Early life environment determines the development of adult phobic‐like fear responses in BALB/cAnN mice

Environmental factors may unleash genetically determined susceptibility to psychopathology. Great effort has been spent in identifying both the genetic basis and environmental sources of exaggerated fear in animal models of anxiety disorders. Here, we show that the origin of inbred mice, probably via subtle differences in breeding and rearing conditions, may have large consequences specifically on acquisition and retention of fear memories, while leaving anxiety‐related behaviours unaffected. These effects could be seen in BALB/cAnN (BALB), but not in C57BL/6N (C57BL/6) mice, thus suggesting their dependency on the genetic background. Increased susceptibility for developing exaggerated fear responses was accompanied by decreased long‐term depression and increased surface trafficking of the AMPA receptor GluR1 subunit at the level of the basolateral amygdala complex. Together, these data raise a novel caveat in the debate about the origins of variation in behavioural studies with experimental animals. Considering that there are currently no animal models which explicitly consider conceptual analogy to the specific gene–environment interactions observed in the aetiology of phobias, our study might suggest a novel approach and direction for further preclinical studies focusing on such aspects of phobic‐like fears.     

Membrane-bound and secreted IgA contain structurally different alpha-chains

Three different forms of alpha-chains are synthesized by BF0.3 and 615.2, two cloned cell lines derived from the murine B lymphoma 1.29. The three forms of alpha-chains differ in size, pI, cellular location, and rate of turnover. They were identified by means of lactoperoxidase-catalyzed radioiodination, internal 14C or 35S labeling, and immunofluorescence techniques as membrane-bound(alpha m), secreted (alpha s), and intracellular (alpha ic) proteins. Comparison of immunoglobulin products of the two lymphoma lines with those of a hybridoma cell line, Id 150, which secretes IgA of the 1.29 idiotype but lacks membrane IgA, confirmed the assignments of alpha m, alpha s, and alpha ic. Results of biosynthetic labeling of BF0.3, 615.2, and Id 150 in the presence and absence of tunicamycin suggest that the difference in m.w. and charge observed between alpha m and alpha s can be attributed to differences in primary amino acid structure rather than different degrees of glycosylation.     

Immunogenicity of loop-structured short synthetic peptides mimicking the antigenic site A of influenza virus hemagglutinin

In order to assess the relevance of conformation for the antigenic site A of the hemagglutinin of influenza virus we synthesized two peptides, comprising two variant sequences of the central part of site A (amino acids 140 - 146 of subunit HA1) inserted into an artificial peptide skeleton, which imposes a loop-like structure on the respective sequence stretch. Assuming that the loop structure in the synthetic peptides would roughly approximate to the structure of the cognate protein sequence we tried to raise protein-reactive anti-peptide antibodies. The antibodies obtained indeed showed reactivity against influenza virus, although the discriminating specificity with regard to a mutation at position 144 was lost for virus binding in contrast to the highly specific peptide binding. Considering the failures in raising anti-hemagglutinin antibodies against the site A by immunization with short flexible peptide our results support the hypothesis that conformation makes a major contribution to the immunogenic and antigenic characteristics of site A in influenza hemagglutinin.     

Lipid composition of PC12 pheochromocytoma cells: characterization of globoside as a major neutral glycolipid

We have studied the lipid composition of PC12 pheochromocytoma cells cultured in the presence and absence of nerve growth factor (NGF). Neutral and acidic lipid fractions were isolated by column chromatography on DEAE-Sephadex and analyzed by high-performance thin-layer chromatography (HPTLC). The total lipid concentration was approximately 220 micrograms/mg of protein, and the concentration of neutral glycolipids was 1.6-1.8 microgram/mg of protein for both NGF-treated and untreated cells. The neutral glycolipid fraction contained a major component, which accounted for approximately 80% of the total and which was characterized as globoside on the basis of HPTLC mobility, carbohydrate analysis, fast atom bombardment mass spectrometry, and mild acid hydrolysis. The major fatty acids of globoside were C16:0 (10%), C18:0 (16%), C22:0 (23%), C24:1 (17%), and C24:0 (24%). C18 sphingenine accounted for almost all of the long-chain bases. The other neutral glycolipids were tentatively identified as glucosylceramide (15%), lactosylceramide (4%), and globotriosylceramide (4.5%). The concentration of ganglioside sialic acid was approximately 0.34 and 0.18 microgram/mg of protein for cells grown in the presence and absence of NGF, respectively. Although there was an increase in ganglioside concentration in NGF-treated cells, NGF did not produce any differential effects on the relative proportions of the individual gangliosides. Several of the gangliosides appear to contain fucose, and one of these was tentatively identified as fucosyl-GM1. Brain-type gangliosides of the ganglio series were also detected by an HPTLC-immunostaining method. However, the fatty acid and long chain base compositions of PC12 cell gangliosides (and their TLC mobility) differ from those of brain gangliosides.(ABSTRACT TRUNCATED AT 250 WORDS)     

Two-stage autolysis of the catalytic subunit initiates activation of calpain I

Calcium-induced autolysis of bovine erythrocyte calpain I occurs in multiple stages. Initially, a 14 amino acid segment is cleaved from the N-terminus of the native 80 kDa catalytic subunit, yielding a 78 kDa form of the subunit. Then, an additional 12 amino acid segment is cleaved from the N-terminus, forming a 76 kDa subunit. The 76 kDa enzyme is the active form of the catalytic subunit that is able to proteolyze the 30 kDa regulatory subunit as well as exogenous substrates. While the initial autolytic step requires high calcium, the 76 kDa enzyme form is active in microM calcium and can cleave the amino termini of native 80 kDa and intermediate 78 kDa enzyme forms at low calcium. Both intramolecular and intermolecular proteolysis of the catalytic subunit appear to yield the same products.     

Halothane metabolism: Kupffer cells carry and partially process trifluoroacetylated protein adducts

Kupffer cells, prepared 18 h after pretreatment of rats with a single dose of halothane, did carry TFA-adducts which were recognized on Western blots by a anti-TFA-antibody. Based on apparent molecular weight, the pattern of the major TFA-adducts within Kupffer cells was similar to that observed in hepatocytes. When kept in primary culture, Kupffer cells processed TFA-adducts of apparent molecular weight of 220 kD, 110 kD and 74 kD within 24 or 48 h; in contrast, other TFA-adducts were persistent for at least 48 h in Kupffer cells. The data suggest a role for Kupffer cells in processing of chemically altered proteins in the liver.     

Über den Kieferapparat der Lytoceratacea (Ammonoidea)

The jaw apparati of Paleozoic and Triassic ammonoids are simìlar in shape to parrots’ beaks; they possess sharp cutting-edges and consist of chitinous material. Together with the similar jaw apparati of recent Coleoids, they constitute the Normal-Type of cephalopod jaws. The jaw apparati of the Jurassic-Cretaceous ammonites possess wide, shovel-like lower jaws without cutting-edges. They consist either of an undivided chitinous plate (Anaptychus) or of this and two additional calcitic plates (Aptychi) on its outer flanks. Jaw apparati of this type are here called Aptychus-Type jaws. New finds in the Upper Cretaceous of Japan suggest the existence of a third type of jaw apparatus which is here called the Rhynchaptychus-Type. Jaws of this type are mainly characterized by possession of calcitic rostra on the tips of the jaws. They seem to be restricted to members of the order Lytoceratacea (excluding the Heteromorphs).