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831.
Peter I. Macreadie Katie Allen Brendan P. Kelaher Peter J. Ralph Charles G. Skilbeck 《Global Change Biology》2012,18(3):891-901
Human activities in coastal areas frequently cause loss of benthic macrophytes (e.g. seagrasses) and concomitant increases in microalgal production through eutrophication. Whether such changes translate into shifts in the composition of sediment detritus is largely unknown, yet such changes could impact the role these ecosystems play in sequestrating CO2. We reconstructed the sedimentary records of cores taken from two sites within Botany Bay, Sydney – the site of European settlement of Australia – to look for human‐induced changes in dominant sources of detritus in this estuary. Cores covered a period from the present day back to the middle Holocene (~6000 years) according to 210Pb profiles and radiocarbon (14C) dating. Depositional histories at both sites could not be characterized by a linear sedimentation rate; sedimentation rates in the last 30–50 years were considerably higher than during the rest of the Holocene. C : N ratios declined and began to exhibit a microalgal source signature from around the time of European settlement, which could be explained by increased nutrient flows into the Bay caused by anthropogenic activity. Analysis of stable isotopic ratios of 12C/13C showed that the relative contribution of seagrass and C3 terrestrial plants (mangroves, saltmarsh) to detritus declined around the time of rapid industrial expansion (~1950s), coinciding with an increase in the contribution of microalgal sources. We conclude that the relative contribution of microalgae to detritus has increased within Botany Bay, and that this shift is the sign of increased industrialization and concomitant eutrophication. Given the lower carbon burial efficiencies of microalgae (~0.1%) relative to seagrasses and C3 terrestrial plants (up to 10%), such changes represent a substantial weakening of the carbon sink potential of Botany Bay – this occurrence is likely to be common to human‐impacted estuaries, and has consequences for the role these systems play in helping to mitigate climate change. 相似文献
832.
Koyama M Kuns RD Olver SD Raffelt NC Wilson YA Don AL Lineburg KE Cheong M Robb RJ Markey KA Varelias A Malissen B Hämmerling GJ Clouston AD Engwerda CR Bhat P MacDonald KP Hill GR 《Nature medicine》2012,18(1):135-142
The presentation pathways by which allogeneic peptides induce graft-versus-host disease (GVHD) are unclear. We developed a bone marrow transplant (BMT) system in mice whereby presentation of a processed recipient peptide within major histocompatibility complex (MHC) class II molecules could be spatially and temporally quantified. Whereas donor antigen presenting cells (APCs) could induce lethal acute GVHD via MHC class II, recipient APCs were 100-1,000 times more potent in this regard. After myeloablative irradiation, T cell activation and memory differentiation occurred in lymphoid organs independently of alloantigen. Unexpectedly, professional hematopoietic-derived recipient APCs within lymphoid organs had only a limited capacity to induce GVHD, and dendritic cells were not required. In contrast, nonhematopoietic recipient APCs within target organs induced universal GVHD mortality and promoted marked alloreactive donor T cell expansion within the gastrointestinal tract and inflammatory cytokine generation. These data challenge current paradigms, suggesting that experimental lethal acute GVHD can be induced by nonhematopoietic recipient APCs. 相似文献
833.
Hae-Eun Kang Chu Chun Weng Eri Saijo Vicki Saylor Jifeng Bian Sehun Kim Laylaa Ramos Rachel Angers Katie Langenfeld Vadim Khaychuk Carla Calvi Jason Bartz Nora Hunter Glenn C. Telling 《The Journal of biological chemistry》2012,287(44):37219-37232
Whereas prion replication involves structural rearrangement of cellular prion protein (PrPC), the existence of conformational epitopes remains speculative and controversial, and PrP transformation is monitored by immunoblot detection of PrP(27–30), a protease-resistant counterpart of the pathogenic scrapie form (PrPSc) of PrP. We now describe the involvement of specific amino acids in conformational determinants of novel monoclonal antibodies (mAbs) raised against randomly chimeric PrP. Epitope recognition of two mAbs depended on polymorphisms controlling disease susceptibility. Detection by one, referred to as PRC5, required alanine and asparagine at discontinuous mouse PrP residues 132 and 158, which acquire proximity when residues 126–218 form a structured globular domain. The discontinuous epitope of glycosylation-dependent mAb PRC7 also mapped within this domain at residues 154 and 185. In accordance with their conformational dependence, tertiary structure perturbations compromised recognition by PRC5, PRC7, as well as previously characterized mAbs whose epitopes also reside in the globular domain, whereas conformation-independent epitopes proximal or distal to this region were refractory to such destabilizing treatments. Our studies also address the paradox of how conformational epitopes remain functional following denaturing treatments and indicate that cellular PrP and PrP(27–30) both renature to a common structure that reconstitutes the globular domain. 相似文献
834.
Katie A. Wilson Rachael A. Wells Minette N. Abendong Colin B. Anderson Ryan W. Kung 《Journal of biomolecular structure & dynamics》2016,34(1):184-200
There were 1765 contacts identified between DNA nucleobases or deoxyribose and cyclic (W, H, F, Y) or acyclic (R, E, D) amino acids in 672 X-ray structures of DNA–protein complexes. In this first study to compare π-interactions between the cyclic and acyclic amino acids, visual inspection was used to categorize amino acid interactions as nucleobase π–π (according to biological edge) or deoxyribose sugar–π (according to sugar edge). Overall, 54% of contacts are nucleobase π–π interactions, which involve all amino acids, but are more common for Y, F, and R, and involve all DNA nucleobases with similar frequencies. Among binding arrangements, cyclic amino acids prefer more planar (stacked) π-systems than the acyclic counterparts. Although sugar–π interactions were only previously identified with the cyclic amino acids and were found to be less common (38%) than nucleobase–cyclic amino acid contacts, sugar–π interactions are more common than nucleobase π–π contacts for the acyclic series (61% of contacts). Similar to DNA–protein π–π interactions, sugar–π contacts most frequently involve Y and R, although all amino acids adopt many binding orientations relative to deoxyribose. These DNA–protein π-interactions stabilize biological systems, by up to approximately ?40 kJ mol?1 for neutral nucleobase or sugar–amino acid interactions, but up to approximately ?95 kJ mol?1 for positively or negatively charged contacts. The high frequency and strength, despite variation in structure and composition, of these π-interactions point to an important function in biological systems. 相似文献
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Anna L. Mitchell Anette B?e Wolff Katie MacArthur Jolanta U. Weaver Bijay Vaidya Sophie Bensing on behalf of The Swedish Addison Registry Study Group Martina M. Erichsen Rebecca Darlay Eystein S. Husebye Heather J. Cordell Simon H. S. Pearce 《PloS one》2015,10(6)
BackgroundAutoimmune Addison’s disease (AAD) is a rare, highly heritable autoimmune endocrinopathy. It is possible that there may be some highly penetrant variants which confer disease susceptibility that have yet to be discovered.MethodsDNA samples from 23 multiplex AAD pedigrees from the UK and Norway (50 cases, 67 controls) were genotyped on the Affymetrix SNP 6.0 array. Linkage analysis was performed using Merlin. EMMAX was used to carry out a genome-wide association analysis comparing the familial AAD cases to 2706 UK WTCCC controls. To explore some of the linkage findings further, a replication study was performed by genotyping 64 SNPs in two of the four linked regions (chromosomes 7 and 18), on the Sequenom iPlex platform in three European AAD case-control cohorts (1097 cases, 1117 controls). The data were analysed using a meta-analysis approach.ResultsIn a parametric analysis, applying a rare dominant model, loci on chromosomes 7, 9 and 18 had LOD scores >2.8. In a non-parametric analysis, a locus corresponding to the HLA region on chromosome 6, known to be associated with AAD, had a LOD score >3.0. In the genome-wide association analysis, a SNP cluster on chromosome 2 and a pair of SNPs on chromosome 6 were associated with AAD (P <5x10-7). A meta-analysis of the replication study data demonstrated that three chromosome 18 SNPs were associated with AAD, including a non-synonymous variant in the NFATC1 gene.ConclusionThis linkage study has implicated a number of novel chromosomal regions in the pathogenesis of AAD in multiplex AAD families and adds further support to the role of HLA in AAD. The genome-wide association analysis has also identified a region of interest on chromosome 2. A replication study has demonstrated that the NFATC1 gene is worthy of future investigation, however each of the regions identified require further, systematic analysis. 相似文献
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