CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans

Immunosuppressive tumor microenvironments can restrain antitumor immunity, particularly in pancreatic ductal adenocarcinoma (PDA). Because CD40 activation can reverse immune suppression and drive antitumor T cell responses, we tested the combination of an agonist CD40 antibody with gemcitabine chemotherapy in a small cohort of patients with surgically incurable PDA and observed tumor regressions in some patients. We reproduced this treatment effect in a genetically engineered mouse model of PDA and found unexpectedly that tumor regression required macrophages but not T cells or gemcitabine. CD40-activated macrophages rapidly infiltrated tumors, became tumoricidal, and facilitated the depletion of tumor stroma. Thus, cancer immune surveillance does not necessarily depend on therapy-induced T cells; rather, our findings demonstrate a CD40-dependent mechanism for targeting tumor stroma in the treatment of cancer.     

New perspectives on ancient Mars

Mars was most active during its first billion years. The core, mantle, and crust formed within approximately 50 million years of solar system formation. A magnetic dynamo in a convecting fluid core magnetized the crust, and the global field shielded a more massive early atmosphere against solar wind stripping. The Tharsis province became a focus for volcanism, deformation, and outgassing of water and carbon dioxide in quantities possibly sufficient to induce episodes of climate warming. Surficial and near-surface water contributed to regionally extensive erosion, sediment transport, and chemical alteration. Deep hydrothermal circulation accelerated crustal cooling, preserved variations in crustal thickness, and modified patterns of crustal magnetization.     

United time-frequency spectroscopy for dynamics and global structure

Ultrashort laser pulses have thus far been used in two distinct modes. In the time domain, the pulses have allowed probing and manipulation of dynamics on a subpicosecond time scale. More recently, phase stabilization has produced optical frequency combs with absolute frequency reference across a broad bandwidth. Here we combine these two applications in a spectroscopic study of rubidium atoms. A wide-bandwidth, phase-stabilized femtosecond laser is used to monitor the real-time dynamic evolution of population transfer. Coherent pulse accumulation and quantum interference effects are observed and well modeled by theory. At the same time, the narrow linewidth of individual comb lines permits a precise and efficient determination of the global energy-level structure, providing a direct connection among the optical, terahertz, and radio-frequency domains. The mechanical action of the optical frequency comb on the atomic sample is explored and controlled, leading to precision spectroscopy with an appreciable reduction in systematic errors.     

Cassini imaging of Jupiter's atmosphere,satellites, and rings

The Cassini Imaging Science Subsystem acquired about 26,000 images of the Jupiter system as the spacecraft encountered the giant planet en route to Saturn. We report findings on Jupiter's zonal winds, convective storms, low-latitude upper troposphere, polar stratosphere, and northern aurora. We also describe previously unseen emissions arising from Io and Europa in eclipse, a giant volcanic plume over Io's north pole, disk-resolved images of the satellite Himalia, circumstantial evidence for a causal relation between the satellites Metis and Adrastea and the main jovian ring, and information on the nature of the ring particles.     

Sex-specific UV and fluorescence signals in jumping spiders

No animals are known to possess both ultraviolet (UV) reflectance and fluorescence that are sex-specific. We provide evidence for this separation in the jumping spider Cosmophasis umbratica, which has UV reflectance and UV-induced green fluorescence restricted to males and females, respectively. During courtship, many of the studied pairs failed to show typical display posturing when UV light was blocked. Occluding the UV component of sunlight to only one of each pair also caused atypical behavior: Females showed no interest in non-UV-reflective courting males, and males either ignored or were lackluster in courting nonfluorescing females. These results demonstrate the importance of both sex-specific hues as sexual signals for effective intraspecific communication.     

Targeting QseC signaling and virulence for antibiotic development

Many bacterial pathogens rely on a conserved membrane histidine sensor kinase, QseC, to respond to host adrenergic signaling molecules and bacterial signals in order to promote the expression of virulence factors. Using a high-throughput screen, we identified a small molecule, LED209, that inhibits the binding of signals to QseC, preventing its autophosphorylation and consequently inhibiting QseC-mediated activation of virulence gene expression. LED209 is not toxic and does not inhibit pathogen growth; however, this compound markedly inhibits the virulence of several pathogens in vitro and in vivo in animals. Inhibition of signaling offers a strategy for the development of broad-spectrum antimicrobial drugs.