Conformation of glycyl residues in globular proteins

Glycine is unique among the amino acids in view of its symmetric nature. While the overall distribution of glycyl residues in the (φ, ø) plane is near-symmetric, there can be certain preferences for the individual conformations. An analysis of the observed glycyl conformations in 70 proteins has been carried out to find the influence of residues adjoining the glycyl residues. For this purpose, the (φ, ø) plane has been divided into two regions: (a) the region in which φ is negative and (b) the region in which φ is positive. The analysis is done in terms of the number of conformations occurring in these regions. It has been found that while the overall percentage distribution of glycyl residues between the positive and the negative φ regions is 54:46, the distribution shows asymmetry when the examples are sorted out in terms of X-Gly and Gly-Y doublets. The asymmetry becomes more prominent when the data are sorted out into triplets X-Gly-Y. Using the available information, it has been possible to designate 25 triplets as P-predominant and 19 as N-predominant. An examination of P-predominant triplets for possible occurrence in β-bends having one of the conformations in the positive φ region shows that only 25% are of this nature. Thus, the P-preference of P-predominant triplets is not an outcome of the bend formation alone and must be an inherent property of these triplets.     

A new metric for quantifying performance impairment on the psychomotor vigilance test

We have developed a new psychomotor vigilance test (PVT) metric for quantifying the effects of sleep loss on performance impairment. The new metric quantifies performance impairment by estimating the probability density of response times (RTs) in a PVT session, and then considering deviations of the density relative to that of a baseline‐session density. Results from a controlled laboratory study involving 12 healthy adults subjected to 85 h of extended wakefulness, followed by 12 h of recovery sleep, revealed that the group performance variability based on the new metric remained relatively uniform throughout wakefulness. In contrast, the variability of PVT lapses, mean RT, median RT and (to a lesser extent) mean speed showed strong time‐of‐day effects, with the PVT lapse variability changing with time of day depending on the selected threshold. Our analysis suggests that the new metric captures more effectively the homeostatic and circadian process underlying sleep regulation than the other metrics, both directly in terms of larger effect sizes (4–61% larger) and indirectly through improved fits to the two‐process model (9–67% larger coefficient of determination). Although the trend of the mean speed results followed those of the new metric, we found that mean speed yields significantly smaller (～50%) intersubject performance variance than the other metrics. Based on these findings, and that the new metric considers performance changes based on the entire set of responses relative to a baseline, we conclude that it provides a number of potential advantages over the traditional PVT metrics.     

A study of lung-specific, cell-mediated immunity in chronic pulmonary diseases

Lung-specific, cellular hypersensitivity was studied in patients with chronic pulmonary diseases. To do this, a leucocyte migration inhibition assay was performed using patient and control leucocytes incubated in the presence and absence of a soluble lung extract. Control antigens consisted of liver and kidney extracts. The immunological reactivity of these control antigens was tested by measuring migration, subsequent to incubation of leucocytes from patients with hepatic or renal disease with the liver and kidney extracts, respectively. As a second in vitro test of cell-mediated immunity, a lymphocyte cytotoxicity assay was performed, using as target cells normal chromium-labelled human lung cells. Leucocyte migration inhibition was produced by the lung extract in four out of six patients with chronic bronchitis, five out of seven patients with tuberculosis, one out of five patients with sarcoidosis and in the single patient studied with rheumatoid lung disease. Inhibition did not occur with the leucocytes from control subjects. Neither was migration inhibited when leucocytes from the patients with lung disease were incubated with the control antigens. The reactivity of these control antigens was confirmed by the fact that leucocyte inhibition occurred in two out of three patients with hepatic disease, studied using the liver extract, and in two out of three patients with renal disease, studied with the kidney extract. The cytotoxic potential of anti-lung lymphocytes was demonstrated by the fact that significant target cell cytotoxicity occurred using lymphocytes from two out of four patients with chronic bronchitis, four out of five patients with tuberculosis and in two out of four patients with sarcoidosis.     

Effects of androgens, prolactin and bromocriptine on seminal vesicular enzymes of the pyruvate malate cycle involved in lipogenesis in castrated mature monkeys, Macaca radiata

The interaction of androgens and prolactin, the major factors regulating the male accessory sex organs, on the specific activity of seminal vesicular enzymes of the pyruvate/malate cycle were studied in castrated mature monkeys. Castration decreased the activity of these enzymes, including NADP+ isocitrate dehydrogenase, ATP citrate lyase, malate dehydrogenase, malic enzyme and fatty acid synthase. Testosterone propionate (TP)/dihydrotestosterone given as replacement to castrates increased the activity of all these enzymes, except for malate dehydrogenase. Prolactin restored normal activity of ATP citrate lyase, malic enzyme and fatty acid synthase but not of isocitrate dehydrogenase and malate dehydrogenase (MDH). Prolactin had a specific control over MDH. Moreover, when prolactin was combined with androgens a further stimulatory influence was observed on fatty acid synthase activity. In order to prove the direct influence of prolactin on enzymes of the pyruvate/malate cycle, bromocriptine was administered and this inhibited all of the enzymes. Thus prolactin was found to have a direct, as well as a synergistic, action with androgens on enzymes of the pyruvate/malate cycle in the seminal vesicles of monkeys.     

NATURE AND TREATMENT OF DELUSIONAL PARASITOSIS: A DIFFERENT EXPERIENCE IN INDIA

Background. Delusional parasitosis has been described as a rare syndrome, often involving elderly women who respond poorly to treatment except to pimozide. Method. Nineteen cases of delusional parasitosis given antipsychotic treatment other than pimozide were followed up and the responses assessed in a structured manner. Results. The frequency of the syndrome was higher than generally reported and the patients were younger and had been ill for a shorter period. There was good response to antipsychotic treatments using trifluoperazine, haloperidol, chlorpromazine, and electroconvulsive therapy, and 11 cases showed complete remission, five of them maintaining the recovery for more than 3 years. Conclusions. Delusional parasitosis is not as rare as described: it does not need to be chronic, and can involve young patients. Antipsychotic treatments other than pimozide are equally effective in delusional parasitosis especially if the patients are young and seen early in the illness. The frequency and nature of the disorder observed could probably be due to regional cultural factors.     

Crystal structure and conformation of two N-tosyl-protected dipeptides containing amino acids with polar side-chains

X-Ray diffraction studies and energy-minimization calculations were carried out on two dipeptides, N-tosyl-l -Ser-Gly-OMe monohydrate (C₁₃H₁₈N₂O₆S·H₂O, compound A) and N-tosyl-l -Thr-Gly-OMe (C₁₄H₂₀N₂O₆, compound B). Compound A crystallized in the monoclinic system, space group P2₁ with unit cell parameters a= 4.915(1), b= 15.625(4), c= 11.003(1) Å, β= 91.28(1)°, V= 844.8 ų. M_r= 348.4, d= 1.37(2) g cm^?3, Z = 2, λ(Cu Kα) = 1.5418 Å, μ= 1.99 mm^?1, T=293 K. R= 0.032 for 1451 unique reflections with I > 2σ(I). Compound B crystallized in the orthorhombic system, space group P2₁2₁2₁, with unit cell parameters a= 5.050(2), b= 16.483(3), c= 20.769(5) Å, V= 1729.3 ų, Z = 4. M_r= 344.4, d= 1.32(2) g cm^?3, μ(Cu Kα)= 1.90 mm^?1. R= 0.040 for 1060 unique reflections with I > 2σ(I). The major difference in the backbone conformation of the two compounds is in their glycine residues, with the glycine residue in compound A adopting an extended conformation with φ= - 132.6(3)° and ψ= 175.3(3)° and that in compound B having a folded conformation with φ=?56.3(6)° and ψ=?42.6(7)°. In compound A the oxygen atom of the Ser side-chain and the carbonyl oxygen atom of glycine are bridged by the water of crystallization through O—H ··· O hydrogen bonds, resulting in the relatively rare trans conformation [χ=? 175.7(2)°] for this side-chain. The Thr side-chain in compound B is in the sterically preferred (tg^?) conformation [χ^1,1=? 179.4(4)° and χ^1,2=?62.3(5)°]. The conformations were found to be in general agreement with those obtained by an energy-minimization procedure. The energy-minimized structure of N-tosyl-l -Ser-Gly-Ome (anhydrous) showed a strong hydrophobic interaction between the methyl substituents of the tosyl group and the methyl ester (C—C = 4.08 Å).     

Conformational characteristics of legume 7S globulins as revealed by circular dichroic., derivative u. v. absorption and fluorescence techniques

The 7S globulin storage proteins, phaseolin, vicilin, and β-conglycinin of, respectively, dry bean, field pea, and soybean, are highly homologous, have similar predicted protein structures, and yet exhibit considerable differences in their susceptibility to various proteinases [Nielsen, S.S., Deshpande, S.S., Hermodson, M.A. & Scott, M.P. (1988) J. Agric. Food Chem. 36 , 896-902]. These differences in their proteolytic behavior were studied in relation to their solution conformational states. The secondary structures of these three proteins determined by far u. v. circular dichroism were characterized by predominantly β-sheet and β-turn parameters. However, characterization of tertiary and quaternary structures using second derivative u. v. absorption spectroscopy, surface hydrophobicity using cis-parinaric acid as hydrophobic probe, and fluorescence quenching studies of intrinsic Trp fluorescence using an ionic (iodide) and a neutral (acrylamide) quencher indicated sharp differences in the conformation of these proteins. About 9.6 and 10.2 out of 13 and 15 tyrosyls/subunit of phaseolin and β-conglycinin, respectively, were exposed to polar solvent, while the surface hydrophobicity varied β-conglycinin > vicilin > phaseolin. The Trp residues in phaseolin were not accessible to iodide, while half those of vicilin and β-conglycinin were quenched. The order of Trp accessibility to acrylamide was vicilin > β-conglycinin > phaseolin. The relative compactness of these three proteins based on these studies was related to the observed differences in their susceptibility to various proteinases.