Stochastic underseepage analysis in dams

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Civil Engineering, 1980.MICROFICHE COPY AVAILABLE IN ARCHIVES AND ENGINEERING.Bibliography: leaves 121-123.by Gary E.B. Choot.M.S

Toll-like receptor 4, but not neutrophil extracellular Traps, Promote IFN Type I expression to enhance Th2 responses to Nippostrongylus brasiliensis

The induction of Th2 responses is thought to be multifactorial, and emerge from specific pathways distinct from those associated with antagonistic antibacterial or antiviral Th1 responses. Here, we show that the recognition of non-viable Nippostrongylus brasiliensis (Nb) in the skin induces a strong recruitment of monocytes and neutrophils and the release of neutrophil extracellular traps (NETs). Nb also activates toll-like receptor 4 (TLR4) signaling with expression of Ifnb transcripts in the skin and the development of an IFN type I signature on helminth antigen-bearing dendritic cells in draining lymph nodes. Co-injection of Nb together with about 10,000 Gram-negative bacteria amplified this TLR4-dependent but NET-independent IFN type I response and enhanced the development of Th2 responses. Thus, a limited activation of antibacterial signaling pathways is able to boost antihelminthic responses, suggesting a role for bacterial sensing in the optimal induction of Th2 immunity

The Lung Is an Important Site for Priming CD4 T-Cell-Mediated Protective Immunity against Gastrointestinal Helminth Parasites▿ ‡

The rodent hookworm Nippostrongylus brasiliensis typically infects its host by penetrating the skin and rapidly migrating to the lungs and gut. Following primary infection, immunocompetent mice become highly protected from reinfection with N. brasiliensis, with the numbers of worms gaining access to the lungs and gut being reduced by up to 90%. We used green fluorescent protein/interleukin-4 (IL-4) reporter mice and truncated infection studies to identify both the tissue site and mechanism(s) by which the host protects itself from reinfection with N. brasiliensis. Strikingly, we demonstrated that the lung is an important site for priming immune protection. Furthermore, a lung-initiated, CD4 T-cell-dependent, and IL-4- and STAT6-dependent response was sufficient to confer protection against reinfection. In conclusion, vaccination strategies which seek to break the cycle of reinfection and egg production by helminths such as hookworms can include strategies which directly stimulate Th2 responses in the lung

Brain-Heart Interaction After Stroke: Therapeutic Effects of Exosomes in Type 2 Diabetic Mice Subjected to Stroke

Aim: Diabetes exacerbates post-stroke cardiac injury. We tested whether treatment with exosomes harvested from human umbilical cord blood derived CD133+/KDR+ cells (CD133+Exo) improves neurological, cognitive and cardiac functional outcome in type 2 diabetes mellitus (T2DM) stroke mice. Methods: Adult (3-4m), male, db/db (T2DM) mice were subjected to distal middle cerebral artery occlusion (dMCAo) and treated with PBS or CD133+Exo (3x10 , i.v.) at 3 days after stroke (n=8/group). Serum exosomal microRNA (miR) expression was measured. Echocardiography, neurological and cognitive tests were performed, and mice were sacrificed at 28 days after stroke. Results: 1) Compared to T2DM-control, T2DM-stroke mice exhibit significantly decreased left ventricular ejection fraction (LVEF: db/db: 67.6±0.6%, db/db-dMCAo: 60.6±1.9%, p\u3c0.05), significant cardiomyocyte hypertrophy, interstitial fibrosis, and decreased capillary density in heart indicating that stroke in T2DM mice induces cardiac dysfunction at 28 days after stroke. 2) Serum exosomal miR29b and miR126 expression was significantly decreased in T2DM-stroke mice compared to T2DM-control mice. CD133+Exo contain high levels of miR126 and miR29b. 3) CD133+Exo treatment in T2DM-stroke mice significantly promotes neurological functional recovery (foot-fault test), significantly improves cognitive outcome (Morris water maze (MWM) test and odor test), and significantly improves cardiac function (LVEF: db/db-dMCAo: 60.6±1.9%, db/dbdMCAo+ CD133+Exo: 68.9±0.7%, p\u3c0.05). 4) In T2DM-stroke mice with PBS or CD133+Exo treatment, cardiac function (LVEF) significantly correlates with cognitive outcome. 5) CD133+Exo treatment in T2DM-stroke mice significantly decreases myocardial fibrosis, decreases TGF-β and NOX2 expression, and increases heart tissue miR126 and miR29b expression, while decreasing expression of miR126 and miR29b target genes such as Spred-1 and DPP4. Conclusions: Stroke in T2DM mice induces significant cardiac dysfunction and CD133+Exo treatment improves neurological and cognitive outcome, and provides significant cardio-protection. The improvement in cardiac functional outcome highly correlates with cognitive functional recovery