A network map of Interleukin-10 signaling pathway

Interleukin-10 (IL-10) is an anti-inflammatory cytokine with important immunoregulatory functions. It is primarily secreted by antigen-presenting cells such as activated T-cells, monocytes, B-cells and macrophages. In biologically functional form, it exists as a homodimer that binds to tetrameric heterodimer IL-10 receptor and induces downstream signaling. IL-10 is associated with survival, proliferation and anti-apoptotic activities of various cancers such as Burkitt lymphoma, non-Hodgkins lymphoma and non-small scell lung cancer. In addition, it plays a central role in survival and persistence of intracellular pathogens such as Leishmania donovani, Mycobacterium tuberculosis and Trypanosoma cruzi inside the host. The signaling mechanisms of IL-10 cytokine are not well explored and a well annotated pathway map has been lacking. To this end, we developed a pathway resource by manually annotating the IL-10 induced signaling molecules derived from literature. The reactions were categorized under molecular associations, activation/inhibition, catalysis, transport and gene regulation. In all, 37 molecules and 76 reactions were annotated. The IL-10 signaling pathway can be freely accessed through NetPath, a resource of signal transduction pathways previously developed by our group.     

Sources of Biomass Feedstock Variability and the Potential Impact on Biofuels Production

Terrestrial lignocellulosic biomass has the potential to be a carbon neutral and domestic source of fuels and chemicals. However, the innate variability of biomass resources, such as herbaceous and woody materials, and the inconsistency within a single resource due to disparate growth and harvesting conditions, presents challenges for downstream processes which often require materials that are physically and chemically consistent. Intrinsic biomass characteristics, including moisture content, carbohydrate and ash compositions, bulk density, and particle size/shape distributions are highly variable and can impact the economics of transforming biomass into value-added products. For instance, ash content increases by an order of magnitude between woody and herbaceous feedstocks (from ～0.5 to 5 %, respectively) while lignin content drops by a factor of two (from ～30 to 15 %, respectively). This increase in ash and reduction in lignin leads to biofuel conversion consequences, such as reduced pyrolysis oil yields for herbaceous products as compared to woody material. In this review, the sources of variability for key biomass characteristics are presented for multiple types of biomass. Additionally, this review investigates the major impacts of the variability in biomass composition on four conversion processes: fermentation, hydrothermal liquefaction, pyrolysis, and direct combustion. Finally, future research processes aimed at reducing the detrimental impacts of biomass variability on conversion to fuels and chemicals are proposed.© 2015 Battelle Energy Alliance, LLC, contract manager for Idaho National Laboratory.     

Association between Cognition and Serum Insulin-Like Growth Factor-1 in Middle-Aged & Older Men: An 8 Year Follow-Up Study

Low levels of insulin-like growth factor-1 (IGF-1), an essential neurotrophic factor, have been associated with worse cognitive function in older adults. However, few studies have assessed the prospective association of serum IGF-1 with cognitive function. We aimed to determine the association between serum IGF-1 on concurrent and prospective cognitive function in a population sample of men aged 40–80 years. Blood samples were assessed for IGF-1 levels at baseline and neuropsychological assessments were performed at baseline (n = 400) and at follow-up after a mean duration of 8.3 years (n = 286). Linear regression analyses were carried out to determine the associations between quintiles of IGF-1 and cognitive function at the baseline and follow-up visits. Results showed that those in the top quintile of IGF-1 had lower processing capacity and global cognition scores at follow-up after controlling for cognitive function at baseline and other confounding factors. Additional analyses exploring associations with IGF-1 separately in middle-aged and older participants, and with quartiles of IGF-1 produced similar results. In those older than 60 years, high IGF-1 levels were also associated with lower baseline processing capacity. These results suggest that high IGF-1 levels are associated with worse long-term cognition in men. Together with past studies, we suggest that both, high and low levels of IGF-1 may be associated with poor cognitive function and that optimum levels of IGF-1 (quintile 2 and 3 in current study) may be associated with better cognitive function.     

Experimental Persistent Infection of BALB/c Mice with Small-Colony Variants of Burkholderia pseudomallei Leads to Concurrent Upregulation of PD-1 on T Cells and Skewed Th1 and Th17 Responses

BackgroundBurkholderia pseudomallei (B. pseudomallei), the causative agent of melioidosis, is a deadly pathogen endemic across parts of tropical South East Asia and Northern Australia. B. pseudomallei can remain latent within the intracellular compartment of the host cell over prolonged periods of time, and cause persistent disease leading to treatment difficulties. Understanding the immunological mechanisms behind persistent infection can result in improved treatment strategies in clinical melioidosis.MethodsTen-day LD₅₀ was determined for the small-colony variant (SCV) and its parental wild-type (WT) via intranasal route in experimental BALB/c mice. Persistent B. pseudomallei infection was generated by administrating sub-lethal dose of the two strains based on previously determined LD₅₀. After two months, peripheral blood mononuclear cells (PBMCs) and plasma were obtained to investigate host immune responses against persistent B. pseudomallei infection. Lungs, livers, and spleens were harvested and bacterial loads in these organs were determined.ResultsBased on the ten-day LD₅₀, the SCV was ~20-fold less virulent than the WT. The SCV caused higher bacterial loads in spleens compared to its WT counterparts with persistent B. pseudomallei infection. We found that the CD4+ T-cell frequencies were decreased, and the expressions of PD-1, but not CTLA-4 were significantly increased on the CD4+ and CD8+ T cells of these mice. Notably, persistent infection with the SCV led to significantly higher levels of PD-1 than the WT B. pseudomallei. Plasma IFN-γ, IL-6, and IL-17A levels were elevated only in SCV-infected mice. In addition, skewed plasma Th1 and Th17 responses were observed in SCV-infected mice relative to WT-infected and uninfected mice.ConclusionB. pseudomallei appears to upregulate the expression of PD-1 on T cells to evade host immune responses, which likely facilitates bacterial persistence in the host. SCVs cause distinct pathology and immune responses in the host as compared to WT B. pseudomallei.     

Occurrence of minute ring-shaped nucleoprotein particles in culture media conditioned by mammalian cells

Summary Conditioned media of 21 mammalian cell lines have been examined by electron microscopic and biochemical techniques for the presence of a minute ring-shaped nucleoprotein particle (RSP). Electron microscopy showed the presence of RSP in 20 of the 21 cell lines tested. Comparative analyses of six cell cultures for radio-active RSP, following³H-thymidine incorporation, suggested that quantitative differences exist in the amount of RSP detectable in conditioned media of normal and pathologic cells. The cell lines tested included cells of different morphologies, origin and function. Supported by a research grant from Claremont Foundation, Inc., Claremont, California.     

Activation and inactivation of the osteoclast Ca2+ receptor by the trivalent cation, La3+.

We report changes in the cytosolic Ca2+ concentration ([Ca2+]i) of single rat osteoclasts in response to Ca2+ receptor activation by micromolar concentrations of the lanthanide metal cation, La3+. The extracellular application of La3+ induced a concentration-dependent elevation of cytosolic [Ca2+]. Prior conditioning of osteoclasts with La3+ resulted in a concentration-dependent reduction of the response to a subsequent application of a maximally effective concentration of Ni2+, a known agonist of the osteoclast Ca2+ receptor. The results establish that the osteoclast Ca2+ receptor is highly sensitive to activation and inactivation by the trivalent cation, La3+.     

The osteoclast Ca2+ receptor is highly sensitive to activation by transition metal cations.

We report changes in the cytosolic Ca2+ concentration ([Ca2+]i) of single rat osteoclasts in response to Ca2+ receptor activation by micromolar concentrations of the transition metal cations, Cd2+ and Ni2+. The extracellular application of Cd2+ or Ni2+ resulted in a concentration-dependent elevation of cytosolic [Ca2+]. Each monophasic [Ca2+]i response consisted of an initial rapid rise of [Ca2+]i to a peak value followed by an exponential decay. Prior application of Cd2+ or Ni2+ induced refractoriness to a second application of the same cation. The results confirm the existence of a divalent cation-sensitive site on the osteoclast showing features of concentration-dependent activation and use-dependent inactivation.     

Functionalized, probe-containing, latex nanospheres.

Synthesis of surface-functionalized, probe-containing latex nanospheres is described. Approximately 40,000 probe ions may be encapsulated in a nanosphere of 50 nm diameter. The probe may be a radionuclide or a lanthanide with long-lived fluorescence. Alternatively, a "cargo" of pharmaceutical interest may be used. The surface of each nanosphere contains thousands of acid groups which may be functionalized for subsequent attachment to biomolecules such as antibodies. Functionalized nanospheres have been successfully coupled to a tobacco virus.     

Comparison of free and immobilizedCephalosporium acremonium for β-lactam antibiotic production

Summary Cephalosporium acremonium cells were immobilized in calcium alginate beads. Immobilized cells were used to produce -lactam antibiotics in rest medium under various oxygen concentrations, and the results were compared with free cell performance. Cell growth rate of immobilized cells was 35% of the growth rate of free cells. -Lactam antibiotic production rate of immobilized cells was also limited by mass transfer of oxygen. -Lactam antibiotic production rate of immobilized cells was 70% of that of free cells at oxygen saturation condition (i.e., 0.27 mM O₂). Specific antibiotic production of immobilized cells was about 200% of that of free cells at 0.27 mM O₂.     

Enhanced β-lactam antibiotic production by coimmobilization of fungus and alga

Summary It was determined thatCephalosporium acremonium, an oxygenconsuming fungus, had a symbiotic relationship withChlorella pyrenoidosa, an oxygen-generating alga. The fungus and the alga were coimmobilized by entrapment in calcium alginate beads. The production rate of -lactam antibiotics was evaluated at various ratios of the fungus and the alga cells in the free and immobilized states. When the ratio of fungus to alga was one to eight in free mixed culture, the production rate of -lactam antibiotics was 240% of the rate in the presence of fungus alone in the free state. In coimmobilized cell system, the increased amount was 370% in comparison with immobilized fungus alone.