9 research outputs found
Efficient precision quantization in AdS/CFT
Understanding finite-size effects is one of the key open questions in solving
planar AdS/CFT. In this paper we discuss these effects in the AdS_5xS^5 string
theory at one-loop in the world-sheet coupling. First we provide a very
general, efficient way to compute the fluctuation frequencies, which allows to
determine the energy shift for very general multi-cut solutions. Then we apply
this to two-cut solutions, in particular the giant magnon and determine the
finite-size corrections at subleading order. The latter are then compared to
the finite-size corrections from Luscher-Klassen-Melzer formulas and found to
be in perfect agreement.Comment: 32 pages, 5 figures; v2: typos corrected, refs adde
Genetic and antigenic variation of the bovine tick-borne pathogen Theileria parva in the Great Lakes region of Central Africa
BACKGROUND : Theileria parva causes East Coast fever (ECF), one of the most economically important tick-borne diseases
of cattle in sub-Saharan Africa. A live immunisation approach using the infection and treatment method (ITM)
provides a strong long-term strain-restricted immunity. However, it typically induces a tick-transmissible carrier state
in cattle and may lead to spread of antigenically distinct parasites. Thus, understanding the genetic composition of T.
parva is needed prior to the use of the ITM vaccine in new areas. This study examined the sequence diversity and the
evolutionary and biogeographical dynamics of T. parva within the African Great Lakes region to better understand the
epidemiology of ECF and to assure vaccine safety. Genetic analyses were performed using sequences of two antigencoding
genes, Tp1 and Tp2, generated among 119 T. parva samples collected from cattle in four agro-ecological zones
of DRC and Burundi.
RESULTS : The results provided evidence of nucleotide and amino acid polymorphisms in both antigens, resulting
in 11 and 10 distinct nucleotide alleles, that predicted 6 and 9 protein variants in Tp1 and Tp2, respectively. Theileria
parva samples showed high variation within populations and a moderate biogeographical sub-structuring due to the
widespread major genotypes. The diversity was greater in samples from lowlands and midlands areas compared to
those from highlands and other African countries. The evolutionary dynamics modelling revealed a signal of selective
evolution which was not preferentially detected within the epitope-coding regions, suggesting that the observed
polymorphism could be more related to gene flow rather than recent host immune-based selection. Most alleles
isolated in the Great Lakes region were closely related to the components of the trivalent Muguga vaccine.
CONCLUSIONS : Our findings suggest that the extensive sequence diversity of T. parva and its biogeographical distribution
mainly depend on host migration and agro-ecological conditions driving tick population dynamics. Such
patterns are likely to contribute to the epidemic and unstable endemic situations of ECF in the region. However, the fact that ubiquitous alleles are genetically similar to the components of the Muguga vaccine together with the limited
geographical clustering may justify testing the existing trivalent vaccine for cross-immunity in the region.Additional file 1: Table S1. Cattle blood sample distribution across agroecological
zones.Additional file 2: Table S2. Nucleotide and amino acid sequences of Tp1
and Tp2 antigen epitopes from T. parva Muguga reference sequence.Additional file 3: Table S3. Characteristics of 119 T. parva samples
obtained from cattle in different agro-ecological zones (AEZs) of The
Democratic Republic of Congo and Burundi.Additional file 4: Figure S1. Multiple sequence alignment of the 11 Tp1
gene alleles obtained in this study.Additional file 5: Table S4. Estimates of evolutionary divergence
between gene alleles for Tp1 and Tp2, using proportion nucleotide
distance.Additional file 6: Table S5. Tp1 and Tp2 genes alleles with their corresponding
antigen variants.Additional file 7: Table S6. Amino acid variants of Tp1 and Tp2 CD8+
T
cell target epitopes of T. parva from DRC and Burundi.Additional file 8: Figure S2. Multiple sequence alignment of the 10 Tp2
gene alleles obtained in this study.Additional file 9: Table S7. Distribution of Tp1 gene alleles of T. parva
from cattle and buffalo in the sub-Saharan region of Africa.Additional file 10: Table S8. Distribution of Tp2 gene alleles of T. parva
from cattle and buffalo in the sub-Saharan region of Africa.Additional file 11: Figure S3. Neighbor-joining tree showing phylogenetic
relationships among 48 Tp1 gene alleles described in Africa.Additional file 12: Figure S4. Phylogenetic tree showing the relationships
among concatenated Tp1 and Tp2 nucleotide sequences of 93 T.
parva samples from cattle in DRC and Burundi.This study is part of the PhD work supported by the University of Namur (UNamur,
Belgium) through the UNamur-CERUNA institutional PhD grant awarded
to GSA for bioinformatic analyses, interpretation of data and manuscript write
up in Belgium. The laboratory aspects (molecular biology analysis) of the
project were supported by the BecA-ILRI Hub through the Africa Biosciences
Challenge Fund (ABCF) programme. The ABCF Programme is funded by
the Australian Department for Foreign Affairs and Trade (DFAT) through the
BecA-CSIRO partnership; the Syngenta Foundation for Sustainable Agriculture
(SFSA); the Bill & Melinda Gates Foundation (BMGF); the UK Department for International Development (DFID); and the Swedish International Development
Cooperation Agency (Sida). The ABCF Fellowship awarded to GAS was
funded by BMGF grant (OPP1075938). Sample collection, field equipment and
preliminary sample processing were supported through the âTheileriaâ project
co-funded to the Université Evangélique en Afrique (UEA) by the Agence
Universitaire de la Francophonie (AUF) and the Communauté Economique
des Pays des Grands Lacs (CEPGL). The International Foundation for Science
(IFS, Stockholm, Sweden) supported the individual scholarship awarded to
GSA (grant no. IFS-92890CA3) for field work and part of field equipment to the
âTheileriaâ project.http://www.parasitesandvectors.comam2020Veterinary Tropical Disease
Strain-dependent cellular immune responses in cattle following <i>Escherichia coli</i> O157:H7 colonization
Enterohemorrhagic Escherichia coli (EHEC) O157:H7 causes hemorrhagic diarrhea and potentially fatal renal failure in humans. Ruminants are considered to be the primary reservoir for human infection. Vaccines that reduce shedding in cattle are only partially protective, and their underlying protective mechanisms are unknown. Studies investigating the response of cattle to colonization generally focus on humoral immunity, leaving the role of cellular immunity unclear. To inform future vaccine development, we studied the cellular immune responses of cattle during EHEC O157:H7 colonization. Calves were challenged either with a phage type 21/28 (PT21/28) strain possessing the Shiga toxin 2a (Stx2a) and Stx2c genes or with a PT32 strain possessing the Stx2c gene only. T-helper cell-associated transcripts at the terminal rectum were analyzed by reverse transcription-quantitative PCR (RT-qPCR). Induction of gamma interferon (IFN-γ) and T-bet was observed with peak expression of both genes at 7 days in PT32-challenged calves, while upregulation was delayed, peaking at 21 days, in PT21/28-challenged calves. Cells isolated from gastrointestinal lymph nodes demonstrated antigen-specific proliferation and IFN-γ release in response to type III secreted proteins (T3SPs); however, responsiveness was suppressed in cells isolated from PT32-challenged calves. Lymph node cells showed increased expression of the proliferation marker Ki67 in CD4(+) T cells from PT21/28-challenged calves, NK cells from PT32-challenged calves, and CD8(+) and γΎ T cells from both PT21/28- and PT32-challenged calves following ex vivo restimulation with T3SPs. This study demonstrates that cattle mount cellular immune responses during colonization with EHEC O157:H7, the temporality of which is strain dependent, with further evidence of strain-specific immunomodulation
CD8 T cell responses against the immunodominant Theileria parva 1 peptide Tp249-59 are composed of two distinct populations specific for 2 overlapping 11-mer and 10-mer epitopes 3 Short title: Overlapping 11- and 10-mer CD8+ T cell epitopes in Tp2. 4
Immunity against Theileria parva is associated with CD8 T-cell responses that exhibit immunodominance, focusing the response against limited numbers of epitopes. As candidates for inclusion in vaccines, characterization of responses against immunodominant epitopes is a key component in novel vaccine development. We have previously demonstrated that the Tp249â59 and Tp1214â224 epitopes dominate CD8 T-cell responses in BoLAA10 and BoLA-18 MHC I homozygous animals, respectively. In this study, peptideâMHC I tetramers for these epitopes, and a subdominant BoLA-A10-restricted epitope (Tp298â106), were generated to facilitate accurate and rapid enumeration of epitope-specific CD8 T cells. During validation of these tetramers a substantial proportion of Tp249â59-reactive T cells failed to bind the tetramer, suggesting that this population was heterogeneous with respect to the recognized epitope. We demonstrate that Tp250â59 represents a distinct epitope and that tetramers produced with Tp50â59 and Tp49â59 show no cross-reactivity. The Tp249â59 and Tp250â59 epitopes use different serine residues as the N-terminal anchor for binding to the presenting MHC I molecule. Molecular dynamic modelling predicts that the two peptideâMHC I complexes adopt structurally different conformations and Tcell receptor b sequence analysis showed that Tp249â59 and Tp250â59 are recognized by non-overlapping T-cell receptor repertoires. Together these data demonstrate that although differing by only a single residue, Tp249â59 and Tp250â59 epitopes form distinct ligands for T-cell receptor recognition. Tetramer analysis of T. parva-specific CD8 T-cell lines confirmed the immunodominance of Tp1214â224 in BoLA-A18 animals and showed in BoLA-A10 animals that the Tp249â59 epitope response was generally more dominant than the Tp250â59 response and confirmed that the Tp298â106 response was subdominant