Synthesis and anti-inflammatory activity of a series of N-substituted naproxen glycolamides: nitric oxide-donor naproxen prodrugs

A series of glycolamide naproxen prodrugs containing a nitrate group as a nitric oxide (NO) donor moiety has been synthesized. These compounds were evaluated for their anti-inflammatory activity, naproxen release, and gastric tolerance. Compounds 4a, 4b, 5a, 5b, 7b, and 7c exhibited anti-inflammatory activity equivalent to that of the parent NSAID, naproxen-Na, in the rat carrageenan paw edema model. At equimolar doses relative to naproxen-Na, the NO-donor glycolamide derivatives 4a, 4b, 5a, 5b, 7b, and 7c were gastro-sparing in the rat. Naproxen formation from these NO-donor glycolamides varied among the structures examined, with the N-substituent on the amide group having a particular influence, and demonstrated their prodrug nature. Compound 7b was selected for exemplary demonstration that the glycolamide nitrates can be bioactivated to release NO. These data open the possibility that naproxen glycolamide nitrates may represent a safer alternative to naproxen as anti-inflammatory medicines.     

The effect of mycorrhizal infection of Abutilon theophrasti on competitiveness of offspring

1. Our goal was to determine whether mycorrhizal infection of one generation of plants could influence the competitiveness of the subsequent generation.
2. We grew the offspring of mycorrhizal (M) and non-mycorrhizal (NM) Abutilon theophrasti plants together in dense populations in large boxes in a greenhouse.
3. Offspring of M plants were larger than offspring of NM plants. As the experiment progressed, the difference in size was magnified and self-thinning occurred.
4. Compared with offspring of NM plants, offspring of M plants had a twofold greater survival and collectively produced a total of nearly four times as many seeds.
5. We conclude that mycorrhizal infection of the parent generation can increase the competitive ability of the offspring.     

Evolution of base composition in the insulin and insulin-like growth factor genes

The genomes of homeothermic (warm-blooded) vertebrates are mosaic interspersions of homogeneously GC-rich and GC-poor regions (isochores). Evolution of genome compartmentalization and GC-rich isochores is hypothesized to reflect either selective advantages of an elevated GC content or chromosome location and mutational pressure associated with the timing of DNA replication in germ cells. To address the present controversy regarding the origins and maintenance of isochores in homeothermic vertebrates, newly obtained as well as published nucleotide sequences of the insulin and insulin-like growth factor (IGF) genes, members of a well-characterized gene family believed to have evolved by repeated duplication and divergence, were utilized to examine the evolution of base composition in nonconstrained (flanking) and weakly constrained (introns and fourfold degenerate sites) regions. A phylogeny derived from amino acid sequences supports a common evolutionary history for the insulin/IGF family genes. In cold- blooded vertebrates, insulin and the IGFs were similar in base composition. In contrast, insulin and IGF-II demonstrate dramatic increases in GC richness in mammals, but no such trend occurred in IGF- I. Base composition of the coding portions of the insulin and IGF genes across vertebrates correlated (r = 0.90) with that of the introns and flanking regions. The GC content of homologous introns differed dramatically between insulin/IGF-II and IGF-I genes in mammals but was similar to the GC level of noncoding regions in neighboring genes. Our findings suggest that the base composition of introns and flanking regions is determined by chromosomal location and the mutational pressure of the isochore in which the sequences are embedded. An elevated GC content at codon third positions in the insulin and the IGF genes may reflect selective constraints on the usage of synonymous codons.      

Regulation of constitutive p50/c-Rel activity via proteasome inhibitor-resistant IkappaBalpha degradation in B cells

Constitutive NF-kappaB activity has emerged as an important cell survival component of physiological and pathological processes, including B-cell development. In B cells, constitutive NF-kappaB activity includes p50/c-Rel and p52/RelB heterodimers, both of which are critical for proper B-cell development. We previously reported that WEHI-231 B cells maintain constitutive p50/c-Rel activity via selective degradation of IkappaBalpha that is mediated by a proteasome inhibitor-resistant, now termed PIR, pathway. Here, we examined the mechanisms of PIR degradation by comparing it to the canonical pathway that involves IkappaB kinase-dependent phosphorylation and beta-TrCP-dependent ubiquitylation of the N-terminal signal response domain of IkappaBalpha. We found a distinct consensus sequence within this domain of IkappaBalpha for PIR degradation. Chimeric analyses of IkappaBalpha and IkappaBbeta further revealed that the ankyrin repeats of IkappaBalpha, but not IkappaBbeta, contained information necessary for PIR degradation, thereby explaining IkappaBalpha selectivity for the PIR pathway. Moreover, we found that PIR degradation of IkappaBalpha and constitutive p50/c-Rel activity in primary murine B cells were maintained in a manner different from B-cell-activating-factor-dependent p52/RelB regulation. Thus, our findings suggest that nonconventional PIR degradation of IkappaBalpha may play a physiological role in the development of B cells in vivo.     

Localisation of the Vacuolar Proton Pump (V-H+-ATPase) and Carbonic Anhydrase II in the Human Eccrine Sweat Gland

The localisation of the vacuolar proton pump (V-H+ -ATPase) and the enzyme carbonic anhydrase II (CAII) was investigated in the human eccrine sweat gland employing standard immunohistochemical techniques after antigen retrieval using microwave heat treatment and high pressure. The high-pressure antigen retrieval unmasked the presence of V-H+ -ATPase in the clear cells of the secretory coil, with a distribution similar to that previously observed for CAII. However, the dark cells were unreactive to both antibodies. In addition, heat and high-pressure antigen retrieval demonstrated the presence of CAII in the apical zone of luminal cells of the reabsorptive duct, a location not previously reported. The localisation of V-H+ -ATPase and CAII in the secretory coil clear cells suggests that the formation of HCO3- and H+ by carbonic anhydrase II and the transport of H+ by V-H+ -ATPase may play an role in sweat fluid secretion. Their presence at the apex of the duct cells indicates involvement in ductal ion reabsorption.     

Versatile and open software for comparing large genomes

The newest version of MUMmer easily handles comparisons of large eukaryotic genomes at varying evolutionary distances, as demonstrated by applications to multiple genomes. Two new graphical viewing tools provide alternative ways to analyze genome alignments. The new system is the first version of MUMmer to be released as open-source software. This allows other developers to contribute to the code base and freely redistribute the code. The MUMmer sources are available at .     

Osmotic Balance in a Marine Pulmonate,Amphibola crenata

The pulmonate mud‐snail Amphibola crenata is an osmoconformer in 25%‐125% sea water, its haemolymph being slightly hyperosmotic and hyperionic to the medium. It maintains its haemolymph markedly hyperosmotic in media below 25% sea water and in freshwater, in which it survives for a week or longer. On exposure to dilute or concentrated media, water which enters or leaves the tissues preferentially enters or leaves the cells. Regulation of cell volume towards initial values is accomplished within 5 days. Measurements of changes in cell volume, and of distribution of tissue water between the intracellular and extracellular compartments, in snails moved from 100% sea water into dilute or concentrated media, and in snails moved back to 100% sea water, indicate that mechanisms of cell volume regulation are minimal in ca 60–65% sea water. Changes in the concentration of tissue free amino acids are in accord with current theories of mechanisms of isosmotic intracellular regulation. The results are discussed in the light of the taxonomic, evolutionary and ecological status of Amphibola as a shore‐living, primitive, marine representative of a predominantly terrestrial and freshwater group of gastropod molluscs.     

The use of aeration as a simple and environmentally sound means to prevent biofouling

Biofouling is a major problem faced by marine industries. Physical and chemical treatments are available to control fouling, but most are costly, time consuming or negatively affect the environment. The use of aeration (ie continuous streams of air bubbles) to prevent fouling was examined. Experiments were conducted at three sites with different benthic communities. Experimental panels (10 cm × 10 cm; PVC and concrete) were deployed with or without aeration. Aeration flowed continuously from spigots 0.5 m below the panels at a rate of ～3.3 to 5.0 l min^?1. After 1 and 4 weeks, aerated PVC panels from all sites had significantly less fouling than non-aerated controls. Aeration reduced fouling on both the PVC and concrete surfaces. Fouling was reduced on panels directly in bubble streams while panels 30 cm and 5 m away had significantly more fouling. Thus, under the conditions used in this study, aeration appears to be an effective and simple way to prevent fouling.     

HABITAT ACOUSTICS OF A NEOTROPICAL LOWLAND RAINFOREST

ABSTRACT

The acoustic characteristics of an Amazonian lowland rain forest study site in southern Venezuela was analysed to determine environmental constraints upon acoustic communication. Signal degradation was measured by conducting transmission experiments at different heights above ground level. Measurements of ambient noise served to determine possible communication distances for various times of day, heights above ground level and frequencies. “Sound windows” for acoustic long-range communication were found for low frequencies, calling heights in the midstorey and calling in the morning or during the night. Sound attenuation was affected by height and frequency but not by time of day. Background noise varied remarkably with time of day and frequency and had a greater impact on communication distance than signal attenuation.