Postembryonic brain development in the monarch butterfly,Danaus plexippus plexippus L.

Development Genes and Evolution -     

Sodium Content of Community Water Supplies in California

The amount of sodium ion in water used for ingestion may be critical in effective use of a low sodium dietary regimen. Waters containing not over 20 mg of sodium per liter are provided for in the sodium restricted diets set forth by the American Heart Association. For diets containing more than 500 mg of sodium a day, waters of greater sodium content may be used if proper dietary adjustments are made.While assessment of the long-term average sodium content of a community water supply is difficult, the determined values for sodium lend to classification within range categories. The larger community water supplies in California are presented within several range categories of sodium content.The more commonly used water softeners add sodium to water. The sodium-restricted patient should be cautioned against their use. Similar consideration should probably be given to water supplies of retirement communities where the potential for disorders requiring sodium restriction is greater than in the general population.     

On the site of action of phosphatide acyl-hydrolase activity of rat brain homogenates on lecithin

The hydrolysis of 2- [14C]acyl-labelled and [Me-3H]choline-labelled lecithins by rat brain homogenates has been studied. The acyl-labelled substrate was hydrolysed with the production of both radioactive lysolecithin and radioactive free fatty acid in the proportions of 60 per cent and 40 per cent; traces of labelled mono- and diglyceride were also formed. In addition to radioactive lysolecithin the [3H]choline-labelled lecithin also gave rise to much smaller amounts of radioactive water soluble derivatives, consisting almost entirely of free choline and phosphorylcholine with only traces of glycerylphosphorylcholine. The results provide evidence for the production of a mixture of 1- and 2-acyl isomers of lysolecithin by phospholipase action in brain homogenates at pH 7.4, the latter predominating slightly.     

Phospholipase C activation in rat pituitary adenoma (GH) cells

The presence of the pertussis toxin (PTX) insensitive GTP-binding proteins (G-proteins) G_q and/or G₁₁ has been demonstrated in three different prolactin (PRL) and growth hormone (GH) producing pituitary adenoma cell lines. Immunoblocking of their coupling to hormone receptors indicates that G_q and/or G₁₁ confer throliberin (TRH) responsive phospholipase C (PL-C) activity in these cells. The contention was substantiated by immunoprecipitation analyses snowing that anti G_q/11-sera coprecipitated PL-C activity. In essence, only G_q/11 (but neither G_i2, G_i3 nor G_o) seems to mediate the TRH-sensitive PL-C activity, while G_o may be coupled to a basal or constitutive PL-C activity. Immunoblocking studies imply that the B-complex also, to some extent, may stimulate GH₃ pituitary cell line PL-C activity. Finally, the steady state levels of G_q/11 mRNA and protein were downregulated upon long term exposure of the GH3 cells to TRH (but not to vasoactive intestinal peptide = VIP).     

QUANTITATIVE GENETICS OF RESPONSE TO COMPETITORS IN NEMOPHILA MENZIESII: A GREENHOUSE STUDY

To determine the potential for adaptation to a local biotic environment, we examined the magnitude and nature of genetic variation in response to neighboring plants within a natural population of the native California annual, Nemophila menziesii. A total of 22 plants from a natural population were crossed in three reciprocal factorials. The progeny were grown in a greenhouse in nine treatments that varied in conspecific density and in the density of a naturally co-occurring grass species, Bromus diandrus. Increasing the density of each species significantly reduced individual survival, fruit number, and dry weight. Among survivors, we found small to moderate heritability of dry weight within treatments. Additive genetic correlations (r_A) of dry weight between competitive regimes were generally large and positive. In no case were they significantly different from 1, as expected under the null hypothesis that the relative performance of the genotypes under consideration is the same in all environments. On the basis of these results, we cannot conclude that the structure of genetic covariation within this population would promote genetic differentiation in response to locally varying conditions of density of these two species. Aspects of the experiment that may have compromised our ability to detect r_A differing from 1 are discussed.     

Higher-order interactions of Bcr-Abl can broaden chronic myeloid leukemia (CML) drug repertoire

Bcr-Abl, a nonreceptor tyrosine kinase, is associated with leukemias, especially chronic myeloid leukemia (CML). Deletion of Abl's N-terminal region, to which myristoyl is linked, renders the Bcr-Abl fusion oncoprotein constitutively active. The substitution of Abl's N-terminal region by Bcr enables Bcr-Abl oligomerization. Oligomerization is critical: it promotes clustering on the membrane, which is essential for potent MAPK signaling and cell proliferation. Here we decipher the Bcr-Abl specific, step-by-step oligomerization process, identify a specific packing surface, determine exactly how the process is structured and identify its key elements. Bcr's coiled coil (CC) domain at the N-terminal controls Bcr-Abl oligomerization. Crystallography validated oligomerization via Bcr-Abl dimerization between two Bcr CC domains, with tetramerization via tight packing between two binary assemblies. However, the structural principles guiding Bcr CC domain oligomerization are unknown, hindering mechanistic understanding and drugs exploiting it. Using molecular dynamics (MD) simulations, we determine that the binary complex of the Bcr CC domain serves as a basic unit in the quaternary complex providing a specific surface for dimer–dimer packing and higher-order oligomerization. We discover that the small α1-helix is the key. In the binary assembly, the helix forms interchain aromatic dimeric packing, and in the quaternary assembly, it contributes to the specific dimer–dimer packing. Our mechanism is supported by the experimental literature. It offers the key elements controlling this process which can expand the drug discovery strategy, including by Bcr CC-derived peptides, and candidate residues for small covalent drugs, toward quenching oligomerization, supplementing competitive and allosteric tyrosine kinase inhibitors.