Variations in thymocyte susceptibility to clonal deletion during ontogeny. Implications for neonatal tolerance.

Activation of immature thymocytes via the TCR results in programmed cell death and clonal deletion. We have examined thymocytes from mice of different ages and observed that, whereas TCR-mediated signaling caused deletion of thymocytes from newborn and 3-week-old mice, it failed to delete thymocytes from mice of 1 week of age. This could not be attributed to differences in cell surface TCR expression, TCR-mediated phosphoinositide hydrolysis or Ca2+ mobilization, or total cellular levels of TCR zeta- and eta-chains. Moreover, thymocytes of all ages were equally susceptible to corticosteroid- and Ca2+ ionophore-induced programmed cell death. These data are consistent with the notion that fetal and neonatal thymocytes represent a relatively synchronous wave of cells passing through phases in which they are susceptible and then resistant to TCR-induced programmed cell death. They also support the notion that the classical phenomenon of neonatal tolerance is due to clonal deletion and that the inability of allogeneic cells to tolerize mice at 1 week of age is because the thymocytes are refractory to TCR-alpha beta-mediated clonal deletion.     

Past,present and future utilisation ofMyrica gale (Myricaceae)

The development ofM. gale oil as an insect repellent has created a requirement for cultivation of the plant. Botanical evidence indicates thatM. gale is likely to thrive on well—aerated acid peatland and could become a valuable crop on land of low agricultural value. Plant growth would be enhanced by the prevention of grazing and could be combined with softwood forestry since the trees would benefit from soil nitrogen enrichment thanks to the symbiotic association ofM. gale andFrankia. The economics of oil production would be improved if additional compounds of value such as pharmacologically active fiavonoids could be extracted from the by-products.     

LptB-LptF coupling mediates the closure of the substrate-binding cavity in the LptB2FGC transporter through a rigid-body mechanism to extract LPS

Lipopolysaccharides (LPS) are essential envelope components in many Gram-negative bacteria and provide intrinsic resistance to antibiotics. LPS molecules are synthesized in the inner membrane and then transported to the cell surface by the LPS transport (Lpt) machinery. In this system, the ATP-binding cassette (ABC) transporter LptB₂FGC extracts LPS from the inner membrane and places it onto a periplasmic protein bridge through a poorly understood mechanism. Here, we show that residue E86 of LptB is essential for coupling the function of this ATPase to that of its partners LptFG, specifically at the step where ATP binding drives the closure of the LptB dimer and the collapse of the LPS-binding cavity in LptFG that moves LPS to the Lpt periplasmic bridge. We also show that defects caused by changing residue E86 are suppressed by mutations altering either LPS structure or transmembrane helices in LptG. Furthermore, these suppressors also fix defects in the coupling helix of LptF, but not of LptG. Together, these results support a transport mechanism in which the ATP-driven movements of LptB and those of the substrate-binding cavity in LptFG are bi-directionally coordinated through the rigid-body coupling, with LptF’s coupling helix being important in coordinating cavity collapse with LptB dimerization.     

Rous sarcoma virus direct repeat cis elements exert effects at several points in the virus life cycle.

Two approximately 135-nucleotide (nt) direct repeats flank the Rous sarcoma virus (RSV) oncogene src and are composed of two smaller repeats, dr1 (approximately 100 nt) and dr2 (approximately 36 nt). These sequences have been reported to contain cis-acting signals necessary for RNA packaging and elements that allow cytoplasmic accumulation of unspliced RNA (cytoplasmic transport elements). In this report, we show that avian fibroblasts infected with the Prague A strain of RSV with precise deletions of both dr1 elements express src and are transformed by this mutant virus but production of virus particles is very low and virus spread throughout the culture requires several weeks. We show that the replication defect is due to complex effects on viral RNA transport, viral RNA half-life, and virus particle assembly. The dr1 elements may contain binding sites for a permissive cell-specific factor(s) that facilitates efficient nuclear-cytoplasmic transport, RNA stability, and cytoplasmic utilization of unspliced viral RNA. The implications of these results for understanding the defects of nonpermissive virus infections in mammalian cells are discussed.     

Central receptor sites for angiotensin-induced drinking: a critical review.

A review of proposed sites of the dipsogenic action of angiotensin II is presented. Techniques used for such localization are critically discussed, and it is suggested that convergence of evidence from several different experimental techniques is required for localization of dipsogenic receptors. Loci suggested as such sites of action include the preoptic regions, the subfornical organ, and the tissue proximal to the optic recess of the third ventricle, including the organum vasculosum laminae terminalis. Current evidence suggests that there are at least two loci within the forebrain that possess dipsogenic receptors for angiotensin II.     

The physiological basis of seed dormancy in Avena fatua. VIII. Action of malonic acid

Adkins, S. W., Symons, S. J. and Simpson, G. M. 1988. The physiological basis of seed dormancy in Avena fatua . VIII. Action of malonic acid - Physiol. Plant, 72: 477–482.
A low concentration of malonic acid (50 m M ) induced germination in four genetically pure dormant lines of Avena fatua L. Sensitivity to this treatment was poor immediately after harvest but increased markedly during after-ripening, indicating that the mode of action of malonic acid (50 m M ) was similar to that of another organic acid, citric acid. Over the concentration range (10–50 m M ) where malonic acid promoted germination, oxygen uptake was also stimulated, and this was before the first visible signs of germination. At higher concentrations (100–300 m M ) where there was no promotion of germination, malonic acid strongly inhibited oxygen uptake. These results show that malonic acid has a dual effect on oxygen uptake and subsequent germination. Low concentrations (10–50 m M ) act by stimulating the Krebs cycle and germination through an acidification reaction like citric acid, and high concentrations (100–300 m M ) act by inhibiting germination through enzymatic restraint of the Krebs cycle.
The stimulation of both oxygen uptake and germination by three established germination promoters (sodium nitrate, citric acid and ethanol) was inhibited by a high concentration of malonic acid (200 m M ) but unaffected by a low concentration (50 m M ). These results show that oxygen uptake, and hence the activity of the Krebs cycle, are important processes involved in the dormancy breaking mechanism of these three promotors.