Elevated myc expression and c-myc amplification in spontaneously occurring B lymphoid cell lines

Recently, a minor subpopulation of murine B lymphocytes, Ly-1+ B cells, has been distinguished by its unique ontogeny, tissue distribution, and prominence in certain autoimmune and neoplastic B cell diseases. We have previously described a simple murine spleen culture system that results in the spontaneous and exclusive outgrowth of long-term Ly-1+ B cell lines (B Ly-1 cells). Here, we report that the immortal growth property of B Ly-1 cells correlates with a 10-45-fold elevation of steady-state myc RNA and 2-10-fold amplification of the c-myc locus. While c-myc amplification has been observed in malignant cell lines derived from several tissues of origin, its occurrence in lymphoid cells has not been previously reported. The consistent c-myc amplification in B Ly-1 cells may reflect a unique state of this locus in the Ly-1+ B lymphocyte lineage, and contribute to the spontaneous immortalization of this B cell population in vitro, and its apparent predilection for malignant transformation in vivo

Positron emission tomography imaging of endometrial cancer using engineered anti-EMP2 antibody fragments.

PurposeAs imaging of the cell surface tetraspan protein epithelial membrane protein-2 (EMP2) expression in malignant tumors may provide important prognostic and predictive diagnostic information, the goal of this study is to determine if antibody fragments to EMP2 may be useful for imaging EMP2 positive tumors.ProceduresThe normal tissue distribution of EMP2 protein expression was evaluated by immunohistochemistry and found to be discretely expressed in both mouse and human tissues. To detect EMP2 in tumors, a recombinant human anti-EMP2 minibody (scFv-hinge-C(H)3 dimer; 80 kDa) was designed to recognize a common epitope in mice and humans and characterized. In human tumor cell lines, the antibody binding induced EMP2 internalization and degradation, prompting the need for a residualizing imaging strategy. Following conjugation to DOTA (1,4,7,10-tetraazacyclododecane-N,N',N',N'″-tetraacetic acid), the minibody was radiolabeled with (64)Cu (t (1/2) = 12.7 h) and evaluated in mice as a positron emission tomography (PET) imaging agent for human EMP2-expressing endometrial tumor xenografts.ResultsThe residualizing agent, (64)Cu-DOTA anti-EMP2 minibody, achieved high uptake in endometrial cancer xenografts overexpressing EMP2 (10.2 ± 2.6, percent injected dose per gram (%ID/g) ± SD) with moderate uptake in wild-type HEC1A tumors (6.0 ± 0.1). In both cases, precise tumor delineation was observed from the PET images. In contrast, low uptake was observed with anti-EMP2 minibodies in EMP2-negative tumors (1.9 ± 0.5).ConclusionsThis new immune-PET agent may be useful for preclinical assessment of anti-EMP2 targeting in vivo. It may also have value for imaging of tumor localization and therapeutic response in patients with EMP2-positive malignancies

Clustering Scatter Plots Using Data Depth Measures.

Clustering is rapidly becoming a powerful data mining technique, and has been broadly applied to many domains such as bioinformatics and text mining. However, the existing methods can only deal with a data matrix of scalars. In this paper, we introduce a hierarchical clustering procedure that can handle a data matrix of scatter plots. To more accurately reflect the nature of data, we introduce a dissimilarity statistic based on "data depth" to measure the discrepancy between two bivariate distributions without oversimplifying the nature of the underlying pattern. We then combine hypothesis testing with hierarchical clustering to simultaneously cluster the rows and columns of the data matrix of scatter plots. We also propose novel painting metrics and construct heat maps to allow visualization of the clusters. We demonstrate the utility and power of our new clustering method through simulation studies and application to a microbe-host-interaction study

α-Synuclein Reduces Tension and Increases Undulations in Simulations of Small Unilamellar Vesicles

AbstractUsing coarse-grained molecular dynamics simulations we have explored the effect of α-Synuclein (αSyn) on the structural and mechanical properties of small unilamellar vesicles in the fluid-phase. The study is motivated by observations that a high density of membrane-bound αSyn inhibits the fusion of synthetic small unilamellar vesicles. By combining three-dimensional pressure tensor calculations with our recently developed spherical harmonics fluctuation analysis approach, we show a reduction in membrane surface tension and increased membrane undulations when αSyn is bound to the vesicle’s outer leaflet at a 200:1 L/P. The protein effects these changes by decreasing the negative pressure in the headgroup region of the outer leaflet and increasing the positive pressure throughout the hydrocarbon core

Tracing/training rebellion - object work in Meyerhold's biomechanics

[First paragraph] Lying in the Russian State Archive of Literature and Arts in Moscow (RGALI) is a nine-page document entitled Programme of Biomechanics, Meyerhold Workshop (1922). Though modest in size, it is an unashamedly ambitious programme, which sought to redefine acting in a post-revolutionary context and to place performer training in Russia on a par with science. ‘The task of the biomechanical laboratory is to work out through experimentation a biomechanical system of acting and of actor’s training’ (Hoover 1974: 314), the document claims, setting out a dedicated model of Practice as Research, seventy years before the term became common place in the UK

The Digital Revolution to Come: Photogrammetry in Archaeological Practice

The three-dimensional (3D) revolution promised to transform archaeological practice. Of the technologies that contribute to the proliferation of 3D data, photogrammetry facilitates the rapid and inexpensive digitization of complex subjects in both field and lab settings. It finds additional use as a tool for public outreach, where it engages audiences ranging from source communities to artifact collectors. But what has photogrammetry’s function been in advancing archaeological analysis? Drawing on our previous work, we review recent applications to understand the role of photogrammetry for contemporary archaeologists. Although photogrammetry is widely used as a visual aid, its analytical potential remains underdeveloped. Considering various scales of inquiry—graduating from objects to landscapes—we address how the technology fits within and expands existing documentation and data visualization routines, while evaluating the opportunity it presents for addressing archaeological questions and problems in innovative ways. We advance an agenda advocating that archaeologists move from proof-of concept papers toward greater integration of photogrammetry with research

Passive Avoidance Training and Recall are Associated With Increased Glutamate Levels in the Intermediate Medial Hyperstriatum Ventrale of the Day-Old Chick

In the young chick, the intermediate medial hyperstriatum ventrale is involved in learning paradigms, including imprinting and passive avoidance learning. Biochemical changes in the intermediate medial hyperstriatum ventrale following learning include an up-regulation of amino-acid transmitter levels and receptor activity. To follow the changes of extracellular amino acid levels during passive avoidance training, we used an in vivo microdialysis technique. Probes were implanted in chicks before training the animals, either on a methyl- anthranylate-or water-coated bead. One hour later, recall was tested in both groups by presenting a similar bead. An increase of extra-cellular glutamate levels accompanied training and testing in both groups; during training, glutamate release was higher in methylanthranylate- trained than in water-trained chicks. When compared with the methylanthranylate-trained chicks during testing, the water-trained chicks showed enhanced extra-cellular glutamate levels. No other amino acid examined showed significant changes. After testing, the chicks were anesthetized and release- stimulated with an infusion of 50 mM potassium. Extra-cellular glutamate and taurine levels were significantly increased in both methylanthranylate-and water-trained chicks. The presentation of methylanthranylate as an. olfactory stimulus significantly enhanced glutamate levels, especially in methylanthranylate-trained chicks. The results suggest that such changes in extra-cellular glutamate levels in the intermediate medial hyperstriatum ventrale accompany pecking at either the water- or the methylanthranylate-bead. The taste of the aversant may be responsible for the greater increases found in methylanthranylate-trained birds

Systemic sclerosis is associated with specific alterations in gastrointestinal microbiota in two independent cohorts.

ObjectiveTo compare faecal microbial composition in patients with systemic sclerosis (SSc) from 2 independent cohorts with controls and to determine whether certain genera are associated with SSc-gastrointestinal tract (GIT) symptoms.DesignAdult patients with SSc from the University of California, Los Angeles (UCLA) and Oslo University Hospital (OUH) and healthy controls participated in this study (1:1:1). All participants provided stool specimens for 16S rRNA sequencing. Linear discriminant analysis effect size demonstrated genera with differential expression in SSc. Differential expression analysis for sequence count data identified specific genera associated with GIT symptoms as assessed by the GIT 2.0 questionnaire.ResultsThe UCLA-SSc and OUH-SSc cohorts were similar in age (52.1 and 60.5 years, respectively), disease duration (median (IQR): 6.6 (2.5-16.4) and 7.0 (1.0-19.2) years, respectively), gender distribution (88% and 71%, respectively), and GIT symptoms (mean (SD) total GIT 2.0 scores of 0.7 (0.6) and 0.6 (0.5), respectively). Principal coordinate analysis illustrated significant microbial community differences between SSc and controls (UCLA: p=0.001; OUH: p=0.002). Patients with SSc had significantly lower levels of commensal genera deemed to protect against inflammation, such as Bacteroides (UCLA and OUH), Faecalibacterium (UCLA), Clostridium (OUH); and significantly higher levels of pathobiont genera, such as Fusobacterium (UCLA), compared with controls. Increased abundance of Clostridium was associated with less severe GIT symptoms in both cohorts.ConclusionsThe present analysis detected specific aberrations in the lower GIT microbiota of patients with SSc from 2 geographically and ethnically distinct cohorts. These findings suggest that GIT dysbiosis may be a pathological feature of the SSc disease state