An oral recombinant Salmonella enterica serovar Typhimurium mutant elicits systemic antigen-specific CD8+ T cell cytokine responses in mice

<p>Abstract</p> <p>Background</p> <p>The induction of antigen-specific CD8+ T cell cytokine responses against an attenuated, oral recombinant <it>Salmonella enterica </it>serovar Typhimurium vaccine expressing a green fluorescent protein (GFP) model antigen was investigated. A GFP expression plasmid was constructed in which the <it>gfp </it>gene was fused in-frame with the 5' domain of the <it>Escherichia coli β</it>-galactosidase <it>α</it>-gene fragment with expression under the <it>lac </it>promoter. Groups of mice were orally immunized three times with the bacteria and systemic CD8+ T cell cytokine responses were evaluated.</p> <p>Results</p> <p>High level of the GFP model antigen was expressed by the recombinant <it>Salmonella </it>vaccine vector. Systemic GFP-specific CD8+ T cell cytokine (IFN-γ and IL-4) immune responses were detected after mice were orally vaccinated with the bacteria. It was shown that 226 net IFN-γ and 132 net IL-4 GFP-specific SFUs/10e6 splenocytes were formed in an ELISPOT assay. The level of IFN-γ produced by GFP peptide-stimulated cells was 65.2-fold above background (p < 0.05). The level of IL-4 produced by the cells was 10.4-fold above background (p < 0.05).</p> <p>Conclusion</p> <p>These results suggested that a high expressing recombinant <it>Salmonella </it>vaccine given orally to mice would elicit antigen-specific CD8+ T cell responses in the spleen. <it>Salmonella </it>bacteria may, therefore, be used as potential mucosal vaccine vectors.</p

Oral vaccination with a recombinant Salmonella vaccine vector provokes systemic HIV-1 subtype C Gag-specific CD4+ Th1 and Th2 cell immune responses in mice

<p>Abstract</p> <p>Background</p> <p>Recombinant <it>Salmonella </it>vaccine vectors may potentially be used to induce specific CD4+ T cell responses against foreign viral antigens. Such immune responses are required features of vaccines against pathogens such as human immunodeficiency virus type 1 (HIV-1). The aim of this study was to investigate the induction of systemic HIV-1-specific CD4+ T helper (Th) responses in mice after oral immunization with a live attenuated <it>Salmonella </it>vaccine vector that expressed HIV-1 subtype C Gag. Groups of BALB/c mice were vaccinated orally three times (4 weeks apart) with this recombinant <it>Salmonella</it>. At sacrifice, 28 days after the last immunization, systemic CD4+ Th1 and Th2 cytokine responses were evaluated by enzyme-linked immunospot assay and cytometric bead array. HIV-1 Gag-specific IgG1 and IgG2a humoral responses in the serum were determined by enzyme-linked immunosorbent assay.</p> <p>Results</p> <p>Mice vaccinated with the recombinant <it>Salmonella </it>elicited both HIV-1-specific Th1 (interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α)) and Th2 (interleukin-4 (IL-4) and interleukin-5 (IL-5)) cytokine responses. The vaccine induced 70 (IFN-γ) spot-forming units (SFUs)/10e6 splenocytes and 238 IL-4 SFUs/10e6 splenocytes. Splenocytes from vaccinated mice also produced high levels of Th1 and Th2 cytokines upon stimulation with a Gag CD4 peptide. The levels of IFN-γ, TNF-α, IL-4 and IL-5 were 7.5-, 29.1-, 26.2- and 89.3-fold above the background, respectively. Both HIV-1 Gag-specific IgG1 and IgG2a antibodies were detected in the sera of vaccinated mice.</p> <p>Conclusion</p> <p>The study highlights the potential of orally-delivered attenuated <it>Salmonella </it>as mucosal vaccine vectors for HIV-1 Subtype C Gag to induce Gag-specific CD4+ Th1 and Th2 cellular immune responses and antibodies which may be important characteristics required for protection against HIV-1 infection.</p

The origins and spread of domestic horses from the Western Eurasian steppes

This is the final version. Available on open access from Nature Research via the DOI in this recordData availability: All collapsed and paired-end sequence data for samples sequenced in this study are available in compressed fastq format through the European Nucleotide Archive under accession number PRJEB44430, together with rescaled and trimmed bam sequence alignments against both the nuclear and mitochondrial horse reference genomes. Previously published ancient data used in this study are available under accession numbers PRJEB7537, PRJEB10098, PRJEB10854, PRJEB22390 and PRJEB31613, and detailed in Supplementary Table 1. The genomes of ten modern horses, publicly available, were also accessed as indicated in their corresponding original publications57,61,85-87.NOTE: see the published version available via the DOI in this record for the full list of authorsDomestication of horses fundamentally transformed long-range mobility and warfare. However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling at Botai, Central Asia around 3500 BC. Other longstanding candidate regions for horse domestication, such as Iberia and Anatolia, have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 BC, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 BC driving the spread of Indo-European languages. This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium BC Sintashta culture

Body condition of returning Atlantic salmon Salmo salar L. correlates with scale δ13C and δ15N content deposited at the last marine foraging location

Patterns of feeding and growth of Atlantic salmon Salmo salar L. in the marine environment are critical to understanding how observed declines in recruitment may reflect warming or other oceanic drivers. The isotopic composition of scales can provide insight into differences in marine feeding location and possibly temperature regime. The authors used archived scale samples to measure δ13C and δ15N deposited in the scales of one sea-winter (1SW) salmon during their last season of growth at sea before they returned to five Irish rivers. δ13C values were related statistically to observed salmon body condition (Fulton’s K), and fish with higher δ13C values tended to show significantly better condition. In contrast, δ15N values were negatively related to body condition. There was no important effect on condition of length at smolt migration, and the effect of duration of marine residence varied among rivers. It is likely that δ13C values partly reflected ambient ocean temperature and recent marine feeding environment before return migration, such that the observed relationship between higher δ13C values and increased body condition may express an advantage for adult fish feeding in warmer, potentially closer, waters. If greater body condition influences fitness, then a changing temperature regime in the Northeast Atlantic may drive shifts in salmon survival and reproduction. This study provides evidence that there is spatial and trophic variation at sea between salmon from rivers of origin that are located relatively close to each other, with potential consequences for body condition and, consequently, fitness and life history; this suggests that salmon populations from geographically proximate rivers within regions may exhibit differential responses to ocean-scale climatic changes across the Northeast Atlantic

Cutting a polytope

We investigate whether it is the case that for every convex d -polytope P and pair of distinct vertices x and y of P , there exists a hyperplane passing through x and y which cuts P into two smaller d -polytopes, one of which has fewer facets than P . Such a result would lead to inductive proofs of Conjectures 1 and 2 below. However, for d ≥4, our answer is in the negative.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42814/1/10711_2005_Article_BF01265345.pd

A study of inclusive Xi /sup -/ production from K/sup -/p interactions at 42 GeV/c

A study of inclusive Xi /sup -/ production from a high statistics K /sup -/p experiment at 4.2 GeV/c has been made. The total Xi /sup -/ production cross section is 157+or-8 mu b. Approximately 15% of the Xi /sup -/ arise from decay of the Xi */sup Q/(1530) resonance. The polarization of Xi /sup -/ is found to be negative and is nearly equal in value to that of the Lambda /sup 0/ from the inclusive reaction K /sup -/+p to Lambda /sup 0/+anything. An analysis of the inclusive production of Xi /sup -/ has been made in the framework of the triple- Regge formalism. (15 refs)