disrupts TLR2-MYD88-p38 signaling early during infection to delay apoptosis of macrophages and promote virulence in the host.

is a zoonotic pathogen and the causative agent of tularemia. replicates to high levels within the cytosol of macrophages and other host cells while subverting the host response to infection. Critical to the success of is its ability to delay macrophage apoptosis to maintain its intracellular replicative niche.

Inflammatory monocytes provide a niche for Salmonella expansion in the lumen of the inflamed intestine.

Salmonella exploit host-derived nitrate for growth in the lumen of the inflamed intestine. The generation of host-derived nitrate is dependent on Nos2, which encodes inducible nitric oxide synthase (iNOS), an enzyme that catalyzes nitric oxide (NO) production. However, the cellular sources of iNOS and, therefore, NO-derived nitrate used by Salmonella for growth in the lumen of the inflamed intestine remain unidentified.

Tumor-intrinsic PIK3CA represses tumor immunogenecity in a model of pancreatic cancer.

The presence of tumor-infiltrating T cells is associated with favorable patient outcomes, yet most pancreatic cancers are immunologically silent and resistant to currently available immunotherapies. Here we show using a syngeneic orthotopic implantation model of pancreatic cancer that Pik3ca regulates tumor immunogenicity. Genetic silencing of Pik3ca in KrasG12D/Trp53R172H-driven pancreatic tumors resulted in infiltration of T cells, complete tumor regression, and 100% survival of immunocompetent host mice.

Contribution of Asparagine Catabolism to Salmonella Virulence.

Salmonellae are pathogenic bacteria that cause significant morbidity and mortality in humans worldwide. Salmonellae establish infection and avoid clearance by the immune system by mechanisms that are not well understood. We previously showed that l-asparaginase II produced by Salmonella enterica serovar Typhimurium (S Typhimurium) inhibits T cell responses and mediates virulence.

Salmonella Gives MARCH(ing) Orders to MHC-II.

How bacterial pathogens evade adaptive immunity is not well understood. In this issue of Cell Host & Microbe, Bayer-Santos et al. (2016) show that the Salmonella effector protein SteD mediates MARCH8-dependent ubiquitination of class II MHC molecules, thereby inhibiting antigen presentation and limiting T cell responses.

The quality and use of regulatory analysis in 2008.

This article assesses the quality and apparent use of regulatory analysis for economically significant regulations proposed by federal agencies in 2008. A nine-member research team used a six-point (0-5) scale to evaluate regulatory analyses according to criteria drawn from Executive Order 12866 and Office of Management and Budget Circular A-4. Principal findings include: (1) the average quality of regulatory analysis, though not high, is somewhat better than previous regulatory scorecards have shown; (2) quality varies widely; (3) biggest strengths are accessibility and clarity; (4) biggest weaknesses are analysis of the systemic problem and retrospective analysis; (5) budget or "transfer" regulations usually receive low-quality analysis; (6) a minority of the regulations contain evidence that the agency used the analysis in significant decisions; (7) quality of analysis is positively correlated with the apparent use of the analysis in regulatory decisions; and (8) greater diffusion of best practices could significantly improve the overall quality of regulatory analysis.

Highly active palladium catalysts supported by bulky proazaphosphatrane ligands for Stille cross-coupling: coupling of aryl and vinyl chlorides, room temperature coupling of aryl bromides, coupling of aryl triflates, and synthesis of sterically hindered biaryls.

A family of proazaphosphatrane ligands [P(RNCH2CH2)2N(R'NCH2CH2): R = R' = i-Bu, 1; R = Bz, R' = i-Bu, 3; R = R' = Bz, 4] for palladium-catalyzed Stille reactions of aryl chlorides is described. Catalysts derived from ligands 1 and 4 efficiently catalyze the coupling of electronically diverse aryl chlorides with an array of organotin reagents. The catalyst system based on the ligand 3 is active for the synthesis of sterically hindered biaryls (di-, tri-, and tetra-ortho substituted).

The effect of talocrural joint manipulation on range of motion at the ankle.

Objective: To determine whether a single high-velocity, low-amplitude thrust manipulation to the talocrural joint altered ankle range of motion.

Design: A randomized, controlled and blinded study.

Subjects: Asymptomatic male and female volunteers (N = 41).