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31.
Key physiological functions of the intestine are governed by nerves and neurotransmitters. This complex control relies on two neuronal systems: an extrinsic innervation supplied by the two branches of the autonomic nervous system and an intrinsic innervation provided by the enteric nervous system. As a result of constant exposure to commensal and pathogenic microflora, the intestine developed a tightly regulated immune system. In this review, we cover the current knowledge on the interactions between the gut innervation and the intestinal immune system. The relations between extrinsic and intrinsic neuronal inputs are highlighted with regards to the intestinal immune response. Moreover, we discuss the latest findings on mechanisms underlying inflammatory neural reflexes and examine their relevance in the context of the intestinal inflammation. Finally, we discuss some of the recent data on the identification of the gut microbiota as an emerging player influencing the brain function. 相似文献
32.
Mehdi Khoshgoftar Wouter Wilson Keita Ito Corrinus C. van Donkelaar 《Biomechanics and modeling in mechanobiology》2013,12(1):43-54
The insufficient load-bearing capacity of today’s tissue-engineered (TE) cartilage limits its clinical application. Focus has been on engineering cartilage with enhanced mechanical stiffness by reproducing native biochemical compositions. More recently, depth dependency of the biochemical content and the collagen network architecture has gained interest. However, it is unknown whether the mechanical performance of TE cartilage would benefit more from higher content of biochemical compositions or from achieving an appropriate collagen organization. Furthermore, the relative synthesis rate of collagen and proteoglycans during the TE process may affect implant performance. Such insights would assist tissue engineers to focus on those aspects that are most important. The aim of the present study is therefore to elucidate the relative importance of implant ground substance stiffness, collagen content, and collagen architecture of the implant, as well as the synthesis rate of the biochemical constituents for the post-implantation mechanical behavior of the implant. We approach this by computing the post-implantation mechanical conditions using a composition-based fibril-reinforced poro-viscoelastic swelling model of the medial tibia plateau. Results show that adverse implant composition and ultrastructure may lead to post-implantation excessive mechanical loads, with collagen orientation being the most critical variable. In addition, we predict that a faster synthesis rate of proteoglycans compared to that of collagen during TE culture may result in excessive loads on collagen fibers post-implantation. This indicates that even with similar final contents, constructs may behave differently depending on their development. Considering these aspects may help to engineer TE cartilage implants with improved survival rates. 相似文献
33.
Wouter L. W. Hazenbos Kimberly K. Kajihara Richard Vandlen J. Hiroshi Morisaki Sophie M. Lehar Mark J. Kwakkenbos Tim Beaumont Arjen Q. Bakker Qui Phung Lee R. Swem Satish Ramakrishnan Janice Kim Min Xu Ishita M. Shah Binh An Diep Tao Sai Andrew Sebrell Yana Khalfin Angela Oh Chris Koth S. Jack Lin Byoung-Chul Lee Magnus Strandh Klaus Koefoed Peter S. Andersen Hergen Spits Eric J. Brown Man-Wah Tan Sanjeev Mariathasan 《PLoS pathogens》2013,9(10)
Infection of host tissues by Staphylococcus aureus and S. epidermidis requires an unusual family of staphylococcal adhesive proteins that contain long stretches of serine-aspartate dipeptide-repeats (SDR). The prototype member of this family is clumping factor A (ClfA), a key virulence factor that mediates adhesion to host tissues by binding to extracellular matrix proteins such as fibrinogen. However, the biological siginificance of the SDR-domain and its implication for pathogenesis remain poorly understood. Here, we identified two novel bacterial glycosyltransferases, SdgA and SdgB, which modify all SDR-proteins in these two bacterial species. Genetic and biochemical data demonstrated that these two glycosyltransferases directly bind and covalently link N-acetylglucosamine (GlcNAc) moieties to the SDR-domain in a step-wise manner, with SdgB appending the sugar residues proximal to the target Ser-Asp repeats, followed by additional modification by SdgA. GlcNAc-modification of SDR-proteins by SdgB creates an immunodominant epitope for highly opsonic human antibodies, which represent up to 1% of total human IgG. Deletion of these glycosyltransferases renders SDR-proteins vulnerable to proteolysis by human neutrophil-derived cathepsin G. Thus, SdgA and SdgB glycosylate staphylococcal SDR-proteins, which protects them against host proteolytic activity, and yet generates major eptopes for the human anti-staphylococcal antibody response, which may represent an ongoing competition between host and pathogen. 相似文献
34.
Susan Kühnast Mieke C. Louwe Mattijs M. Heemskerk Elsbet J. Pieterman Jan B. van Klinken Sjoerd A. A. van den Berg Johannes W. A. Smit Louis M. Havekes Patrick C. N. Rensen José W. A. van der Hoorn Hans M. G. Princen J. Wouter Jukema 《PloS one》2013,8(6)
Objective
Niacin potently lowers triglycerides, mildly decreases LDL-cholesterol, and largely increases HDL-cholesterol. Despite evidence for an atheroprotective effect of niacin from previous small clinical studies, the large outcome trials, AIM-HIGH and HPS2-THRIVE did not reveal additional beneficial effects of niacin (alone or in combination with laropiprant) on top of statin treatment. We aimed to address this apparent discrepancy by investigating the effects of niacin without and with simvastatin on atherosclerosis development and determine the underlying mechanisms, in APOE*3Leiden.CETP mice, a model for familial dysbetalipoproteinemia (FD).Approach and Results
Mice were fed a western-type diet containing cholesterol without or with niacin (120 mg/kg/day), simvastatin (36 mg/kg/day) or their combination for 18 weeks. Similarly as in FD patients, niacin reduced total cholesterol by -39% and triglycerides by −50%, (both P<0.001). Simvastatin and the combination reduced total cholesterol (−30%; −55%, P<0.001) where the combination revealed a greater reduction compared to simvastatin (−36%, P<0.001). Niacin decreased total cholesterol and triglycerides primarily by increasing VLDL clearance. Niacin increased HDL-cholesterol (+28%, P<0.01) and mildly increased reverse cholesterol transport. All treatments reduced monocyte adhesion to the endothelium (−46%; −47%, P<0.01; −53%, P<0.001), atherosclerotic lesion area (−78%; −49%, P<0.01; −87%, P<0.001) and severity. Compared to simvastatin, the combination increased plaque stability index [(SMC+collagen)/macrophages] (3-fold, P<0.01). Niacin and the combination reduced T cells in the aortic root (−71%, P<0.01; −81%, P<0.001). Lesion area was strongly predicted by nonHDL-cholesterol (R2 = 0.69, P<0.001) and to a much lesser extent by HDL-cholesterol (R2 = 0.20, P<0.001).Conclusion
Niacin decreases atherosclerosis development mainly by reducing nonHDL-cholesterol with modest HDL-cholesterol-raising and additional anti-inflammatory effects. The additive effect of niacin on top of simvastatin is mostly dependent on its nonHDL-cholesterol-lowering capacities. These data suggest that clinical beneficial effects of niacin are largely dependent on its ability to lower LDL-cholesterol on top of concomitant lipid-lowering therapy. 相似文献35.
Laetitia Aerts Marie-ève Hamelin Chantal Rhéaume Sophie Lavigne Christian Couture WooJin Kim Delia Susan-Resiga Annik Prat Nabil G. Seidah Nathalie Vergnolle Beatrice Riteau Guy Boivin 《PloS one》2013,8(8)
Human metapneumovirus (hMPV) infection causes acute respiratory tract infections (RTI) which can result in hospitalization of both children and adults. To date, no antiviral or vaccine is available for this common viral infection. Immunomodulators could represent an interesting strategy for the treatment of severe viral infection. Recently, the role of protease-activated receptors (PAR) in inflammation, coagulation and infection processes has been of growing interest. Herein, the effects of a PAR1 agonist and a PAR1 antagonist on hMPV infection were investigated in BALB/c mice. Intranasal administration of the PAR1 agonist resulted in increased weight loss and mortality of infected mice. Conversely, the PAR1 antagonist was beneficial to hMPV infection by decreasing weight loss and clinical signs and by significantly reducing pulmonary inflammation, pro-inflammatory cytokine levels (including IL-6, KC and MCP-1) and recruitment of immune cells to the lungs. In addition, a significant reduction in pulmonary viral titers was also observed in the lungs of PAR1 antagonist-treated mice. Despite no apparent direct effect on virus replication during in vitro experiments, an important role for PAR1 in the regulation of furin expression in the lungs was shown for the first time. Further experiments indicated that the hMPV fusion protein can be cleaved by furin thus suggesting that PAR1 could have an effect on viral infectivity in addition to its immunomodulatory properties. Thus, inhibition of PAR1 by selected antagonists could represent an interesting strategy for decreasing the severity of paramyxovirus infections. 相似文献
36.
Wouter Schellekens Richard J. A. Van Wezel Natalia Petridou Nick F. Ramsey Mathijs Raemaekers 《PloS one》2013,8(6)
Recent imaging studies have reported directional motion biases in human visual cortex when perceiving moving random dot patterns. It has been hypothesized that these biases occur as a result of the integration of motion detector activation along the path of motion in visual cortex. In this study we investigate the nature of such motion integration with functional MRI (fMRI) using different motion stimuli. Three types of moving random dot stimuli were presented, showing either coherent motion, motion with spatial decorrelations or motion with temporal decorrelations. The results from the coherent motion stimulus reproduced the centripetal and centrifugal directional motion biases in V1, V2 and V3 as previously reported. The temporally decorrelated motion stimulus resulted in both centripetal and centrifugal biases similar to coherent motion. In contrast, the spatially decorrelated motion stimulus resulted in small directional motion biases that were only present in parts of visual cortex coding for higher eccentricities of the visual field. In combination with previous results, these findings indicate that biased motion responses in early visual cortical areas most likely depend on the spatial integration of a simultaneously activated motion detector chain. 相似文献
37.
Vincent Marion Selvakumari Sankaranarayanan Chiel de Theije Paul van Dijk Theo B. M. Hakvoort Wouter H. Lamers Eleonore S. K?hler 《PloS one》2013,8(6)
Suckling mammals, including mice, differ from adults in the abundant expression of enzymes that synthesize arginine from citrulline in their enterocytes. To investigate the importance of the small-intestinal arginine synthesis for whole-body arginine production in suckling mice, we floxed exon 13 of the argininosuccinate synthetase (Ass) gene, which codes for a key enzyme in arginine biosynthesis, and specifically and completely ablated Ass in enterocytes by crossing Ass
fl and Villin-Cre mice. Unexpectedly, Ass
fl/fl
/VilCre
tg/- mice showed no developmental impairments. Amino-acid fluxes across the intestine, liver, and kidneys were calculated after determining the blood flow in the portal vein, and hepatic and renal arteries (86%, 14%, and 33%, respectively, of the transhepatic blood flow in 14-day-old mice). Relative to control mice, citrulline production in the splanchnic region of Ass
fl/fl
/VilCre
tg/- mice doubled, while arginine production was abolished. Furthermore, the net production of arginine and most other amino acids in the liver of suckling control mice declined to naught or even changed to consumption in Ass
fl/fl
/VilCre
tg/- mice, and had, thus, become remarkably similar to that of post-weaning wild-type mice, which no longer express arginine-biosynthesizing enzymes in their small intestine. The adaptive changes in liver function were accompanied by an increased expression of genes involved in arginine metabolism (Asl, Got1, Gpt2, Glud1, Arg1, and Arg2) and transport (Slc25a13, Slc25a15, and Slc3a2), whereas no such changes were found in the intestine. Our findings suggest that the genetic premature deletion of arginine synthesis in enterocytes causes a premature induction of the post-weaning pattern of amino-acid metabolism in the liver. 相似文献
38.
Francisco Cuesta Carolina Tovar Luis D. Llambí William D. Gosling Stephan Halloy Julieta Carilla Priscilla Muriel Rosa I. Meneses Stephan Beck Carmen Ulloa Ulloa Karina Yager Nikolay Aguirre Paul Viñas Jorge Jácome David Suárez-Duque Wouter Buytaert Harald Pauli 《Journal of Biogeography》2020,47(2):408-420
39.
Georgios A. Pavlopoulos Parveen Kumar Alejandro Sifrim Ryo Sakai Meng Lay Lin Thierry Voet Yves Moreau Jan Aerts 《Nucleic acids research》2013,41(11):e118
The introduction of next generation sequencing methods in genome studies has made it possible to shift research from a gene-centric approach to a genome wide view. Although methods and tools to detect single nucleotide polymorphisms are becoming more mature, methods to identify and visualize structural variation (SV) are still in their infancy. Most genome browsers can only compare a given sequence to a reference genome; therefore, direct comparison of multiple individuals still remains a challenge. Therefore, the implementation of efficient approaches to explore and visualize SVs and directly compare two or more individuals is desirable. In this article, we present a visualization approach that uses space-filling Hilbert curves to explore SVs based on both read-depth and pair-end information. An interactive open-source Java application, called Meander, implements the proposed methodology, and its functionality is demonstrated using two cases. With Meander, users can explore variations at different levels of resolution and simultaneously compare up to four different individuals against a common reference. The application was developed using Java version 1.6 and Processing.org and can be run on any platform. It can be found at http://homes.esat.kuleuven.be/~bioiuser/meander. 相似文献
40.
Fiona Wegman F. Cumhur Öner Wouter J.A. Dhert 《Biotechnology & genetic engineering reviews》2013,29(2):206-220
The possibilities of using gene therapy for bone regeneration have been extensively investigated. Improvements in the design of new transfection agents, combining vectors and delivery/release systems to diminish cytotoxicity and increase transfection efficiencies have led to several successful in vitro, ex vivo and in vivo strategies. These include growth factor or short interfering ribonucleic acid (siRNA) delivery, or even enzyme replacement therapies, and have led to increased osteogenic differentiation and bone formation in vivo. These results provide optimism to consider use in humans with some of these gene-delivery strategies in the near future. 相似文献