Characterization of sodium transport in gustatory epithelia from the hamster and rat

The transduction of sodium salts occurs through a variety of mechanisms, including sodium influx through amiloride-sensitive sodium channels, anion-dependent sodium movement through intercellular junctions and unidentified amiloride-insensitive mechanisms. Characterizations of sodium transport in lingual epithelium mounted in Ussing chambers have focused almost exclusively on epithelia containing only fungiform taste buds. In the present study we have investigated sodium transport by measuring NaCl-induced short-circuit current from lingual epithelia containing fungiform, foliate, vallate and palatine taste buds in the hamster and the rat. All areas show measurable sodium transport, yet significant differences were noted between the epithelia from the rat and the hamster and among the different epithelia within a single species in terms of current density, transepithelial resistance and mucosal amiloride sensitivity. In general, epithelia from the anterior tongue were of a lower resistance and transported sodium more effectively than from the posterior tongue. Moreover, fungiform- and vallate-containing epithelia in the rat had a greater current density than did the corresponding tissues in the hamster. Amiloride sensitivity also differed between the rat and the hamster. In the hamster all gustatory areas showed some amiloride sensitivity, while in the rat the vallate-containing epithelia were devoid of amiloride- sensitive sodium transport. The results are consistent with the interpretation that all chemosensitive areas may participate in the detection of salts but the degree of salt transport and the mechanism of transport is variable among different lingual epithelia and different species.      

Array-based evolution of DNA aptamers allows modelling of an explicit sequence-fitness landscape

Mapping the landscape of possible macromolecular polymer sequences to their fitness in performing biological functions is a challenge across the biosciences. A paradigm is the case of aptamers, nucleic acids that can be selected to bind particular target molecules. We have characterized the sequence-fitness landscape for aptamers binding allophycocyanin (APC) protein via a novel Closed Loop Aptameric Directed Evolution (CLADE) approach. In contrast to the conventional SELEX methodology, selection and mutation of aptamer sequences was carried out in silico, with explicit fitness assays for 44 131 aptamers of known sequence using DNA microarrays in vitro. We capture the landscape using a predictive machine learning model linking sequence features and function and validate this model using 5500 entirely separate test sequences, which give a very high observed versus predicted correlation of 0.87. This approach reveals a complex sequence-fitness mapping, and hypotheses for the physical basis of aptameric binding; it also enables rapid design of novel aptamers with desired binding properties. We demonstrate an extension to the approach by incorporating prior knowledge into CLADE, resulting in some of the tightest binding sequences.     

Kin recognition by the predatory mite Iphiseius degenerans: discrimination among own, conspecific, and heterospecific eggs

1. Kin recognition is important in many social insects, but has also been found in several nonsocial insects such as parasitoids, where it plays an important role in oviposition behaviour. In nonparasitic arthropods, however, the fitness of ovipositing females also depends on the oviposition behaviour of related and unrelated females, especially when eggs are oviposited in clusters by several females. 2. In this paper, kin recognition in a predatory mite, Iphiseius degenerans, is studied. Mothers are capable of determining offspring sex ratio, and cannibalism on juvenile stages is a common phenomenon. Therefore, kin recognition is expected to occur in this predator. 3. Oviposition behaviour of this species is particularly interesting because it alternates foraging bouts in flowers with deposition of a single egg at a time on a leaf, where predation risk is lower. The eggs are not scattered but are deposited in clusters. After feeding in a flower, females therefore have to locate clusters of eggs. 4. Experiments on two‐choice arenas showed that females prefer to oviposit close to conspecific eggs rather than close to heterospecific eggs. Females also showed a preference for ovipositing near closely related conspecific eggs rather than more distantly related eggs. 5. Females tended to displace eggs of heterospecifics more frequently than eggs of conspecifics. 6. These behavioural observations show that females can discriminate not only between conspecific and heterospecific eggs but also between eggs that vary in degree of relatedness. This enables females to oviposit in clusters containing related eggs and thus avoid cannibalism by non‐kin and/or produce adaptive sex ratios despite the fact that the adults commute between flowers and leaves.     

Noncontact dipole effects on channel permeation. III. Anomalous proton conductance effects in gramicidin

Proton transport on water wires, of interest for many problems in membrane biology, is analyzed in side-chain analogs of gramicidin A channels. In symmetrical 0.1 N HCl solutions, fluorination of channel Trp(11), Trp-(13), or Trp(15) side chains is found to inhibit proton transport, and replacement of one or more Trps with Phe enhances proton transport, the opposite of the effects on K(+) transport in lecithin bilayers. The current-voltage relations are superlinear, indicating that some membrane field-dependent process is rate limiting. The interfacial dipole effects are usually assumed to affect the rate of cation translocation across the channel. For proton conductance, however, water reorientation after proton translocation is anticipated to be rate limiting. We propose that the findings reported here are most readily interpreted as the result of dipole-dipole interactions between channel waters and polar side chains or lipid headgroups. In particular, if reorientation of the water column begins with the water nearest the channel exit, this hypothesis explains the negative impact of fluorination and the positive impact of headgroup dipole on proton conductance.     

Polymorphic variants of the third component of complement in Graves' disease

We have examined electrophoretic variants of the third complement component (C3) in 294 controls and in 44 patients suffering from Graves' disease, drawn from the Avalon Peninsula of Newfoundland. Two common C3 variants, S and F, account for 99% of the gene frequencies. The S homozygote phenotype was observed in 170 controls and in 27 patients; 18 controls were found to be homozygous for the F allele (3 patients), and the FS phenotype was observed in 103 controls and 14 patients. The phenotypic frequencies did not differ significantly between controls and patients. It is concluded that C3 variants do not distinguish individuals who have Graves' disease.     

Polymorphonuclear leucocyte function in hypothyroidism.

The quantitative nitroblue-tetrazolium test demonstrated that polymorphonuclear leucocytes from patients with hypothyroidism reduced the dye less well than leucocytes from euthyroid persons. The ability of these cells to ingest and kill staphylococci were unimpaired. The abnormality of the nitroblue-tetrazolium test in hypothyroid patients was corrected after their treatment with thyroxine.     

Glycolytic, Pentose-Phosphate Shunt and Transaminase Enzymes in Gastrocnemius Muscle, Liver, Heart, and Brain of Two Mouse Mutants, 129 J-dy and A2G-adr, with Abnormal Muscle Function

Abstract: Aldolase and phosphoglycerate kinase activity were markedly reduced in muscle from two mouse mutants, 129 J-dy and A2G-adr, with abnormal muscle development. The pentose-phosphate shunt enzymes, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, were both greatly increased in the gastrocnemius of 129 J-dy mice, but only the former was slightly increased in A2G-adr muscle. Alanine and aspartate aminotransferase activities were normal or low in 129 J-dy muscle but increased to approximately 200% in A2G-adr muscle. Liver from 129 J-dy mice showed increased activity of glucose-6-phosphate dehydrogenase. These findings are compatible with the well-recognised lipid involvement in the 129 J-dy mutant but indicate that an abnormality of amino acid metabolism in relation to energy supply is probably more important in the A2G-adr mutant.