The Role of Peptide-Based Tumor Vaccines on Cytokines of Adaptive Immunity: A Review

International Journal of Peptide Research and Therapeutics - Recently, peptide-based materials have been applied to solving many therapeutic problems and have shown particular efficacy as cancer...     

Elevated nutrient inputs to marshes differentially impact carbon and nitrogen cycling in two northern Gulf of Mexico saltmarsh plants

Peatlands have accumulated vast quantities of organic carbon over thousands of years but it is unclear how these sensitive ecosystems will respond to future climate change. If emissions of methane from peatlands increase, then they may contribute increasingly towards climatic warming due to the higher greenhouse warming potential of this gas. We investigated the radiocarbon concentration of methane emissions from a temperate bog over 1.5 years, which we supported with measurements of the surface flux of methane and carbon dioxide. The radiocarbon content of methane emissions varied greatly, from modern (i.e. fixed from the atmosphere within recent decades) to ~ 1400 years BP. Flux rates of methane were spatially and temporally highly variable. A vegetation clipping experiment showed that plants had a great influence on the carbon isotope composition and flux of methane emitted from the peat surface, consistent with earlier studies showing the key role of plants in peatland methane emissions. When plants were absent, emission rates were 70–94% lower and the radiocarbon age of methane emissions was much younger and less variable. Our radiocarbon measurements show that at this peatland, plant-associated methane emissions contain carbon originally fixed from the atmosphere up to hundreds of years earlier, consistent with a contribution from plant mediated transport of methane sourced from sub-surface layers.

     

Hepatoprotective Effect of Manganese Chloride Against CCl4-Induced Liver Injury in Rats

The aim of the present study is to evaluate the protective effect of manganese chloride against carbon tetrachloride (CCl₄)-induced liver injury in rats. Manganese chloride (0.001, 0.01, 0.05 and 0.1 g/kg bw) was administered intragastrically for 28 consecutive days to male CCl₄-treated rats. The hepatoprotective activity was assessed using various biochemical parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyltransferase (GGT) and superoxide dismutase (SOD). Histopathological changes in the liver of different groups were also studied. Administration of CCl₄ increased the serum ALT, AST, ALP and GGT but decreased SOD levels in rats. Treatment with manganese chloride significantly attenuated these changes to nearly normal levels. The animals treated with manganese chloride have shown decreased necrotic zones and hepatocellular degeneration when compared to the liver exposed to CCl₄ intoxication alone. Thus, the histopathalogical studies also supported the protective effect of manganese chloride. Therefore, the results of this study suggest that manganese chloride exerts hepatoprotection via promoting antioxidative properties against CCl₄-induced oxidative liver damage.     

Diurnal patterns of gas‐exchange and metabolic pools in tundra plants during three phases of the arctic growing season

Arctic tundra plant communities are subject to a short growing season that is the primary period in which carbon is sequestered for growth and survival. This period is often characterized by 24‐h photoperiods for several months a year. To compensate for the short growing season tundra plants may extend their carbon uptake capacity on a diurnal basis, but whether this is true remains unknown. Here, we examined in situ diurnal patterns of physiological activity and foliar metabolites during the early, mid, and late growing season in seven arctic species under light‐saturated conditions. We found clear diurnal patterns in photosynthesis and respiration, with midday peaks and midnight lulls indicative of circadian regulation. Diurnal patterns in foliar metabolite concentrations were less distinct between the species and across seasons, suggesting that metabolic pools are likely governed by proximate external factors. This understanding of diurnal physiology will also enhance the parameterization of process‐based models, which will aid in better predicting future carbon dynamics for the tundra. This becomes even more critical considering the rapid changes that are occurring circumpolarly that are altering plant community structure, function, and ultimately regional and global carbon budgets.     

Parallel Mapping of Antibiotic Resistance Alleles in Escherichia coli

Chemical genomics expands our understanding of microbial tolerance to inhibitory chemicals, but its scope is often limited by the throughput of genome-scale library construction and genotype-phenotype mapping. Here we report a method for rapid, parallel, and deep characterization of the response to antibiotics in Escherichia coli using a barcoded genome-scale library, next-generation sequencing, and streamlined bioinformatics software. The method provides quantitative growth data (over 200,000 measurements) and identifies contributing antimicrobial resistance and susceptibility alleles. Using multivariate analysis, we also find that subtle differences in the population responses resonate across multiple levels of functional hierarchy. Finally, we use machine learning to identify a unique allelic and proteomic fingerprint for each antibiotic. The method can be broadly applied to tolerance for any chemical from toxic metabolites to next-generation biofuels and antibiotics.     

Immunoresolvents in asthma and allergic diseases: Review and update

Asthma and allergic diseases are inflammatory conditions developed by excessive reaction of the immune system against normally harmless environmental substances. Although acute inflammation is necessary to eradicate the damaging agents, shifting to chronic inflammation can be potentially detrimental. Essential fatty-acids-derived immunoresolvents, namely, lipoxins, resolvins, protectins, and maresins, are anti-inflammatory compounds that are believed to have protective and beneficial effects in inflammatory disorders, including asthma and allergies. Accordingly, impaired biosynthesis and defective production of immunoresolvents could be involved in the development of chronic inflammation. In this review, recent evidence on the anti-inflam]matory effects of immunoresolvents, their enzymatic biosynthesis routes, as well as their receptors are discussed.     

Affinity maturation and characterization of the ofatumumab monoclonal antibody

CD20 molecule, a phosphoprotein with 297 amino acids and four transmembrane domains, is a member of MS4A protein family. Anti-CD20 antibodies such as ofatumumab, which have been developed for cancer treatment and has demonstrated efficacy in relapsed/refractory chronic lymphocytic leukemia, are among the most successful therapies to date. Rational engineering methods can be applied with reasonable success to improve functional characteristics of antibodies. Considering the importance of this issue, we have used in silico modeling approach for the improvement of ofatumumab monoclonal antibody. Four mutated variants of ofatumumab were developed and expressed in Chinese hamster ovary (CHO) cells along with the unmodified antibody. Analysis of affinity of the purified antibodies with CD20 showed significant improvement in antigen-binding characteristics of one of the variants compared with the control antibody. This study represents the first step toward development of the second generation ofatumumab antibody with improved affinity.     

Skeletons, noise and population growth: the end of an old debate?

Population dynamics models remain largely deterministic, although the presence of random fluctuations in nature is well recognized. This deterministic approach is based on the implicit assumption that systems can be separated into a deterministic part that captures the essential features of the system and a random part that can be neglected. But is it possible, in general, to understand population dynamics without the explicit consideration of random fluctuations? Here, we suggest perhaps not, and argue that the dynamics of many systems are a result of interactions between the deterministic nonlinear skeleton and noise.     

Cholera toxin B pretreatment of macrophages and monocytes diminishes their proinflammatory responsiveness to lipopolysaccharide

The cholera toxin B chain (CTB) has been reported to suppress T cell-dependent autoimmune diseases and to potentiate tolerance of the adaptive immune system. We have analyzed the effects of CTB on macrophages in vitro and have found that preincubation with CTB (10 microg/ml) suppresses the proinflammatory reaction to LPS challenge, as demonstrated by suppressed production of TNF-alpha, IL-6, IL-12(p70), and NO (p < 0.01) in cells of macrophage lines. Pre-exposure to CTB also suppresses LPS-induced TNF-alpha and IL-12(p70) formation in human PBMC. Both native and recombinant CTB exhibited suppressive activity, which was shared by intact cholera toxin. In cells of the human monocyte line Mono Mac 6, exposure to CTB failed to suppress the production of IL-10 in response to LPS. Control experiments excluded a role of possible contamination of CTB by endotoxin or intact cholera toxin. The suppression of TNF-alpha production occurred at the level of mRNA formation. Tolerance induction by CTB was dose and time dependent. The suppression of TNF-alpha and IL-6 production could be counteracted by the addition of Abs to IL-10 and TGF-beta. IFN-gamma also antagonized the actions of CTB on macrophages. In contrast to desensitization by low doses of LPS, tolerance induction by CTB occurred silently, i.e., in the absence of a measurable proinflammatory response. These findings identify immune-deviating properties of CTB at the level of innate immune cells and may be relevant to the use of CTB in modulating immune-mediated diseases.