Transcriptional factor PU.1 regulates decidual C1q expression in early pregnancy in human

"Copyright: © 2015 Madhukaran, Kishore, Jamil, Teo, Choolani and Lu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms."C1q is the first recognition subcomponent of the complement classical pathway, which in addition to being synthesized in the liver, is also expressed by macrophages and dendritic cells (DCs). Trophoblast invasion during early placentation results in accumulation of debris that triggers the complement system. Hence, both early and late components of the classical pathway are widely distributed in the placenta and decidua. In addition, C1q has recently been shown to significantly contribute to feto-maternal tolerance, trophoblast migration, and spiral artery remodeling, although the exact mechanism remains unknown. Pregnancy in mice, genetically deficient in C1q, mirrors symptoms similar to that of human preeclampsia. Thus, regulated complement activation has been proposed as an essential requirement for normal successful pregnancy. Little is known about the molecular pathways that regulate C1q expression in pregnancy. PU.1, an Ets-family transcription factor, is required for the development of hematopoietic myeloid lineage immune cells, and its expression is tissue-specific. Recently, PU.1 has been shown to regulate C1q gene expression in DCs and macrophages. Here, we have examined if PU.1 transcription factor regulates decidual C1q expression. We used immune-histochemical analysis, PCR, and immunostaining to localize and study the gene expression of PU.1 transcription factor in early human decidua. PU.1 was highly expressed at gene and protein level in early human decidual cells including trophoblast and stromal cells. Surprisingly, nuclear as well as cytoplasmic PU.1 expression was observed. Decidual cells with predominantly nuclear PU.1 expression had higher C1q expression. It is likely that nuclear and cytoplasmic PU.1 localization has a role to play in early pregnancy via regulating C1q expression in the decidua during implantation

Scaffolding problem-based learning with CSCL tools

Small-group medical problem-based learning (PBL) was a pioneering form of collaborative learning at the university level. It has traditionally been delivered in face-to-face text-based format. With the advancement of computer technology and progress in CSCL, educational researchers are now exploring how to design digitally-implemented scaffolding tools to facilitate medical PBL. The "deteriorating patient" (DP) role play was created as a medical simulation that extends traditional PBL and can be implemented digitally. We present a case study of classroom usage of the DP role play that examines teacher scaffolding of PBL under two conditions: using a traditional whiteboard (TW) and using an interactive whiteboard (IW). The introduction of the IW technology changed the way that the teacher scaffolded the learning. The IW showed the teacher all the information shared within the various subgroups of a class, broadening the basis for informed classroom scaffolding. The visual records of IW usage demonstrated what students understood and reduced the need to structure the task. This allowed more time for engaging students in challenging situations by increasing the complexity of the problem. Although appropriate scaffolding is still based on the teacher's domain knowledge and pedagogy experience, technology can help by expanding the scaffolding choices that an instructor can make in a medical training context. © 2010 The Author(s).published_or_final_versionSpringer Open Choice, 01 Dec 201

Segment and track neurons in 3D by repulsive snake method

We present a snake (active contour) model based on repulsive force to segment neurons obtained from microscopy. Based on these segmentation results, we track the neurons in 3D image to look for its branch structure. These segmentation results allow user to study morphology of neurons to further investigate neuronal function and connectivity. This repulsive snake model can successfully segment two or multiple neurons that are close to each other by some alternating repulsive force generated from the neighboring objects. We apply our results on real data to demonstrate the performance of our method. © 2005 IEEE.published_or_final_versio

The role of CD44 and ERM proteins in expression and functionality of P-glycoprotein in breast cancer cells

© 2016 by the authors. Multidrug resistance (MDR) is often attributed to the over-expression of P-glycoprotein (P-gp), which prevents the accumulation of anticancer drugs within cells by virtue of its active drug efflux capacity. We have previously described the intercellular transfer of P-gp via extracellular vesicles (EVs) and proposed the involvement of a unique protein complex in regulating this process. In this paper, we investigate the role of these mediators in the regulation of P-gp functionality and hence the acquisition of MDR following cell to cell transfer. By sequentially silencing the FERM domain-binding proteins, Ezrin, Radixin and Moesin (ERM), as well as CD44, which we also report a selective packaging in breast cancer derived EVs, we have established a role for these proteins, in particular Radixin and CD44, in influencing the P-gp-mediated MDR in whole cells. We also report for the first time the role of ERM proteins in the vesicular transfer of functional P-gp. Specifically, we demonstrate that intercellular membrane insertion is dependent on Ezrin and Moesin, whilst P-gp functionality is governed by the integrity of all ERM proteins in the recipient cell. This study identifies these candidate proteins as potential new therapeutic targets in circumventing MDR clinically

Proteome analysis of multidrug-resistant, breast cancer-derived microparticles

© 2014 Deep Pokharel et al. Cancer multidrug resistance (MDR) occurswhen cancer cells evade the cytotoxic actions of chemotherapeutics through the active efflux of drugs from within the cells. Our group have previously demonstrated that multidrug-resistant breast cancer cells spontaneously shed microparticles (MPs) and that these MPs can transfer resistance to drug-responsive cells and confer MDR on those cells in as little as 4 h. Furthermore, we also showed that, unlike MPs derived from leukaemia cells, breast cancer-derived MPs display a tissue selectivity in the transfer of P-glycoprotein (P-gp), transferring the resistance protein only to malignant breast cells. This study aims to define the proteome of breast cancer-derived MPs in order to understand the differences in protein profiles between those shed from drug-resistant versus drug-sensitive breast cancer cells. In doing so, we detail the protein cargo required for the intercellular transfer of MDR to drug-sensitive recipient cells and the factors governing the transfer selectivity to malignant breast cells. We describe the first proteomic analysis of MPs derived from human breast cancer cells using SDS PAGE and liquid chromatography-tandem mass spectrometry (LC/MS/MS), in which we identify 120 unique proteins found only in drug-resistant, breast cancer-derived MPs. Our results demonstrate that the MP-mediated transfer of P-gp to recipient cells occurs alongside CD44; the Ezrin, Radixin and Moesin protein family (ERM); and cytoskeleton motor proteins within the MP cargo

Large enhancement of the thermopower in Nax_xCoO2_2 at high Na doping

Research on the oxide perovskites has uncovered electronic properties that are strikingly enhanced compared with those in conventional metals. Examples are the high critical temperatures of the cuprate superconductors and the colossal magnetoresistance in the manganites. The conducting layered cobaltate $\rm Na_xCoO_2$ displays several interesting electronic phases as $x$ is varied including water-induced superconductivity and an insulating state that is destroyed by field. Initial measurements showed that, in the as-grown composition, $\rm Na_xCoO_2$ displays moderately large thermopower $S$ and conductivity $\sigma$. However, the prospects for thermoelectric cooling applications faded when the figure of merit $Z$ was found to be small at this composition (0.6$<x<$0.7). Here we report that, in the poorly-explored high-doping region $x>$0.75, $S$ undergoes an even steeper enhancement. At the critical doping $x_p\sim$ 0.85, $Z$ (at 80 K) reaches values $\sim$40 times larger than in the as-grown crystals. We discuss prospects for low-temperature thermoelectric applications.Comment: 6 pages, 7 figure

Bridge-specific fragility analysis: when is it really necessary?

In seismic assessment of bridges the research focus has recently shifted on the derivation of bridge-specific fragility curves that account for the effect of different geometry, structural system, component and soil properties, on the seismic behaviour. In this context, a new, component-based methodology for the derivation of bridge-specific fragility curves has been recently proposed by the authors, with a view to overcoming the inherent difficulties in assessing all bridges of a road network and the drawbacks of existing methodologies, which use the same group of fragility curves for bridges within the same typological class. The main objective of this paper is to critically assess the necessity of bridge-specific fragility analysis, starting from the effect of structure-specific parameters on component capacity (limit state thresholds), seismic demand, and fragility curves. The aforementioned methodology is used to derive fragility curves for all bridges within an actual road network, with a view to investigating the consistency of adopting generic fragility curves for bridges that fall within the same class and quantifying the degree of over- or under-estimation of the probability of damage when generic bridge classes are considered. Moreover, fragility curves for all representative bridges of the analysed concrete bridge classes are presented to illustrate the differentiation in bridge fragility for varying structural systems, bridge geometry, total bridge length and maximum pier height. Based on the above, the relevance of bridge-specific fragility analysis is assessed, and pertinent conclusions are drawn

Tellurium quantum dots: Preparation and optical properties

Herein, we report an effective and simple method for producing Tellurium Quantum dots (TeQDs), zero-dimensional nanomaterials with great prospects for biomedical applications. Their preparation is based on the ultrasonic exfoliation of Te powder dispersed in 1-methyl-2-pyrrolidone. Sonication causes the van der Waals forces between the structural hexagons of Te to break so that the relatively coarse powder breaks down into nanoscale particles. The TeQDs have an average size of about 4 nm. UV-Vis absorption spectra of the TeQDs showed an absorption peak at 288 nm. Photoluminescence excitation (PLE) and photoluminescence (PL) are used to study the optical properties of TeQDs. Both the PLE and PL peaks revealed a linear relationship against the emission and excitation energies, respectively. TeQDs have important potential applications in biological imaging and catalysis as well as optoelectronics

Does timing of decisions in a mixed duopoly matter?

We determine the endogenous order of moves in a mixed pricesetting duopoly. In contrast to the existing literature on mixed oligopolies we establish the payo equivalence of the games with an exogenously given order of moves if the most plausible equilibrium is realized in the market. Hence, in this case it does not matter whether one becomes a leader or a follower. We also establish that replacing a private firm by a public firm in the standard Bertrand-Edgeworth game with capacity constraints increases social welfare and that a pure-strategy equilibrium always exists