Predicting Research Productivity in International Evaluation Journals across Countries

Background: Progress in evaluation research depends on the continuous generation of scholarly knowledge and its dissemination in the community. One way of disseminating findings is to publish in scientific journals and researchers, institutions, and even whole countries are assessed by their output in these journals. Particularly with regard to countries, there is an uneven distribution of research productivity in evaluation journals. A viable model for predicting countries’ research output in international evaluation journals, however, has not yet been developed. Purpose: The purpose of this study was to develop and test a model for the prediction of countries’ research output in international evaluation journals by predictors from the research, economic, and social/political system. Setting: NA Intervention: NA Research Design: A cross-sectional design was used for predicting research output in evaluation journals across countries. Data Collection and Analysis: Our sample consists of 65 countries that made contributions to ten international peer-reviewed evaluation journals. We collected data for the period from 2009 to 2013 and predicted the number of authorships across countries by using boosted regression trees, a machine learning procedure. Findings: Our model provided accurate predictions of countries’ research output. Research productivity in the social sciences had the strongest effect, followed by economic prosperity, control of corruption, and age of evaluation society. The model was generalizable to another period of time with only marginal loss in predictive accuracy

Generalized Lévy walks and the role of chemokines in migration of effector CD8+ T cells.

Chemokines have a central role in regulating processes essential to the immune function of T cells, such as their migration within lymphoid tissues and targeting of pathogens in sites of inflammation. Here we track T cells using multi-photon microscopy to demonstrate that the chemokine CXCL10 enhances the ability of CD8+ T cells to control the pathogen Toxoplasma gondii in the brains of chronically infected mice. This chemokine boosts T-cell function in two different ways: it maintains the effector T-cell population in the brain and speeds up the average migration speed without changing the nature of the walk statistics. Notably, these statistics are not Brownian; rather, CD8+ T-cell motility in the brain is well described by a generalized Lévy walk. According to our model, this unexpected feature enables T cells to find rare targets with more than an order of magnitude more efficiency than Brownian random walkers. Thus, CD8+ T-cell behaviour is similar to Lévy strategies reported in organisms ranging from mussels to marine predators and monkeys, and CXCL10 aids T cells in shortening the average time taken to find rare targets

Imaging pathogen, endothelial cell and T cell interactions in the vascular compartment

Non UBCUnreviewedAuthor affiliation: University of PennsylvaniaPostdoctora

Cross-talk zwischen Shigella und Zellen des Adaptiven Immunsystems: Der TTS Effektor IpgD inhibiert die T Zell Migration

Shigellosis, or bacillary dysentery, is a rectocolitis caused by the gram-negative, enteroinvasive bacteria of the genus Shigella. Shigellosis still remains a major public health burden with an estimated 80 million cases of bloody diarrhoea and 700.000 deaths per year, primarily in children under the age of 5. Shigella disrupts, invades, and causes inflammatory destruction of the colonic epithelium in humans through virulence effectors secreted by the type III secretion apparatus (TTSA). In contrast to the Shigella-induced manipulation of the host innate immune response, the impact of Shigella on the adaptive immunity has been poorly studied thus far. In order to understand why the naturally induced protective humoral response requires several infections to be primed and is of short duration, the work presented here investigates if Shigella is able to directly interact with T cells. Indeed, it has been shown that Shigella was able to invade and proliferate inside T cells. Furthermore, Shigella was able to inhibit T cell migration through a TTSA effector. Moreover, the Shigella effector IpgD, a phosphoinositide 4-phosphatase that specifically dephosphorylates phosphatidylinositol-(4,5)-bisphosphate (PIP2) into phosphatidylinositol-(5)-monophosphate (PI(5)P), was identified as the effector responsible for the observed inhibition. It could be demonstrated that IpgD was responsible for a reduction of intracellular PIP2 levels in T cells. Further experiments showed a reduced level of phosphorylated ezrin, radixin and moesin (ERM) proteins in infected, as well as with IpgD transfected, T cells. The ERM protein family plays an imported role in signal transduction and motility and their activity is closely related to the binding of PIP2. Therefore, the low level of PIP2 leads to a dephosphorylation of the ERM proteins which inhibits T cells response to chemokine stimulation. Indeed, IpgD transfected T cells show a reduced ability to re-localise the ERM proteins upon chemokine stimulation. Targeting T cell motility, via TTSA effectors, could explain the low level of specific T cell priming during Shigella infection. This is the first report of Shigella induced manipulation of T cell function and on the inhibition of T cell migration by a bacterial effector.Shigellose oder Bakterieruhr ist eine von Bakterien der Gattung Shigella ausgelöste Dysenterie Erkrankung des Dickdarms. Mit jährlich über 80 Millionen Fällen von blutigen Durchfällen und 700000 Todesfällen, hauptsächlich bei Kindern unter 5 Jahren, stellt Shigella immer noch ein ernsthaftes Gesundheitsproblem dar. Shigella destabilisiert das menschliche Dickdarmgewebe und dringt in dieses ein, wo es eine akute Entzündung auslöst, die das Gewebe weiterhin zerstört. Verursacht wird dies durch bakterielle Effektoren, die durch ein Type III Sekretionssytem (TTSA) sekretiert werden. Verglichen mit der Anzahl an Studien über die Manipulation der angeborenen Immunabwehr gibt es nur wenige Studien über die Interaktionen von Shigella mit dem adaptiven Immunsystem. Um zu verstehen, warum für die Entwicklung einer humoralen Immunantwort mehrere Infektionen erforderlich sind, wurde im Rahmen dieser Arbeit untersucht, ob Shigella in der Lage ist, direkt mit TZellen zu interagieren. Es konnte gezeigt werden, dass Shigella in T-Zellen eindringen und sich vermehren kann. Darüber hinaus zeigt sich, dass Shigella in der Lage ist, durch TTSA-Effektoren die T-Zell-Migration zu hemmen. Der Shigella Effektor IpgD konnte als der für die Hemmung verantwortliche Effektor identifiziert werden. Bei IpgD handelt es sich um eine 4-Phosphoinositid-Phosphatase, die Phosphatidylinositol-(4,5)-bisphosphat (PIP2) zu Phosphatidyl-inositol-(5)- monophosphat (PI(5)P) dephosphoryliert. Es wurde deutlich, dass der Effektor IpgD, neben der Menge an PIP2, auch die Menge an phosphorylierten Ezrin, Radixin und Moesin (ERM) Proteinen in T-Zellen reduziert. Die ERM-Protein-Familie spielt in der Signaltransduktion und bei der Motilität von T-Zellen eine wichtige Rolle und ihre Phosphorylierung ist eng an die Bindung von PIP2 gekoppelt. Daher führt eine geringe Menge an PIP2 zu einer Dephosphorylierung der ERM-Proteine, was eine Stimulierung der T-Zellen durch Chemokine hemmt. In der Tat zeigten IpgDtransfizierte T-Zellen eine verminderte Fähigkeit zur Relokalisierung der ERM-Proteine nach einer Chemokine-Stimulation. In dieser Arbeit konnte erstmals die Manipulation von T-Zell-Funktionen durch Shigella und die Hemmung der T-Zell-Migration, ausgelöst durch einen bakteriellen TTSA-Effektor, gezeigt werden

Predicting Research Productivity in International Evaluation Journals across Countries

Background: Progress in evaluation research depends on the continuous generation of scholarly knowledge and its dissemination in the community. One way of disseminating findings is to publish in scientific journals and researchers, institutions, and even whole countries are assessed by their output in these journals. Particularly with regard to countries, there is an uneven distribution of research productivity in evaluation journals. A viable model for predicting countries’ research output in international evaluation journals, however, has not yet been developed. Purpose: The purpose of this study was to develop and test a model for the prediction of countries’ research output in international evaluation journals by predictors from the research, economic, and social/political system. Setting: NA Intervention: NA Research Design: A cross-sectional design was used for predicting research output in evaluation journals across countries. Data Collection and Analysis: Our sample consists of 65 countries that made contributions to ten international peer-reviewed evaluation journals. We collected data for the period from 2009 to 2013 and predicted the number of authorships across countries by using boosted regression trees, a machine learning procedure. Findings: Our model provided accurate predictions of countries’ research output. Research productivity in the social sciences had the strongest effect, followed by economic prosperity, control of corruption, and age of evaluation society. The model was generalizable to another period of time with only marginal loss in predictive accuracy

New insights into the crosstalk between Shigella and T lymphocytes

International audienceSubversion of host immune responses is the key infection strategy employed by most, if not all, human pathogens. Modulation of the host innate response by pathogens has been vastly documented. Yet, especially for bacterial infections, it was only recently that cells of the adaptive immune response were recognized as targets of bacterial weapons such as the type III secretion system (T3SS) and its effector proteins. In this review, we focus on the recent advances made in the understanding of how the enteroinvasive bacterium Shigella flexneri interferes with the host adaptive response by targeting T lymphocytes, especially their migration capacities

Disruption of <i>TgPHIL1</i> Alters Specific Parameters of <i>Toxoplasma gondii</i> Motility Measured in a Quantitative, Three-Dimensional Live Motility Assay

<div><p><i>T. gondii</i> uses substrate-dependent gliding motility to invade cells of its hosts, egress from these cells at the end of its lytic cycle and disseminate through the host organism during infection. The ability of the parasite to move is therefore critical for its virulence. <i>T. gondii</i> engages in three distinct types of gliding motility on coated two-dimensional surfaces: twirling, circular gliding and helical gliding. We show here that motility in a three-dimensional Matrigel-based environment is strikingly different, in that all parasites move in irregular corkscrew-like trajectories. Methods developed for quantitative analysis of motility parameters along the smoothed trajectories demonstrate a complex but periodic pattern of motility with mean and maximum velocities of 0.58±0.07 µm/s and 2.01±0.17 µm/s, respectively. To test how a change in the parasite's crescent shape might affect trajectory parameters, we compared the motility of Δ<i>phil1</i> parasites, which are shorter and wider than wild type, to the corresponding parental and complemented lines. Although comparable percentages of parasites were moving for all three lines, the Δ<i>phil1</i> mutant exhibited significantly decreased trajectory lengths and mean and maximum velocities compared to the parental parasite line. These effects were either partially or fully restored upon complementation of the Δ<i>phil1</i> mutant. These results show that alterations in morphology may have a significant impact on <i>T. gondii</i> motility in an extracellular matrix-like environment, provide a possible explanation for the decreased fitness of Δ<i>phil1</i> parasites <i>in vivo</i>, and demonstrate the utility of the quantitative three-dimensional assay for studying parasite motility.</p></div