Identification and Structural Characterization of Interneurons of the Drosophila Brain by Monoclonal Antibodies of the Würzburg Hybridoma Library

Several novel synaptic proteins have been identified by monoclonal antibodies (mAbs) of the Würzburg hybridoma library generated against homogenized Drosophila brains, e.g. cysteine string protein, synapse-associated protein of 47 kDa, and Bruchpilot. However, at present no routine technique exists to identify the antigens of mAbs of our library that label only a small number of cells in the brain. Yet these antibodies can be used to reproducibly label and thereby identify these cells by immunohistochemical staining. Here we describe the staining patterns in the Drosophila brain for ten mAbs of the Würzburg hybridoma library. Besides revealing the neuroanatomical structure and distribution of ten different sets of cells we compare the staining patterns with those of antibodies against known antigens and GFP expression patterns driven by selected Gal4 lines employing regulatory sequences of neuronal genes. We present examples where our antibodies apparently stain the same cells in different Gal4 lines suggesting that the corresponding regulatory sequences can be exploited by the split-Gal4 technique for transgene expression exclusively in these cells. The detection of Gal4 expression in cells labeled by mAbs may also help in the identification of the antigens recognized by the antibodies which then in addition to their value for neuroanatomy will represent important tools for the characterization of the antigens. Implications and future strategies for the identification of the antigens are discussed

Identification of Eps15 as Antigen Recognized by the Monoclonal Antibodies aa2 and ab52 of the Wuerzburg Hybridoma Library against Drosophila Brain

The Wuerzburg Hybridoma Library against the Drosophila brain represents a collection of around 200 monoclonal antibodies that bind to specific structures in the Drosophila brain. Here we describe the immunohistochemical staining patterns, the Western blot signals of one- and two-dimensional electrophoretic separation, and the mass spectrometric characterization of the target protein candidates recognized by the monoclonal antibodies aa2 and ab52 from the library. Analysis of a mutant of a candidate gene identified the Drosophila homolog of the Epidermal growth factor receptor Pathway Substrate clone 15 (Eps15) as the antigen for these two antibodies

Monoclonal antibody labels olfactory and visual pathways in Drosophila and Apis brains

We employed a monoclonal antibody raised against Drosophila brain homogenate for a comparative immunocytochemical analysis of visual and olfactory pathways in brains of two insect species. On Western blots of Drosophila and Apis nervous tissue, antibody fb45 recognized an antigen with an apparent molecular weight higher than 180 kD. Application of the antibody to sections of Drosophila and Apis brain stained certain interneurons which conspicuously fasciculate in common tracts or neuropilar compartments. Both in Drosophila and in Apis, the antigen was also expressed on the perineural sheath and granular cell compartments in the majority of neuronal cell bodies.The antibody stained monopolar cells in the visual system of both species, and in Apis those fibers of the anterior superior optic tract which link the medulla with the mushroom bodies. In Drosophila, bundles of Kenyon cells of the mushroom bodies were stained. In worker bees and drones, the relay neurons of the median and lateral antennoglomerular tracts were labelled.Since the recognition of the antigen does not require fixation, the antibody can be employed to label selectively living neurons in dissociated cell culture. This opens up the possibility for future functional studies on the role of the antigen in vitro

GRAND-4 : the German retrospective analysis of long-term persistence in women with osteoporosis treated with bisphosphonates or denosumab

Summary: This retrospective database study assessed 2-year persistence with bisphosphonates or denosumab in a large German cohort of women with a first-time prescription for osteoporosis treatment. Compared with intravenous or oral bisphosphonates, 2-year persistence was 1.5–2 times higher and risk of discontinuation was significantly lower (P < 0.0001) with denosumab. Introduction: Persistence with osteoporosis therapies is critical for fracture risk reduction. Detailed data on long-term persistence (≥2 years) with bisphosphonates and denosumab are sparse. Methods: From the German IMS® database, we included women aged 40 years or older with a first-time prescription for bisphosphonates or denosumab between July 2010 and August 2014; patients were followed up until December 2014. The main outcome was treatment discontinuation, with a 60-day permissible gap between filled prescriptions. Two-year persistence was estimated using Kaplan–Meier survival curves, with treatment discontinuation as the failure event. Denosumab was compared with intravenous (i.v.) and oral bisphosphonates separately. Cox proportional hazard ratios (HRs) for the 2-year risk of discontinuation were calculated, with adjustment for age, physician specialty, health insurance status, and previous medication use. Results: Two-year persistence with denosumab was significantly higher than with i.v. or oral bisphosphonates (39.8 % [n = 21,154] vs 20.9 % [i.v. ibandronate; n = 20,472] and 24.8 % [i.v. zoledronic acid; n = 3966] and 16.7–17.5 % [oral bisphosphonates; n = 114,401]; all P < 0.001). Patients receiving i.v. ibandronate, i.v. zoledronic acid, or oral bisphosphonates had a significantly increased risk of treatment discontinuation than did those receiving denosumab (HR = 1.65, 1.28, and 1.96–2.02, respectively; all P < 0.0001). Conclusions: Two-year persistence with denosumab was 1.5–2 times higher than with i.v. or oral bisphosphonates, and risk of discontinuation was significantly lower with denosumab than with bisphosphonates. A more detailed understanding of factors affecting medication-taking behavior may improve persistence and thereby reduce rates of fracture

Fraudulent Accounting and Other Doping Games

From a game theoretic point of view, fraudulent accounting to em-bellishnthe financial status of a firm and the use of drugs to enhancenperformance in sports are very similar. We study the replicator dy-namicsnof both applications within the same model. We allow for het-erogenousnpopulations, such as highly talented versus more mediocrenathletes, or high quality managers versus less able colleagues. Inter-estingly,nfor some parameters, the replicator dynamics is character-izednby cycles. Thus, we may see cycles of doping and clean sport,nand cycles of fraudulent and honest accounting. Moreover, in somencases, high ability players are more likely to commit fraud than lownability types