Wirkungen von L-glutaminsäure auf grösse und puff-muster der Larvalen Speicheldrüsenchromosomen von Drosophila melanogaster in vivo

The ratio DNA: RNA in the dry substance of Drosophila melanogaster larvae changes when L-glutamic acid is added to the substratum. The number of cells in the salivary glands is not affected (Fahrig et al., 1967). The present paper deals with the effect of this altered ratio on the puffing pattern of the salivary gland chromosomes.Compared to controls of the same game age, glutamic acid fed prepupae younger than 15 min have five additional puffs. In all, 98 pairs of homologous puffs were studied. In 54 of these, size differences were tested statistically; in the glutamic acid series, 20 puffs were larger and 18 smaller than in the controls whereas 16 had the same size. Size reduction was stronger in the more prominent puffs. In prepupae reared at lower temperatures, chromosomes were significantly longer. Glutamic acid causes a significant increase in chromosome width. Combined measurements of both effects were made by determining the surface area of tested segments. Lowering the temperature adds higher size classes, whereas addition of glutamic acid causes a significant shift of the distributional peak towards the higher size classes. This excludes the possibility of an additional replication cycle. In salivary glands of glutamic acid fed prepupae the majority of nuclei have reached the highest degree of polyteny, which in controls is never found at 25° C but sometimes at 18° C. The agent causing both additional puffing and enhanced growth is effective only via the alimentary tract of the larva.     

Genlokalisation auf den larvalen speicheldrüsenchromosomen der stechmücke Culex pipiens L.

Zusammenfassung Die Austauschhäufigkeiten zwischen cytologisch bekannten Bruchkontaktpunkten in den larvalen Speicheldrüsenchromosomen und Mutationen erlauben bei der Stechmücke Culex pipiens L. erstmals die Zuordnung von Genorten zu chromosomalen Strukturen oder Abschnitten. Die vorliegenden Kreuzungsergebnisse stimmen mit der bereits bekannten Zuordnung der drei Koppelungsgruppen zu den cytologisch sichtbaren Chromosomen überein.Um Kreuzungsergebnisse innerhalb eines Chromosoms jedoch sicher miteinander in Bezug setzen zu können, mußte das Problem der unterschiedlichen Austauschhäufigkeiten geklärt werden. Gründe dafür sind weder Alter noch Geschlecht, noch kleine chromosomale Aberrationen der heterozygoten Individuen. Die Höhe des Austausches zwischen zwei Faktoren ist jeweils eine Stamm-spezifische Eigenschaft, die vermutlich faktoriell bedingt ist. Dies konnte durch den Vergleich einer allelen Mutation in zwei Stämmen erarbeitet werden. Es sind deshalb nur solche Austauschwerte vergleichbar, die in ein und demselben Stamm gewonnen wurden, oder bei verschiedenen Stämmen, wenn diese in einen festen Bezug gebracht werden können.Im kleinen Chromosom I ist die Zuordnung des Geschlechts-bestimmenden Allelenpaares M bzw. m zu der heteromorphen Bande 10 C 3 in Arm I L durch Austausch-Analyse mit Bruchkontaktpunkten geschlechtsgekoppelter Translokationen bestätigt. Der Locus der Augenfarbmutation w liegt in unmittelbarer Nähe davon. Der Genort der Augenfarbmutation r ist in Arm I R, in Abschnitt 3 B/C gelegen.Im mittellangen Chromosom II werden zwei Genorte eingegrenzt: die Larvenfarbmutation d ist am distalen Ende des Armes II L gelegen; die Augenfarbmutation ru im zentralen Teil des Armes II R, zwischen den Abschnitten 29 A-21 A. Im langen Chromosom III ist der Genort der Männchen-begrenzten Palpenmutation kps dem Arm III L zugeordnet worden.Eine Zuordnung zu einer distinkten Bande oder Struktur war nur für den Geschlechtsfaktor möglich. Mit den vorliegenden Werten wird für Culex pipiens erstmals eine grobe cytologische Genkarte erstellt.

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Gene mapping on the salivary gland chromosomes of the mosquito Culex pipiens L.

Summary Crossing experiments were done with several mutations and aberrant lines of the mosquito Culex pipiens L. Gene loci and chromosomal structure could be correlated by comparing crossover rates of mutations with breakage points of chromosomal aberrations in the larval salivary gland chromosomes. This confirms linkage groups and their correlated chromosomes.Before comparing crossover rates in one chromosome in different experiments, the problem of different crossover rates between two distinct factors should be solved. The reason for these different rates is not sex, age or small chromosomal aberrations in the heterozygous individuals. It could be interstrain behaviour, characteristic for each strain. This was shown by comparing crossover rates of an allelomorph mutation in two different laboratory strains. Therefore, only results within one pure strain or between two strains with known correlation can be compared. In the small chromosome I, the correlation of the sex-determining allelomorphs M and m with the heteromorphic band 10 C 3 in arm I L was confirmed. This was done by crossover analysis of breakpoints in sex-linked aberrations. The locus of the eye colour mutation w is situated near this band. The eye colour mutation r is located in the segment 3 B/C in arm I R.In chromosome II, two gene loci are narrowed down: the larval colour mutation d is situated on the distal end of arm II L, the eye colour mutation ru in the central part of arm II R. In chromosome III, the male-limited mutation kps is located in arm III L.Hitherto only the sex-factor could be correlated which a distinct structure, i.e. the heteromorphic band 10 C 3 in arm I L. The results of the described experiments made it possible for the first time to establish a cytological gene map of Culex pipiens.

     

SorCS1 variants and amyloid precursor protein (APP) are co‐transported in neurons but only SorCS1c modulates anterograde APP transport

Processing of amyloid precursor protein (APP) into amyloid‐β peptide (Aβ) is crucial for the development of Alzheimer's disease (AD). Because this processing is highly dependent on its intracellular itinerary, altered subcellular targeting of APP is thought to directly affect the degree to which Aβ is generated. The sorting receptor SorCS1 has been genetically linked to AD, but the underlying molecular mechanisms are poorly understood. We analyze two SorCS1 variants; one, SorCS1c, conveys internalization of surface‐bound ligands whereas the other, SorCS1b, does not. In agreement with previous studies, we demonstrate co‐immunoprecipitation and co‐localization of both SorCS1 variants with APP. Our results suggest that SorCS1c and APP are internalized independently, although they mostly share a common post‐endocytic pathway. We introduce functional Venus‐tagged constructs to study SorCS1b and SorCS1c in living cells. Both variants are transported by fast anterograde axonal transport machinery and about 30% of anterograde APP‐positive transport vesicles contain SorCS1. Co‐expression of SorCS1b caused no change of APP transport kinetics, but SorCS1c reduced the anterograde transport rate of APP and increased the number of APP‐positive stationary vesicles. These data suggest that SorCS1 and APP share trafficking pathways and that SorCS1c can retain APP from insertion into anterograde transport vesicles.

     

Cysteine Oxidation Targets Peroxiredoxins 1 and 2 for Exosomal Release through a Novel Mechanism of Redox-Dependent Secretion

Nonclassical protein secretion is of major importance as a number of cytokines and inflammatory mediators are secreted via this route. Current evidence indicates that there are several mechanistically distinct methods of nonclassical secretion. We have shown recently that peroxiredoxin (Prdx) 1 and Prdx2 are released by various cells upon exposure to inflammatory stimuli such as lipopolysaccharide (LPS) or tumor necrosis factor alpha (TNF-α). The released Prdx then acts to induce production of inflammatory cytokines. However, Prdx1 and 2 do not have signal peptides and therefore must be secreted by alternative mechanisms, as has been postulated for the inflammatory mediators interleukin-1β (IL-1β) and high mobility group box-1 (HMGB1). We show here that circulating Prdx1 and 2 are present exclusively as disulfide-linked homodimers. Inflammatory stimuli also induce in vitro release of Prdx1 and 2 as disulfide-linked homodimers. Mutation of cysteines Cys51 or Cys172 (but not Cys70) in Prdx2, and Cys52 or Cys173 (but not Cys71 or Cys83) in Prdx1 prevented dimer formation and this was associated with inhibition of their TNF-α-induced release. Thus, the presence and oxidation of key cysteine residues in these proteins are a prerequisite for their secretion in response to TNF-α, and this release can be induced with an oxidant. By contrast, the secretion of the nuclear-associated danger signal HMGB1 is independent of cysteine oxidation, as shown by experiments with a cysteine-free HMGB1 mutant. Release of Prdx1 and 2 is not prevented by inhibitors of the classical secretory pathway, instead, both Prdx1 and 2 are released in exosomes from both human embryonic kidney (HEK) cells and monocytic cells. Serum Prdx1 and 2 also are associated with the exosomes. These results describe a novel pathway of protein secretion mediated by cysteine oxidation that underlines the importance of redox-dependent signaling mechanisms in inflammation.     

The extracellular microenvironment plays a key role in regulating the redox status of cell surface proteins in HIV-infected subjects

There is an overwhelming interest in the study of the redox status of the cell surface affecting redox signaling in the cells and also predicting the total redox status of the cells. Measuring the total surface thiols (cell surface molecule thiols, csm-SH) we have shown that the overall level of surface thiols is tightly controlled. In vitro, the total concentration of intracellular glutathione (iGSH) seems to play a regulatory role in determination of the amounts of reduced proteins on cells. In addition, short term exposure of the cell surface to glutathione disulfide (GSSG, oxidized GSH) seems to reduce the overall levels of csm-SH suggesting that the function of some cysteine containing proteins on the cell surface may be regulated by the amount of GSSG secreted from the cells or the GSSG available in the extracellular environment. Examination of peripheral blood mononuclear cells (PBMCs) from healthy or HIV-infected subjects failed to reveal a similar correlation between the intra- and extracellular thiol status of cells. Although there is a relatively wide variation between individuals in both csm-SH and iGSH there is no correlation between the iGSH and csm-SH levels measured for healthy and HIV-infected individuals. There are many reports suggesting different redox active proteins on the cell surface to be the key players in the total cell surface redox regulation. However, we suggest that the redox status of the cells is regulated through a complex and tightly regulated mechanism that needs further investigation. In the mean time, overall surface thiol measurements together with case specific protein determinations may offer the most informative approach. In this review, we discuss our own results as well as results from other laboratories to argue that the overall levels of surface thiols on the exofacial membrane are regulated primarily by redox status of the cell surface microenvironment.     

Acarbose attenuates experimental non-alcoholic steatohepatitis

The alpha-glucosidase inhibitor acarbose is beneficial in the prevention of type 2 diabetes. To determine whether it attenuates the commonly associated non-alcoholic steatohepatitis (NASH), we used an experimental NASH model. Rats were fed ad libitum a nutritionally adequate high fat diet (71% of calories as fat) with or without acarbose (200 mg/1000 calories) for 3 weeks. All rats given the high fat diet only developed typical NASH whereas acarbose attenuated several of the characteristic hepatic alterations of NASH: there was less steatosis and inflammation, with a significant reduction in the mRNA of the hepatic inflammatory cytokine TNF-alpha and of its protein. There was also a decrease in the CYP2E1 mRNA and in collagen, with similar trends for CYP2E1 protein and procollagen mRNA. Because acarbose attenuates many of the hepatic alterations associated with experimental NASH, it is now indicated to determine whether it exerts similar beneficial effects in patients afflicted by this disease.     

Die Puppenfärbungen des Kohlweißlings,Pieris brassicae L. Fünfter Teil: Kontrollversuche zur spezifischen Wirkung der Spektralbezirke mit anderen Faktoren

Ohne Zusammenfassung Mit Tafel I und 5 Textabbildungen. Ein Auszug dieser Arbeit erschien mit gleichlautendem Titel als Mitteilung Nr. 40 aus der Biolog. Versuchsanstalt der Akad. d. Wiss., Zool. Abteil., Vorstand H. Przibram, im Akad. Sitzungsanzeiger Nr. 18, 1919. Mit Tafel I und 5 Textabbildungen.     

Untersuchungen über den induzierten Phototropismus bei Keimwurzeln von Helianthus annuus

Ohne ZusammenfassungMit 14 Textabbildungen (18 Einzelbildern).D 9     

Übereinstimmung positiver und negativer Dopareaktiönen an Gefrierschnitten mit jenen an Extrakten

Zusammenfassung WährendChodat (1922),Meirowsky (1923) undPrzibram (1921) eine spezifische Dopaoxydase ablehnen, da nach des letzteren Befunden das 3, 4 Dioxyphenylalanin sowohl spontan als auch bei Alkali- oder Tyrosinasezusatz sich schwärzt, hältBloch an der Spezifität der Dopase und an ihrem Nachweis durch Dopazusatz fest. Gegenüber den vergeblichen Versuchen, die Dopase zu isolieren, beruft er sich auf die Verschiedenheit der benutzten Methoden. Diesen Einwand könnte er auch den VersuchenSatos undBrechers (1923 u. d. Heft) wegen des ebenfalls negativen Ausfalles der für Dopa charakteristischen Reaktionen (mit Eisenchlorid Grünfärbung, dann bei Natriumkarbonatzusatz Umschlag nach Purpurrot usw.) in den Extrakten der melaninbildenden Gewebe machen. Seiner Forderung nach Anwendung der Gefrierschnittmethode folgend, wurden nur solche namentlich von denselben Objekten, die er verwendet hatte, mikrochemisch auf Dopa untersucht. Weder Augen noch schwarze oder weiße Stellen einer 7 Tage alten oder älteren Ratte noch die Kopfhaut von Menschen zeigten die erwähnte Grünbzw. Rotfärbung. Ebenso negativ fielen die analogen Proben an Puppen verschiedenen Farbtypus vonVanessa urticae aus, ferner am Kokon desBombyx mori.Hingegen zeigten die Gefrierschnitte der Kokone vonSaturnia pavonia undEriogaster lanestris, an denenPrzibram (1922) mittels Extraktion durch Wasser den Dopanachweis in der Eprouvette erbracht hatte, deutlich positiven Ausfall.Es besteht demnach keine Veranlassung, einen Unterschied in der Feststellbarkeit von Dopa anzunehmen, je nachdem man Gefrierschnitt oder Extrakt untersucht.Ein Auszug dieser Arbeit erschien unter dem Titel: Mitteilungen aus der Biologischen Versuchsanstalt der Akademie der Wissenschaften, Zoologische Abteilung, VorstandH. Przibram, Nr. 108. Übereinstimmung positiver und negativer Dopareaktionen an Gefrierschnitten mit jenen an Extrakten (zugleich: Ursachen tierischer Farbkleidung. XI) vonLeonore Brecher undFerdinand Winkler im Akademischen Anzeiger der Akademie der Wissenschaften in Wien, Nr. 17, 1923.     

Restorative effect of various androgens on copulatory behavior of the male golden hamster

Adult male hamsters were castrated, and four weeks later, after a single mating test, began receiving daily 100 μg injections of testosterone (T), androstenedione (AD), or testosterone propionate (TP). Mating tests were conducted at regular intervals during the eight week treatment period. Results indicated the superiority of TP in reinstating intromissions and ejaculations. The T and AD groups did not differ on any of the measures, a result which agrees with previous similar experiments using rats.