Thyroid hormone-responsive elements of the prolactin gene: evidence for both positive and negative regulation

To analyze the regulation of PRL gene expression by thyroid hormone (T3), fusion gene constructs containing various lengths of the rat PRL gene 5'-flanking sequence linked to the bacterial chloramphenicol acetyltransferase (CAT) gene were transfected into the GH3 cell line. Thyroid hormone had no effect on basal or cAMP-stimulated CAT expression in constructs containing more than 1.7 kilobasepairs of the 5'-sequence. However, deletion to 1.5 or 0.6 kilobasepairs resulted in an inhibition of both basal and cAMP-stimulated expression by T3. A construct containing the proximal enhancer region (positions -292 to -38 basepairs) linked to the herpes simplex thymidine kinase promoter (TK) and the CAT reporter gene also responded to T3 with inhibition of basal and cAMP-induced CAT expression. The distal enhancer region (positions -1714 to -1495) linked to thymidine kinase promoter CAT responded to T3 with a stimulation of CAT expression, and the response was additive with the stimulatory response to cAMP. Deletion analysis of the distal enhancer region revealed that the sequence between positions -1530 and -1565 was required for the stimulatory response to T3. The stimulatory response to T3 was additive with the response to estradiol, suggesting distinct elements, but deletion to position -1565 abolished the response to estradiol and permitted an inhibitory response to T3. Mutation of the estrogen response element prevents the response to estradiol, but only blunted the response to T3. Mutation of the sequence GGTCA at positions -1555 to -1551 resulted in an inhibitory response to T3, implicating this sequence in the stimulatory response.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fas modulates both positive and negative selection of thymocytes.

We studied the functional role of Fas (CD95) in thymic T cell development using the TCR transgenic mice homozygous for the lpr mutation, DO10 lpr/lpr mice. In DO10 lpr/lpr mice, the differentiation of CD4(+)CD8(+) double-positive (DP) thymocytes to CD4(+) single-positive (SP) thymocytes was markedly impaired, as indicated by decreased generation of CD4(+) SP thymocytes and reduced ratio of CD4(+) SP thymocytes to DP thymocytes in lpr/lpr mice compared with those of +/+ mice. Activation of DP thymocytes in the process of positive selection was also significantly inhibited in DO10 lpr/lpr mice, as shown by the lower levels of CD69 expression on DP thymocytes in lpr/lpr mice compared to +/+ mice. Furthermore, the deletion of DP thymocytes induced by in vivo administration of OVA peptide (up to 150 micrograms) and anti-TCR clonotype mAb did not occur in DO10 lpr/lpr mice, whereas these treatments significantly decreased DP thymocytes in DO10 +/+ mice. On the other hand, no significant difference in DO10 transgenic TCR expression on DP thymocytes was found between DO10 lpr/lpr and +/+ mice. Together, these results indicate that Fas is importantly involved in both positive and negative selection of thymocytes.     

Biodiversity vs. biocontrol: positive and negative effects of alternative prey on control of slugs by carabid beetles

Environment-friendly farming techniques seek to increase invertebrate biodiversity in part with the intention of encouraging greater numbers of predators that will help to control crop pests. However, in theory, this effect may be negated if the availability of a greater abundance and diversity of alternative prey diverts predators away from feeding on pests. The hypothesis that access to alternative prey can lead to reduced pest suppression under semi-field conditions was tested. Alternative prey type and diversity were manipulated in 70 mesocosms over 7+ weeks in the presence of the carabid Pterostichus melanarius (Illiger), a known predator of slugs, and reproducing populations of the slug Deroceras reticulatum (Müller). Significantly fewer slugs survived where no alternative prey were provided. Maximum slug numbers and biomass were found in treatments containing either carabids plus a high diversity of alternative prey (many species of earthworm and three of Diptera larvae) or a single additional prey (blowfly larvae, Calliphora vomitoria Linnaeus). In these treatments slug numbers and biomass were as high as in plots lacking predators. The effects of alternative prey were taxon-specific. Alternative prey strongly affected carabid fitness in terms of biomass and egg load. The fittest predators (those with access to high alternative prey diversity or C. vomitoria larvae) reduced slug numbers the least. The mean individual slug weights were greater in treatments with alternative prey than where no alternative prey were provided to the carabids. These results suggest that pests may survive and reproduce more rapidly in patches where predators have access to alternative prey.     

TGF-beta signaling: positive and negative effects on tumorigenesis.

TGF-beta binding to the cell surface triggers activation of multiple signal transduction pathways that are connected in intricate ways with each other, and with other response networks involved in sensing cellular information input. Recent data indicate that changes in signal intensity and connectivity of these pathways may underlie the complex transition of the TGF-beta pathway from tumor suppressor to oncogene during tumorigenesis.     

Interspecific interactions between feral pigs and native birds reveal both positive and negative effects

In tropical Australian rainforests, predators and scavengers aggregate beneath emergent trees that house large colonies of metallic starlings (Aplonis metallica), feeding in the nutrient‐rich open areas below. Analysis of camera‐trap records shows that the presence of feral pigs (Sus scrofa) is associated with an absence of birds (cockatoos and brush turkeys), presumably reflecting behavioural avoidance (pigs pose a direct danger to birds). However, bird numbers increase as soon as pigs depart, then fall if pigs are absent for long periods. Feral pigs thus displace native birds from these resource hotspots; but by turning over the soil and enhancing the birds' access to food, the pigs also have a positive impact on food availability for the avifauna. Thus, although invasive species have caused irreparable environmental damages worldwide, they may also provide positive benefits for certain species. The net benefit of such interspecific interactions will depend on the outcome of both positive and negative effects.     

Host plant nitrogen enrichment has both positive and negative effects on the larval growth of a specialist butterfly

1. The nitrogen limitation hypothesis posits that phytophagous insects benefit from nitrogen enrichment of their host plants through a reduction of the concentration of toxic compounds and an increase of free amino acids and proteins. However, species' response to nitrogen enrichment varies substantially and high nitrogen levels are associated with population decline, suggesting there are major costs to feeding on nitrogen‐rich host plants. 2. To test the hypothesis that larval growth performance is maximal at intermediate nitrogen enrichment, nitrogen levels were measured in 18 populations of the host plant of Lycaena helle, a specialist butterfly inhabiting nutrient‐poor wet meadows. The nitrogen content of host plants was then modified to mirror average natural nitrogen levels (C), highest field‐recorded levels (T1), and levels higher than those observed across our study populations (T2). 3. Caterpillars fed with T1 leaves had a greater maximum body mass than caterpillars of the C group because of their improved food assimilation during the early stages of their development. Caterpillars of C and T2 groups had similar growth patterns but high nitrogen content had detrimental effects, as caterpillars fed with T2 leaves had a slower ingestion rate than C and T1 groups. 4. Quantifying the fitness consequences of these changes in growth performance is necessary to fully understand the implications of nitrogen enrichment for L. helle (rapid growth may result in fitness costs). However, conservation plans for this emblematic glacial relict species should also consider the preservation of its host plant quality to ensure its persistence.     

Similarities and differences of the alpha and beta components of tropomyosin.

Rabbit skeletal tropomyosin was separated into two components, alpha and beta, by CM cellulose column chromatography in the presence of urea. The two components are apparently different from TN-T, since, 1) upon addition of the components to F-actin solutions, they increase the degree of flow birefringence delta n, while TN-T does not, 2) the reduced mean residue elipticities [theta] at 220 nm are about 2.5-fold higher than for TN-T, and they contain no proline. These features are similar to those of intact tropomyosin, but the two components are not identical for the following reasons; 1) leucine is the C-terminus of the beta component and isoleucine is the C-terminus of the alpha component, 2) the beta component has a lower helicity and a somewhate lower capacity to increase delta n of F-actin solutions than the alpha component, and 3) the beta component has a higher content of glutamic acid and methionine than the alpha component. The two components can be crystallized into paracrystals in the presence of magnesium. Electron micrographs of the paracrystals of both components show a band pattern with 400 A periodicity. Bovine cardiac tropomyosin migrates on SDS gels as two poorly resolved bands, which could be separated by CM cellulose column chromatography. The C-terminus of the slower moving component was leucine, and that of the faster moving component was isoleucine, corresponding to the beta and alpha components of skeletal tropomyosin.