Synthesis and opioid activity of novel 6-substituted-6-demethoxy-ethenomorphinans

A set of novel 6-substituted orvinols was synthesized and pharmacologically characterized in order to explore the effect of the polarity and steric effects of these new moieties on the opioid activity. It was revealed that longer 6-O-alkyl chains led to increased agonistic activities, while the lack of C6-etheral oxygen gave rise to an antagonistic profile at the opioid receptors in the mouse ileum.     

Interpretation of intramolecular stacking effect on the fluorescence intensity decay of 3-methylbenzimidazolyl(5′-5′)guanosine dinucleotides using a model of lifetime distribution

Time-resolved fluorescence of 3-methylbenzimidazole (m³B) was used to study stacking interaction between base moieties in di-, tri- and tetra-phosphate analogues of 3-methylbenzimidazolyl(5′-5′)guanosine (m³Bp _n G, n = 2, 3, 4), using 5′-triphosphate of 3-methylbenzimidazole riboside (m³BTP) as reference. Fluorescence intensity decays of all compounds cannot be satisfactory fitted with single-exponential function. Although an increase of a number of exponents led to better fits, interpretation of the individual exponential terms, i.e. pre-exponential amplitudes and fluorescence lifetimes, cannot be adequately characterized. We show that these fluorescence decays are best fitted by power-like function derived from physically justified distribution of the fluorescence lifetimes, and characterized by the mean value of the excited-state lifetime and relative variance of lifetime fluctuations around the mean value. The latter led to the parameter of heterogeneity and number of decay paths, which depend on the factors responsible for non-radiative decay of the excited state, including base–base stacking interaction. This was studied by means of changes of temperature and the number of phosphate groups in dinucleotides. It was shown that the strongest effect of stacking interactions, characterized by lowest values of both fluorescence mean decay time and relative variance, occurs in the case of m³Bp₃G containing the same number of phosphates as natural mRNA cap. The possible importance of these results for interpretation of the mechanism of function of the mRNA cap structure is discussed.     

Linking Foliar Chemistry to Forest Floor Solid and Solution Phase Organic C and N in Picea abies [L.] Karst Stands in Northern Bohemia

Dissolved organic carbon and nitrogen (DOC and DON) produced in the forest floor are important for ecosystem functions such as microbial metabolism, pedogenesis and pollutant transport. Past work has shown that both DOC and DON production are related to litterfall and standing stocks of C and N in the forest floor. This study, conducted in spring, 2003, investigated variation in forest floor water extractable DOC (WEDOC) and DON (WEDON) and forest floor C and N as a function of lignin, cellulose and N contained in live canopy foliage across eight Picea abies [L.] Karst stands in northern Bohemia. Based on Near Infrared Spectroscopy (NIR) analysis of foliar materials, lignin:N and cellulose:N content of the youngest needles (those produced in 2002) were positively and significantly related to WEDOC (R² = 0.82–0.97; P<0.01) and to forest floor C:N ratio (R = 0.72–0.78; P<0.01). Foliar N was strongly and negatively related to WEDOC and C:N ratio (R = −0.91 and 0.72; P<0.05) among our study sites. WEDON was positively correlated to foliar lignin:N (R = 0.48; P<0.05; n=40). Forest floor C pools were not positively correlated with foliar lignin and cellulose and forest floor N pools were not positively correlated with foliar N. Instead, a significant negative correlation was found between forest floor N pools and foliar cellulose (R=−0.41; P<0.05), and between forest floor C pools and foliar N (R = −0.44; P<0.05). From a remote sensing standpoint, our results are important because canopy reflectance properties are primarily influenced by the most recent foliage, and it was the chemistry of the most recently produced needles that showed a stronger relationship with forest floor WEDOC and C:N ratio suggesting forest floor production of WEDOC can be calculated regionally with remote sensing.     

Insulin and oxidative stress modulate proliferation of rat ovarian theca-interstitial cells through diverse signal transduction pathways

Insulin and moderate oxidative stress stimulate proliferation of ovarian theca-interstitial cells. The effects of these agents on selected signal transduction pathways were examined. PD98059 (inhibitor of MAP2K1, also known as MEK-1, upstream of extracellular signal-regulated protein kinases MAPK3/1, also known as ERK1/2), wortmannin (inhibitor of PIK3C2A, also known as PI3K), and rapamycin (inhibitor of FRAP1, also known as mTOR, upstream of RPS6KB1) each significantly decreased insulin and oxidative stress-induced proliferation of theca-interstitial cells. The greatest inhibition was observed in the presence of rapamycin; this effect occurred without a significant change in cell viability. Phosphorylation of AKT was stimulated by insulin only, while phosphorylation of MAPK3/1 and RPS6KB1 was increased by insulin and oxidative stress. Insulin-induced and oxidative stress-induced phosphorylation of RPS6KB1 was partly inhibited by wortmannin and partly by PD98059; the greatest inhibition was observed in the presence of a combination of wortmannin plus PD98059. Effects of insulin and oxidative stress on phosphorylation of RPS6KB1 were confirmed by kinase activity assays. These findings indicate that actions of insulin and oxidative stress converge on MAPK3/1 and RPS6KB1. Furthermore, we speculate that activation of RPS6KB1 may be in part induced via the MAPK3/1 pathway.     

Habitat-specific sensory-exploitative signals in birds: propensity of dipteran prey to cause evolution of plumage variation in flush-pursuit insectivores

Sensory exploitation occurs when signals trigger behavioral reactions that diminish the receiver's fitness. Research in this area focuses on the match between the signal's form and the receiver's sensitivity, but the effect of habitat on interspecific sensory exploitation is rarely addressed. Myioborus redstarts use conspicuous wing and tail displays of contrasting black-and-white plumage patches to flush dipteran insects, which are then pursued and captured in flight. Previous studies have shown that by increasing the distance at which insects perform an escape response, conspicuous visual displays improve the birds' foraging performance. We tested the hypothesis that selection for a visual signal that maximizes prey escape distance under local habitat conditions can lead to the evolution of geographic variation in plumage pattern among Myioborus redstarts. Using models of foraging birds, we recorded the escape responses of Dipterous insects to a range of plumage patterns and background tones (from light to dark) to determine whether the plumage pattern that maximizes prey flushing is dependent upon that habitat (background) against which birds are viewed by their prey. Our results indicate that the effectiveness of a particular plumage pattern in flushing dipteran prey depends strongly on the background against which that plumage pattern is displayed, and darker habitat (background) conditions generally favor plumages with more extensive patches of white in the tail. However, the addition of white wing patches that imitate the plumage of the painted redstart (Myioborus pictus) generally increases insect escape responses but reduces the effect that tail pattern variation and background tone have on escape behavior. These experiments support the hypothesis that habitat-specific natural selection to enhance sensory exploitation of prey escape responses could produce geographic variation in plumage patterns of flush-pursuers.     

The strength of direct selection against female promiscuity is associated with rates of extrapair fertilizations in socially monogamous songbirds

A costs-benefits approach has frequently been used to understand the evolutionary origin and maintenance of promiscuity in animal populations. Recent meta-analyses suggest that direct costs to unfaithful females outweigh indirect benefits from infidelity in socially monogamous songbirds, suggesting that in this taxa, extrapair fertilization (EPF) evolved primarily as a self-interest male tactic. Here we present results of comparative analysis to show that standardized selection gradients acting against female infidelity (direct costs of promiscuity) explain variation in EPF rates at an interspecific level in passerines. This result confirms that costs to females resulting from reduced parental care from cheated males constrain promiscuity in this group. Our data indicate that females exert resistance over EPFs when the costs of infidelity are high and, conversely, that the rate of EPFs increases when selection on females to defend themselves against EPF attempts by males is weak and costs of infidelity are low.     

Micro CT-based multiscale elasticity of double-porous (pre-cracked) hydroxyapatite granules for regenerative medicine

Hundred micrometers-sized porous hydroxyapatite globules have proved as a successful tissue engineering strategy for bone defects in vivo, as was shown in studies on human mandibles. These granules need to provide enough porous space for bone ingrowth, while maintaining sufficient mechanical competence (stiffness and strength) in this highly load-bearing organ. This double challenge motivates us to scrutinize more deeply the micro- and nanomechanical characteristics of such globules, as to identify possible optimization routes. Therefore, we imaged such a (pre-cracked) granule in a microCT scanner, transformed the attenuation coefficients into voxel-specific nanoporosities, from which we determined, via polycrystal micromechanics, voxel-specific (heterogeneous) elastic properties. The importance of the latter and of the presence of one to several hundred micrometers-sized cracks for realistically estimating the load-carrying behavior of the globule under a typical two-point compressive loading (as in a "splitting" test) is shown through results of large-scale Finite Element analyses, in comparison to analytical results for a sphere loaded at its poles: Use of homogeneous instead of heterogeneous elastic properties would overestimate the structure's stiffness by 5% (when employing a micromechanics-based process as to attain homogeneous properties)-the cracks, in comparison, weaken the structure by one to two orders of magnitudes.     

Short‐term exposure to 50 Hz ELF‐EMF alters the cisplatin‐induced oxidative response in AT478 murine squamous cell carcinoma cells

The aim of this study was to assess the influence of cisplatin and an extremely low frequency electromagnetic field (ELF‐EMF) on antioxidant enzyme activity and the lipid peroxidation ratio, as well as the level of DNA damage and reactive oxygen species (ROS) production in AT478 carcinoma cells. Cells were cultured for 24 and 72 h in culture medium with cisplatin. Additionally, the cells were irradiated with 50 Hz/1 mT ELF‐EMF for 16 min using a solenoid as a source of the ELF‐EMF. The amount of ROS, superoxide dismutase (SOD) isoenzyme activity, glutathione peroxidase (GSH‐Px) activity, DNA damage, and malondialdehyde (MDA) levels were assessed. Cells that were exposed to cisplatin exhibited a significant increase in ROS and antioxidant enzyme activity. The addition of ELF‐EMF exposure to cisplatin treatment resulted in decreased ROS levels and antioxidant enzyme activity. A significant reduction in MDA concentrations was observed in all of the study groups, with the greatest decrease associated with treatment by both cisplatin and ELF‐EMF. Cisplatin induced the most severe DNA damage; however, when cells were also irradiated with ELF‐EMF, less DNA damage occurred. Exposure to ELF‐EMF alone resulted in an increase in DNA damage compared to control cells. ELF‐EMF lessened the effects of oxidative stress and DNA damage that were induced by cisplatin; however, ELF‐EMF alone was a mild oxidative stressor and DNA damage inducer. We speculate that ELF‐EMF exerts differential effects depending on the exogenous conditions. This information may be of value for appraising the pathophysiologic consequences of exposure to ELF‐EMF. Bioelectromagnetics 33:641–651, 2012. © 2012 Wiley Periodicals, Inc.     

Habitat selection of the Ortolan bunting Emberiza hortulana in Poland: predictions from large-scale habitat elements

The Ortolan bunting Emberiza hortulana was censused in Poland during the Common Breeding Birds Monitoring Project in 2003–2009. Data from 683 monitoring polygons, covering in total more than 0.23% of the country, were used in the analysis. Based on the data and environmental information gathered in GIS databases (Corine land cover “CLC2000 and 2006” database, digital elevation model “GTOPO30” dataset, “Wordclim” dataset, and NDVI dataset), we modeled a habitat- and spatial-related variation of the Ortolan bunting’s presence. Birds were recorded in 13.2% grid cells. The mean density was 0.5 individual/km². We modeled the spatial presence of birds using multivariate adaptive regression splines (MARS). Then models were cross-validated to check their consistency. The environment-use model shows that the Ortolan bunting prefers extensively cultivated farmland dominated by non-irrigated arable fields, small coniferous and mixed forests, complex cultivation patterns, and meadows. The preferred areas are located on lowlands in western and central parts of the country where the climate is the driest and warmest. Such a repeatable spatial pattern model of the population helped to create a predictive map of the Ortolan bunting’s presence in Poland. The general rule is that the probability gradient of its presence increases from the northeastern part of the country to the central and southwestern parts of Poland. Additionally, the Ortolan bunting avoids severe continental climate and regions with dense ground-level vegetation.