The Relationship between Reversed Masked Priming and the Tri-Phasic Pattern of the Lateralised Readiness Potential

One of the potential explanations for negative compatibility effects (NCE) in subliminal motor priming tasks has been perceptual prime-target interactions. Here, we investigate whether the characteristic tri-phasic LRP pattern associated with the NCE is caused by these prime-target interactions. We found that both the prime-related phase and the critical reversal phase remain present even on trials where the target is omitted, confirming they are elicited by the prime and mask, not by prime-target interactions. We also report that shape and size of the reversal phase are associated with response speed, consistent with a causal role for the reversal for the subsequent response latency. Additionally, we analysed sequential modulation of the NCE by previous conflicting events, even though such conflict is subliminal. In accordance with previous literature, this modulation is small but significant.     

THE LIMITED PROTEOLYSIS OF BOVINE NEUROPHYSINS BY CATHEPSIN D

Abstract— The limited proteolysis of the bovine neurophysins at acid pH has been studied and the enzyme responsible has been characterized. Only 15 per cent of the catheptic activity in 4-year-old acetone-dried posterior pituitary lobe powder is soluble at pH 4.0. Solubility increases as the age of the powder decreases and the cathepsin is completely soluble in the presence of 1% Triton X-100. Acid proteinase activity in the neurohypophysis is not thiol activated and is inhibited by 3-phenylpyruvic acid. Bovine serum albumin was degraded at only 1 per cent of the rate of haemoglobin but with the same pH optimum (3.7). On this basis the enzyme was identified as cathepsin D. Neurophysin-I is degraded in two stages by cathepsin D; the first product (neurophysin-I′) runs faster and the second product (neurophysin-I″) runs slower than the native protein on starch-gel electrophoresis at pH 8.1. Neurophysin-II is also degraded in two stages; the first product has a higher electrophoretic mobility than the native protein and is identical in mobility with the faster-running component of the so-called neurophysin-M of Hollenberg and Hope (1967b). Prolonged incubation with the cathepsin gives rise to a slower-running component. Neurophysin-C is not attacked by the acid proteinase. Neurophysin-I′ and I″ have been isolated by ion-exchange chromotography. They have the same N-terminal amino acid (alanine) and C-terminal sequence (Ala-Phe-Ser) as the native protein and both bind 8-argininevasopressin. Neurophysin-I′ is identical in amino acid composition with the native protein but neurophysin-I″ has lost one leucine and two aspartic acid residues. Reduction, ¹⁴C-alkylation and separation of the fragments by starch-gel electrophoresis shows that the structural and functional integrity of neurophysin-I″ is maintained by the disulphide bonds, even though a tripeptide has been split out of the interior of the molecule. The low molecular weight material produced by catheptic digestion of neurophysin-I has been purified and shown to have a composition of one leucine and two aspartic acid residues. It is suggested that extensive in vivo proteolysis of neurophysin by lysosomal cathepsin, with consequent abolition of hormone-binding ability, is unlikely.     

Cyclic Nucleotides and the Release of Vasopressin from the Rat Posterior Pituitary Gland

Abstract: The effect of ATP, Mg²⁺, or MgATP on the release of luteinizing hormone-releasing hormone (LH-RH) from hypothalamic granules was examined under in vitro conditions. Granules, isolated from adult male hypothalami, were incubated at 37°C in a buffered (pH 7.8) medium containing 0.15 m -KCl. The addition of ATP to the incubation mixture did not stimulate the release of LH-RH. In contrast, the addition of MgATP stimulated the release of LH-RH, the release being 62% greater than control. The addition of Mg²⁺ to the incubated granules also stimulated the release of LH-RH. However, the magnitude of this Mg²⁺-stimulated release of LH–RH was significantly ( P < 0.01) lower than that of the MgATP-stimulated release, indicating that ATP stimulates LH-RH release in a Mg²⁺-dependent manner. As both MgATP and Mg²⁺ alone stimulated LH-RH release, we characterized further these two release processes by incubating the granules under one of the following conditions: incubation at 4°C in a buffered medium containing 0.15 m -KCl or incubation at 37°C in a medium that does not contain KCl. Under these two incubation conditions, the MgATP-stimulated release of LH-RH was not manifested, whereas the Mg²⁺-stimulated release of LH-RH was manifested. On the basis of these differences, we propose that two different processes can lead to the release of LH-RH from isolated hypothalamic granules: one process involves ATP and Mg²⁺ (MgATP) and another process involves Mg²⁺ alone.     

Anti‐inflammaging effects of human alpha‐1 antitrypsin

Inflammaging plays an important role in most age‐related diseases. However, the mechanism of inflammaging is largely unknown, and therapeutic control of inflammaging is challenging. Human alpha‐1 antitrypsin (hAAT) has immune‐regulatory, anti‐inflammatory, and cytoprotective properties as demonstrated in several disease models including type 1 diabetes, arthritis, lupus, osteoporosis, and stroke. To test the potential anti‐inflammaging effect of hAAT, we generated transgenic Drosophila lines expressing hAAT. Surprisingly, the lifespan of hAAT‐expressing lines was significantly longer than that of genetically matched controls. To understand the mechanism underlying the anti‐aging effect of hAAT, we monitored the expression of aging‐associated genes and found that aging‐induced expressions of Relish (NF‐?B orthologue) and Diptericin were significantly lower in hAAT lines than in control lines. RNA‐seq analysis revealed that innate immunity genes regulated by NF‐kB were significantly and specifically inhibited in hAAT transgenic Drosophila lines. To confirm this anti‐inflammaging effect in human cells, we treated X‐ray‐induced senescence cells with hAAT and showed that hAAT treatment significantly decreased the expression and maturation of IL‐6 and IL‐8, two major factors of senescence‐associated secretory phenotype. Consistent with results from Drosophila,RNA‐seq analysis also showed that hAAT treatment significantly inhibited inflammation related genes and pathways. Together, our results demonstrated that hAAT significantly inhibited inflammaging in both Drosophila and human cell models. As hAAT is a FDA‐approved drug with a confirmed safety profile, this novel therapeutic potential may make hAAT a promising candidate to combat aging and aging‐related diseases.     

PROANTHOCYANIDINS IN NEEDLES FROM SIX GENERA OF THE TAXODIACEAE

Proanthocyanidin contents of needles ranged from a mean of 150 to 300 μg per mg dry wt in five species from five genera of the Taxodiaceae, Sequoiadendron giganteum (Lindl.) Bucch., Metasequoiaglyptostroboides H. Hu and Cheng, Sequoia sempervirens (D. Don) Endl., Taxodium distichum L. Rich., and Sciadopitys verticillata Siebold and Zucc. However, significantly lower amounts (70 μg per mg dry wt) were found in Cryptomeria japonica (L.f.) D. Don. This latter species as well as Sciadopitys verticillata, contained little or no prodelphinidin, while the other four species contained a ratio of procyanidin to prodelphinidin up to about 1:5. These data were based on analyses from three trees from each species. In addition, one tree from each species was examined in more detail. The major flavan-3-ol in all cases was (+)-catechin, with only non-detectable or trace amounts of (–)-epicatechin. The triphenolic flavan-3-ol, (+)-gallocatechin, was a minor constituent in all species, except Sciadopitys and Cryptomeria. The (–)-epigallocatechin was detected in Metasequoia, Sequoiadendron and Sequoia. All contained either (–)-epicatechin-(+)-catechin or (+)-catechin-(+)-catechin as the major procyanidin dimer. Prodelphinidin dimers were only tentatively identified.     

Development of a diploid cell line from fetal rhesus monkey lung for virus vaccine production

Summary The primary goal of this study was to develop and characterize diploid cell lines from fetal tissues of subhuman primates for use in virus vaccine production. Cell lines have been established from fetal tissues of rhesus and African green monkeys, and these have been characterized according to the general criteria recommended by the International Cell Committee for Microbiological Standardization. Of these cell lines, DBS-FRhL-2, developed from lung tissue of a rhesus monkey fetus, has been found to meet the requirements of populations proposed as substrates for virus vaccines. Characterization studies show that DBS-FRhL-2 cells have a finite life of more than 50 population doublings in vitro and maintain the diploid karyotype through an active growth phase. The cells are nontumorigenic, and tests have not revealed the presence of adventitious agents. They are susceptible to a number of human viruses and can be preserved by freezing without change in virus susceptibility, cytogenetic, or growth characteristics. These results indicate the need for further evaluation of this rhesus monkey diploid cell line for acceptability as an alternate substrate in the manufacture of human virus vaccines. The research upon which this publication is based was performed pursuant to Contract No. NIH-69-100 with the Division of Biologics Standards of the National Institutes of Health.