Concentration-dependent inducing activity of activin A

Summary Human recombinant activin A, which is identical with erythroid differentiation factor (EDF), was tested for its mesoderm-inducing activity in concentrations from 0.3–50 ng/ml, using ectoderm of Xenopus late blastula (Stage 9) as the responding tissue. At a low concentration of activin A, blood-like cells, mesenchyme, and coelomic epithelium were induced; at a moderate concentration muscle and neural tissue, and at a high concentration notochord. Activin A thus induced all mesodermal tissues in a dose-dependent manner, such that a low dose induced ventral structures and a high dose induced dorsal structures. Activin may act as an intrinsic inducing molecule responsible for establishing the dorso-ventral axis in early Xenopus development. Offprint requests to: M. Asashima     

Phosphorus-containing inhibitors of aspartate transcarbamoylase from Escherichia coli

A tetrahedral intermediate is the prominent feature of the generally accepted mechanism for aspartate transcarbamoylase. We have synthesized N-pyrophosphoryl-L-aspartate as a charged analogue of the postulated intermediate. Surprisingly, its affinity for the enzyme from Escherichia coli was substantially lower than that of the previously known inhibitor phosphonoacetyl-L-aspartate which contained a trigonal carbonyl group. Similar results were obtained with the corresponding mercaptosuccinate derivatives. We also tested a number of new pyrophosphate analogues as inhibitors. Our results cast doubt on some aspects of the current model for the mechanism of this enzyme.     

Inhibitory effects of interleukin-1 on follicle-stimulating hormone induction of aromatase activity, progesterone secretion, and functional luteinizing hormone receptors in cultures of porcine granulosa cells

Effects of interleukin-1 (IL-1) on FSH-induced differentiation of immature porcine granulosa cells in vitro were examined in short-term (48-h) cultures. IL-1 inhibited FSH induction of aromatase activity and of LH-stimulated cAMP accumulation by granulosa cells. Both these inhibitory actions of IL-1 were concentration-dependent. Significant inhibitory effects were observed with as low as 0.05-0.25 ng/ml of IL-1, with maximal effects at 25 ng/ml. IL-1 also significantly inhibited increases in [125I]iodo-LH binding and progesterone secretion induced by FSH, as well as reducing basal levels of aromatase activity and LH-stimulated cAMP accumulation. Studies on the mechanisms of IL-1 actions on FSH-induced differentiation of immature porcine granulosa cells revealed that IL-1 reduced cAMP accumulation by the cells in response to FSH in a time- and concentration-dependent manner. IL-1 also inhibited induction of aromatase activity and LH-stimulated cAMP accumulation induced by dibutyryl cAMP, suggesting that IL-1 also affects the steps distal to cAMP generation. In contrast, IL-1 had no effect on progesterone secretion induced by dibutyryl cAMP, suggesting that post-cAMP steps of progesterone secretion were unaffected by IL-1.     

Localization of aldosterone-producing adenoma: venous sampling in primary aldosteronism

Adrenal venous sampling of blood was performed for nine patients with aldosterone-producing adenoma (APA). Measurement of adrenal venous aldosterone is useful for localization of APA but difficult, because catheterization of the right adrenal vein is not easy, and the blood is diluted by nonadrenal flow. To solve these problems, levels of aldosterone (A; ng/dl) and cortisol (C; micrograms/dl) were measured in samples from the left adrenal vein (LAV) and the inferior vena cava (IVC), and the LAV A/C and (LAV A/C)/(IVC A/C) ratios were calculated. These ratios were also obtained for 16 patients with essential hypertension. The adenoma could be localized in three of the nine cases by the measurement of aldosterone alone, but the use of a LAV A/C ratio greater than 5 x 10(-3) and a (LAV A/C)/(IVA A/C) ratio less than 1.0 as criteria separated the patients into those with a left APA, right APA, or essential hypertension. Consequently, adrenal venous sampling and the calculation of these ratios enables preoperative localization of APA with more accuracy, especially when the tumor is small or the result of CT and adrenal scintigraphy is not consistent.     

Proposal for Naming Host Cell-Derived Inserts in Retrovirus Genomes

We propose a system for naming inserted sequences in transforming retroviruses (i.e., onc genes), based on using trivial names derived from a prototype strain of virus.     

Glucagon and epinephrine-stimulated phospholipid methylation in hepatic microsomes

Phospholipid methylation by hepatic microsomes was measured following glucagon or epinephrine administration either to intact rats or to the isolated perfused liver. Both hormones stimulated the methylation measured as the incorporation of S-adenosyl-L-[methyl-³H]methionine into phospholipids. The labeled products were identified by thin layer chromatography and most of the counts were found to be incorporated into phosphatidylcholine. The stimulatory effects of the hormones were evident already 5 minutes following hormone administration both in $\text{in vivo}$ and in $\text{in vitro}$. The observed stimulation of the methylation process by glucagon and epinephrine might be related to the previously reported stimulatory effect of these hormones on the microsomal Ca²⁺-ATPase, and indicate that methylation process(es) might mediate some of the effects of these hormones.     

Structure and distribution of inverted repeats (palindromes)

The size and distribution of renatured inverted repeats (palindromes) in D. melanogaster DNA were studied by electron microscopy (EM). The results of these studies differ from the previously published observations regarding the number, distribution and the size of inverted repeats (ir) present in DNA. -1. In contrast to the previous published observation almost all (96%) of the ir were found in crowded clusters. The DNA strands with clustered palindromes contained 2-21 palindromes (4-42 ir), with an average of 7.25 palindromes (14.5 ir) per strand. No correlation could be found between the length of the DNA strands and the number of ir per strand. -2, Also contrary to some previously published results, most (80%) of the ir formed on renaturation unlooped palindromes and these were always clustered. Looped palindromes (hairpins, formed by renaturation of ir separated by a non-homologous sequence long enough to be seen in EM as single-stranded loop) were found 1-2 per DNA strand, as part of clusters or as solitary palindromes in a DNA strand. The average spacing length (inside clusters) between centers of all palindromes was 2.349 kb, and between centers of looped palindromes 7.6 kb. - 3. The length of the ir was found to be smaller than documented in most of the previously published results. The majority, 80-90%, of the ir found in the unlooped and looped palindromes, respectively, belonged to one main-size class with a range of 30-210 bp and an average length of 100 bp, but longer ir were also observed. The average length of the ir in unlooped palindromes was 124 bp, in looped 244 bp, and the total average was 148 bp - 4. It was calculated that there are about 30,000 palindromes (60,000 ir) in the D, melanogaster genome, of which about 24,000 are unlooped and 6,000 looped, with the spacing between centers of all palindromes averaging about 4.4 kb in length.     

Hemin feedback inhibition at reticulocyte δ-aminolevulinic acid synthetase and δ-aminolevulinic acid dehydratase

Addition of hemin (5–200 μM) to a rabbit reticulocyte iron-free incubation medium, resulted in a progressive inhibition of heme synthesis as measured by incorporation of (¹⁴C)-glycine. In contrast when (¹⁴C) δ-aminolevulinic acid incorporation into heme was studied, significant inhibition below that of the (¹⁴C)-glycine control only occurred with hemin concentrations greater than 100 μM. Hemin progressively inhibited cellular and mitochondrialδ-aminolevulinic acid synthetase activity, as well as cellular δ-aminolevulinic acid dehydratase activity. The results indicated that elevated levels of hemin initially control heme synthesis by feedback inhibition at the rate-limiting enzyme of heme synthesis, δ-aminolevulinic acid synthetase. Hemin inhibition of δ-aminolevulinic acid dehydratase is only significant for the entrire heme synthetic pathway when greater than one-third of this enzyme's activity is inhibited.     

Starling Flock Networks Manage Uncertainty in Consensus at Low Cost

Flocks of starlings exhibit a remarkable ability to maintain cohesion as a group in highly uncertain environments and with limited, noisy information. Recent work demonstrated that individual starlings within large flocks respond to a fixed number of nearest neighbors, but until now it was not understood why this number is seven. We analyze robustness to uncertainty of consensus in empirical data from multiple starling flocks and show that the flock interaction networks with six or seven neighbors optimize the trade-off between group cohesion and individual effort. We can distinguish these numbers of neighbors from fewer or greater numbers using our systems-theoretic approach to measuring robustness of interaction networks as a function of the network structure, i.e., who is sensing whom. The metric quantifies the disagreement within the network due to disturbances and noise during consensus behavior and can be evaluated over a parameterized family of hypothesized sensing strategies (here the parameter is number of neighbors). We use this approach to further show that for the range of flocks studied the optimal number of neighbors does not depend on the number of birds within a flock; rather, it depends on the shape, notably the thickness, of the flock. The results suggest that robustness to uncertainty may have been a factor in the evolution of flocking for starlings. More generally, our results elucidate the role of the interaction network on uncertainty management in collective behavior, and motivate the application of our approach to other biological networks.