Interleukin 7 from Maternal Milk Crosses the Intestinal Barrier and Modulates T- Cell Development in Offspring

Background Breastfeeding protects against illnesses and death in hazardous environments, an effect partly mediated by improved immune function. One hypothesis suggests that factors within milk supplement the inadequate immune response of the offspring, but this has not been able to account for a series of observations showing that factors within maternally derived milk may supplement the development of the immune system through a direct effect on the primary lymphoid organs. In a previous human study we reported evidence suggesting a link between IL-7 in breast milk and the thymic output of infants. Here we report evidence in mice of direct action of maternally-derived IL-7 on T cell development in the offspring. Methods and Findings  We have used recombinant IL-7 labelled with a fluorescent dye to trace the movement in live mice of IL-7 from the stomach across the gut and into the lymphoid tissues. To validate the functional ability of maternally derived IL- 7 we cross fostered IL-7 knock-out mice onto normal wild type mothers. Subsets of thymocytes and populations of peripheral T cells were significantly higher than those found in knock-out mice receiving milk from IL-7 knock-out mothers. Conclusions/Significance Our study provides direct evidence that interleukin 7, a factor which is critical in the development of T lymphocytes, when maternally derived can transfer across the intestine of the offspring, increase T cell production in the thymus and support the survival of T cells in the peripheral secondary lymphoid tissue

Mobile resource guarantees (evaluation paper)

This paper summarises the main outcomes of the Mobile Resource Guarantees (MRG) project, which focused on a proof-carrying-code (PCC) infrastructure for resources to be applied to mobile code. MRG was a three year project funded by the EC under the FET proactive initiative on Global Computing. We give an overview of the projects\u2019 results, discuss the lessons learnt from it and introduce follow-up work in new projects that will build on these results

What lies beneath: exploring links between asylum policy and hate crime in the UK

This paper explores the link between increasing incidents of hate crime and the asylum policy of successive British governments with its central emphasis on deterrence. The constant problematisation of asylum seekers in the media and political discourse ensures that 'anti-immigrant' prejudice becomes mainstr earned as a common-sense response. The victims are not only the asylum seekers hoping for a better life but democratic society itself with its inherent values of pluralism and tolerance debased and destabilised

UK-Wide Multicenter Evaluation of Second-line Therapies in Primary Biliary Cholangitis

Background & Aims: Thirty-to-forty percent of patients with primary biliary cholangitis inadequately respond to ursodeoxycholic acid. Our aim was to assemble national, real-world data on the effectiveness of obeticholic acid (OCA) as a second-line treatment, alongside non-licensed therapy with fibric acid derivatives (bezafibrate or fenofibrate). Methods: This was a nationwide observational cohort study conducted from August 2017 until June 2021. Results: We accrued data from 457 patients; 349 treated with OCA and 108 with fibric acid derivatives. At baseline/pre-treatment, individuals in the OCA group manifest higher risk features compared with those taking fibric acid derivatives, evidenced by more elevated alkaline phosphatase values, and a larger proportion of individuals with cirrhosis, abnormal bilirubin, prior non-response to ursodeoxycholic acid, and elastography readings >9.6kPa (P <.05 for all). Overall, 259 patients (OCA) and 80 patients (fibric acid derivatives) completed 12 months of second-line therapy, yielding a dropout rate of 25.7% and 25.9%, respectively. At 12 months, the magnitude of alkaline phosphatase reduction was 29.5% and 56.7% in OCA and fibric acid groups (P <.001). Conversely, 55.9% and 36.4% of patients normalized serum alanine transaminase and bilirubin in the OCA group (P <.001). The proportion with normal alanine transaminase or bilirubin values in the fibric acid group was no different at 12 months compared with baseline. Twelve-month biochemical response rates were 70.6% with OCA and 80% under fibric acid treatment (P =.121). Response rates between treatment groups were no different on propensity-score matching or on sub-analysis of high-risk groups defined at baseline. Conclusion: Across the population of patients with primary biliary cholangitis in the United Kingdom, rates of biochemical response and drug discontinuation appear similar under fibric acid and OCA treatment

Gut Homing Receptors on CD8 T Cells Are Retinoic Acid Dependent and Not Maintained by Liver Dendritic or Stellate Cells

BACKGROUND & AIMS: Lymphocytes primed by intestinal dendritic cells (DC) express the gut-homing receptors CCR9 and α4β7, which recognize CCL25 and mucosal addressin cell-adhesion molecule-1 in the intestine promoting the development of regional immunity. In mice, imprinting of CCR9 and α4β7 is dependent on retinoic acid during T-cell activation. Tissue specificity is lost in primary sclerosing cholangitis (PSC), an extraintestinal manifestation of inflammatory bowel disease, when ectopic expression of mucosal addressin cell-adhesion molecule-1 and CCL25 in the liver promotes recruitment of CCR9+α4β7+ T cells to the liver. We investigated the processes that control enterohepatic T-cell migration and whether the ability to imprint CCR9 and α4β7 is restricted to intestinal DCs or can under some circumstances be acquired by hepatic DCs in diseases such as PSC. METHODS: Human and murine DCs from gut, liver, or portal lymph nodes and hepatic stellate cells were used to activate CD8 T cells. Imprinting of CCR9 and α4β7 and functional migration responses were determined. Crossover activation protocols assessed plasticity of gut homing. RESULTS: Activation by gut DCs imprinted high levels of functional CCR9 and α4β7 on naïve CD8 T cells, whereas hepatic DCs and stellate cells proved inferior. Imprinting was RA dependent and demonstrated plasticity. CONCLUSIONS: Imprinting and plasticity of gut-homing human CD8 T cells requires primary activation or reactivation by gut DCs and is retinoic acid dependent. The inability of liver DCs to imprint gut tropism implies that α4β7+CCR9+ T cell that infiltrate the liver in PSC are primed in the gut

Campylobacter Infection as a Trigger for Guillain-Barré Syndrome in Egypt

BACKGROUND: Most studies of Campylobacter infection triggering Guillain-Barré Syndrome (GBS) are conducted in western nations were Campylobacter infection and immunity is relatively rare. In this study, we explored Campylobacter infections, Campylobacter serotypes, autoantibodies to gangliosides, and GBS in Egypt, a country where Campylobacter exposure is common. METHODS: GBS cases (n = 133) were compared to age- and hospital-matched patient controls (n = 374). A nerve conduction study was performed on cases and a clinical history, serum sample, and stool specimen obtained for all subjects. RESULTS: Most (63.3%) cases were demyelinating type; median age four years. Cases were more likely than controls to have diarrhea (29.5% vs. 22.5%, Adjusted Odds Ratio (ORa) = 1.69, P = 0.03), to have higher geometric mean IgM anti-Campylobacter antibody titers (8.18 vs. 7.25 P<0.001), and to produce antiganglioside antibodies (e.g., anti-Gd1a, 35.3 vs. 11.5, ORa = 4.39, P<0.0001). Of 26 Penner:Lior Campylobacter serotypes isolated, only one (41:27, C. jejuni, P = 0.02) was associated with GBS. CONCLUSIONS: Unlike results from western nations, data suggested that GBS cases were primarily in the young and cases and many controls had a history of infection to a variety of Campylobacter serotypes. Still, the higher rates of diarrhea and greater antibody production against Campylobacter and gangliosides in GBS patients were consistent with findings from western countries

Sequential application of hyperspectral indices for delineation of stripe rust infection and nitrogen deficiency in wheat

© 2015, Springer Science+Business Media New York. Nitrogen (N) fertilization is crucial for the growth and development of wheat crops, and yet increased use of N can also result in increased stripe rust severity. Stripe rust infection and N deficiency both cause changes in foliar physiological activity and reduction in plant pigments that result in chlorosis. Furthermore, stripe rust produce pustules on the leaf surface which similar to chlorotic regions have a yellow color. Quantifying the severity of each factor is critical for adopting appropriate management practices. Eleven widely-used vegetation indices, based on mathematic combinations of narrow-band optical reflectance measurements in the visible/near infrared wavelength range were evaluated for their ability to discriminate and quantify stripe rust severity and N deficiency in a rust-susceptible wheat variety (H45) under varying conditions of nitrogen status. The physiological reflectance index (PhRI) and leaf and canopy chlorophyll index (LCCI) provided the strongest correlation with levels of rust infection and N-deficiency, respectively. When PhRI and LCCI were used in a sequence, both N deficiency and rust infection levels were correctly classified in 82.5 and 55 % of the plots at Zadoks growth stage 47 and 75, respectively. In misclassified plots, an overestimation of N deficiency was accompanied by an underestimation of the rust infection level or vice versa. In 18 % of the plots, there was a tendency to underestimate the severity of stripe rust infection even though the N-deficiency level was correctly predicted. The contrasting responses of the PhRI and LCCI to stripe rust infection and N deficiency, respectively, and the relative insensitivity of these indices to the other parameter makes their use in combination suitable for quantifying levels of stripe rust infection and N deficiency in wheat crops under field conditions