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Activatory and inhibitory Fcy receptors augment rituximab-mediated internalization of CD20 independent of signaling via the cytoplasmic domain
No full textType I anti-CD20 mAb such as rituximab and ofatumumab engage with the inhibitory Fc?R, Fc?RIIb on the surface of B cells, resulting in immunoreceptor tyrosine-based inhibitory motif (ITIM) phosphorylation. Internalization of the CD20·mAb·Fc?RIIb complex follows, the rate of which correlates with Fc?RIIb expression. In contrast, although type II anti-CD20 mAb such as tositumomab and obinutuzumab also interact with and activate Fc?RIIb, this interaction fails to augment the rate of CD20·mAb internalization, raising the question of whether ITIM phosphorylation plays any role in this process. We have assessed the molecular requirements for the internalization process and demonstrate that in contrast to internalization of IgG immune complexes, Fc?RIIb-augmented internalization of rituximab-ligated CD20 occurs independently of the Fc?RIIb ITIM, indicating that signaling downstream of Fc?RIIb is not required. In transfected cells, activatory Fc?RI, Fc?RIIa, and Fc?RIIIa augmented internalization of rituximab-ligated CD20 in a similar manner. However, Fc?RIIa mediated a slower rate of internalization than cells expressing equivalent levels of the highly homologous Fc?RIIb. The difference was maintained in cells expressing Fc?RIIa and Fc?RIIb lacking cytoplasmic domains and in which the transmembrane domains had been exchanged. This difference may be due to increased degradation of Fc?RIIa, which traffics to lysosomes independently of rituximab. We conclude that the cytoplasmic domain of Fc?R is not required for promoting internalization of rituximab-ligated CD20. Instead, we propose that Fc?R provides a structural role in augmenting endocytosis that differs from that employed during the endocytosis of immune complexes
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Immunotherapy targeting inhibitory Fc? receptor IIB (CD32b) in the mouse is limited by monoclonal antibody consumption and receptor internalization
No full textGenetic deficiency of the inhibitory Fc receptor, Fc?RIIB (CD32b), has been shown to augment the activity of activatory Fc?R and promote mAb immunotherapy. To investigate whether mAbs capable of blocking Fc?RIIB have similar capacity, we recently generated a panel of specific anti-mouse Fc?RIIB mAbs that do not cross-react with other FcRs, allowing us to study the potential of Fc?RIIB as a therapeutic target. Previous work revealed a number of these mAbs capable of eliciting programmed cell death of targets, and in the present study we demonstrated their ability to promote target cell phagocytosis. However, in a variety of murine tumor models, anti-Fc?RIIB mAbs demonstrated limited therapeutic activity despite optimized treatment regimens. Unexpectedly, we observed that the anti-Fc?RIIB mAbs are rapidly and extensively consumed in vivo, both by the tumor and host cells, including B cells, leading to a precipitous loss from the circulation. Closer analysis revealed that the anti-Fc?RIIB mAbs become extensively internalized from the cell surface within 24 h in vivo, likely explaining their suboptimal efficacy. Subsequent studies revealed that anti-Fc?RIIB mAb immunotherapy was effective when used against Fc?RIIB+ tumors in Fc?RIIB?/? recipients, indicating that consumption of the mAb by nontumor cells is the primary limitation of these reagents. Importantly, similar rates of internalization were not seen on human target cells, at least in vitro. These studies further highlight the need to determine the propensity of mAb therapeutics to internalize target receptors and also identify potential key differences between human and mouse cells in this respect
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Inhibitory FcyRIIb (CD32b) becomes activated by therapeutic mAb in both cis and trans and drives internalization according to antibody specificity
No full textA major feature that distinguishes type I from type II anti-CD20 monoclonal antibodies (mAbs) and reduces their therapeutic efficacy is the tendency to internalize from the cell surface. We have shown previously that the extent of internalization correlates with the capacity of type I mAb to simultaneously engage both CD20 and the inhibitory Fc? receptor, Fc?RIIb, in a bipolar configuration. Here, we investigated whether mAbs directed at other B-cell surface receptors also engaged Fc?RIIb and whether this interaction promoted internalization. Most mAbs engaged and activated Fc?RIIb, with the strength of activation related to the level of mAb bound to the cell surface. However, engagement did not affect internalization of most mAb-ligated receptors, either in cell lines or primary chronic lymphocytic leukemia cells with the exception of CD19 and CD38. Furthermore, at high cell concentrations/density both cis and trans interactions between cell-surface bound mAb and Fc?RIIb were evident, but trans interactions did not inhibit type I anti-CD20 mAb-mediated internalization. These data identify that Fc?RIIb is engaged by many mAbs in both cis and trans configurations, triggering its activation, but that internalization via Fc?RIIb occurs for only a select subset. These findings have implications when designing new antibody-based therapeutics
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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