Antigen Complexed with a TLR9 Agonist Bolsters c-Myc and mTORC1 Activity in Germinal Center B Lymphocytes.

The germinal center (GC) is the anatomical site where humoral immunity evolves. B cells undergo cycles of proliferation and selection to produce high-affinity Abs against Ag. Direct linkage of a TLR9 agonist (CpG) to a T-dependent Ag increases the number of GC B cells. We used a T-dependent Ag complexed with CpG and a genetic model for ablating the TLR9 signaling adaptor molecule MyD88 specifically in B cells (B-MyD88- mice) together with transcriptomics to determine how this innate pathway positively regulates the GC. GC B cells from complex Ag-immunized B-MyD88- mice were defective in inducing gene expression signatures downstream of c-Myc and mTORC1. In agreement with the latter gene signature, ribosomal protein S6 phosphorylation was increased in GC B cells from wild-type mice compared with B-MyD88- mice. However, GC B cell expression of a c-Myc protein reporter was enhanced by CpG attached to Ag in both wild-type and B-MyD88- mice, indicating a B cell-extrinsic effect on c-Myc protein expression combined with a B cell-intrinsic enhancement of gene expression downstream of c-Myc. Both mTORC1 activity and c-Myc are directly induced by T cell help, indicating that TLR9 signaling in GC B cells either enhances their access to T cell help or directly influences these pathways to further enhance the effect of T cell help. Taken together, these findings indicate that TLR9 signaling in the GC could provide a surrogate prosurvival stimulus, "TLR help," thus lowering the threshold for selection and increasing the magnitude of the GC response

Benefits from synergies and advanced technologies for an advanced-technology space station

A configuration for a second-generation advanced technology space station has been defined in a series of NASA-sponsored studies. Definitions of subsystems specifically addressed opportunities for beneficial synergistic interactions and those potential synergies and their benefits are identified. One of the more significant synergistic benefits involves the multi-function utilization of water within a large system that generates artificial gravity by rotation. In such a system, water not only provides the necessary crew life support, but also serves as counterrotator mass, as moveable ballast, and as a source for propellant gases. Additionally, the synergistic effects between advanced technology materials, operation at reduced artificial gravity, and lower cabin atmospheric pressure levels show beneficial interactions that can be quantified in terms of reduced mass to orbit

Method of delivering lunar generated fluid to earth orbit using an external tank

A method and apparatus are provided for delivering lunar generated fluid to Earth orbit from lunar orbit. Transport takes place in an external tank of a shuttle which has been suitably outfitted in Earth orbit for reusable travel between Earth orbit and a lunar orbit. The outfitting of the external tank includes the adding of an engine, an electrical system, a communication system, a guidance system, an aerobraking device, and a plurality of interconnected fluid storage tanks to the hydrogen and oxygen tanks of the external tank. The external tank is then propelled to lunar orbit the first time using Earth-based propellant. In lunar orbit, the storage tanks are filled with the lunar generated fluid with the remainder tank volumes filled with lunar generated liquid oxygen and hydrogen which serve as propellants for returning the tank to Earth orbit where the fluid is off-loaded. The remaining lunar generated oxygen and hydrogen is then sufficient to return the external tank to lunar orbit so that a subsequent cycle of fluid delivery is repeated. A space station in a higher Earth orbit is preferably used to outfit the external tank, and a lunar node in lunar orbit is used to store and transfer the fluid and liquid oxygen and hydrogen to the external tank. The lunar generated fluid is preferably .sup.3 He

Increased Hematopoietic Extracellular RNAs and Vesicles in the Lung during Allergic Airway Responses.

Extracellular RNAs (exRNAs) can be released by numerous cell types in vitro, are often protected within vesicles, and can modify recipient cell function. To determine how the composition and cellular sources of exRNAs and the extracellular vesicles (EVs) that carry them change in vivo during tissue inflammation, we analyzed bronchoalveolar lavage fluid (BALF) from mice before and after lung allergen challenge. In the lung, extracellular microRNAs (ex-miRNAs) had a composition that was highly correlated with airway-lining epithelium. Using cell type-specific membrane tagging and single vesicle flow, we also found that 80% of detected vesicles were of epithelial origin. After the induction of allergic airway inflammation, miRNAs selectively expressed by immune cells, including miR-223 and miR-142a, increased and hematopoietic-cell-derived EVs also increased >2-fold. These data demonstrate that infiltrating immune cells release ex-miRNAs and EVs in inflamed tissues to alter the local extracellular environment