Short Toxin-like Proteins Attack the Defense Line of Innate Immunity

ClanTox (classifier of animal toxins) was developed for identifying toxin-like candidates from complete proteomes. Searching mammalian proteomes for short toxin-like proteins (coined TOLIPs) revealed a number of overlooked secreted short proteins with an abundance of cysteines throughout their sequences. We applied bioinformatics and data-mining methods to infer the function of several top predicted candidates. We focused on cysteine-rich peptides that adopt the fold of the three-finger proteins (TFPs). We identified a cluster of duplicated genes that share a structural similarity with elapid neurotoxins, such as α-bungarotoxin. In the murine proteome, there are about 60 such proteins that belong to the Ly6/uPAR family. These proteins are secreted or anchored to the cell membrane. Ly6/uPAR proteins are associated with a rich repertoire of functions, including binding to receptors and adhesion. Ly6/uPAR proteins modulate cell signaling in the context of brain functions and cells of the innate immune system. We postulate that TOLIPs, as modulators of cell signaling, may be associated with pathologies and cellular imbalance. We show that proteins of the Ly6/uPAR family are associated with cancer diagnosis and malfunction of the immune system.     

Subchronic fluoxetine administration to rats: effects on 5-HT autoreceptor activity as measured by in vivo microdialysis.

Subchronic administration of fluoxetine to rats has been shown to induce subsensitivity of presynaptic 5-HT(1A) and 5-HT(1B) autoreceptors, and also postsynaptic 5-HT(1A) receptors in the hypothalamus. We investigated the effects of administration of fluoxetine (10 mg/kg i.p.) to rats for 6 days on presynaptic 5-HT(1A) receptor activity in the hypothalamus, postsynaptic 5-HT(1A) receptor activity in the hippocampus, and presynaptic 5-HT(1B) autoreceptor activity in both areas, using in vivo microdialysis. The effect of the 5-HT(1B/1D) antagonist (N-[4-methoxy-3-(4-methyl-1-piperizinyl)phenyl]-2'-methyl-4'-(5- methyl-1,2,4-oxadiazole-3-yl)[1,1'-biphenyl]-carboxamide (GR 127935) (5 mg/kg s.c.) to elevate 5-hydroxytryptamine (5-HT) levels was reduced in hippocampus but not hypothalamus of fluoxetine-treated rats. Fluoxetine did not alter either presynaptic 5-HT(1A) autoreceptor activity, as measured by the effect of injection of 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT) (0.2 mg/kg or 50 microg/kg s.c.) on 5-HT levels in the hypothalamus, or postsynaptic 5-HT(1A) receptor activity, as measured by the effect of 8-OH-DPAT (0.2 mg/kg s.c.) on cyclic AMP accumulation, in the hippocampus.     

Signaling through protein kinases during egg activation.

Following penetration of the zona pellucida, the mammalian spermatozoon binds and fuses with the egg plasma membrane, thereby fertilizing the egg that is still arrested at the second metaphase. Fertilization initiates in the egg a sequence of events referred to as 'egg activation'. An initial increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) appears to be the very early cellular event observed which leads to the cortical granules exocytosis and resumption of meiosis. Various treatments can induce parthenogenetic activation mimicking at least part of the fertilization events. Similar to somatic cells, studies in mammalian eggs suggest that signal transduction pathways mediate egg activation. The initial increase in [Ca(2+)](i) appears to be critical for egg activation. However, other messengers such as protein kinase C (PKC) and protein tyrosine kinases (PTKs), were suggested as possible inducers of some aspects of egg activation. In the present work, studies concerning the involvement of protein kinases during egg activation in our laboratory and in others are summarized.     

Functional effects of corticosterone on 5-HT(1A) and 5-HT(1B) receptor activity in rat brain: in vivo microdialysis studies

Glucocorticoid hormones are known to be elevated in depression, and to interact with serotonin 5-HT(1A) receptors at both the presynaptic and postsynaptic levels. Since one of the presumed mechanisms of action of antidepressant drugs is induction of changes in sensitivity of 5-HT(1A) and also 5-HT(1B) receptors, the effects of repeated administration of corticosterone (50 mg/kg s.c. b.i.d. for 10 days) on activities of these receptors were determined using in vivo microdialysis in freely moving rats. Presynaptic 5-HT(1A) receptor activity, as measured by the effect of a challenge dose (0.2 mg/kg s.c.) of the 5-HT(1A) agonist 8-hydroxy-2 (di-n-propylamino) tetralin (8-OH-DPAT) to reduce 5-HT levels in the hypothalamus, was not affected by corticosterone administration. Presynaptic 5-HT(1B) receptor activity, as measured by the effect of the 5-HT(1B) receptor antagonist (N-[4-methoxy-3-(4-methyl-1-piperizinyl)phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazole-3-yl)[1,1'-biphenyl]-carboxamide (GR 127935) (5 mg/kg s.c.) to increase 5-HT levels, was increased in hypothalamus but not hippocampus of corticosterone-treated rats. Postsynaptic 5-HT(1A) receptor activity, as measured by the effect of 8-OH-DPAT to increase cyclic AMP levels in the hippocampus, was not affected by corticosterone administration. The decrease in presynaptic 5-HT(1B) receptor activity after chronic administration of antidepressant drugs complements the increases in 5-HT(1B) receptor number observed in animal models of depression.     

Humour in Psychotherapy

ABSTRACT. Utilisation of humour by psychotherapists attracts increased interest. While the constructive and untoward potential of the use of humour in therapy has been discussed in the clinical literature, the issue has hardly been investigated empirically. The present study explored the reactions of patients to therapist interventions which employed humorous as compared to nonhumorous control reactions. The sample consisted of 60 female patients, of three personality types: obsessive, hysterical and depressive. They were asked to rate on 8-point scales twelve simulated, tape-recorded therapist interventions of three functional categories: anxiety reduction, perspective building and emotional confrontation. The results indicated a persistent preference for the nonhumorous over the humorous intervention. Statistical analysis revealed no main effects of either personality type or kind of humour, but these two variables were shown to interact significantly in determining the extent of preference for the nonhumorous over the humorous communications. Analysis of open-ended responses indicated more ambivalent attitudes toward the use of humour by patients. The implications of the findings for therapeutic theory and practice are discussed.