A New Record of Deepwater Sculpin, Myoxocephalus thompsonii, in Northeastern Alberta

We present the first documented records of Deepwater Sculpin, Myoxocephalus thompsonii, from northern Alberta, and the second record for the province. Three specimens of Deepwater Sculpin were taken in gill nets set at 17 to 20 m depth in Colin Lake, Alberta, on 15 September 2001. Colin Lake, located in the Canadian Shield region of northeastern Alberta about 125 km northeast of Fort Chipewyan, drains into Lake Athabasca via the Colin River. The only other known Alberta population of Deepwater Sculpin inhabits Upper Waterton Lake in the southwestern corner of the province. This record is approximately 300 km SSE of the nearest verified record in the Northwest Territories and 400 km NW of the nearest verified record in Saskatchewan

The chaotic solar cycle II. Analysis of cosmogenic 10Be data

Context. The variations of solar activity over long time intervals using a solar activity reconstruction based on the cosmogenic radionuclide 10Be measured in polar ice cores are studied. Methods. By applying methods of nonlinear dynamics, the solar activity cycle is studied using solar activity proxies that have been reaching into the past for over 9300 years. The complexity of the system is expressed by several parameters of nonlinear dynamics, such as embedding dimension or false nearest neighbors, and the method of delay coordinates is applied to the time series. We also fit a damped random walk model, which accurately describes the variability of quasars, to the solar 10Be data and investigate the corresponding power spectral distribution. The periods in the data series were searched by the Fourier and wavelet analyses. The solar activity on the long-term scale is found to be on the edge of chaotic behavior. This can explain the observed intermittent period of longer lasting solar activity minima. Filtering the data by eliminating variations below a certain period (the periods of 380 yr and 57 yr were used) yields a far more regular behavior of solar activity. A comparison between the results for the 10Be data with the 14C data shows many similarities. Both cosmogenic isotopes are strongly correlated mutually and with solar activity. Finally, we find that a series of damped random walk models provides a good fit to the 10Be data with a fixed characteristic time scale of 1000 years, which is roughly consistent with the quasi-periods found by the Fourier and wavelet analyses.Comment: 8 pages, 11 figure

Geology and ground-water resources of Cerro Gordo County, Iowa

https://ir.uiowa.edu/igs_wsb/1008/thumbnail.jp

Estimating Kinetic Parameters for the Spontaneous Polymerization of Glycidol at Elevated Temperatures

The ring-opening polymerization of glycidol at elevated temperatures is investigated. To improve the synthesis of dendritic polyether polyols, experiments are carried out without initiator to identify the influence of thermal side reactions. This results in a step-growth polymerization caused by the spontaneous combination of monomers. Kinetic parameters of the side reactions are estimated by fitting simulated number- and weight-average molecular weights to the experimental values measured at different reaction times during the polymerization. The reactions are conducted at three different temperatures of 90, 105, and 120 8C. It is shown that thermal side reactions lead to high dispersities of the final product and are highly sensitive to the reactor operating temperature

2-(4-(Biphenyl-4-ylamino)-6-chloropyrimidin-2-ylthio)octanoic acid (HZ52) - a novel type 5-lipoxygenase inhibitor with favorable molecular pharmacology and efficacy in vivo.

BACKGROUND AND PURPOSE: 5-Lipoxygenase (5-LO) is the key enzyme in the biosynthesis of pro-inflammatory leukotrienes (LTs) representing a potential target for pharmacological intervention with inflammation and allergic disorders. Although many LT synthesis inhibitors are effective in simple in vitro test systems, they frequently fail in vivo due to lack of efficacy. Here, we attempted to assess the pharmacological potential of the previously identified 5-LO inhibitor 2-(4-(biphenyl-4-ylamino)-6-chloropyrimidin-2-ylthio)octanoic acid (HZ52). EXPERIMENTAL APPROACH: We evaluated the efficacy of HZ52 in vivo using carrageenan-induced pleurisy in rats and platelet-activating factor (PAF)-induced lethal shock in mice. We also characterized 5-LO inhibition by HZ52 at the cellular and molecular level in comparison with other types of 5-LO inhibitor, that is, BWA4C, ZM230487 and hyperforin. KEY RESULTS: HZ52, 1.5 mg·kg⁻¹ i.p., prevented carrageenan-induced pleurisy accompanied by reduced LTB(4) levels and protected mice (10 mg·kg⁻¹, i.p.) against PAF-induced shock. Detailed analysis in cell-based and cell-free assays revealed that inhibition of 5-LO by HZ52 (i) does not depend on radical scavenging properties and is reversible; (ii) is not impaired by an increased peroxide tone or by elevated substrate concentrations; and (iii) is little affected by the cell stimulus or by phospholipids, glycerides, membranes or Ca²⁺. CONCLUSIONS AND IMPLICATIONS: HZ52 is a promising new type of 5-LO inhibitor with efficacy in vivo and with a favourable pharmacological profile. It possesses a unique 5-LO inhibitory mechanism different from classical 5-LO inhibitors and seemingly lacks the typical disadvantages of former classes of LT synthesis blockers

Iron-dependent trafficking of 5-lipoxygenase and impact on human macrophage activation

5-lipoxygenase (5-LOX) is a non-heme iron-containing dioxygenase expressed in immune cells that catalyzes the two initial steps in the biosynthesis of leukotrienes. It is well known that 5-LOX activation in innate immunity cells is related to different iron-associated proinflammatory disorders, including cancer, neurodegenerative diseases, and atherosclerosis. However, the molecular and cellular mechanism(s) underlying the interplay between iron and 5-LOX activation are largely unexplored. In this study, we investigated whether iron (in the form of Fe3+ and hemin) might modulate 5-LOX influencing its membrane binding, subcellular distribution, and functional activity. We proved by fluorescence resonance energy transfer approach that metal removal from the recombinant human 5-LOX, not only altered the catalytic activity of the enzyme, but also impaired its membrane-binding. To ascertain whether iron can modulate the subcellular distribution of 5-LOX in immune cells, we exposed THP-1 macrophages and human primary macrophages to exogenous iron. Cells exposed to increasing amounts of Fe3+ showed a redistribution (ranging from ~45 to 75%) of the cytosolic 5-LOX to the nuclear fraction. Accordingly, confocal microscopy revealed that acute exposure to extracellular Fe3+, as well as hemin, caused an overt increase in the nuclear fluorescence of 5-LOX, accompanied by a co-localization with the 5-LOX activating protein (FLAP) both in THP-1 macrophages and human macrophages. The functional relevance of iron overloading was demonstrated by a marked induction of the expression of interleukin-6 in iron-treated macrophages. Importantly, pre-treatment of cells with the iron-chelating agent deferoxamine completely abolished the hemin-dependent translocation of 5-LOX to the nuclear fraction, and significantly reverted its effect on interleukin-6 overexpression. These results suggest that exogenous iron modulates the biological activity of 5-LOX in macrophages by increasing its ability to bind to nuclear membranes, further supporting a role for iron in inflammation-based diseases where its homeostasis is altered and suggesting further evidence of risks related to iron overload

CD69 is a TGF-β/1α,25-dihydroxyvitamin D3 target gene in monocytes

CD69 is a transmembrane lectin that can be expressed on most hematopoietic cells. In monocytes, it has been functionally linked to the 5-lipoxygenase pathway in which the leukotrienes, a class of highly potent inflammatory mediators, are produced. However, regarding CD69 gene expression and its regulatory mechanisms in monocytes, only scarce data are available. Here, we report that CD69 mRNA expression, analogous to that of 5-lipoxygenase, is induced by the physiologic stimuli transforming growth factor-β (TGF-β) and 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) in monocytic cells. Comparison with T- and B-cell lines showed that the effect was specific for monocytes. CD69 expression levels were increased in a concentration-dependent manner, and kinetic analysis revealed a rapid onset of mRNA expression, indicating that CD69 is a primary TGF-β/1α,25(OH)2D3 target gene. PCR analysis of different regions of the CD69 mRNA revealed that de novo transcription was initiated and proximal and distal parts were induced concomitantly. In common with 5-lipoxygenase, no activation of 0.7 kb or ~2.3 kb promoter fragments by TGF-β and 1α,25(OH)2D3 could be observed in transient reporter assays for CD69. Analysis of mRNA stability using a transcription inhibitor and a 3′UTR reporter construct showed that TGF-β and 1α,25(OH)2D3 do not influence CD69 mRNA stability. Functional knockdown of Smad3 clearly demonstrated that upregulation of CD69 mRNA, in contrast to 5-LO, depends on Smad3. Comparative studies with different inhibitors for mitogen activated protein kinases (MAPKs) revealed that MAPK signalling is involved in CD69 gene regulation, whereas 5-lipoxygenase gene expression was only partly affected. Mechanistically, we found evidence that CD69 gene upregulation depends on TAK1-mediated p38 activation. In summary, our data indicate that CD69 gene expression, conforming with 5-lipoxygenase, is regulated monocyte-specifically by the physiologic stimuli TGF-β and 1α,25(OH)2D3 on mRNA level, although different mechanisms account for the upregulation of each gene

The solar magnetic field since 1700: II. Physical reconstruction of total, polar and open flux

We have used semi-synthetic records of emerging sunspot groups based on sunspot number data as input for a surface flux transport model to reconstruct the evolution of the large-scale solar magnetic field and the open heliospheric flux from the year 1700 onward. The statistical properties of the semi-synthetic sunspot group records reflect those of the observed the Royal Greenwich Observatory photoheliographic results. These include correlations between the sunspot numbers and sunspot group latitudes, longitudes, areas and tilt angles. The reconstruction results for the total surface flux, the polar field, and the heliospheric open flux (determined by a current sheet source surface extrapolation) agree well with the available observational or empirically derived data and reconstructions. We confirm a significant positive correlation between the polar field during activity minimum periods and the strength of the subsequent sunspot cycle, which has implications for flux transport dynamo models for the solar cycle. Just prior to the Dalton minimum, at the end of the 18th century, a long cycle was followed by a weak cycle. We find that introducing a possibly `lost' cycle between 1793 and 1800 leads to a shift of the minimum of the open flux by 15 years which is inconsistent with the cosmogenic isotope record.Comment: A&A, accepte

Boosting Anti-Inflammatory Potency of Zafirlukast by Designed Polypharmacology

Multitarget design offers access to bioactive small molecules with potentially superior efficacy and safety. Particularly multifactorial chronic inflammatory diseases demand multiple pharmacological interventions for stable treatment. By minor structural changes, we have developed a close analogue of the cysteinyl-leukotriene receptor antagonist zafirlukast that simultaneously inhibits soluble epoxide hydrolase and activates peroxisome proliferator-activated receptor \u3b3. The triple modulator exhibits robust anti-inflammatory activity in vivo and highlights the therapeutic potential of designed multitarget agents

Estimating the frequency of extremely energetic solar events, based on solar, stellar, lunar, and terrestrial records

The most powerful explosions on the Sun [...] drive the most severe space-weather storms. Proxy records of flare energies based on SEPs in principle may offer the longest time base to study infrequent large events. We conclude that one suggested proxy, nitrate concentrations in polar ice cores, does not map reliably to SEP events. Concentrations of select radionuclides measured in natural archives may prove useful in extending the time interval of direct observations up to ten millennia, but as their calibration to solar flare fluences depends on multiple poorly known properties and processes, these proxies cannot presently be used to help determine the flare energy frequency distribution. Being thus limited to the use of direct flare observations, we evaluate the probabilities of large-energy solar explosions by combining solar flare observations with an ensemble of stellar flare observations. We conclude that solar flare energies form a relatively smooth distribution from small events to large flares, while flares on magnetically-active, young Sun-like stars have energies and frequencies markedly in excess of strong solar flares, even after an empirical scaling with the mean activity level of these stars. In order to empirically quantify the frequency of uncommonly large solar flares extensive surveys of stars of near-solar age need to be obtained, such as is feasible with the Kepler satellite. Because the likelihood of flares larger than approximately X30 remains empirically unconstrained, we present indirect arguments, based on records of sunspots and on statistical arguments, that solar flares in the past four centuries have likely not substantially exceeded the level of the largest flares observed in the space era, and that there is at most about a 10% chance of a flare larger than about X30 in the next 30 years.Comment: 14 pages, 3 figures (in press as of 2012/06/18); Journal of Geophysical Research (Space Physics), 201