15 research outputs found

    Peptide exchange on MHC-I by TAPBPR is driven by a negative allostery release cycle.

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    Chaperones TAPBPR and tapasin associate with class I major histocompatibility complexes (MHC-I) to promote optimization (editing) of peptide cargo. Here, we use solution NMR to investigate the mechanism of peptide exchange. We identify TAPBPR-induced conformational changes on conserved MHC-I molecular surfaces, consistent with our independently determined X-ray structure of the complex. Dynamics present in the empty MHC-I are stabilized by TAPBPR and become progressively dampened with increasing peptide occupancy. Incoming peptides are recognized according to the global stability of the final pMHC-I product and anneal in a native-like conformation to be edited by TAPBPR. Our results demonstrate an inverse relationship between MHC-I peptide occupancy and TAPBPR binding affinity, wherein the lifetime and structural features of transiently bound peptides control the regulation of a conformational switch located near the TAPBPR binding site, which triggers TAPBPR release. These results suggest a similar mechanism for the function of tapasin in the peptide-loading complex

    General destabilizing effects of eutrophication on grassland productivity at multiple spatial scales

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    Eutrophication is a widespread environmental change that usually reduces the stabilizing effect of plant diversity on productivity in local communities. Whether this effect is scale dependent remains to be elucidated. Here, we determine the relationship between plant diversity and temporal stability of productivity for 243 plant communities from 42 grasslands across the globe and quantify the effect of chronic fertilization on these relationships. Unfertilized local communities with more plant species exhibit greater asynchronous dynamics among species in response to natural environmental fluctuations, resulting in greater local stability (alpha stability). Moreover, neighborhood communities that have greater spatial variation in plant species composition within sites (higher beta diversity) have greater spatial asynchrony of productivity among communities, resulting in greater stability at the larger scale (gamma stability). Importantly, fertilization consistently weakens the contribution of plant diversity to both of these stabilizing mechanisms, thus diminishing the positive effect of biodiversity on stability at differing spatial scales. Our findings suggest that preserving grassland functional stability requires conservation of plant diversity within and among ecological communities

    Emerging concepts in biomarker discovery; The US-Japan workshop on immunological molecular markers in oncology

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    Supported by the Office of International Affairs, National Cancer Institute (NCI), the "US-Japan Workshop on Immunological Biomarkers in Oncology" was held in March 2009. The workshop was related to a task force launched by the International Society for the Biological Therapy of Cancer (iSBTc) and the United States Food and Drug Administration (FDA) to identify strategies for biomarker discovery and validation in the field of biotherapy. The effort will culminate on October 28th 2009 in the "iSBTc-FDA-NCI Workshop on Prognostic and Predictive Immunologic Biomarkers in Cancer", which will be held in Washington DC in association with the Annual Meeting. The purposes of the US-Japan workshop were a) to discuss novel approaches to enhance the discovery of predictive and/or prognostic markers in cancer immunotherapy; b) to define the state of the science in biomarker discovery and validation. The participation of Japanese and US scientists provided the opportunity to identify shared or discordant themes across the distinct immune genetic background and the diverse prevalence of disease between the two Nations

    Composition, diversity and structure of vascular epiphytes in two contrasting Central Amazonian floodplain ecosystems

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    Research focusing on assemblages of vascular epiphytes in the Amazon are scarce. This is especially true for Amazonian floodplain forests, for which only two previous studies have been published. We compared composition, richness and structure of epiphyte assemblages in white-water and black-water floodplains (vĂĄrzea and igapĂł) in Central Amazonia in order to close knowledge gaps concerning the distribution and richness of epiphytes. We established sixteen 25x25 m plots in each forest type, and counted and identified all species of vascular epiphytes occurring on trees with a diameter at breast height (DBH) ≄10 cm. We observed a clear distinction in epiphytic species composition (r2=0.83, p=0.001) and diversity (t=3.24, P=0.003) between the two environments, with 61.5 % of species being restricted to vĂĄrzea, 22.9 % restricted to igapĂł and only 15.6 % common to both ecosystems. The floodplains were also structurally different for the most abundant species and those with the highest Epiphytic Importance Value (IVe). The diversity of trees did not influence the epiphyte diversity in either ecosystem. The forests were found to differ in the composition, diversity and structure of their epiphytic assemblages, which must be taken into account when designing conservation action plans for these ecosystems and for their vascular epiphytes

    Biased-corrected richness estimates for the Amazonian tree flora

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    Amazonian forests are extraordinarily diverse, but the estimated species richness is very much debated. Here, we apply an ensemble of parametric estimators and a novel technique that includes conspecific spatial aggregation to an extended database of forest plots with up-to-date taxonomy. We show that the species abundance distribution of Amazonia is best approximated by a logseries with aggregated individuals, where aggregation increases with rarity. By averaging several methods to estimate total richness, we confirm that over 15,000 tree species are expected to occur in Amazonia. We also show that using ten times the number of plots would result in an increase to just similar to 50% of those 15,000 estimated species. To get a more complete sample of all tree species, rigorous field campaigns may be needed but the number of trees in Amazonia will remain an estimate for years to come
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