Despite the importance of aggression in the behavioral repertoire of most animals, relatively little is known of its proximate causation and control. To take advantage of modern methods of genetic analysis for studying this complex behavior, we have developed a quantitative framework for studying aggression in common laboratory strains of the fruit fly, Drosophila melanogaster. In the present study we analyze 73 experiments in which socially naive male fruit flies interacted in more than 2,000 individual agonistic interactions. This allows us to (i) generate an ethogram of the behaviors that occur during agonistic interactions; (ii) calculate descriptive statistics for these behaviors; and (iii) identify their temporal patterns by using sequence analysis. Thirty-minute paired trials between flies contained an average of 27 individual agonistic interactions, lasting a mean of 11 seconds and featuring a variety of intensity levels. Only few fights progressed to the highest intensity levels (boxing and tussling). A sequential analysis demonstrated the existence of recurrent patterns in behaviors with some similarity to those seen during courtship. Based on the patterns characterized in the present report, a detailed examination of aggressive behavior by using mutant strains and other techniques of genetic analysis becomes possible.
Gliomatosis cerebri is a rare diffusely infiltrating primary neoplastic glial process of the brain. Our objective is to review clinical presentation, management, and outcome in a large single institution series of gliomatosis cerebri patients. 54 consecutive gliomatosis cerebri cases presenting to Mayo Clinic Rochester between 1991 and 2008 were retrospectively reviewed. Inclusion criteria included involvement of at least three cerebral lobes, lack of a single discrete mass and pathological confirmation of diffuse glioma. Median overall survival (OS) was 18.5 months. Age, gender, presenting symptoms, and contrast enhancement did not correlate significantly with survival, though there was a trend toward decreased overall survival in patients above the median age of 46 years. Karnofsky performance score <70 was associated with poor OS (median 9.5 vs. 20.5 months, p = 0.02). Higher histologic grade was associated with poor progression-free survival (PFS; median for WHO grades II, III, and IV: 21.5, 6.5, and 4 months; p = 0.03) and OS (median 34, 15.5, and 8.5 months; p < 0.05). Radiation therapy was strongly associated with better prognosis (PFS 16.5 vs. 4.5 months, p < 0.01; OS 27.5 vs. 6.5, p < 0.01), but chemotherapy was not. Gliomatosis cerebri patients have a poor prognosis. Lower KPS upon presentation and higher histologic grade predict decreased survival. Surgery’s role is limited beyond biopsy for diagnostic purposes. Radiotherapy appears beneficial, although selection bias could be present in this retrospective study. Chemotherapy’s value is not as clear but this must be interpreted with caution given variable treatment regimens in this series.
Increasing glioma-associated macrophages in intracranial GL261 glioma decreases survival and markedly increases intratumoral and systemic MDSC's, many of which originate directly from glioma-associated macrophages. This is associated with decreased spontaneous immune responses to a model antigen. To our knowledge, this is the first evidence in cancer that systemic MDSC's can arise directly from normal monocytes that have undergone intratumoral immunosuppressive education.
Translocator protein (18 kDa) (TSPO) is a marker of inflammation in the brain. Positron emission tomography (PET) scans with ligands for this receptor show increased expression of TSPO in many neuropathologic conditions. However, expression of TSPO in the periphery and its possible correlation to central nervous system (CNS) inflammation has been largely unstudied. In this paper PBR28, a recently synthesized ligand for TSPO that is shown to have 80-fold higher specific binding than its predecessor PK11195, is used to quantify peripheral TSPO. Data presented in this study show that monocytes account for the majority of TSPO measured in peripheral blood mononuclear cells (PBMC), and that TSPO expression is stable over time in healthy individuals. Previous studies show that areas of increased PBR28 binding in the brains of multiple sclerosis (MS) patients correlate with active demylinating lesions found during magnetic resonance imaging (MRI). To measure peripheral TSPO expression in an inflammatory disease of the CNS, PBR28 is used in an in vitro radioligand binding assay to measure the amount of TSPO in the PBMC of MS and healthy donor cohorts. Surprisingly, MS patients are found to have a significantly lower amount of peripheral TSPO than healthy donors. We suggest that TSPO protein expression is a potential peripheral biomarker of MS, more research is needed to determine if peripheral TSPO expression may also be altered in other neuroinflammatory conditions.
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