Epithelial cell specific Raptor is required for initiation of type 2 mucosal immunity in small intestine

AbstractIntestinal tuft cells are one of 4 secretory cell linages in the small intestine and the source of IL-25, a critical initiator of the type 2 immune response to parasite infection. When Raptor, a critical scaffold protein for mammalian target of rapamycin complex 1 (mTORC1), was acutely deleted in intestinal epithelium via Tamoxifen injection in Tritrichomonas muris (Tm) infected mice, tuft cells, IL-25 in epithelium and IL-13 in the mesenchyme were significantly reduced, but Tm burden was not affected. When Tm infected mice were treated with rapamycin, DCLK1 and IL-25 expression in enterocytes and IL-13 expression in mesenchyme were diminished. After massive small bowel resection, tuft cells and Tm were diminished due to the diet used postoperatively. The elimination of Tm and subsequent re-infection of mice with Tm led to type 2 immune response only in WT, but Tm colonization in both WT and Raptor deficient mice. When intestinal organoids were stimulated with IL-4, tuft cells and IL-25 were induced in both WT and Raptor deficient organoids. In summary, our study reveals that enterocyte specific Raptor is required for initiating a type 2 immune response which appears to function through the regulation of mTORC1 activity.</jats:p

Dying Declarations and the Confrontation Clause

Article published in the Michigan State University School of Law Student Scholarship Collection

Use of Cellular Automata Modelling Approaches to Understand Potential Impacts of GM Grasses on Grassland Communities

In order to predict the potential unintended ecological impacts of genetically modified (GM) grasses, we must understand how the engineered traits, in this case herbicide resistance, are expressed in an ecological context. It would be a daunting task to experimentally evaluate the full multiplicity of potential pair-wise interactions between GM plants and native plants under a broad variety of actual environmental conditions. We have employed the modelling methodology of cellular automata (CA), where a plant\u27s distribution within a two-dimensional environmental grid is determined by rules relating to phenomena such as seed dispersal, clonal expansion and interactions with adjacent plants. We have used CA simulation to model interactions between GM grasses and the natural environment by describing the plants and the effect of the GM trait in terms of plant functional types. This approach takes the external factors which limit the amount of plant material present in any habitat and classifies them into two categories: (1) stress, defined with regard to the availability of nutrients and (2) disturbance, which refers to the destruction of plant material. The ecological characteristics of all the plants can be described based on three functional types C (competitor), S (stress-tolerator) and R (ruderal) as determined by their quantifiable physiological relationships to stress and disturbance. By ascribing the large number of plant ecological characteristics to a smaller number of functional types the problem, of describing how the engineered trait of herbicide resistance is expressed in an ecological context, becomes tractable

CD4 T lymphocyte autophagy is upregulated in the salivary glands of primary Sjögren’s syndrome patients and correlates with focus score and disease activity

Background: Primary Sjögren’s syndrome (pSS) is a common chronic autoimmune disease characterized by lymphocytic infiltration of exocrine glands and peripheral lymphocyte perturbation. In the current study, we aimed to investigate the possible pathogenic implication of autophagy in T lymphocytes in patients with pSS. Methods: Thirty consecutive pSS patients were recruited together with 20 patients affected by sicca syndrome a nd/or chronic sialoadenitis and 30 healthy controls. Disease activity and damage were evaluated according to SS disease activity index, EULAR SS disease activity index, and SS disease damage index. T lymphocytes were analyzed for the expression of autophagy-specific markers by biochemical, molecular, and histological assays in peripheral blood and labial gland biopsies. Serum interleukin (IL)-23 and IL-21 levels were quantified by enzyme-linked immunosorbent assay. Results: Our study provides evidence for the first time that autophagy is upregulated in CD4+ T lymphocyte salivary glands from pSS patients. Furthermore, a statistically significant correlation was detected between lymphocyte autophagy levels, disease activity, and damage indexes. We also found a positive correlation between autophagy enhancement and the increased salivary gland expression of IL-21 and IL-23, providing a further link between innate and adaptive immune responses in pSS. Conclusions: These findings suggest that CD4+ T lymphocyte autophagy could play a key role in pSS pathogenesis. Additionally, our data highlight the potential exploitation of T cell autophagy as a biomarker of disease activity and provide new ground to verify the therapeutic implications of autophagy as an innovative drug target in pSS

Dying Declarations and the Confrontation Clause

Article published in the Michigan State University School of Law Student Scholarship Collection

Management of Obstructive Hydrocephalus Associated with Pineal Region Cysts and Tumors and Its Implication in Long-Term Outcome

BACKGROUND: Different treatment options have been proposed for obstructive hydrocephalus associated with pineal lesions. We discuss the obstructive hydrocephalus management associated with pineal region tumors and cysts in Helsinki Neurosurgery. METHODS: In this article, hydrocephalus treatment by tumor-cyst removal (n = 40), shunt surgery (n = 25), and endoscopic ventriculostomies (n = 3) is evaluated in 68 patients with obstructive hydrocephalus among 136 patients with pineal region tumor and cyst. Multivariate statistical analysis was followed by univariate and multivariate regression models of last functional status, last tumor-free imaging, and disease-specific mortality of the study population. RESULTS: Preoperative hydrocephalus was linked to higher World Health Organization tumor grades, poor functional status, higher mortality, and incomplete resection of pineal region cysts and tumors. Preoperative hydrocephalus remained a predictor of poor last functional status after multivariate regression. Pineal lesion removal with the posterior third ventricle opening as primary hydrocephalus treatment resulted in better last functional status, fewer postoperative shunts, fewer hydrocephalus related procedures, and fewer postoperative infections than in the shunt-treatment group. Multivariate regression analysis linked higher World Health Organization tumor & nbsp;grade, poor immediate functional status, postoperative complications, and incomplete surgical resection as independent predictors of disease mortality in patients with hydrocephalus. Same variables (except immediate modified Rankin Scale score) and higher number of shunt surgeries became independent predictors of poor last functional status at multivariate analysis. Incomplete resection was the only independent predictor of tumor-free magnetic resonance imaging at the last evaluation. CONCLUSIONS: Direct removal of pineal lesions with the opening of the posterior third ventricle could represent effective and reliable management of the associated obstructive hydrocephalus. Further research is required to generalize our inferences.Peer reviewe

Real communities of virtual plants explain biodiversity on just three assumptions

To illuminate mechanisms supporting diversity in plant communities, we construct 2D cellular automata and 'grow' virtual plants in real experiments. The plants are 19 different, fully validated functional types drawn from universal adaptive strategy theory. The scale of approach is far beyond that of even the most ambitious investigations in the physical world. By simulating 496 billion plant-environment interactions, we succeed in creating conditions that sustain high diversity realistically and indefinitely. Our simulations manipulate the levels of, and degree of heterogeneity in the supply of, resources, external disturbances and invading propagules. We fail to reproduce this outcome when we adopt the assumptions of unified neutral theory. The 19 functional types in our experiments respond in complete accordance with universal adaptive strategy theory. We find that spatial heterogeneity is a strong contributor to long-term diversity, but temporal heterogeneity is less so. The strongest support of all comes when an incursion of propagules is simulated. We enter caveats and suggest further directions for working with cellular automata in plant science. We conclude that although (i) the differentiation of plant life into distinct functional types, (ii) the presence of environmental heterogeneity and (iii) the opportunity for invasion by propagules can all individually promote plant biodiversity, all three appear to be necessary simultaneously for its long-term maintenance. Though further, and possibly more complex, sets of processes could additionally be involved, we consider it unlikely that any set of conditions more minimal than those described here would be sufficient to deliver the same outcome

Short-Burst Bipolar Coagulation for Repairing Partially Damaged Brain Arteries Preserving Their Flow : Technical Note

Peer reviewe