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Manuel J. Steinbauer Richard Field John‐Arvid Grytnes Panayiotis Trigas Claudine Ah‐Peng Fabio Attorre H. John B. Birks Paulo A. V. Borges Pedro Cardoso Chang‐Hung Chou Michele De Sanctis Miguel M. de Sequeira Maria C. Duarte Rui B. Elias José María Fernández‐Palacios Rosalina Gabriel Roy E. Gereau Rosemary G. Gillespie Josef Greimler David E. V. Harter Tsurng‐Juhn Huang Severin D. H. Irl Daniel Jeanmonod Anke Jentsch Alistair S. Jump Christoph Kueffer Sandra Nogué Rüdiger Otto Jonathan Price Maria M. Romeiras Dominique Strasberg Tod Stuessy Jens‐Christian Svenning Ole R. Vetaas Carl Beierkuhnlein 《Global Ecology and Biogeography》2016,25(9):1097-1107
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Geert P. M. Mommen Fabio Marino Hugo D. Meiring Martien C. M. Poelen Jacqueline A. M. van Gaans-van den Brink Shabaz Mohammed Albert J. R. Heck Cécile A. C. M. van Els 《Molecular & cellular proteomics : MCP》2016,15(4):1412-1423
Comprehensive analysis of the complex nature of the Human Leukocyte Antigen (HLA) class II ligandome is of utmost importance to understand the basis for CD4+ T cell mediated immunity and tolerance. Here, we implemented important improvements in the analysis of the repertoire of HLA-DR-presented peptides, using hybrid mass spectrometry-based peptide fragmentation techniques on a ligandome sample isolated from matured human monocyte-derived dendritic cells (DC). The reported data set constitutes nearly 14 thousand unique high-confident peptides, i.e. the largest single inventory of human DC derived HLA-DR ligands to date. From a technical viewpoint the most prominent finding is that no single peptide fragmentation technique could elucidate the majority of HLA-DR ligands, because of the wide range of physical chemical properties displayed by the HLA-DR ligandome. Our in-depth profiling allowed us to reveal a strikingly poor correlation between the source proteins identified in the HLA class II ligandome and the DC cellular proteome. Important selective sieving from the sampled proteome to the ligandome was evidenced by specificity in the sequences of the core regions both at their N- and C- termini, hence not only reflecting binding motifs but also dominant protease activity associated to the endolysosomal compartments. Moreover, we demonstrate that the HLA-DR ligandome reflects a surface representation of cell-compartments specific for biological events linked to the maturation of monocytes into antigen presenting cells. Our results present new perspectives into the complex nature of the HLA class II system and will aid future immunological studies in characterizing the full breadth of potential CD4+ T cell epitopes relevant in health and disease.Human Leukocyte Antigen (HLA)1 class II molecules on professional antigen presenting cells such as dendritic cells (DC) expose peptide fragments derived from exogenous and endogenous proteins to be screened by CD4+ T cells (1, 2). The activation and recruitment of CD4+ T cells recognizing disease-related peptide antigens is critical for the development of efficient antipathogen or antitumor immunity. Furthermore, the presentation of self-peptides and their interaction with CD4+ T cells is essential to maintain immunological tolerance and homeostasis (3). Knowledge of the nature of HLA class II-presented peptides on DC is of great importance to understand the rules of antigen processing and peptide binding motifs (4), whereas the identity of disease-related antigens may provide new knowledge on immunogenicity and leads for the development of vaccines and immunotherapy (5, 6).Mass spectrometry (MS) has proven effective for the analysis HLA class II-presented peptides (4, 7, 8). MS-based ligandome studies have demonstrated that HLA class II molecules predominantly present peptides derived from exogenous proteins that entered the cells by endocytosis and endogenous proteins that are associated with the endo-lysosomal compartments (4). Yet proteins residing in the cytosol, nucleus or mitochondria can also be presented by HLA class II molecules, primarily through autophagy (9–11). Multiple studies have mapped the HLA class II ligandome of antigen presenting cells in the context of infectious pathogens (12), autoimmune diseases (13–17) or cancer (14, 18, 19), or those that are essential for self-tolerance in the human thymus (3, 20). Notwithstanding these efforts, and certainly not in line with the extensive knowledge on the HLA class I ligandome (21), the nature of the HLA class II-presented peptide repertoire and particular its relationship to the cellular source proteome remains poorly understood.To advance our knowledge on the HLA-DR ligandome on activated DC without having to deal with limitations in cell yield from peripheral human blood (12, 21, 22) or tissue isolates (3), we explored the use of MUTZ-3 cells. This cell line has been used as a model of human monocyte-derived DCs. MUTZ-3 cells can be matured to act as antigen presenting cells and express then high levels of HLA class II molecules, and can be propagated in vitro to large cell densities (23–25). We also evaluated the performance of complementary and hybrid MS fragmentation techniques electron-transfer dissociation (ETD), electron-transfer/higher-energy collision dissociation (EThcD) (26), and higher-energy collision dissociation (HCD) to sequence and identify the HLA class II ligandome. Together this workflow allowed for the identification of an unprecedented large set of about 14 thousand unique peptide sequences presented by DC derived HLA-DR molecules, providing an in-depth view of the complexity of the HLA class II ligandome, revealing underlying features of antigen processing and surface-presentation to CD4+ T cells. 相似文献
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Key message
Apical and lateral growth are seasonal in a Cerrado species, and these events are related to each other and linked with climatic and environmental features.Abstract
In the Cerrado, a tropical ecosystem with seasonal rainfall, we investigated the timing of leaf production and cambial activity, and checked whether these features are related to each other and with climatic and environmental factors. Between September 2011 and December 2012, sampling of main stem and vegetative phenological observations of Kielmeyera grandiflora (Wawra) Saddi (Calophyllaceae) were done monthly to assess seasonality in leaf production and cambial activity, and to compare these features with each other. To check the relationship of bud opening and the onset of cambial activity with climatic and environmental features, the average temperature and day length, and the precipitation sum in a time window ranging from 1 to 30 days before the occurrence of these events were recorded, and the coefficient of variation was calculated. Leaf production and cambial activity were seasonal. Bud opening occurred in September 2011 and August 2012, during the dry season. The onset of cambial activity occurred in October both in 2011 and 2012, 1–2 months after bud opening, at the beginning of the rainy season. The cambium was dormant in May, during the rainy season. Photoperiod and temperature showed low coefficients of variation in the time window before bud opening and onset of cambial activity, while rainfall presented a high coefficient of variation. Thus, both apical and lateral growth are seasonal events in Cerrado species, and are related to each other. A set of climatic and environmental features is related with seasonal growth, among which photoperiod and temperature may be important in the regulation of these events.86.
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Bingxin Wang Daniel G. Rocha Mark I. Abrahams Andr P. Antunes Hugo C. M. Costa Andr Luis Sousa Gonalves Wilson Roberto Spironello Milton Jos de Paula Carlos A. Peres Juarez Pezzuti Emiliano Ramalho Marcelo Lima Reis Elildo Carvalho Jr Fabio Rohe David W. Macdonald Cedric Kai Wei Tan 《Ecology and evolution》2019,9(9):5049-5062
Amazonia forest plays a major role in providing ecosystem services for human and sanctuaries for wildlife. However, ongoing deforestation and habitat fragmentation in the Brazilian Amazon has threatened both. The ocelot is an ecologically important mesopredator and a potential conservation ambassador species, yet there are no previous studies on its habitat preference and spatial patterns in this biome. From 2010 to 2017, twelve sites were surveyed, totaling 899 camera trap stations, the largest known dataset for this species. Using occupancy modeling incorporating spatial autocorrelation, we assessed habitat use for ocelot populations across the Brazilian Amazon. Our results revealed a positive sigmoidal correlation between remote‐sensing derived metrics of forest cover, disjunct core area density, elevation, distance to roads, distance to settlements and habitat use, and that habitat use by ocelots was negatively associated with slope and distance to river/lake. These findings shed light on the regional scale habitat use of ocelots and indicate important species–habitat relationships, thus providing valuable information for conservation management and land‐use planning. 相似文献
89.
In this paper, we report investigations on the nested structure, the high-definition mapping, and the molecular basis of the classical Giemsa and Reverse bands in human chromosomes. We found the rules according to which the approximately 3,200 isochores of the human genome are assembled in high (850-band) resolution bands, and the latter in low (400-band) resolution bands, so forming the nested mosaic structure of chromosomes. Moreover, we identified the borders of both sets of chromosomal bands at the DNA sequence level on the basis of our recent map of isochores, which represent the highest-resolution, ultimate bands. Indeed, beyond the 100-kb resolution of the isochore map, the guanine and cytosine (GC) profile of DNA becomes turbulent owing to the contribution of specific sequences such as exons, introns, interspersed repeats, CpG islands, etc. The isochore-based level of definition (100 kb) of chromosomal bands is much higher than the cytogenetic definition level (2-3 Mb). The major conclusions of this work concern the high degree of order found in the structure of chromosomal bands, their mapping at a high definition, and the solution of the long-standing problem of the molecular basis of chromosomal bands, as these could be defined on the basis of compositional DNA properties alone. 相似文献
90.
Friedberg I Nika K Tautz L Saito K Cerignoli F Friedberg I Godzik A Mustelin T 《FEBS letters》2007,581(13):2527-2533
A novel human dual-specific protein phosphatase (DSP), designated DUSP27, is here described. The DUSP27 gene contains three exons, rather than the predicted 4-14 exons, and encodes a 220 amino acid protein. DUSP27 is structurally similar to other small DSPs, like VHR and DUSP13. The location of DUSP27 on chromosome 10q22, 50 kb upstream of DUSP13, suggests that these two genes arose by gene duplication. DUSP27 is an active enzyme, and its kinetic parameters and were determined. DUSP27 is a cytosolic enzyme, expressed in skeletal muscle, liver and adipose tissue, suggesting its possible role in energy metabolism. 相似文献