35 research outputs found

    System immunology-based identification of blood transcriptional modules correlating to antibody responses in sheep.

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    Inactivated vaccines lack immunogenicity and therefore require potent adjuvants. To understand the in vivo effects of adjuvants, we used a system immunology-based analysis of ovine blood transcriptional modules (BTMs) to dissect innate immune responses relating to either antibody or haptoglobin levels. Using inactivated foot-and-mouth disease virus as an antigen, we compared non-adjuvanted to liposomal-formulated vaccines complemented or not with TLR4 and TLR7 ligands. Early after vaccination, BTM relating to myeloid cells, innate immune responses, dendritic cells, and antigen presentation correlated positively, whereas BTM relating to T and natural killer cells, as well as cell cycle correlated negatively with antibody responses. Interestingly, similar BTM also correlated with haptoglobin, but in a reversed manner, indicating that acute systemic inflammation is not beneficial for early antibody responses. Analysis of vaccine-dependent BTM modulation showed that liposomal formulations induced similar responses to those correlating to antibody levels. Surprisingly, the addition of the TLR ligands appeared to reduce early immunological perturbations and mediated anti-inflammatory effects, despite promoting antibody responses. When pre-vaccination BTM were analyzed, we found that high vaccine responders expressed higher levels of many BTM relating to cell cycle, antigen-presenting cells, and innate responses as compared with low responders. In conclusion, we have transferred human BTM to sheep and identified early vaccine-induced responses associated with antibody levels or unwanted inflammation in a heterogeneous and small group of animals. Such readouts are applicable to other veterinary species and very useful to identify efficient vaccine adjuvants, their mechanism of action, and factors related to low responders

    Excess cerebral TNF causing glutamate excitotoxicity rationalizes treatment of neurodegenerative diseases and neurogenic pain by anti-TNF agents

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    Silent infection of human dendritic cells by African and Asian strains of Zika virus.

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    While Zika virus (ZIKV) circulated for decades (African lineage strains) without report of outbreaks and severe complications, its emergence in French Polynesia and subsequently in the Americas (Asian lineage strains) was associated with description of severe neurological defects in newborns/neonates and adults. With the aim to identify virus lineage-dependent factors, we compared cell susceptibility, virus replication, cell death and innate immune responses following infection with two African and three contemporary Asian lineage strains of ZIKV. To this end, we used green monkey Vero and Aedes albopictus C6/36 cells and human monocyte-derived dendritic cells (DCs). The latter are involved in the pathogenesis of several mosquito-borne Flavivirus infections. In Vero and C6/36 cells, we observed strain- but not lineage-dependent differences in infection profiles. Nevertheless, in human DCs, no significant differences in susceptibility and virus replication were found between lineages and strains. ZIKV induced antiviral interferon type I/III in a limited fashion, with the exception of one African strain. None of the strains induced cell death or DC maturation in terms of MHC II, CD40, CD80/86 or CCR7 expression. Taken together, our data suggest that a large collection of virus isolates needs to be investigated before conclusions on lineage differences can be made

    Seasonal energy storage using bioenergy production from abandoned croplands

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    Bioenergy has the unique potential to provide a dispatchable and carbon-negative component to renewable energy portfolios. However, the sustainability, spatial distribution, and capacity for bioenergy are critically dependent on highly uncertain land-use impacts of biomass agriculture. Biomass cultivation on abandoned agriculture lands is thought to reduce land-use impacts relative to biomass production on currently used croplands. While coarse global estimates of abandoned agriculture lands have been used for large-scale bioenergy assessments, more practical technological and policy applications will require regional, high-resolution information on land availability. Here, we present US county-level estimates of the magnitude and distribution of abandoned cropland and potential bioenergy production on this land using remote sensing data, agriculture inventories, and land-use modeling. These abandoned land estimates are 61% larger than previous estimates for the US, mainly due to the coarse resolution of data applied in previous studies. We apply the land availability results to consider the capacity of biomass electricity to meet the seasonal energy storage requirement in a national energy system that is dominated by wind and solar electricity production. Bioenergy from abandoned croplands can supply most of the seasonal storage needs for a range of energy production scenarios, regions, and biomass yield estimates. These data provide the basis for further down-scaling using models of spatially gridded land-use areas as well as a range of applications for the exploration of bioenergy sustainability

    Cardiac glycosides initiate Apo2L/TRAIL-induced apoptosis in non-small cell lung cancer cells by up-regulation of death receptors 4 and 5

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    The adhesion of neurons depends on the interplay between attractive as well as repellant cues in the cell membrane and adhesion ligands in their cellular environment. In this study, an easy and versatile strategy is presented to control the density of cell binding sites embedded in a cell repulsive environment attached to a solid surface. Gold nanoparticles modified by positively charged aminoalkyl thiols are used as artificial neuron adhesion ligands. The density of the nanoparticles and their environment is varied by applying either no backfill, poly(ethylene glycol)-silane, or octyltrichlorosilane backfill. By this means the chemical composition of both cell attractive adhesion ligands and surrounding repellant cues is tuned on the nanometer scale. Primary rat cortical neurons are cultured on these particle modified surfaces. The viability and neuritogenesis of neurons is investigated as a function of particle density and background composition. A strong dependence of neuron viability on both averaged particle density and backfill composition is found in particular for intermediate particle packing. At high particle densities, the kind of backfill does not affect the cell viability but influences the development of neurites. This knowledge is used to enhance the guiding efficiency of neuron adhesion to more than 90% on nanopatterned surfaces

    Seasonal electricity storage required for Western electric grid, Eastern electric grid and ERCOT (Texas) electric grid based on an energy production system that is entirely wind, entirely solar, or a 50% mix of wind and solar

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    <p><strong>Figure 6.</strong> Seasonal electricity storage required for Western electric grid, Eastern electric grid and ERCOT (Texas) electric grid based on an energy production system that is entirely wind, entirely solar, or a 50% mix of wind and solar.</p> <p><strong>Abstract</strong></p> <p>Bioenergy has the unique potential to provide a dispatchable and carbon-negative component to renewable energy portfolios. However, the sustainability, spatial distribution, and capacity for bioenergy are critically dependent on highly uncertain land-use impacts of biomass agriculture. Biomass cultivation on abandoned agriculture lands is thought to reduce land-use impacts relative to biomass production on currently used croplands. While coarse global estimates of abandoned agriculture lands have been used for large-scale bioenergy assessments, more practical technological and policy applications will require regional, high-resolution information on land availability. Here, we present US county-level estimates of the magnitude and distribution of abandoned cropland and potential bioenergy production on this land using remote sensing data, agriculture inventories, and land-use modeling. These abandoned land estimates are 61% larger than previous estimates for the US, mainly due to the coarse resolution of data applied in previous studies. We apply the land availability results to consider the capacity of biomass electricity to meet the seasonal energy storage requirement in a national energy system that is dominated by wind and solar electricity production. Bioenergy from abandoned croplands can supply most of the seasonal storage needs for a range of energy production scenarios, regions, and biomass yield estimates. These data provide the basis for further down-scaling using models of spatially gridded land-use areas as well as a range of applications for the exploration of bioenergy sustainability.</p

    Screening of Swiss hot spring resorts for potentially pathogenic free-living amoebae

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    Free-living amoebae (FLA) belonging to Acanthamoeba spp., Naegleria fowleri, Balamuthia mandrillaris, and Sappinia pedata are known to cause infections in humans and animals leading to severe brain pathologies. Worldwide, warm aquatic environments have been found to be suitable habitats for pathogenic FLA. The present study reports on screening for potentially pathogenic FLA in four hot spring resorts in Switzerland. Water samples were taken from water filtration units and from the pools, respectively. Amoebae isolated from samples taken during, or before, the filtration process were demonstrated to be morphologically and phylogenetically related to Stenoamoeba sp., Hartmannella vermiformis, Echinamoeba exundans, and Acanthamoeba healyi. With regard to the swimming pools, FLA were isolated only in one resort, and the isolate was identified as non-pathogenic and as related to E. exundans. Further investigations showed that the isolates morphologically and phylogenetically related to A. healyi displayed a pronounced thermotolerance, and exhibited a marked in vitro cytotoxicity upon 5-day exposure to murine L929 fibroblasts. Experimental intranasal infection of Rag2-immunodeficient mice with these isolates led to severe brain pathologies, and viable trophozoites were isolated from the nasal mucosa, brain tissue, and lungs post mortem. In summary, isolates related to A. healyi were suggestive of being potentially pathogenic to immunocompromised persons. However, the presence of these isolates was limited to the filtration units, and an effective threat for health can therefore be excluded
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