Demonstration of immune responses against devil facial tumour disease in wild Tasmanian devils

Devil facial tumour disease (DFTD) is a recently emerged fatal transmissible cancer decimating the wild population of Tasmanian devils (Sarcophilus harrisii). Biting transmits the cancer cells and the tumour develops in the new host as an allograft. The literature reports that immune escape mechanisms employed by DFTD inevitably result in host death. Here we present the first evidence that DFTD regression can occur and that wild devils can mount an immune response against the disease. Of the 52 devils tested, six had serum antibodies against DFTD cells and, in one case, prominent T lymphocyte infiltration in its tumour. Notably, four of the six devils with serum antibody had histories of DFTD regression. The novel demonstration of an immune response against DFTD in wild Tasmanian devils suggests that a proportion of wild devils can produce a protective immune response against naturally acquired DFTD. This has implications for tumour-host coevolution and vaccine development.Ruth Pye, Rodrigo Hamede, Hannah V. Siddle, Alison Caldwell, Graeme W. Knowles, Kate Swift, Alexandre Kreiss, Menna E. Jones, A. Bruce Lyons, Gregory M. Wood

Heisenberg exchange enhancement by orbital relaxation in cuprate compounds

We calculate the Heisenberg exchange J in the quasi-2D antiferromagnetic cuprates La2CuO4, YBa2Cu3O6, Nd2CuO4 and Sr2CuO2Cl2. We apply all-electron (MC)SCF and non-orthogonal CI calculations to [Cu2O11]18-, [Cu2O9]14-, [Cu2O7]10- and [Cu2O7Cl4]14- clusters in a model charge embedding. The (MC)SCF triplet and singlet ground states are well characterized by Cu2+ (dx2-y2) and O2-. The antiferromagnetic exchange is strongly enhanced by admixing relaxed (MC)SCF triplet and singlet excited states, in which a single electron is transferred from the central O ion to Cu. We ascribe this effect to orbital relaxation in the charge transfer component of the wave function. Close agreement with experiment is obtained.Comment: publishe

Effective Field Theory for Layered Quantum Antiferromagnets with Non-Magnetic Impurities

We propose an effective two-dimensional quantum non-linear sigma model combined with classical percolation theory to study the magnetic properties of site diluted layered quantum antiferromagnets like La$_{2}$Cu$_{1-x}$M$_x$O$_{4}$ (M$=$Zn, Mg). We calculate the staggered magnetization at zero temperature, $M_s(x)$, the magnetic correlation length, $\xi(x,T)$, the NMR relaxation rate, $1/T_1(x,T)$, and the N\'eel temperature, $T_N(x)$, in the renormalized classical regime. Due to quantum fluctuations we find a quantum critical point (QCP) at $x_c \approx 0.305$ at lower doping than the two-dimensional percolation threshold $x_p \approx 0.41$. We compare our results with the available experimental data.Comment: Final version accepted for publication as a Rapid Communication on Physical Review B. A new discussion on the effect of disorder in layered quantum antiferromagnets is include

Absolutely continuous spectrum for multi-type Galton Watson trees

We consider multi-type Galton Watson trees that are close to a tree of finite cone type in distribution. Moreover, we impose that each vertex has at least one forward neighbor. Then, we show that the spectrum of the Laplace operator exhibits almost surely a purely absolutely continuous component which is included in the absolutely continuous spectrum of the tree of finite cone type.Comment: to appear in Annales Henri Poincar\'

Tasmanian devil CD28 and CTLA4 capture CD80 and CD86 from adjacent cells

Immune checkpoint immunotherapy is a pillar of human oncology treatment with potential for non-human species. The first checkpoint immunotherapy approved for human cancers targeted the CTLA4 protein. CTLA4 can inhibit T cell activation by capturing and internalizing CD80 and CD86 from antigen presenting cells, a process called trans-endocytosis. Similarly, CD28 can capture CD80 and CD86 via trogocytosis and retain the captured ligands on the surface of the CD28-expressing cells. The wild Tasmanian devil (Sarcophilus harrisii) population has declined by 77% due to transmissible cancers that evade immune defenses despite genetic mismatches between the host and tumors. We used a live cell-based assay to demonstrate that devil CTLA4 and CD28 can capture CD80 and CD86. Mutation of evolutionarily conserved motifs in CTLA4 altered functional interactions with CD80 and CD86 in accordance with patterns observed in other species. These results suggest that checkpoint immunotherapies can be translated to evolutionarily divergent species.</p

The frequency of transforming growth factor-TGF-B gene polymorphisms in a normal southern Iranian population

Several single nucleotide polymorphisms (SNPs) of the transforming growth factor-β1 gene (TGFB1) have been reported. Determination of TGFB1 SNPs allele frequencies in different ethnic groups is useful for both population genetic analyses and association studies with immunological diseases. In this study, five SNPs of TGFB1 were determined in 325 individuals from a normal southern Iranian population using polymerase chain reaction-restriction fragment length polymorphism method. This population was in Hardy-Weinberg equilibrium for these SNPs. Of the 12 constructed haplotypes, GTCGC and GCTGC were the most frequent in the normal southern Iranian population. Comparison of genotype and allele frequencies of TGFB SNPs between Iranian and other populations (meta-analysis) showed significant differences, and in this case the southern Iranian population seems genetically similar to Caucasoid populations. However, neighbour-joining tree using Nei's genetic distances based on TGF-β1 allele frequencies showed that southern Iranians are genetically far from people from the USA, Germany, UK, Denmark and the Czech Republic. In conclusion, this is the first report of the distribution of TGFB1 SNPs in an Iranian population and the results of this investigation may provide useful information for both population genetic and disease studies. © 2008 The Authors

Composite quarks and leptons in higher space-time dimensions

A new approach towards the composite structure of quarks and leptons in the context of the higher dimensional unified theories is proposed. Owing to the certain strong dynamics, much like an ordinary QCD, every possible vectorlike multiplets of composites appear in higher dimensional bulk space-time, however, through a proper Sherk-Schwarz compactification only chiral set of composite quarks and leptons survive as the massless states in four dimensions. In this scenario restrictions related with the 't Hooft's anomaly matching condition are turned out to be avoided and, as a result, the composite models look rather simple and economic. We demonstrate our approach by an explicit construction of model of preons and their composites unified in the supersymmetric SU(5) GUT in five space-time dimensions. The model predicts exactly three families of the composite quarks and leptons being the triplets of the chiral horizontal symmetry SU(3)_h which automatically appears in the composite spectrum when going to ordinary four dimensions.Comment: 13 pages, tcilatex, no figures, v2 - misprints correcte

A novel system to map protein interactions reveals evolutionarily conserved immune evasion pathways on transmissible cancers

Around 40% of humans and Tasmanian devils (Sarcophilus harrisii) develop cancer in their lifetime, compared to less than 10% for most species. In addition, devils are affected by two of the three known transmissible cancers in mammals. Immune checkpoint immunotherapy has transformed human medicine, but a lack of species-specific reagents has limited checkpoint immunology in most species. We developed a cut-and-paste reagent development system and used the fluorescent fusion protein system to show that immune checkpoint interactions are conserved across 160,000,000 years of evolution, CD200 is highly expressed on transmissible tumor cells, and coexpression of CD200R1 can block CD200 surface expression. The system’s versatility across species was demonstrated by fusing a fluorescent reporter to a camelid-derived nanobody that binds human programmed death ligand 1. The evolutionarily conserved pathways suggest that naturally occurring cancers in devils and other species can be used to advance our understanding of cancer and immunological tolerance.</p

Global Search for New Physics with 2.0/fb at CDF

Data collected in Run II of the Fermilab Tevatron are searched for indications of new electroweak-scale physics. Rather than focusing on particular new physics scenarios, CDF data are analyzed for discrepancies with the standard model prediction. A model-independent approach (Vista) considers gross features of the data, and is sensitive to new large cross-section physics. Further sensitivity to new physics is provided by two additional algorithms: a Bump Hunter searches invariant mass distributions for "bumps" that could indicate resonant production of new particles; and the Sleuth procedure scans for data excesses at large summed transverse momentum. This combined global search for new physics in 2.0/fb of ppbar collisions at sqrt(s)=1.96 TeV reveals no indication of physics beyond the standard model.Comment: 8 pages, 7 figures. Final version which appeared in Physical Review D Rapid Communication