Selective inhibition of prostaglandin biosynthesis by gold salts and phenylbutazone

Gold salts and phenylbutazone selectively inhibit the synthesis of PGF_2α and PGE₂ respectively. Lowered production of one prostaglandin species is accompanied by an increased production of the other. Selective inhibition by these drugs was observed in the presence of adrenaline, reduced glutathione and copper sulphate under conditions when most anti-inflammatory compounds inhibited PGE₂ and PGF_2α syntheses equally. It is postulated that selective inhibitors may have a different mode of action and beneficial effects may be related to the endogenous ratio of PGE to PGF required for normal function.     

RAPID AXOPLASMIC TRANSPORT IN DYSTROPHIC MICE

Abstract— Rapid axoplasmic transport was studied in dystrophic mice of the 129/ReJ-dy strain. Proteins transported in vivo through α-motoneurons of the sciatic nerve were labeled by injections of [³H] or [³⁵S] amino acids into the ventral horn of the lumbar spinal cord. Following an 18 h incubation, axoplasmic transport was quantitated by summing the radioactivity in the 10 mm length of sciatic nerve proximal to a ligation. Although the amount of transported radioactivity was small, transport appeared depressed when adult dystrophic mice were compared to controls. Transport was also studied in the sensory fibers of the sciatic nerve under in vitro conditions, resulting in high levels of transported radioactivity. In this system transport was strongly depressed. The severity of the deficiency varied with age, being small in animals with early clinical signs and becoming maximal (80–90%) in animals over 60 days of age. Proteins transported by adult dy/dy and +/+ animals were compared by gel electrophoresis using double-label techniques. Transport of nearly all proteins was depressed in dy/dy mice, although the possibility exists that small differences occur. The data suggest that the dystrophic state produces a significant deficiency in rapid axoplasmic transport in both motor and sensory fibers, and may interfere with transport processes in all neurons. Since rapid axoplasmic transport has been associated with membranes, the data are consistent with a general alteration of cellular membranes in dystrophic animals.     

The evolution and ecology of multiple antipredator defences

Prey seldom rely on a single type of antipredator defence, often using multiple defences to avoid predation. In many cases, selection in different contexts may favour the evolution of multiple defences in a prey. However, a prey may use multiple defences to protect itself during a single predator encounter. Such “defence portfolios” that defend prey against a single instance of predation are distributed across and within successive stages of the predation sequence (encounter, detection, identification, approach (attack), subjugation and consumption). We contend that at present, our understanding of defence portfolio evolution is incomplete, and seen from the fragmentary perspective of specific sensory systems (e.g., visual) or specific types of defences (especially aposematism). In this review, we aim to build a comprehensive framework for conceptualizing the evolution of multiple prey defences, beginning with hypotheses for the evolution of multiple defences in general, and defence portfolios in particular. We then examine idealized models of resource trade-offs and functional interactions between traits, along with evidence supporting them. We find that defence portfolios are constrained by resource allocation to other aspects of life history, as well as functional incompatibilities between different defences. We also find that selection is likely to favour combinations of defences that have synergistic effects on predator behaviour and prey survival. Next, we examine specific aspects of prey ecology, genetics and development, and predator cognition that modify the predictions of current hypotheses or introduce competing hypotheses. We outline schema for gathering data on the distribution of prey defences across species and geography, determining how multiple defences are produced, and testing the proximate mechanisms by which multiple prey defences impact predator behaviour. Adopting these approaches will strengthen our understanding of multiple defensive strategies.     

A Method for Staining Nematode Secretions and Structures

Secretions from amphids, phasmids, and excretory system were stained by incubating nematodes in 0.1% coomassie brilliant blue G-250 in 40% aqueous methanol containing 10% acetic acid on slides with coverslips sealed with nail polish or Zut. Nematodes incubated in this staining solution usually produced copious amounts of secretions from their amphids and excretory pore. Phasmids also stained dark blue, enabling them to be easily observed. Other biological dyes stained these secretions or were useful for differentiating specific morphological features of nematodes.     

Development of accelerated net nitrate uptake : effects of nitrate concentration and exposure time

Upon initial nitrate exposure, net nitrate uptake rates in roots of a wide variety of plants accelerate within 6 to 8 hours to substantially greater rates. Effects of solution nitrate concentrations and short pulses of nitrate (≤1 hour) upon `nitrate-induced' acceleration of nitrate uptake in maize (Zea mays L.) were determined. Root cultures of dark-grown seedlings, grown without nitrate, were exposed to 250 micromolar nitrate for 0.25 to 1 hour or to various solution nitrate concentrations (10-250 micromolar) for 1 hour before returning them to a nitrate-free solution. Net nitrate uptake rates were assayed at various periods following nitrate exposure and compared to rates of roots grown either in the absence of nitrate (CaSO₄-grown) or with continuous nitrate for at least 20 hours. Three hours after initial nitrate exposure, nitrate pulse treatments increased nitrate uptake rates three- to four-fold compared to the rates of CaSO₄-grown roots. When cycloheximide (5 micrograms per milliliter) was included during a 1-hour pulse with 250 micromolar nitrate, development of the accelerated nitrate uptake state was delayed. Otherwise, nitrate uptake rates reached maximum values within 6 hours before declining. Maximum rates, however, were significantly less than those of roots exposed continuously for 20, 32, or 44 hours. Pulsing for only 0.25 hour with 250 micromolar nitrate and for 1 hour with 10 micromolar caused acceleration of nitrate uptake, but the rates attained were either less than or not sustained for a duration comparable to those of roots pulsed for 1 hour with 250 micromolar nitrate. These results indicate that substantial development of the nitrate-induced accelerated nitrate uptake state can be achieved by small endogenous accumulations of nitrate, which appear to moderate the activity or level of root nitrate uptake.     

Discovery of morpholine-based aryl sulfonamides as Nav1.7 inhibitors

Replacement of the piperidine ring in the lead benzenesulfonamide Na_v1.7 inhibitor 1 with a weakly basic morpholine core resulted in a significant reduction in Na_v1.7 inhibitory activity, but the activity was restored by shortening the linkage from methyleneoxy to oxygen. These efforts led to a series of morpholine-based aryl sulfonamides as isoform-selective Na_v1.7 inhibitors. This report describes the synthesis and SAR of these analogs.     

Molecular evolution of mitochondrial 12S RNA and cytochrome b sequences in the pantherine lineage of Felidae

DNA sequence comparisons of two mitochondrial DNA genes were used to infer phylogenetic relationships among 17 Felidae species, notably 15 in the previously described pantherine lineage. The polymerase chain reaction (PCR) was used to generate sequences of 358 base pairs of the mitochondrial 12S RNA gene and 289 base pairs of the cytochrome b protein coding gene. DNA sequences were compared within and between 17 felid and five nonfelid carnivore species. Evolutionary trees were constructed using phenetic, cladistic, and maximum likelihood algorithms. The combined results suggested several phylogenetic relationships including (1) the recognition of a recently evolved monophyletic genus Panthera consisting of Panthera leo, P. pardus, P. onca, P. uncia, P. tigris, and Neofelis nebulosa; (2) the recent common ancestry of Acinonyx jubatus, the African cheetah, and Puma concolor, the American puma; and (3) two golden cat species, Profelis temmincki and Profelis aurata, are not sister species, and the latter is strongly associated with Caracal caracal. These data add to the growing database of vertebrate mtDNA sequences and, given the relatively recent divergence among the felids represented here (1-10 Myr), allow 12S and cytochrome b sequence evolution to be addressed over a time scale different from those addressed in most work on vertebrate mtDNA.