Isotope signatures in winter moulted feathers predict malaria prevalence in a breeding avian host

It is widely accepted that animal distribution and migration strategy might have co-evolved in relation to selection pressures exerted by parasites. Here, we first determined the prevalence and types of malaria blood parasites in a breeding population of great reed warblers Acrocephalus arundinaceus using PCR. Secondly, we tested for differences in individual feather stable isotope signatures (delta (13)C, delta (15)N, deltaD and delta (34)S) to investigate whether malaria infected and non-infected birds had occupied different areas in winter. We show that birds moulting in Afro-tropical habitats with significantly higher delta (13)C and delta (15)N but lower deltaD and delta(34)S values were more frequently infected with malaria parasites. Based on established patterns of isotopic distributions, our results indicate that moulting sites with higher incidence of malaria are generally drier and situated further to the north in West Africa than sites with lower incidence of malaria. Our findings are pertinent to the general hypothesis that animal distribution and particularly avian migration strategy might evolve in response to selection pressures exerted by parasites at different geographic scales. Tradeoffs between investment in energy demanding life history traits (e.g. migration and winter moult) and immune function are suggested to contribute to the particular choice of habitat during migration and at wintering sites.     

Incubation temperature affects growth and energy metabolism in blue tit nestlings

Because the maintenance of proper developmental temperatures during avian incubation is costly to parents, embryos of many species experience pronounced variation in incubation temperature. However, the effects of such temperature variation on nestling development remain relatively unexplored. To investigate this, we artificially incubated wild blue tit (Cyanistes caeruleus L.) clutches at 35.0°, 36.5°, or 38.0°C for two-thirds of the incubation period. We returned clutches to their original nests before hatching and subsequently recorded nestling growth and resting metabolic rate. The length of the incubation period decreased with temperature, whereas hatching success increased. Nestlings from the lowest incubation temperature group had shorter tarsus lengths at 2 weeks of age, but body mass and wing length were not affected by temperature. In addition, nestlings from the lowest temperature group had a significantly higher resting metabolic rate compared with mid- and high-temperature nestlings, which may partly explain observed size differences between the groups. These findings suggest that nest microclimate can influence nestling phenotype, but whether observed differences carry over to later life-history stages remains unknown.     

Posttranslational modification of gluten shapes TCR usage in celiac disease

Posttranslational modification of Ag is implicated in several autoimmune diseases. In celiac disease, a cereal gluten-induced enteropathy with several autoimmune features, T cell recognition of the gluten Ag is heavily dependent on the posttranslational conversion of Gln to Glu residues. Evidence suggests that the enhanced recognition of deamidated gluten peptides results from improved peptide binding to the MHC and TCR interaction with the peptide-MHC complex. In this study, we report that there is a biased usage of TCR Vβ6.7 chain among TCRs reactive to the immunodominant DQ2-α-II gliadin epitope. We isolated Vβ6.7 and DQ2-αII tetramer-positive CD4(+) T cells from peripheral blood of gluten-challenged celiac patients and sequenced the TCRs of a large number of single T cells. TCR sequence analysis revealed in vivo clonal expansion, convergent recombination, semipublic response, and the notable conservation of a non-germline-encoded Arg residue in the CDR3β loop. Functional testing of a prototype DQ2-α-II-reactive TCR by analysis of TCR transfectants and soluble single-chain TCRs indicate that the deamidated residue in the DQ2-α-II peptide poses constraints on the TCR structure in which the conserved Arg residue is a critical element. The findings have implications for understanding T cell responses to posttranslationally modified Ags.     

Duplicability of self-interacting human genes

Background  

There is increasing interest in the evolution of protein-protein interactions because this should ultimately be informative of the patterns of evolution of new protein functions within the cell. One model proposes that the evolution of new protein-protein interactions and protein complexes proceeds through the duplication of self-interacting genes. This model is supported by data from yeast. We examined the relationship between gene duplication and self-interaction in the human genome.     

Chromosome 17 abnormalities and lack of TP53 mutations in paediatric central nervous system tumours

Central nervous system (CNS) tumours are the most common solid tumours in children. Cytogenetic and molecular genetic studies of these neoplasms have previously shown abnormalities of chromosome 17, implicating genes on this autosome in tumorigenesis. To identify mutations in the TP53 tumour suppressor gene (17p13.1), we have sequenced the five highly conserved regions of this gene in 29 mixed paediatric CNS tumors. No mutations were detected by this analysis. In order to identify other candidate disease loci on chromosome 17, we have carried out a detailed deletion mapping analysis using 16 polymorphic DNA markers on 19 of the above tumours and an additional four cases. Abnormalities of chromosome 17 occurred in nine cases (39%), six of which were primitive neuroectodermal tumour (PNET)-medulloblastomas. These findings suggest that it is unlikely that the TP53 gene is directly involved in the development of common paediatric brain tumours. This is in contrast to findings from adult brain and other tumour types. Moreover, the frequency of chromosome 17 aberrations, especially in PNET-medulloblastomas, suggests that other genes on this chromosome contribute to tumourigenesis.     

Disruption of serine/threonine protein phosphatase 5 (PP5:PPP5c) in mice reveals a novel role for PP5 in the regulation of ultraviolet light-induced phosphorylation of serine/threonine protein kinase Chk1 (CHEK1)

PP5 is a ubiquitously expressed Ser/Thr protein phosphatase. High levels of PP5 have been observed in human cancers, and constitutive PP5 overexpression aids tumor progression in mouse models of tumor development. However, PP5 is highly conserved among species, and the roles of PP5 in normal tissues are not clear. Here, to help evaluate the biological actions of PP5, a Cre/loxP-conditional mouse line was generated. In marked contrast to the early embryonic lethality associated with the genetic disruption of other PPP family phosphatases (e.g. PP2A and PP4), intercrosses with mouse lines that ubiquitously express Cre recombinase starting early in development (e.g. MeuCre40 and ACTB-Cre) produced viable and fertile PP5-deficient mice. Phenotypic differences caused by the total disruption of PP5 were minor, suggesting that small molecule inhibitors of PP5 will not have widespread systemic toxicity. Examination of roles for PP5 in fibroblasts generated from PP5-deficient embryos (PP5(-/-) mouse embryonic fibroblasts) confirmed some known roles and identified new actions for PP5. PP5(-/-) mouse embryonic fibroblasts demonstrated increased sensitivity to UV light, hydroxyurea, and camptothecin, which are known activators of ATR (ataxia-telangiectasia and Rad3-related) kinase. Further study revealed a previously unrecognized role for PP5 downstream of ATR activation in a UV light-induced response. The genetic disruption of PP5 is associated with enhanced and prolonged phosphorylation of a single serine (Ser-345) on Chk1, increased phosphorylation of the p53 tumor suppressor protein (p53) at serine 18, and increased p53 protein levels. A comparable role for PP5 in the regulation of Chk1 phosphorylation was also observed in human cells.     

Pisolithus tinctorius promotes germination and forms mycorrhizal structures in Scots pine somatic embryos in vitro

The results of the present study show that inoculation with the ectomycorrhizal fungus Pisolithus tinctorius (Pers.) Coker and Couch potentially enhances the germination of Scots pine (Pinus sylvestris L.) somatic embryos in vitro. Stimulation by Pisolithus tinctorius was only observed in the absence of direct contact between the symbionts; mature embryos were not sufficiently robust for balanced interaction with the fungus on half-strength DCR medium. Subsequently, on MMN medium with a reduced sugar concentration, direct contact between somatic embryo-derived plants and the fungus resulted in in vitro formation of mycorrhiza. Ex vitro inoculation also improved adaptation of the somatic embryo-derived plants, even though mycorrhizal structures were not observed. The reactions to Pisolithus tinctorius varied between different Scots pine cell lines both in vitro and ex vitro.     

Unprecedented 34S‐enrichment of pyrite formed following microbial sulfate reduction in fractured crystalline rocks

In the deep biosphere, microbial sulfate reduction (MSR) is exploited for energy. Here, we show that, in fractured continental crystalline bedrock in three areas in Sweden, this process produced sulfide that reacted with iron to form pyrite extremely enriched in ³⁴S relative to ³²S. As documented by secondary ion mass spectrometry (SIMS) microanalyses, the δ³⁴S_pyrite values are up to +132‰V‐CDT and with a total range of 186‰. The lightest δ³⁴S_pyrite values (?54‰) suggest very large fractionation during MSR from an initial sulfate with δ³⁴S values (δ³⁴S_sulfate,0) of +14 to +28‰. Fractionation of this magnitude requires a slow MSR rate, a feature we attribute to nutrient and electron donor shortage as well as initial sulfate abundance. The superheavy δ³⁴S_pyrite values were produced by Rayleigh fractionation effects in a diminishing sulfate pool. Large volumes of pyrite with superheavy values (+120 ± 15‰) within single fracture intercepts in the boreholes, associated heavy average values up to +75‰ and heavy minimum δ³⁴S_pyrite values, suggest isolation of significant amounts of isotopically light sulfide in other parts of the fracture system. Large fracture‐specific δ³⁴S_pyrite variability and overall average δ³⁴S_pyrite values (+11 to +16‰) lower than the anticipated δ³⁴S_sulfate,0 support this hypothesis. The superheavy pyrite found locally in the borehole intercepts thus represents a late stage in a much larger fracture system undergoing Rayleigh fractionation. Microscale Rb–Sr dating and U/Th–He dating of cogenetic minerals reveal that most pyrite formed in the early Paleozoic era, but crystal overgrowths may be significantly younger. The δ¹³C values in cogenetic calcite suggest that the superheavy δ³⁴S_pyrite values are related to organotrophic MSR, in contrast to findings from marine sediments where superheavy pyrite has been proposed to be linked to anaerobic oxidation of methane. The findings provide new insights into MSR‐related S‐isotope systematics, particularly regarding formation of large fractions of ³⁴S‐rich pyrite.