Producer Nutritional Quality Controls Ecosystem Trophic Structure

Trophic structure, or the distribution of biomass among producers and consumers, determines key ecosystem values, such as the abundance of infectious, harvestable or conservation target species, and the storage and cycling of carbon and nutrients. There has been much debate on what controls ecosystem trophic structure, yet the answer is still elusive. Here we show that the nutritional quality of primary producers controls the trophic structure of ecosystems. By increasing the efficiency of trophic transfer, higher producer nutritional quality results in steeper ecosystem trophic structure, and those changes are more pronounced in terrestrial than in aquatic ecosystems probably due to the more stringent nutritional limitation of terrestrial herbivores. These results explain why ecosystems composed of highly nutritional primary producers feature high consumer productivity, fast energy recycling, and reduced carbon accumulation. Anthropogenic changes in producer nutritional quality, via changes in trophic structure, may alter the values and functions of ecosystems, and those alterations may be more important in terrestrial ecosystems

Positively Selected Codons in Immune-Exposed Loops of the Vaccine Candidate OMP-P1 of Haemophilus influenzae

The high levels of variation in surface epitopes can be considered as an evolutionary hallmark of immune selection. New computational tools enable analysis of this variation by identifying codons that exhibit high rates of amino acid changes relative to the synonymous substitution rate. In the outer membrane protein P1 of Haemophilus influenzae, a vaccine candidate for nontypeable strains, we identified four codons with this attribute in domains that did not correspond to known or assumed B- and T-cell epitopes of OMP-P1. These codons flank hypervariable domains and do not appear to be false positives as judged from parsimony and maximum likelihood analyses. Some closely spaced positively selected codons have been previously considered part of a transmembrane domain, which would render this region unsuited for inclusion in a vaccine. Secondary structure analysis, three-dimensional structural database searches, and homology modeling using FadL of E. coli as a structural homologue, however, revealed that all positively selected codons are located in or near extracellular looping domains. The spacing and level of diversity of these positively selected and exposed codons in OMP-P1 suggest that vaccine targets based on these and conserved flanking residues may provide broad coverage in H. influenzae

Combined Tumor Cell-Based Vaccination and Interleukin-12 Gene Therapy Polarizes the Tumor Microenvironment in Mice

Tumor progression depends on tumor milieu, which influences neovasculature formation and immunosuppression. Combining immunotherapy with antiangiogenic/antivascular therapy might be an effective therapeutic approach. The aim of our study was to elaborate an anticancer therapeutic strategy based on the induction of immune response which leads to polarization of tumor milieu. To achieve this, we developed a tumor cell-based vaccine. CAMEL peptide was used as a B16-F10 cell death-inducing agent. The lysates were used as a vaccine to immunize mice bearing B16-F10 melanoma tumors. To further improve the therapeutic effect of the vaccine, we combined it with interleukin (IL)-12 gene therapy. IL-12, a cytokine with antiangiogenic properties, activates nonspecific and specific immune responses. We observed that combined therapy is significantly more effective (as compared with monotherapies) in inhibiting tumor growth. Furthermore, the tested combination polarizes the tumor microenvironment, which results in a switch from a proangiogenic/immunosuppressive to an antiangiogenic/immunostimulatory one. The switch manifests itself as a decreased number of tumor blood vessels, increased levels of tumor-infiltrating CD4+, CD8+ and NK cells, as well as lower level of suppressor lymphocytes (Treg). Our results suggest that polarizing tumor milieu by such combined therapy does inhibit tumor growth and seems to be a promising therapeutic strategy

Re-defining response and treatment effects for neuro-oncology immunotherapy clinical trials

In much of medical oncology, including neuro-oncology, there is great interest to evaluate the therapeutic potential of immune-based therapies including vaccines, adoptive T cell strategies and modulators of immune checkpoint regulators such as cytotoxic T lymphocyte antigen 4 and programmed death 1. Immune-based treatments exert an indirect anti-tumor effect by generating potent, tumor-targeting immune responses. Robust anti-tumor immune responses have been shown to achieve encouraging radiographic responses across the spectrum of applied immunotherapeutics which are felt to be indicative of a bona fide anti-tumor effect. Conversely, worsening of imaging findings, particularly early in the course of immunotherapy administration, can be challenging to interpret with growing evidence demonstrating that at least a subset of such patients ultimately will derive meaningful clinical benefit. The immune related response criteria were generated to provide guidance regarding the interpretation of such complex imaging findings, for general medical oncologists prescribing immunotherapeutics. An analogous effort that addresses challenges associated with imaging assessment and incorporates nuances associated with neuro-oncology patients is underway and is referred to as the immunotherapy response assessment in neuro-oncology criteria