Transneuronal Dpr12/DIP‐δ interactions facilitate compartmentalized dopaminergic innervation of Drosophila mushroom body axons

The mechanisms controlling wiring of neuronal networks are not completely understood. The stereotypic architecture of the Drosophila mushroom body (MB) offers a unique system to study circuit assembly. The adult medial MB γ‐lobe is comprised of a long bundle of axons that wire with specific modulatory and output neurons in a tiled manner, defining five distinct zones. We found that the immunoglobulin superfamily protein Dpr12 is cell‐autonomously required in γ‐neurons for their developmental regrowth into the distal γ4/5 zones, where both Dpr12 and its interacting protein, DIP‐δ, are enriched. DIP‐δ functions in a subset of dopaminergic neurons that wire with γ‐neurons within the γ4/5 zone. During metamorphosis, these dopaminergic projections arrive to the γ4/5 zone prior to γ‐axons, suggesting that γ‐axons extend through a prepatterned region. Thus, Dpr12/DIP‐δ transneuronal interaction is required for γ4/5 zone formation. Our study sheds light onto molecular and cellular mechanisms underlying circuit formation within subcellular resolution.     

Macrophages in resistance to rickettsial infection: susceptibility to lethal effects of Rickettsia akari infection in mouse strains with defective macrophage function

We have confirmed the requirement of macrophages in the antigen-induced T-lymphocyte proliferative response and in the generation of migration inhibition factor (MIF) by immune lymphocytes. Extending these observations, we have found that autologous and non-syngeneic, oil-induced peritoneal exudate macrophages were equally effective in restoring the proliferative response and MIF production by column-purified lymph node T cells. MIF activity was optimally restored when T cells were reconstituted with 1 to 40% exudate-derived macrophages whereas 10 to 30% macrophages were needed to optimally restore the T-cell proliferative response. Normal resident macrophages from the peritoneal cavity were also capable of restoring T-cell reactivity as were normal or BCG-activated pulmonary alveolar macrophages. It was also found that the addition of as few as 1.0% glycogen-elicited peritoneal exudate cells restored the production of MIF by T cells. Quantitative considerations demonstrated that the responsible cells in these preparations were polymorphonuclear cells rather than macrophages. In contrast, neither MIF production nor the proliferative response by T cells were restored by the addition of red blood cells. In these studies we were able to demonstrate that freeze-thawed macrophages could restore antigen-induced MIF production, but not antigen-induced cellular proliferation. The ability of freeze-thawed macrophages to stimulate T cells to produce MIF was apparently associated with the macrophage membranes and not with a soluble factor in the macrophage extracts. These results demonstrate that multiple sources of phagocytic cells may interact cooperatively with lymphocytes in reactions of cell-mediated immunity. Further, at least in the case of MIF production, this interaction involves a membrane-bound determinant that is effective even in the absence of viable macrophages.     

Inhibition of calmodulin-activated Ca2+-ATPase by propranolol and nadolol

Propranolol, at concentrations ranging from 0.05 to 0.5 mM, inhibits the calmodulin-activated Ca²⁺-ATPase of human erythrocyte membranes. In the same concentration range it is without effect on the basal Ca²⁺-ATPase. The inhibition is competitive and appears to be due to membrane binding, rather than to combination with cytoplasmic calmodulin as is the case for phenothiazines. This effect of propranolol may explain its ability to open the calcium-gated potassium channel, and could also be related to its action as a β-adrenergic blocker. Nadolol, another β-adrenergic blocker, is also an inhibitor of calmodulin-activated Ca²⁺-ATPase.     

Effect of quipazine on rat plasma prolactin levels

Quipazine (2-(1-piperazinyl) quinoline maleate), a serotonin agonist which also has other effects on serotonin metabolism, in doses from 2.5 – 20 mg/kg, i.p., was found to markedly increase plasma prolactin levels in male rats. This increase was blocked by the serotonin antagonists methysergide and brom-lysergic acid diethylamide and potentiated by para-chlorophenylalanine, an inhibitor of serotonin synthesis. These findings suggest that the increase in plasma prolactin levels is due to the serotonin agonist properties of quipazine. Apomorphine and 2-Br-α-ergocryptine pretreatment blocked the effect on plasma prolactin of quipazine, while apomorphine given 15 min after quipazine brought about a rapid decline in the elevated plasma prolactin levels produced by quipazine.     

Intradimensional and extradimensional shifts in conditional discrimination

Two groups of pigeons learned a two key conditional discrimination. Color was the conditional stimulus and form the choice stimulus for subjects in one group. Form was the conditional stimulus and color the choice stimulus in the other group. Half the subjects in each group then underwent an intradimensional shift: The conditional stimulus dimension and choice stimulus dimension were unchanged but the correct and incorrect stimulus compounds were reversed. The remaining subjects underwent an extra-dimensional shift in which the conditional stimulus dimension and choice stimulus dimension were reversed. Subjects which experienced an intradimensional shift learned the new conditional discrimination more quickly. It was concluded that subjects followed rules to solve conditional discriminations but also learned the functions of each stimulus dimension.     

Twelve amplified and expressed genes localized in a single domain in glioma

Gene amplification has been associated both with tumor stage and progression in human gliomas. Several distinct amplified loci have been identified by comparative genomic hybridization and Southern blot analysis. It has been increasingly recognized that amplified domains comprise multiple genes. Here, we demonstrate amplification of up to 12 different genes from an amplified domain at 12q13–15 that has been found in approximately 15% of astrocytomas and glioblastomas. The amplified genes were GLI, WNT1, MDM2, SAS, CDK4, OS-4, GAS16, GAS27, GAS41, GAS56, GAS 64 and GAS89. In one glioblastoma all 12 amplified genes were also found to be expressed. These results strongly warrant the search for as yet unidentified genes in regions previously reported to be amplified. Received: 3 June 1996 / Revised: 4 July 1996     

Development and utilization of a somatic cell hybrid mapping panel to assign NotI linking probes to the long arm of human chromosome 6.

A somatic cell hybrid mapping panel that defines seven regions of the long arm and one region of the short arm of human chromosome 6 has been developed. Utilizing this panel, 17 NotI boundary clones from a NotI linking library were regionally assigned to the long arm of chromosome 6. The majority of these clones (11) were found to localize within band regions 6q24-q27. The nonuniform distribution of NotI sites may indicate a cluster of HTF islands and likely represents a coincidence of coding sequences in this region of chromosome 6. Cross-hybridization of these linking clones to DNA from other species (zoo blots) provides further evidence for transcribed sequences in 7 of the NotI clones. These NotI clones were also used to identify corresponding NotI fragments using pulsed-field gel electrophoresis, facilitating further physical mapping of this region. Finally, regional assignment of five polymorphic probes to the long arm of chromosome 6 is also presented. These hybrids and probes should facilitate the construction of a physical and genetic linkage map to assist in the identification of disease loci along chromosome 6.     

Colony-stimulating factors and regulation of macrophage tumoricidal and microbicidal activities

Conditioned medium from antigen- or mitogen-stimulated spleen cells, lymphokines, contained factors that induced formation of granulocyte and macrophage colonies in cultures of bone marrow cells (CSF). Lymphokines also contained factors that induced macrophage non-specific tumoricidal activity against fibrosarcoma 1023, antibody-dependent tumoricidal activity against lymphoma 18-8, and antimicrobial activities against amastigotes of the protozoan parasite, Leishmania tropica. The factors that regulated macrophage effector functions, however, were different from those that induced colony formation, and could be distinguished from CSF by Sephadex gel chromatography or heat sensitivity. To further analyze a role for CSF in induction of macrophage effector activities, conditioned medium from several nonlymphoid cell sources (L-929, WEHI-3, and endotoxin-treated lung cells) were assayed for CSF activities and capacity to induce tumoricidal and microbicidal activities. Conditioned medium that contained either macrophages CSF (CSF-1) or the factor that induced formation of both macrophage and granulocyte colonies failed to activate macrophages for effector activities against fibrosarcoma 1023, lymphoma 18-8, and L. tropica amastigotes (either resistance to infection or intracellular destruction). These data suggest that CSF has no direct role in activation of macrophages for tumoricidal and microbicidal activities against these targets.