Caloric restriction maintains OX40 agonist-mediated tumor immunity and CD4 T cell priming during aging

Immune responses wane during aging, posing challenges to the potential effectiveness of cancer immunotherapies. We previously demonstrated that in the context of a promising immunotherapeutic, OX40 agonist (αOX40), older animals exhibited impaired anti-tumor immune responses and diminished CD4 T cell effector differentiation. In this study, we hypothesized that tumor immune responses could be maintained during aging through caloric restriction (CR) or dietary supplementation with resveratrol (RES), a CR mimetic. Mice were placed on either a calorically restricted diet or a RES-formulated diet starting between 4 and 6 months of age and continued until mice reached 12 months of age. Tumor immune responses were assessed after challenging with either sarcoma or breast tumor cells followed by αOX40 treatment. Our results show that CR, but not RES, maintained OX40-mediated anti-tumor immunity. In addition, CR fully sustained antigen-specific CD4 T cell priming in aged hosts (12 months old), whereas tumor-specific CD8 T cell priming was not fully maintained compared to young reference animals (2 months old). Thus, CR appears to maintain immunological fitness of the CD4 T cell priming environment during aging, which is critical for optimal OX40-mediated responses.     

Performance evaluation of broadcast and global combine operations in all-port wormhole-routed OTIS-Mesh interconnection networks

OTIS (Optical Transpose Interconnection System) optoelectronic architecture is an attractive high-speed interconnection network. As a continuation for the research work performed on OTIS, this paper investigates broadcast and global combine communication operations on the promising all-port wormhole-routed OTIS-Mesh using the Extended Dominating Node (EDN) approach, referred to as EDN-OTIS-Mesh. The performance of broadcast and global combine operations is evaluated, both analytically and by simulation, in terms of the number of communication steps, latency, and latency improvement. A comparative study is conducted among three interconnection networks’ architectures: the single-port wormhole-routed OTIS-Mesh, all-port wormhole-routed OTIS-Mesh, and all-port wormhole-routed EDN-OTIS-Mesh. The obtained analytical and simulation results show that the broadcast and global combine operations on all-port EDN-OTIS-Mesh significantly outperform the single-port and all-port OTIS-Mesh.     

Delayed fluorescence from Chlorella: I. Low temperature observations

Delayed fluorescence has been observed from Chlorella whole cells at 0.5 ms following flash excitation and at temperatures from 293 °K to 120 °K. Cells which are cooled while pre-illuminated before flashes produce less observed delayed fluorescence than cells cooled without pre-illumination. There exists a small component of delayed fluorescence whose magnitude is independent of pre-illumination effects. The effect of pre-illumination upon delayed fluorescence emission is eliminated by prior freezing of the algae.     

Fibroblast Activation Protein Cleaves and Inactivates Fibroblast Growth Factor 21

FGF21 is a stress-induced hormone with potent anti-obesity, insulin-sensitizing, and hepatoprotective properties. Although proteolytic cleavage of recombinant human FGF21 in preclinical species has been observed previously, the regulation of endogenously produced FGF21 is not well understood. Here we identify fibroblast activation protein (FAP) as the enzyme that cleaves and inactivates human FGF21. A selective chemical inhibitor, immunodepletion, or genetic deletion of Fap stabilized recombinant human FGF21 in serum. In addition, administration of a selective FAP inhibitor acutely increased circulating intact FGF21 levels in cynomolgus monkeys. On the basis of our findings, we propose selective FAP inhibition as a potential therapeutic approach to increase endogenous FGF21 activity for the treatment of obesity, type 2 diabetes, non-alcoholic steatohepatitis, and related metabolic disorders.     

Luminous Enteric Bacteria of Marine Fishes: a Study of Their Distribution, Densities, and Dispersion

Three taxa of luminous bacteria (Photobacterium fischeri, P. phosphoreum, and Beneckea spp.) were found in the enteric microbial populations of 22 species of surface- and midwater-dwelling fishes. These bacteria often occurred in concentrations ranging between 10⁵ and 10⁷ colony-forming units per ml of enteric contents. By using a genetically marked strain, it was determined that luminous cells entering the fish during ingestion of seawater or contaminated particles traversed the alimentary tract and survived the digestive processes. After excretion, luminous bacteria proliferated extensively on the fecal material and became distributed into the surrounding seawater. Thus, this enteric habitat may serve as an enrichment of viable cells entering the planktonic luminous population.     

Decoding Cellular Mechanisms for Mechanosensory Discrimination

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