Neuroendocrine mechanisms underlying sensory integration of social signals.

Individuals integrate information about their environment into adaptive behavioural responses, yet how different sensory modalities contribute to these decisions and where in the brain this integration occurs is not well understood. We presented male cichlid fish (Astatotilapia burtoni) with sensory information in three social contexts: intruder challenge, reproductive opportunity and a socially neutral situation. We then measured behavioural and hormonal responses along with induction of the immediate early gene c-Fos in candidate forebrain regions. In the intruder challenge context, males were exposed to either a visual stimulus of a dominant male, the putative male pheromone androstenedione, or both. We found that, compared to the neutral context, a visual stimulus was necessary and sufficient for an aggressive response, whereas both chemical and visual stimuli were needed for an androgen response. In the reproductive opportunity context, males were exposed to either a visual stimulus of a receptive female, a progesterone metabolite (female pheromone) only, or both. We further found that the visual stimulus is necessary and sufficient for an androgen response in the reproductive opportunity context. In the brain, we observed c-Fos induction in response to a visual challenge stimulus specifically in dopaminergic neurones of area Vc (the central region of the ventral telencephalon), a putative striatal homologue, whereas presentation of a chemical stimulus did not induce c-Fos induction in the intruder challenge context. Our results suggest that different sensory cues are processed in a social context-specific manner as part of adaptive decision-making processes.

Cholesterol movement in Niemann-Pick type C cells and in cells treated with amphiphiles.

Cholesterol accumulates to massive levels in cells from Niemann-Pick type C (NP-C) patients and in cells treated with class 2 amphiphiles that mimic NP-C disease. This behavior has been attributed to the failure of cholesterol released from ingested low density lipoproteins to exit the lysosomes. However, we now show that the rate of movement of cholesterol from lysosomes to plasma membranes in NP-C cells is at least as great as normal, as was also found previously for amphiphile-treated cells. Furthermore, the lysosomes in these cells filled with plasma membrane cholesterol in the absence of lipoproteins. In addition, we showed that the size of the endoplasmic reticulum cholesterol pool and the set point of the homeostatic sensor of cell cholesterol were approximately normal in NP-C cells. The plasma membrane cholesterol pools in both NP-C and amphiphile-treated cells were also normal. Furthermore, the build up of cholesterol in NP-C lysosomes was not a physiological response to cholesterol overload. Rather, it appeared that the accumulation in NP-C lysosomes results from an imbalance in the brisk flow of cholesterol among membrane compartments. In related experiments, we found that NP-C cells did not respond to class 2 amphiphiles (e.g. trifluoperazine, imipramine, and U18666A); these agents may therefore act directly on the NPC1 protein or on its pathway. Finally, we showed that the lysosomal cholesterol pool in NP-C cells was substantially and preferentially reduced by incubating cells with the oxysterols, 25-hydroxycholesterol and 7-ketocholesterol; these findings suggest a new pharmacological approach to the treatment of NP-C disease.

Regulation of endoplasmic reticulum cholesterol by plasma membrane cholesterol.

The abundance of cell cholesterol is governed by multiple regulatory proteins in the endoplasmic reticulum (ER) which, in turn, are under the control of the cholesterol in that organelle. But how does ER cholesterol reflect cell (mostly plasma membrane) cholesterol? We have systematically quantitated this relationship for the first time. We found that ER cholesterol in resting human fibroblasts comprised approximately 0.5% of the cell total. The ER pool rose by more than 10-fold in less than 1 h as cell cholesterol was increased by approximately 50% from below to above its physiological value. The curve describing the dependence of ER on plasma membrane cholesterol had a J shape. Its vertex was at the ambient level of cell cholesterol and thus could correspond to a threshold. A variety of class 2 amphiphiles (e.g., U18666A) rapidly reduced ER cholesterol but caused only minor alterations in the J-curve. In contrast, brief exposure of cells to the oxysterol, 25-hydroxycholesterol, elevated and linearized the J-curve, increasing ER cholesterol at all values of cell cholesterol. This finding can explain the rapid action of oxysterols on cholesterol homeostasis. Other functions have also been observed to depend acutely on the level of plasma membrane cholesterol near its physiological level, perhaps reflecting a cholesterol-dependent structural or organizational transition in the bilayer. Such a physical transition could serve as a set-point above which excess plasma membrane cholesterol is transported to the ER where it would signal regulatory proteins to down-regulate its further accumulation.

Graft hyporeactivity induced by donor-specific bone marrow.

Much interest has recently focused on administration of donor cells with organ transplantation to improve graft outcome. However, whether donor cell administration actually confers donor-specific (DS) hyporeactivity is unknown. The intra-graft events after DS bone marrow (BM) infusion were therefore examined in an in vivo sponge matrix allograft model. Recipient C57BL/6J (B6,H2b) mice (five per group) received either media alone, 10(7) syngeneic (B6), or allogeneic (DBA/2J,H2d) BM cells intravenously. Seven days later, a sponge matrix allograft containing 10(7) allogeneic (DBA) splenocytes was implanted. On various days after grafting, graft-infiltrating cells were tested for in vitro cytotoxicity by 51Cr release assay. Previous DSBM infusion significantly reduced intragraft allospecific cytolytic T-cell (CTL) activity compared with mice receiving syngeneic BM or media alone (3.5 +/- 5.1% vs. 46.2 +/- 13.3% and 47.9 +/- 13.5% at 100:1 E:T, respectively, P < 0.001). Time course studies showed that DSBM impaired allospecific CTL activity whether given on day -10 (3.3% at 100:1 E:T), day -7 (2.2%), day -2(7.7%), or day 0 (6.5%), but was not as effective when given on day +7 (27.1%). Flow cytometry of graft-infiltrating cells on day +12 showed a decreased percentage of CD8+ cells after DSBM, compared with syngeneic BM or media alone (13.1% vs. 38.0% and 36% respectively, P = 0.01), but the percentage of CD4+ cells was similar in all groups (5.5%, 6.9%, and 4%, respectively). Thus, (1) DSBM inhibits allospecific CTL development in the allograft, (2) decreased intra-graft CTL activity after DSBM correlates with a decreased percentage of intragraft CD8+ cells, and (3) DSBM induces hyporeactivity up until the day of the allograft placement, but not thereafter. DSBM may, thus, induce graft hyporeactivity by impairing intragraft immune activation.

Chemistry of zirconia and its use in chromatography.

The purpose of this review is to shed some light on the complex properties of zirconia's surface chemistry in order to better understand its behaviour under chromatographic conditions. We emphasize the great differences between the much better known chemistry of a silica surface and the chemistry of zirconia's surface. The review describes both the physical and chemical properties of zirconium dioxide from a chromatographic point of view. The chemistry of monoclinic zirconia surface is developed from its underlying crystalline structure. The paper describes the dependence of the specific surface area, pore volume, porosity and mechanical strength on thermal treatment. Methods of synthesis of chromatographically useful zirconia are outlined. The review also covers the adsorption properties of zirconia at both gas-solid and liquid-solid interfaces. Adsorption of water, carbon dioxide, carbon monoxide and ammonia are described and the controversies concerning the surface concentration of adsorption sites are presented. The complex chemistry of a zirconia surface is pointed out and the importance of ligand exchange reactions is emphasized. In contrast to a silica surface, ligand exchange plays an important role in liquid chromatographic applications of zirconia. Strong, hard Lewis acid sites, present on a zirconia surface, can interact with hard Lewis bases and these interactions, sometimes troublesome, can be successfully exploited even for protein separations. Zirconia's surface can be modified in many ways: dynamically, by addition of competing Lewis bases to the mobile phase, or permanently, by covering its surface with polymers or by depositing carbon. The review also shows that the main difficulty in achieving a wider variety of applications is probably our lack of knowledge and poor understanding of zirconia's surface chemistry.

Bacterial Florae in Larvae of the Lake Fly Chironomus plumosus.

Chironomus plumosus midge larvae were collected from Lake Winnebago, Wisconsin, for 10 weeks in the summer of 1985 and 10 weeks in the summer of 1986 in order to determine their bacterial floras. Altogether, 18 genera and 29 species of bacteria were found and identified. Some spirillum-like bacteria which were not isolated in culture were found by electron microscopy. Scanning electron micrographs of sectioned larvae revealed bacteria throughout the intestines. Gram-positive organisms were most prevalent in the larvae in the early part of the summer, and gram-negative organisms were most prevalent during the later part. Larvae accumulate bacteria within their intestines.

Pathogenicity ofAeromonas hydrophila in red leg disease in frogs.

Endotoxin and hemolysin fromAeromonas hydrophila A(3) were studied to understand the pathogenicity of the organism. Neither the endotoxin nor the hemolysin alone produced typical red leg disease symptoms or death in frogs, even at a very high dosage of 8,000 µg; however, endotoxin and hemolysin together did. Further, histamine-stressed frogs died from hemolysin but not endotoxin. Hemolytic activity of hemolysin increased in cells that were preincubated with endotoxin. Results point to the conclusion that red leg disease in frogs represents a complex interaction between endotoxin and hemolysin and that stress-producing factors other than the endotoxin might trigger disease production.

Growth temperatures and temperature characteristics of Aeromonas.

Six of the 13 Aeromonas hydrophila, 1 of 10 A. shigelloides, and none of 10 A. salmonicida were found to be psychrophiles. All of the rest of the strains were mesophiles. The mu values (temperature characteristics) could not be used to distinguish psychrophiles from mesophiles.

Amino acid requirements of Aeromonas.

Four of the 12 cultures of Aeromonas hydrophila, 5 of the 10 A. shigelloides, and 9 of the 10 A. salmonicida that were studied required arginine and lysine, among other amino acids, for their growth.

Characteristics of the Hemagglutinin Produced During Plasmodium lophurae Malaria in Chickens.

During the course of Plasmodium lophurae infections in normal chickens, there was a sharp increase in the titer of a hemagglutinin which reacted better with trypsinized than with normal erythrocytes. This hemagglutinin was a typical "cold hemagglutinin" in that it was much more active at 4 C than at 37 C, was found in the macroglobulin fraction of the serum, was eluted from erythrocytes at 37 C, and was easily destroyed by 2-mercaptoethanol reduction. The injection of allogeneic erythrocytes into chickens prior to their exposure to P. lophurae resulted in a coexistent increase in cold hemagglutinin titers and enhanced resistance to parasitemia. Since this antibody was more active against altered erythrocytes than against normal erythrocytes, it may moderate resistance to malarial infections by specifically stimulating phagocytosis of parasitized erythrocytes.