Polypeptide translocation machinery of the yeast endoplasmic reticulum

Proteins enter the secretory pathway by two general routes. In one, the complete polypeptide is made in the cytoplasm and held in an incompletely folded state by chaperoning adenosine triphosphatases (ATPases) such as hsp70. InSaccharomyces cerevisiae, fully synthesized secretory precursors engage the endoplasmic reticulum (ER) membrane by interaction with a set of Sec proteins comprising the polypeptide translocation apparatus (Sec61p, Sec62p, Sec63p, Sec71p, Sec72p). Productive interaction requires displacement of hsp70 from the precursor, a reaction that is facilitated by Ydj1p, a homologue of theEscherichia coli DnaJ protein. Both DnaJ and Ydj1p regulate chaperone activity by stimulating the ATPase activity of their respective hsp70 partners (E. coli DnaK andS. cerevisiae Ssa1p, resepectively). In the ER lumen, another hsp70 chaperone, BiP, binds ATP and interacts with the ER membrane via its contact with a peptide loop of Sec63p. This loop represents yet another DnaJ homologue in that it contains a region of 70 residue similarity to the J box, the most conserved region of the DnaJ family of proteins. In the presence of ATP, under conditions in which BiP can bind to Sec63p, the secretory precursor passes from the cytosol into the lumen through a membrane channel formed by Sec61 p. A second route to the membrane pore that is used by many other secretory precursors, particularly in mammalian cells, requires that the polypeptide engage the ER membrane as the nascent chain emerges from the ribosome. Such cotranslational translocation bypasses the need for certain Sec proteins, instead utilizing an alternate set of cytosolic and membrane factors that allows the nascent chain to be inserted directly into the Sec61p channel.     

Antiviral activities of anthraquinones,bianthrones and hypericin derivatives from lichens

The antiviral activities of some naturally occurring anthraquinones bianthrones, and hypericin derivatives were compared by the end-point CPE (viral cytopathic effects) method and plaque assays. Under optimal conditions of exposure to light, hypericin, 7,7-dichlorohypericin and 5,7-dichloroemodin exhibited strong inhibitory activity against HSV-1 (herpes simplex virus type 1) in both assays. Partial inactivation of the virus was shown by emodin, 7-chloroemodin and 7-chloro-1-O-methylemodin; the bianthrones and other anthraquinones were found to be inactive. Antiviral activity appeared to be, positively correlated with increasing substitution of chlorine in the anthraquinone structure. In the absence of light, only hypericin and 7,7-dichlorohypericin displayed detectable activity.     

The use of cyclophosphamide as an enhancer of the vaccine against foot-and-mouth disease

The immunization of biungulate animals with killed foot-and-mouth disease virus (FMDV) requires periodic vaccinations due to a low vaccine immunogenicity. Therefore, FMDV antigens need to be combined with adjuvants such as aluminum hydroxide, saponin or oil emulsions. Animal handling for periodic inoculations, and the repeated doses of vaccines that have to be administered increase the commercialization costs. Moreover, the use of adjuvants may induce adverse effects.In the present work we show that it is possible to increase the life span of neutralizing antibodies in serum when a single dose of cyclophosphamide (Cy) is administered four days before vaccination with aluminum hydroxidesaponin FMDV vaccine.     

Studies of a key protein in the mechanism of the excitation-contraction coupling process of frog skeletal muscle,using phenylglyoxal

The excitation-contraction (E-C) coupling process in single twitch fibres from frog toe muscle was inhibited selectively by phenylglyoxal (PGO), a specific guanidyl modifying reagent. A new protein (31.5 kDa), which has PGO-binding ability and seems to play a key role in the E-C coupling process, was solubilized from transverse tubule membrane-junctional sarcoplasmic reticulum complexes (TTM-JSR) of frog skeletal muscles, using¹⁴C-PGO. The monoclonal antibody against this protein applied extracellularly inhibited the E-C coupling process of the single fibres. This protein appears to constitute the very first step of input for E-C coupling. It is considered to behave as an indispensable part of an electrometer to measure membrane potentials. Therefore, the name electrometrin is suggested for the new protein.     

Effects of atmospheric pollution on human health

Most air pollutants do not lead to specific diseases. Depending on the pollutant, the concentration and the duration of exposure, some organs are more affected than others. The most frequent disorders are those caused by irritant gases and particulates on the mucous membranes and respiratory organs. The consequences are eye, nose and throat inflammations, diminished lung function, increased susceptability to respiratory infection and a higher incidence of chronic bronchitis. These disorders and diseases are, of course, influenced by other factors as well, such as immune deficiency, allergies, occupational exposure to pollutants, and particularly smoking. The effects of air pollutants are, therefore, multifactorially conditioned and nonspecific disorders are placed in the foreground. Evidence for an association of air pollution with adverse effects on human health is drawn from three sources: animal experiments, experimental human exposures, and epidemiologic studies of exposed human populations. The burden of atmospheric pollution must be reduced to protect human health by an adequate safety margin. In particular, the increased sensitivity of sick and aged people as well as children should be taken into account. In defining the maximum emmission levels, preventive aspects should have priority so as to keep the risk of damage to health and the harmful influences on the environment to a minimum.This article Effects of atmospheric pollution on human health by H. U. Wanner is a revised version of the same article that was first published in the Proceedings of the 1990 European Aerosol Conference; special issue of the J. Aerosol Sci., Vol. 21, Suppl. 1 (1990) 389–396.Reprinted with kind permission from Pergamon Press Ltd, Headington Hill Hall, Oxford OX3 0BW, Great Britain.     

Differential sensitivity to ethidium bromide of replicative DNA synthesis and bleomycin-induced unscheduled DNA synthesis in permeable mouse sarcoma cells1

Summary Replicative DNA synthesis in permeable mouse sarcoma cells was more sensitive to ethidium bromide (EtBr) than bleomycin-induced unscheduled DNA synthesis (UDS). A similar difference in sensitivity to EtBr was observed between DNA polymerases and . The difference in sensitivity to EtBr of replicative DNA synthesis and UDS in the present system seems to reflect mainly the sensitivity difference between DNA polymerases and .Acknowledgments. The authors wish to thank Nippon Kayaku Co. (Tokyo, Japan) for providing copper-free bleomycin A₂. This research was supported in part by a grant from the Japan Ministry of Education, Science and Culture.     

Potentiating action of hexoprenaline on14C-aminopyrine uptake by isolated rat parietal cells

Summary Hexoprenaline potentiated the¹⁴C-aminopyrine uptake (a reliable index of H⁺ generation) of isolated rat gastric cells stimulated by 10^–6–10^–4 mol/l carbachol, and inhibited that in response to 10^–4 mol/l histamine without and in the presence of propranolol. It is concluded that hexoprenaline acts as a partial agonist on parietal cell H₂-receptors and that -adrenoceptor activation may functionally modualte gastric acid secretion.Acknowledgments. S. Maliski, Institute of Rheumatology, Warszawa, held a fellowship of the Alexander v. Humboldt-Foundation. The study was supported by the Deutsche Forschungsgemeinschaft. The skilful technical assistance of Mrs R. Maier and Mr R. Beer is gratefully acknowledged.