex nature of cultural heritage conservation it is the need for enhancing a systematic but flexible organization of expert knowledge in the field. Such organization should address comprehensively the interrelations and complementariness among the different factors that come into play in the understanding of diagnostic and intervention problems. The purpose of MONDIS is to endorse this kind of organization. The approach consists in applying an ontological representation to the field of heritage conservation in order to establish an appropriate processing of data. The system allows replicating in a computer readable form the basic dependence among factors influencing the description, diagnosis and intervention of damages to immovable objects. More specifically MONDIS allows to input and search entries concerning object description, structural evolution, location characteristics and risk, component, material properties, surveys and measurements, damage typology, damage triggering events and possible interventions. The system supports searching features typical of standard databases, as it allows for the digitalization of a wide range of information including professional reports, books, articles and scientific papers. It also allows for computer aided retrieval of information tailored to user's requirements. The foreseen outputs will include a web user interface and a mobile application for visual inspection purposes.

The organic matter produced and accumulated by plants is a crucial component in the ecosystems on environmentally disturbed sites. The aim of our study was to evaluate the influence of initial fertilising on the aboveground and belowground tree biomass of Norway spruce. The biomass amount, distribution and chemical composition were studied in a young spruce stand growing on an acidified mountain clear-cut tract. The fertilised trees accumulated a higher amount of tree biomass. They nonetheless showed lower concentrations of P, N, and K in some root compartments than control trees, which could be ascribed to a dilution effect. As for the aboveground compartments, no significant differences in element concentrations were proved.

Cardiac surgery is inseparably linked to the activation of innate immunity cells recognizing danger signals of both endogenous and exogenous origin via pattern recognition receptors such as TLR receptors. Therefore, we followed by flow cytometry TLR2 and TLR4 expression on blood monocytes and granulocytes of patients who underwent coronary artery bypass grafting using beating heart surgery (off-pump, n = 34), with use of standard cardiopulmonary bypass (CPB), (on-pump, n = 30), and miniinvasive CPB (mini on-pump, n = 25), respectively, before, during surgery, and up to 7th postoperative day. TLR2 and TLR4 expression both on monocytes and granulocytes was significantly diminished already at the end of CPB being highly significantly decreased at the end of surgery in all patients’ groups. TLR2 and TLR4 expression reached preoperative value at the 1st postoperative day being significantly higher at the 3rd postoperative day. Using intracellular staining we found the peak of TLR2 and TLR4 expression inside of monocytes and granulocytes at the first postoperative day in a subgroup of on-pump patients. In conclusion, TLR2 and TLR4 expression is significantly modulated in patients undergoing coronary artery bypass grafting as a part of adaptive homeostatic mechanisms induced by major surgery. The very surgical trauma is responsible for TLR2 and TLR4 modulation. Surprisingly, cardiopulmonary bypass itself was little contributing to the modulation of TLR2 and TLR4 expression.

The results of a fifteen-year period of investigations conducted on Norway spruce in the upper plateau of the Jizerské hory Mts. were summarised. The objectives were to evaluate the growth performance of an experimental plantation under harsh environmental conditions and assess the effects of amendments as well as the influence of the forest site variability on growth performance and survival of young spruces. The following treatments were distinguished: (1) lower control, (2) limestone and (3) amphibolite treatments on a less exposed slope of the ridge and (4) upper control on a summit of the mountain ridge. Principle characteristics such as mortality rate, height, annual height increment, stem base diameter, crown diameter and nutritional status were summarized and evaluated. Significant differences between treatments were recorded in heights. The trees fertilized with amphibolite were significantly taller than the control ones in thirteen out of the fifteen evaluated years and the applied limestone improved heights in ten years out of the fifteen evaluated years. A positive effect of amphibolite treatment on stem base diameter was proved in three of the four assessed years and was persisting till 2007 (last measurement of this characteristic), the positive effect of limestone was lasting up to 2006. The considerable role of the site variability was apparent from a comparison between the upper and lower control although they were in a very close position to each other, growth increment of the spruces on the ridge was significantly lower. Temporarily lower N concentration was recorded in the fertilized treatments in comparison with their respective control. The concentration of P was low and decreased to the limit of deficiency in all treatments, P seems to be the most limiting macroelement in the area.

The aims of the paper were as follows: (1) to assess the applicability of speckled alder for pioneer stands on the mountainous clear-cut tracts and (2) to evaluate the effects of slow-release fertilizer on the survival and growth of speckled alder under harsh environmental conditions. On the basis of seven-year results we can presume that speckled alder is a convenient pioneer species that can be cultivated on harsh mountain sites where the climatic extremes need to be alleviated and a layer of surface humus renewed. The initial slow-release fertilization is, nonetheless, highly desirable. As contrasted to the control the surface and planting hole applications of amendment reduced the total seven-year mortality rate by 9.5% and 20.1%, respectively, and the periodic annual height increment (2003-2009) was promoted by 47% and 59%, respectively. Analogous results were obtained when the values of basal stem diameter and crown diameter were compared. As for the method of application, the placement of the slow-release amendment in the planting holes seems to be more efficient mainly in terms of survival promoting. The surface application is, nonetheless, less laborious and also yielded satisfactory results.

CD200 and its receptor were recognized as having the multiple immunoregulatory functions. Their immunoregulatory, suppressive, and tolerogenic potentials could be very effectively exploited in the treatment of many diseases, e.g. Alzheimer disease, rheumatoid arthritis, and allergy to name only some. Many research projects are aimed to develop clinically valuable methods being based on the structure and function of these paired molecules. In this review, we would like to introduce CD200/CD200R functions in a clinical context.

CD200/CD200R are highly conserved type I paired membrane glycoproteins that belong to the Ig superfamily containing a two immunoglobulin‑like domain (V, C). CD200 is broadly distributed in a variety of cell types, whereas CD200R is primarily expressed in myeloid and lymphoid cells. They fulfill multiple functions in regulating inflammation. The interaction between CD200/CD200R results in activation of the intracellular inhibitory pathway with RasGAP recruitment and thus contributes to effector cell inhibition. It was confirmed that the CD200R activation stimulates the differentiation of T cells to the Treg subset, upregulates indoleamine 2,3‑dioxygenase activity, modulates cytokine environment from a Th1 to a Th2 pattern, and facilitates an antiinflammatory IL‑10 and TGF‑β synthesis. CD200/CD200R are required for maintaining self‑tolerance. Many studies have demonstrated the importance of CD200 in controlling autoimmunity, inflammation, the development and spread of cancer, hypersensitivity, and spontaneous fetal loss.

An experiment with seedlings of Alnus viridis was established on a clear-felled tract situated on a summit tableland of the Jizerské hory Mts. (central Europe, Czech Republic) at an altitude of 980 m a.s.l. The aims of the experiment were (i) to evaluate the response of A. viridis to the application of a basic mixture containing crushed limestone and amphibolite and (ii) to assess the growth potential of the species in a poor acidic site under climatically harsh conditions. Alnus viridis showed a good growth performance and survival rate, its initial response to fertilization was positive. The height growth and expansion of crowns were slightly but significantly stimulated by the treatment, the survival rate was also increased, though not significantly. The amendment application temporarily increased the foliar Ca and Mg concentrations. The content of foliar P, of the most deficient macroelement, was not improved by the treatment. However, the positive effect of fertilization was short-lasting and unconvincing from the aspect of practical use. In the second half of the reference period the control started to gain on the fertilized variant and as for mean height and crown diameter, both variants got almost equalized eight growing seasons after the treatment.

The major objectives of this paper are: (1) to review the pros and cons of the scenarios of past anthropogenic land cover change (ALCC) developed during the last ten years, (2) to discuss issues related to pollen-based reconstruction of the past land-cover and introduce a new method, REVEALS (Regional Estimates of VEgetation Abundance from Large Sites), to infer long-term records of past land-cover from pollen data, (3) to present a new project (LANDCLIM: LAND cover – CLIMate interactions in NW Europe during the Holocene) currently underway, and show preliminary results of REVEALS reconstructions of the regional land-cover in the Czech Republic for five selected time windows of the Holocene, and (4) to discuss the implications and future directions in climate and vegetation/land-cover modeling, and in the assessment of the effects of human-induced changes in land-cover on the regional climate through altered feedbacks. The existing ALCC scenarios show large discrepancies between them, and few cover time periods older than AD 800. When these scenarios are used to assess the impact of human land-use on climate, contrasting results are obtained. It emphasizes the need for methods such as the REVEALS model-based land-cover reconstructions. They might help to fine-tune descriptions of past land-cover and lead to a better understanding of how long-term changes in ALCC might have influenced climate. The REVEALS model is demonstrated to provide better estimates of the regional vegetation/land-cover changes than the traditional use of pollen percentages. This will achieve a robust assessment of land cover at regional- to continental-spatial scale throughout the Holocene. We present maps of REVEALS estimates for the percentage cover of 10 plant functional types (PFTs) at 200 BP and 6000 BP, and of the two open-land PFTs "grassland" and "agricultural land" at five time-windows from 6000 BP to recent time. The LANDCLIM results are expected to provide crucial data to reassess ALCC estimates for a better understanding of the land suface-atmosphere interactions.

The crystal electric field (CEF) scheme of YbNi _4 P _2 is determined, based on experimental data from inelastic neutron scattering, heat capacity, susceptibility and NMR measurements. Despite the tetragonal crystal structure, 9 parameters are needed to describe the crystal field in YbNi _4 P _2 due to the orthorhombic site symmetry of the Yb ion. A large basal plane anisotropy is detected by the local probe NMR. Our analysis yields CEF excitation energies of 8.5, 12.5 and roughly 30 meV and a ground state wave function that is dominated by the $5/2$ state. Furthermore, we present an analysis of the CEF scheme based on density functional theory calculations, which confirms the large basal plane anisotropy.

The recently recognized cytokine interleukin-33 and its receptor ST2 play a favorable role during atherogenesis by inducing a Th1→Th2 shift of the immune response. IL-33 also protects the failing human heart from harmful biomechanical forces which lead to cardiomyocyte hypertrophy and exaggerated interstitial fibrosis. IL-33 inevitably displays side effects common to other Th2 cytokines, the most grave of which is a predisposition to allergic reactions. IL-33 is a nuclear transcription factor of endothelial cells. As such, it is abundant in nonproliferating vessels. Its down-regulation is required for angiogenesis, which may be profitable in wound healing or deleterious in tumor growth.

A young speckled alder (Alnus incana [L.] Moench) stand was planted on a tract clear-felled due to air pollution and located on a summit plateau of the Jizerské hory Mts. (Central Europe, Czech Republic) at an altitude of 950 m a.s.l. The aim of the experiment was to test the suitability of Alnus incana to form preparatory stands covering the site and thus enabling the reintroduction of more sensitive target species. A potential of Alnus incana to respond to slow-release fertilizing was tested as well. The control treatment showed sufficient growth dynamics, nevertheless, the fertilization significantly promoted the growth (documented by height, height increment and stem-base diameter). If some limitations of alder such as high light requirements are respected, the speckled alder can be recommended as a suitable species for preparatory stands even in the 7th and 8th altitudinal (vegetation) zones, especially when fertilized.

The condensation of chlorides of substituted pyrazinecarboxylic acids with ringsubstituted anilines yielded twelve substituted pyrazinecarboxylic acid amides. The synthetic approach, analytical, and lipophilicity data of the newly synthesized compounds are presented. Two antituberculosis assays were used. Firstly, the antimycobacterial activity against four different Mycobacterium strains in a series of pyrazine derivatives was investigated. Secondly, the antimycobacterial evaluation was performed at the Tuberculosis Antimicrobial Acquisition and Coordinating Facility (TAACF) program. Interesting in vitro antimycobacterial activity was found, N-(3-iodo-4-methylphenyl) pyrazine-2-carboxamide (9) was most active derivative compound against M. tuberculosis (MIC < 2.0 μmol/L), while another iodo derivative 5-tert-butyl-6-chloro-N-(3-iodo-4-methyl-phenyl)pyrazine-2-carboxamide (12) was the most active compound in the TAACF antituberculosis screening program (IC90 = 0.819 μg/mL).

Background: Cardiac surgery provokes a systemic inflammatory response in any patient. This complex body reaction involves also RANK/RANKL molecules which have been recently identified as principal regulators of bone metabolism. Aims: To follow the changes in the expression of RANK/RANKL molecules on innate immune cells of cardiac surgical patients. Patients and Methods: Twenty-six patients undergoing cardiac surgical were assigned to undergo coronary artery bypass grafting using either cardiopulmonary bypass (“on-pump”) or modified “miniinvasive on-pump”. The expression of RANK/RANKL was performed by flow cytometry. Results: Significantly increased expression of RANK on monocytes of “miniinvasive on-pump” patients was found at the 1st, the 3nd, and 7th postoperative days. The similar pattern was found also for monocyte RANKL expression. In addition, RANKL expression was significantly increased at the 3rd postoperative day in “on-pump” patient. No significant differences between “miniinvasive on-pump” and “on-pump” cardiac surgical patients were found. Conclusion: The expression of both RANK and RANKL molecules is significantly enhanced on monocytes of “miniinvasive on-pump” cardiac surgical patients.

Practically all mammalian cells including human can switch, according to micro- or macroenvironmental conditions, from states of cellular quiescence to inflammatory activation and vice versa. Along with recent knowledge, cellular quiescence is not a passive, but a highly active state with broad engagement of the cell synthetic and secretory machinery. Inflammatory activation is a beneficial process in cases of infection; however, if its control fails, it may degrade into autoimmune diseases or cancer growth. Control over cellular quiescence is exerted predominantly by a set of zincfinger transcription proteins, referred to as Krüppel-like factors (KLFs). This review article offers recent information concerning activities of Krüppel-like factor 4 in the vascular wall.