A protective role for the Lectin CD169/Siglec-1 against a pathogenic murine retrovirus

Lymph- and blood-borne retroviruses exploit CD169/Siglec-1-mediated capture by subcapsular sinus and marginal zone metallophilic macrophages for trans-infection of permissive lymphocytes. However, the impact of CD169-mediated virus capture on retrovirus dissemination and pathogenesis in vivo is unknown. In a murine model of the splenomegaly-inducing retrovirus Friend virus complex (FVC) infection, we find that while CD169 promoted draining lymph node infection, it limited systemic spread to the spleen. At the spleen, CD169-expressing macrophages captured incoming blood-borne retroviruses and limited their spread to the erythroblasts in the red pulp where FVC manifests its pathogenesis. CD169-mediated retroviral capture activated conventional dendritic cells 1 (cDC1s) and promoted cytotoxic CD8+ T cell responses, resulting in efficient clearing of FVC-infected cells. Accordingly, CD169 blockade led to higher viral loads and accelerated death in susceptible mouse strains. Thus, CD169 plays a protective role during FVC pathogenesis by reducing viral dissemination to erythroblasts and eliciting an effective cytotoxic T lymphocyte response via cDC1s

A pentapeptide as minimal antigenic determinant for MHC class I-restricted T lymphocytes

Peptides that are antigenic for T lymphocytes are ligands for two receptors, the class I or II glycoproteins that are encoded by genes in the major histocompatibility complex, and the idiotypic / chain T-cell antigen receptor1–9. That a peptide must bind to an MHC molecule to interact with a T-cell antigen receptor is the molecular basis of the MHC restriction of antigen-recognition by T lymphocytes10,11. In such a trimolecular interaction the amino-acid sequence of the peptide must specify the contact with both receptors: agretope residues bind to the MHC receptor and epitope residues bind to the T-cell antigen receptor12,13. From a compilation of known antigenic peptides, two algorithms have been proposed to predict antigenic sites in proteins. One algorithm uses linear motifs in the sequence14, whereas the other considers peptide conformation and predicts antigenicity for amphipathic -helices15,16. We report here that a systematic delimitation of an antigenic site precisely identifies a predicted pentapeptide motif as the minimal antigenic determinant presented by a class I MHC molecule and recognized by a cytolytic T lymphocyte clone

Negative and positive selection of antigen-specific cytotoxic T lymphocytes affected by the α3 domain of MHC I molecules

THE α1 and α2 domains of major histocompatibility complex (MHC) class I molecules function in the binding and presentation of foreign peptides to the T-cell antigen receptor and control both negative and positive selection of the T-cell repertoire. Although the α3 domain of class I is not involved in peptide binding, it does interact with the T-cell accessory molecule, CDS. CDS is important in the selection of T cells as anti-CDS antibody injected into perinatal mice interfers with this process. We previously used a hybrid class I molecule with the α1/α2 domains from L^d and the α3 domain from Q7^b and showed that this molecule binds an L^d-restricted peptide but does not interact with CD8-dependent cytotoxic T lymphocytes. Expression of this molecule in transgenic mice fails to negatively select a subpopulation of anti-L^d cytotoxic T lymphocytes. In addition, positive selection of virus-specific L^d-restricted cytotoxic T lymphocytes does not occur. We conclude that besides the α1/α2 domains of class I, the α3 domain plays an important part in both positive and negative selection of antigen-specific cells

The Distribution of Fitness Effects of Beneficial Mutations in Pseudomonas aeruginosa

Understanding how beneficial mutations affect fitness is crucial to our understanding of adaptation by natural selection. Here, using adaptation to the antibiotic rifampicin in the opportunistic pathogen Pseudomonas aeruginosa as a model system, we investigate the underlying distribution of fitness effects of beneficial mutations on which natural selection acts. Consistent with theory, the effects of beneficial mutations are exponentially distributed where the fitness of the wild type is moderate to high. However, when the fitness of the wild type is low, the data no longer follow an exponential distribution, because many beneficial mutations have large effects on fitness. There is no existing population genetic theory to explain this bias towards mutations of large effects, but it can be readily explained by the underlying biochemistry of rifampicin–RNA polymerase interactions. These results demonstrate the limitations of current population genetic theory for predicting adaptation to severe sources of stress, such as antibiotics, and they highlight the utility of integrating statistical and biophysical approaches to adaptation

Significant associations of PAI-1 genetic polymorphisms with osteonecrosis of the femoral head

<p>Abstract</p> <p>Background</p> <p>The pathogenesis of osteonecrosis of the femoral head (ONFH) has been implicated in hypofibrinolysis and blood supply interruption. Previous studies have demonstrated that decreased fibrinolytic activity due to elevated plasminogen activator inhibitor-1 (PAI-1) levels correlates with ONFH pathogenesis. The -675 4G/5G single nucleotide polymorphism (SNP rs1799889) in the PAI-1 gene promoter is associated with PAI-1 plasma level. We investigated whether rs1799889 and two other SNPs of the PAI-1 gene (rs2227631, -844 G/A in the promoter; rs11178, +10700 C/T in the 3'UTR) are associated with increased ONFH risk.</p> <p>Methods</p> <p>Three SNPs in PAI-1 were genotyped in 206 ONFH patients and 251 control subjects, using direct sequencing and a TaqMan^®5' allelic discrimination assay. We performed association analysis for genotyped SNPs and haplotypes with ONFH.</p> <p>Results</p> <p>The 4G allele of rs1799889, A allele of rs2227631, and C allele of rs11178 were significantly associated with increased ONFH risk (p = 0.03, p = 0.003, and p = 0.002, respectively). When we divided the population according to gender, an association between the three SNPs and increased risk of ONFH was found only in men. In another subgroup analysis based on the etiology of ONFH, rs2227631 (A allele) and rs11178 (C allele) in the idiopathic subgroup (p = 0.007 and p = 0.021) and rs1799889 (4G allele) and rs11178 (C allele) in the alcohol-induced subgroup (p = 0.042 and p = 0.015) were associated with increased risk of ONFH. In addition, a certain haplotype (A-4G-C) of PAI-1 was also significantly associated with ONFH (p < 0.001).</p> <p>Conclusion</p> <p>Our findings demonstrated that three SNPs (rs1799889, rs2227631, and rs11178) of the PAI-1 gene were associated with ONFH risk. This study also suggests that PAI-1 SNPs may play an important role in ONFH.</p

Future challenges in colloid and interfacial science

This article deals with topics where I expect special future challenges, exemplifying these by experiments out of my own department. One area where I expect large progress also in view of many technical developments in the past concerns the understanding of the structure of fluid interfaces at the atomic level. It is shown by non-linear optical spectroscopies that the free water surface is ice-like and can be “liquefied” by ion adsorption. X-ray fluorescence from the interface demonstrates that ion binding is very specific which cannot be explained by existing theories. A second major area are nonequilibrium features, and one of the old and new ones here is nucleation and growth. This presentation concentrates on effects produced by ultrasound, a well-defined trigger of gas bubble formation. It exhibits high potential for chemistry at extreme conditions but with a reactor at normal conditions. It has special importance for treatment of surfaces that can be also manipulated via controlled surface energies. A third area will concern complex and smart systems with multiple functions in materials and biosciences. As next generation, I anticipate those with feedback control, and examples on this are self-repairing coatings

Dead or Alive? Long-term evolution of SN 2015bh (SNhunt275)

This is the final version of the article. It first appeared from Oxford University Press via http://dx.doi.org/10.1093/mnras/stw2253Supernova (SN) 2015bh (or SNhunt275) was discovered in NGC 2770 on 2015 February with an absolute magnitude of M$_r$ ~ −13.4 mag, and was initially classified as an SN impostor. Here, we present the photometric and spectroscopic evolution of SN 2015bh from discovery to late phases (~1 yr after). In addition, we inspect archival images of the host galaxy up to ~21 yr before discovery, finding a burst ~1 yr before discovery, and further signatures of stellar instability until late 2014. Later on, the luminosity of the transient slowly increases, and a broad light-curve peak is reached after about three months. We propose that the transient discovered in early 2015 could be a core-collapse SN explosion. The pre-SN luminosity variability history, the long-lasting rise and faintness first light-curve peak suggests that the progenitor was a very massive, unstable and blue star, which exploded as a faint SN because of severe fallback of material. Later on, the object experiences a sudden brightening of 3 mag, which results from the interaction of the SN ejecta with circumstellar material formed through repeated past mass-loss events. Spectroscopic signatures of interaction are however visible at all epochs. A similar chain of events was previously proposed for the similar interacting SN 2009ip.European Research Council under the European Union's Seventh Framework Programme, Science and Technology Facilities Counci

Association of antigen processing machinery and HLA class I defects with clinicopathological outcome in cervical carcinoma

HLA class I loss is a significant mechanism of immune evasion by cervical carcinoma, interfering with the development of immunotherapies and cancer vaccines. We report the systematic investigation of HLA class I and antigen processing machinery component expression and association with clinical outcome. A tissue microarray containing carcinoma lesions from 109 cervical carcinoma patients was stained for HLA class I heavy chains, β2-microglobulin, LMP2, LMP7, LMP10, TAP1, TAP2, ERAP1, tapasin, calreticulin, calnexin and ERp57. A novel staining evaluation method was used to ensure optimal accuracy and reliability of expression data, which were correlated with known clinicopathological parameters. Partial HLA class I loss was significantly associated with decreased 5-years overall survival (61% vs. 83% for normal expression; P < 0.05) and was associated with decreased 5-years disease-free survival (DFS) (65% vs. 82% for normal expression; P = 0.05). All APM components except LMP10, calnexin and calreticulin were down-regulated in a substantial number of cases and, except ERAP1, correlated significantly with HLA class I down-regulation. LMP7, TAP1 and ERAP1 loss was significantly associated with decreased overall and (except LMP7) DFS (P < 0.05 and 0.005, respectively). ERAP1 down-regulation was an independent predictor for worse overall and DFS in multivariate analysis (HR 3.08; P < 0.05 and HR 2.84; P < 0.05, respectively). HLA class I and APM component down-regulation occur frequently in cervical carcinoma, while peptide repertoire alterations due to ERAP1 loss are a major contributing factor to tumour progression and mortality

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Plantation vs. natural forest: Matrix quality determines pollinator abundance in crop fields

In terrestrial ecosystems, ecological processes and patterns within focal patches frequently depend on their matrix. Crop fields (focal patches) are often surrounded by a mosaic of other land-use types (matrix), which may act as habitats for organisms and differ in terms of the immigration activities of organisms to the fields. We examined whether matrix quality affects wild pollinator abundance in crop fields, given that the species (Apis cerana) generally nest in the cavities of natural trees. We examined fields of a pollination-dependent crop surrounded by plantations and natural forests, which comprised the matrix. Our analysis revealed a clear positive effect of the natural forest on the pollinator abundance, but the plantation forest had little effects. These indicate that agricultural patches are influenced by their matrix quality and the resulting crop pollinator abundance, suggesting the importance of matrix management initiatives such as forest restoration surrounding agricultural fields to improve crop production