Post-Translational Inhibition of IP-10 Secretion in IEC by Probiotic Bacteria: Impact on Chronic Inflammation

Background: Clinical and experimental studies suggest that the probiotic mixture VSL#3 has protective activities in the context of inflammatory bowel disease (IBD). The aim of the study was to reveal bacterial strain-specific molecular mechanisms underlying the anti-inflammatory potential of VSL#3 in intestinal epithelial cells (IEC).

Methodology/Principal Findings: VSL#3 inhibited TNF-induced secretion of the T-cell chemokine interferon-inducible protein (IP-10) in Mode-K cells. Lactobacillus casei (L. casei) cell surface proteins were identified as active anti-inflammatory components of VSL#3. Interestingly, L. casei failed to block TNF-induced IP-10 promoter activity or IP-10 gene transcription at the mRNA expression level but completely inhibited IP-10 protein secretion as well as IP-10-mediated T-cell transmigration. Kinetic studies, pulse-chase experiments and the use of a pharmacological inhibitor for the export machinery (brefeldin A) showed that L. casei did not impair initial IP-10 production but decreased intracellular IP-10 protein stability as a result of blocked IP-10 secretion. Although L. casei induced IP-10 ubiquitination, the inhibition of proteasomal or lysosomal degradation did not prevent the loss of intracellular IP-10. Most important for the mechanistic understanding, the inhibition of vesicular trafficking by 3-methyladenine (3-MA) inhibited IP-10 but not IL-6 expression, mimicking the inhibitory effects of L. casei. These findings suggest that L. casei impairs vesicular pathways important for the secretion of IP-10, followed by subsequent degradation of the proinflammatory chemokine. Feeding studies in TNF Delta ARE and IL-10(-/-) mice revealed a compartimentalized protection of VSL#3 on the development of cecal but not on ileal or colonic inflammation. Consistent with reduced tissue pathology in IL-10(-/-) mice, IP-10 protein expression was reduced in primary epithelial cells.

Conclusions/Significance: We demonstrate segment specific effects of probiotic intervention that correlate with reduced IP-10 protein expression in the native epithelium. Furthermore, we revealed post-translational degradation of IP-10 protein in IEC to be the molecular mechanism underlying the anti-inflammatory effect.

Regularized Online Mixture of Gaussians for Background Subtraction

Mixture of Gaussians (MoG) modelling [13] is a popular approach to background subtraction in video sequences. Although the algorithm shows good empirical performance, it lacks theoretical justification. In this paper, we give a justification for it from an online stochastic expectation maximization (EM) viewpoint and extend it to a general framework of regularized online classification EM for MoG with guaranteed convergence. By choosing a special regularization function, l1 norm, we derived a new set of updating equations for l1 regularized online MoG. It is shown empirically that l1 regularized online MoG converge faster than the original online MoG .

Gaussian mixture background modelling optimisation for micro-controllers

This paper proposes an optimisation of the adaptive Gaussian mixture background model that allows the deployment of the method on processors with low memory capacity. The effect of the granularity of the Gaussian mean-value and variance in an integer-based implementation is investigated and novel updating rules of the mixture weights are described. Based on the proposed framework, an implementation for a very low power consumption micro-controller is presented. Results show that the proposed method operates in real time on the micro-controller and has similar performance to the original model. © 2012 Springer-Verlag.

Heavier-than-water silicone oil mixture as a long-term tamponade agent:A pilot study

Purpose: To evaluate the tamponade effect on the retina of a heavier-than-water silicone oil mixture and to compare it with the effect of silicone oil. Methods: Prospective, non-randomised, comparative pilot study. Phakic/pseudophakic patients with retinal detachment undergoing vitrectomy with Densiron 68 or silicone oil were recruited. The 'separation volume', defined as the relative volume of the space between intraocular tamponade agent and retina, was estimated using magnetic resonance imaging in both groups and compared. Results: Nine participants were included; 4 received silicone oil and 5 Densiron 68. The mean separation volume was statistically significantly larger in the silicone oil group (0.477 ± 0.419 cm ) than in the Densiron group (0.042 ± 0.013 cm ; p = 0.014). Conclusions: In this study Densiron achieved an excellent tamponade effect in the retina. © 2011 S. Karger AG, Basel.

Taking as Giving, Appropriation as Access: Transfers of Land Development Rights and China’s Recent Experiments

Economic development at both the domestic and global levels is associated with increasing tensions which are inextricably linked to the meaning and allocation of property rights, which has a great impact on appropriation of resources and may lead to different paths of development. “Taking”-- the appropriation of private land for public needs -- is a typical example that exhibits those tensions, posing a challenge to the conventional conception of property as individualistic and exclusive rights of possession, use, and disposition and to the associated neoliberal model of development. Should the individual landowner be left to bear the cost of a regulatory intervention which endures to the wider benefit of the whole community? How to mitigate the tensions between private ownership and public regulation? If we take the liberal concept of property, then private property seems to be in constant conflict with public interests and wider social concerns. Meanwhile, community, situating between the state and the individuals, and community’s relationship to development rights, have not provoked enough discussion. The paper explores the different ways land development rights might be seen both in Western, essentially common law systems, and in China, especially now and in view of two case studies. An empirical example in Wugang, China reveals the importance of integrating the “community lens” proposed by Roger Cotterrell into studies of the transfer of land development rights. Reading through the community lens, taking could be giving and appropriation could also be access. This approach provides a new perspective to re-evaluate the relationship between legal appropriation and development.

Participation of adult mouse bone marrow cells in reconstitution of skin

Results of recent studies have indicated that bone marrow cells can differentiate into various cells of ectodermal, mesodermal, and endodermal origins when transplanted into the body. However, the problems associated with those experiments such as the long latent period, rareness of the event, and difficulty in controlling the processes have hampered detailed mechanistic studies. In the present study, we examined the potency of mouse bone marrow cells to differentiate into cells comprising skin tissues using a skin reconstitution assay. Bone marrow cells from adult green fluorescent protein (GFP)-transgenic mice were transplanted in a mixture of embryonic mouse skin cells (17.5 days post-coitus) onto skin defects made on the backs of nude mice. Within 3 weeks, fully differentiated skin with hair was reconstituted. GFP-positive cells were found in the epidermis, hair follicles, sebaceous glands, and dermis. The localization and morphology of the cells, results of immunohistochemistry, and results of specific staining confirmed that the bone marrow cells had differentiated into epidermal keratinocytes, sebaceous gland cells, follicular epithelial cells, dendritic cells, and endothelial cells under the present conditions. These results indicate that this system is suitable for molecular and cellular mechanistic studies on differentiation of stem cells to various epidermal and dermal cells.

Guidelines and considerations for conducting experiments using tissue microarrays

Tissue microarrays (TMAs) represent a powerful method for undertaking large-scale tissue-based biomarker studies. While TMAs offer several advantages, there are a number of issues specific to their use which need to be considered when employing this method. Given the investment in TMA-based research, guidance on design and execution of experiments will be of benefit and should help researchers new to TMA-based studies to avoid known pitfalls. Furthermore, a consensus on quality standards for TMA-based experiments should improve the robustness and reproducibility of studies, thereby increasing the likelihood of identifying clinically useful biomarkers. In order to address these issues, the National Cancer Research Institute Biomarker and Imaging Clinical Studies Group organized a 1-day TMA workshop held in Nottingham in May 2012. The document herein summarizes the conclusions from the workshop. It includes guidance and considerations on all aspects of TMA-based research, including the pre-analytical stages of experimental design, the analytical stages of data acquisition, and the postanalytical stages of data analysis. A checklist is presented which can be used both for planning a TMA experiment and interpreting the results of such an experiment. For studies of cancer biomarkers, this checklist could be used as a supplement to the REMARK guidelines.

Natural convection experiments on a heated horizontal cylinder in a differentially heated square cavity

Natural convection heat transfer from a heat generating horizontal cylinder enclosed in a square cavity, where a temperature difference exists across its vertical walls has been experimentally investigated for the range 2×104

Hardware Acceleration of Background Modeling in the Compressed Domain

In intelligent video surveillance systems, scalability (of the number of simultaneous video streams) is important. Two key factors which hinder scalability are the time spent in decompressing the input video streams, and the limited computational power of the processor. This paper demonstrates how a combination of algorithmic and hardware techniques can overcome these limitations, and significantly increase the number of simultaneous streams. The techniques used are processing in the compressed domain, and exploitation of the multicore and vector processing capability of modern processors. The paper presents a system which performs background modeling, using a Mixture of Gaussians approach. This is an important first step in the segmentation of moving targets. The paper explores the effects of reducing the number of coefficients in the compressed domain, in terms of throughput speed and quality of the background modeling. The speedups achieved by exploiting compressed domain processing, multicore and vector processing are explored individually. Experiments show that a combination of all these techniques can give a speedup of 170 times on a single CPU compared to a purely serial, spatial domain implementation, with a slight gain in quality.

Flow due to multiple jets downstream of a barrage: Experiments, 3-D CFD and depth-averaged modelling

The flow through and downstream of a row of seven open draft tubes in a barrage has been investigated through laboratory experiments in a wide flume, a three-dimensional (3D) computational fluid dynamics simulation, and a two-dimensional depth-averaged computation. Agreement between the experiments and the 3D modeling is shown to be good, including the prediction of an asymmetric Coandă effect. One aim is to determine the distance downstream at which depth-averaged modeling provides a reasonable prediction; this is shown to be approximately 20 tube diameters downstream of the barrage. Upstream of this, the depth-averaged modeling inaccurately predicts water level, bed shear, and the 3D flow field. The 3D model shows that bed shear stress can be markedly magnified near the barrage, particularly where the jets become attached.