Abstract
Background
Intestinal epithelial cells (IECs) play a central role in the coordination of intestinal homeostasis. They must strike a careful balance to temper pro-inflammatory responses ...against the intestinal microbiota, while remaining vigilant and rapidly responsive when exposed to a noxious stimulus such as an enteric pathogen. One early response mechanism by which IECs engage in immune defense is through the activation of an IEC-specific inflammasome. This activation triggers the extrusion of infected IEC into the gut lumen, ultimately restricting Salmonella enterica serovar Typhimurium from escaping the gut and spreading systemically. However, it appears the role of the inflammasome in gut defense is not just restricted to IEC shedding but it also plays a key role in mucin secretion and antimicrobial lectin production.
Aims
Here, we investigate the role of the inflammasome in mucosal defense against S. Typhimurium SL1344.
Methods
This study employed a streptomycin pretreatment S. Typhimurium mouse infection model as well as various cell and immunofluorescent staining to characterize the role of the intestinal inflammasome.
Results
Streptomycin-pretreated C57BL/6, Casp1/11 deficient (−/−) and Casp11−/− mice were orally infected and S. Typhimurium loads determined for each respective tissue at 18h and 72h post infection. Increased pathogen burdens were observed for both caspase-deficient mice compared to wild type, with increased systemic spread seen in the mesenteric lymph nodes, liver and spleen at both time points for Casp1/11−/− mice but only at 72h for Casp11 −/−. Interestingly, at 18h, despite increased bacterial loads, cecal pathology scores were decreased in both Casp1/11−/− and Casp11−/− mice, as compared to wild type. This was accompanied by increased intracellular S. Typhimurium immunofluorescence staining. Also, cecal mucin layer thickness, as measured by Alcian Blue as well as MUC2 immunofluorescence staining were similar amongst all mouse strains before infection, but were decreased in both Casp1/11−/− and Casp11−/− mice as compared to wild type after infection. Finally, expression of the antimicrobial lectins REG3γ and REG3β were significantly decreased in Casp11−/− mice as compared to wild type mice and minimal staining for REG3β was observed in both caspase deficient mice.
Conclusions
These results indicate that the gut epithelium utilizes inflammasome signaling to coordinate multiple layers of innate defense at the gut mucosal surface to ultimately restrict enteric pathogen infections and systemic spread.
Funding Agencies
CCC, CIHRNSERC, UBC
The collision of anticyclonic, lens‐like eddies with a meridional western boundary is investigated as a function of two independent, nondimensional numbers: β = β0R/f0 and ε = ω/f0, where f0 and β0 ...are the Coriolis parameter and its rate of change with latitude, respectively, both evaluated at the reference latitude. R is the eddy's radius, and ω is its angular frequency. The numerical experiments show that in all cases there is a southward expulsion of mass proportional to both β and ε. which is estimated during the eddy‐boundary interaction. The eddies are invariably deformed with the initial collision, but afterward, they reacquire a new circular shape. There is a meridional translation of the eddy along the boundary which depends exclusively on the initial ratio r = ε/β. If r>1, the eddy goes southward, but if r<1, the eddy goes northward first and then southward. As the eddy loses mass and reacquires a new circular shape, there is a readjustment of β and ε such that β decreases because its radius becomes smaller and ε increases by energy conservation. This implies that the eddies ultimately migrate southward. A formula, derived for the meridional speed of the center of mass of the eddy is consistent with the numerical results. A physical interpretation shows that after collision a zonal force is exerted on the eddy by the wall which is balanced by a meridional migration. Nonlinearities induce a southward motion, while high β values could produce northward motion, depending on the mass distribution along the wall.
Statement of problem Despite good clinical success rates of ceramic restorations, fractures of substructures made from high-strength dental ceramics remain an issue. Transillumination of ceramic ...restorations has been proposed as a means of quality assurance. Purpose The purpose of this study was to compare the sensitivity of transillumination and the fluorescent penetrant method (FPM) in detecting microcracks in zirconia and feldspathic ceramic materials. Material and methods Two groups (n=20) of standardized plates were fabricated from zirconia ceramic (Cercon) and feldspathic ceramic (VITABLOCS Mark II for CEREC) materials, and central holes were created to induce microcracks. The plates were microscopically analyzed at ×20 magnification by means of transillumination and FPM. Based on whether the criterion crack was recognized or not recognized, contingency tables were developed. Fisher's exact test for count data was used to compare frequency distributions (α=.05). Results Minimum crack length as detected by FPM was 18 μm in zirconia ceramic and 17 μm in feldspathic ceramic. For transillumination, minimum detectable crack length was 54 μm in zirconia ceramic and 33 μm in feldspathic ceramic. Thirty-seven percent of cracks in feldspathic ceramic plates and 64% of cracks in zirconia ceramic plates could not be detected by means of transillumination. The conditional probabilities for a crack being detected by transillumination, although it was detected by FPM, were significantly lower than 1 for both materials ( P <.001). Although transillumination was less sensitive than FPM on a relative scale, it was not possible to demonstrate a general difference between the 2 analyzing techniques by using statistical methods. Conclusions Using FPM as a relative reference system, transillumination appears to be less sensitive in detecting microcracks in ceramic components.
Abstract
Background
Group 3 innate lymphoid cells (ILC3s) are a class of innate lymphocytes that are emerging as key players in regulating intestinal inflammation, immunity and homeostasis. Through ...the production of the cytokine IL-22, ILC3s can modulate the function of intestinal epithelial cells (IECs), helping to maintain the IEC barrier integrity and promoting host defense against bacterial pathogens (such as Citrobacter rodentium). Recently, a handful studies have shown that ILC3s can communicate with the nervous system in the gut where neurons and immune cells are enriched. It remains largely unexplored how this neuroimmune communication regulates the number and function of ILC3s in the gut.
Aims
To understand how the neuropeptide - vasoactive intestinal peptide (VIP), controls the expansion and function of ILC3s thereby regulating intestinal immunity under baseline and infection conditions.
Methods
Wildtype (WT), Vip-/- and Rag1-/- mice were used. ILC3s and dendritic cells were isolated from the intestinal lamina propria using percoll gradients. ILC3s migration towards VIP was measured by a chemotaxis assay. The number and function of ILC3s was assessed using FACS. IL-22, RegIII-β, and RegIII-γ production was quantified by qPCR and/or ELISA. WT and Vip-/- mice were infected with C. rodentium for 4–10 days, and their susceptibility to infection assessed by measuring body weight loss, bacterial counts, and histological changes. Recombinant VIP, IL-22 or retinoic acid (RA) was IP injected into Vip-/- mice, with the mice subsequently analyzed for their susceptibility to C. rodentium infection. ILC3s were also isolated from Rag1-/- mice and injected into Vip-/- mice by the IV route, followed by infection with C. rodentium.
Results
VIP induced ILC3s migration through the receptor VPAC2. VIP also promoted gut homing receptor CCR9 expression on intestinal ILC3s, by enhancing RA production by intestinal dendritic cells. The loss of VIP led to reduced activation and recruitment of intestinal ILC3 cells, less IL-22 production, and abnormal IEC barrier function. Accordingly, Vip-/- mice proved highly susceptible to C. rodentium infection, suffering dramatic body weight loss, increased pathogen colonization, and worsened intestinal damage. Notably, recombinant IL-22 adminstration was sufficient to rescue Vip-/- mice from C. rodentium infection. Moreover, treatment with RA or VIP, or adoptive transfer of ILC3 cells were all able to increase the intestinal production of IL-22 and protect Vip-/- mice from infection.
Conclusions
Our results reveal a novel neuroimmune axis whereby the neuropeptide VIP controls the activation and recruitment of ILC3s in the gut, thereby playing a key role in promoting mucosal defense against intestinal pathogens.
Funding Agencies
CCC, CIHRNSERC
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A major objective of the European Commission Monitoring Working Group (MWG) on Guidance Notes supplementing Annex VII of Directive 2001/18/EC was to explore the possibility of European Union ...(EU)-wide coordination and harmonisation of data resulting from monitoring of genetically modified (GM) crops.
Firstly, we present concepts for the coordination and harmonisation of monitoring data of cultivated GM crops. We argue that data coordination is necessary at both national and EU level and that data harmonisation is advisable at different technical levels of monitoring.
Secondly, we explore the applicability of existing monitoring programmes and data infrastructure schemes run at EU level for monitoring of GM crops, and options for implementing data coordination and harmonisation. Our work identifies useful European monitoring programmes and data infrastructure schemes for the monitoring of GM crops. Their relevance, however, needs to be analysed in more depth.
Abstract
Background
Vasoactive intestinal peptide (VIP), a 28 amino acid neuropeptide, exhibits potent anti-inflammatory effects in autoimmune and inflammatory diseases. Interestingly, recent ex vivo ...studies suggest that VIP can promote the production of proinflammatory Th17 cells (primarily secrete cytokine IL-17A). While Th17 cells likely aggravate inflammation in autoimmune diseases, they are known to be protective against Citrobacter rodentium induced colitis-a mouse model of colitis.
Aims
The aim of this study was to examine the in vivo significance of VIP-Th17 signaling axis during an enteric pathogen (Citrobacter rodentium) infection.
Methods
Wild type mice, VIP deficient (Vip-/-
) mice and VIP treated Vip-/-
mice were infected with C. rodentium for 10 days. Body weight loss and survival rates were recorded daily. Bacterial counts in the intestinal and systemic sites were determined by an in vivo imaging system and plating method. Mucosal damages were analyzed by Haemotoxylin and Eosin staining. The production of cytokines (such as IL-1β, IL-6, IL-17A, IL-22 and TNF-α) were quantified by quantitative PCR, ELISA and FACS.
Results
Vip-/-
mice infected with C. rodentium showed dramatic body weight loss, decreased survival rates, increased bacterial colonization in intestinal and systemic sites, worsened mucosal damages/inflammatory responses as well as reduced production of Th17 cell responses. Importantly, exogenous treatment of Vip-/-
mice with recombinant VIP ameliorated C. rodentium-induced colitis, accompanied by restoration of Th17 cell responses.
Conclusions
We provide the first in vivo evidence that VIP promotes Th17 immune responses thereby protecting against C. rodentium induced colitis.
Funding Agencies
CCC
Pedogenesis and diagenesis of paleosols that are intercalated amid basalt flows of Late Pliocene age (∼ 3.7-3.1 m.y.B.P.) have been studied on the southwestern slopes of the Golan Heights. The data ...obtained suggest that environmental conditions resembled present-day ones, being characterized by a warm climate with seasonal moisture contrasts. All soils show evidence of redeposition as well as stratification of the parent material. On very low relief sites, vertisols with a large content of smectitic clay, influenced by aeolian deposition with a large content of smectic clay formed. Rubefaction took place, as well as clay translocation and possibly also carbonatisation. The burial of the soils by lava flows resulted in partial erosion and distinct fritting, indicated by compaction, cementation and hematization. After burial, various types of alteration affected the soils, such as clay illuviation, strong carbonatisation, and tectonic movements. Pedogenic features were preserved very well, but have subsequently been overprinted by diagenetic processes, especially carbonate precipitation. e4
14C ages of the carbonates indicate continuous rejuvenation by meteoric moisture. Persistence of smectite indicated that conditions affecting soil solution chemistry had not changed significantly since burial.
A methodology for retrieval and mapping of spatial soil and terrain data based on the SOTER approach has been developed for semi-arid Niger. Remote sensing technics and detailed ground transect ...investigations are used, and the collected data are integrated into a SOTER database and a Geographic Information System. Transect selection, their realization and the related problems with transect-based calculations are discussed. The method permits estimations of soil type coverages, present land use and soil degradation at different scale levels. The significant dynamics of soil redistribution are pointed out and attributed to present and past erosion events.
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