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61.
Annelene Pengerud Marie-France Dignac Giacomo Certini Line Tau Strand Claudia Forte Daniel P. Rasse 《Biogeochemistry》2017,135(3):277-292
Increased mineralization of the organic matter (OM) stored in permafrost is expected to constitute the largest additional global warming potential from terrestrial ecosystems exposed to a warmer climate. Chemical composition of permafrost OM is thought to be a key factor controlling the sensitivity of decomposition to warming. Our objective was to characterise OM from permafrost soils of the European Arctic: two mineral soils—Adventdalen, Svalbard, Norway and Vorkuta, northwest Russia—and a “palsa” (ice-cored peat mound patterning in heterogeneous permafrost landscapes) soil in Neiden, northern Norway, in terms of molecular composition and state of decomposition. At all sites, the OM stored in the permafrost was at an advanced stage of decomposition, although somewhat less so in the palsa peat. By comparing permafrost and active layers, we found no consistent effect of depth or permafrost on soil organic matter (SOM) chemistry across sites. The permafrost-affected palsa peat displayed better preservation of plant material in the deeper layer, as indicated by increasing contribution of lignin carbon to total carbon with depth, associated to decreasing acid (Ac) to aldehyde (Al) ratio of the syringyl (S) and vanillyl (V) units, and increasing S/V and contribution of plant-derived sugars. By contrast, in Adventdalen, the Ac/Al ratio of lignin and the Alkyl C to O-alkyl C ratio in the NMR spectra increased with depth, which suggests less oxidized SOM in the active layer compared to the permafrost layer. In Vorkuta, SOM characteristics in the permafrost profile did not change substantially with depth, probably due to mixing of soil layers by cryoturbation. The composition and state of decomposition of SOM appeared to be site-specific, in particular bound to the prevailing organic or mineral nature of soil when attempting to predict the SOM proneness to degradation. The occurrence of processes such as palsa formation in organic soils and cryoturbation should be considered when up-scaling and predicting the responses of OM to climate change in arctic soils. 相似文献
62.
Identification of two homologs of the Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in retroperitoneal fibromatosis of different macaque species. 总被引:6,自引:4,他引:6 下载免费PDF全文
T M Rose K B Strand E R Schultz G Schaefer G W Rankin Jr M E Thouless C C Tsai M L Bosch 《Journal of virology》1997,71(5):4138-4144
Simian retroperitoneal fibromatosis (RF) is a vascular fibroproliferative neoplasm which has many morphological and histological similarities to human Kaposi's sarcoma (KS). Like epidemic KS in AIDS patients, RF is highly associated with an immunodeficiency syndrome (simian acquired immunodeficiency syndrome [SAIDS]) caused by a retrovirus infection. Recently, a new gammaherpesvirus, called Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV8), has been identified in KS tumors, suggesting that KS has a viral etiology. Our previous experimental transmission studies and epidemiological data suggest that RF also has an infectious etiology. In order to determine whether a similar virus is also associated with RF, we have assayed for the presence of an unknown herpesvirus using degenerate PCR primers targeting the highly conserved DNA polymerase genes of the herpesvirus family. Here we provide DNA sequence evidence for two new herpesviruses closely related to KSHV from RF tissues of two macaque species, Macaca nemestrina and Macaca mulatta. Our data suggest that KSHV and the putative macaque herpesviruses define a new group within the subfamily Gammaherpesvirinae whose members are implicated in the pathogenesis of KS and KS-like neoplasms in different primate species. 相似文献
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We here describe that soluble HLA-DQ2 (sDQ2) molecules, when expressed in Drosophila melanogaster S2 insect cells without a covalently tethered peptide, associate tightly with the D. melanogaster calcium binding protein DCB-45. The interaction between the proteins is stable in S2 cell culture and during affinity purification,
which is done at high salt concentrations and pH 11.5. After affinity purification, the sDQ2/DCB-45 complex exists in substantial
quantities next to a small amount of free heterodimeric sDQ2 and large amounts of aggregated sDQ2 free of DCB-45. Motivated
by the stable complex formation and our interest in the development of reagents which inhibit HLA-DQ2 peptide binding, we
have further characterized the sDQ2/DCB-45 interaction. Several lines of evidence indicate that an N-terminal fragment of
DCB-45 is involved in the interaction with the peptide binding groove of sDQ2. Further mapping of this fragment of 54 residues
identified a pentadecapeptide with high affinity for sDQ2 which may serve as a lead compound for the design of HLA-DQ2 blockers. 相似文献
66.
Binley JM Lybarger EA Crooks ET Seaman MS Gray E Davis KL Decker JM Wycuff D Harris L Hawkins N Wood B Nathe C Richman D Tomaras GD Bibollet-Ruche F Robinson JE Morris L Shaw GM Montefiori DC Mascola JR 《Journal of virology》2008,82(23):11651-11668
Identifying the viral epitopes targeted by broad neutralizing antibodies (NAbs) that sometimes develop in human immunodeficiency virus type 1 (HIV-1)-infected subjects should assist in the design of vaccines to elicit similar responses. Here, we investigated the activities of a panel of 24 broadly neutralizing plasmas from subtype B- and C-infected donors using a series of complementary mapping methods, focusing mostly on JR-FL as a prototype subtype B primary isolate. Adsorption with gp120 immobilized on beads revealed that an often large but variable fraction of plasma neutralization was directed to gp120 and that in some cases, neutralization was largely mediated by CD4 binding site (CD4bs) Abs. The results of a native polyacrylamide gel electrophoresis assay using JR-FL trimers further suggested that half of the subtype B and a smaller fraction of subtype C plasmas contained a significant proportion of NAbs directed to the CD4bs. Anti-gp41 neutralizing activity was detected in several plasmas of both subtypes, but in all but one case, constituted only a minor fraction of the overall neutralization activity. Assessment of the activities of the subtype B plasmas against chimeric HIV-2 viruses bearing various fragments of the membrane proximal external region (MPER) of HIV-1 gp41 revealed mixed patterns, implying that MPER neutralization was not dominated by any single specificity akin to known MPER-specific monoclonal Abs. V3 and 2G12-like NAbs appeared to make little or no contribution to JR-FL neutralization titers. Overall, we observed significant titers of anti-CD4bs NAbs in several plasmas, but approximately two-thirds of the neutralizing activity remained undefined, suggesting the existence of NAbs with specificities unlike any characterized to date. 相似文献
67.
- Large and small mammalian herbivores are present in most vegetated areas in the Arctic and often have large impacts on plant community composition and ecosystem functioning. The relative importance of different herbivores and especially how their specific impact on the vegetation varies across the Arctic is however poorly understood.
- Here, we investigate how large and small herbivores influence vegetation density and plant community composition in four arctic vegetation types in Scandinavia and Alaska. We used a unique set of exclosures, excluding only large (reindeer and muskoxen) or all mammalian herbivores (also voles and lemmings) for at least 20 years.
- We found that mammalian herbivores in general decreased leaf area index, NDVI, and abundance of vascular plants in all four locations, even though the strength of the effect and which herbivore type caused these effects differed across locations. In three locations, herbivore presence caused contrasting plant communities, but not in the location with lowest productivity. Large herbivores had a negative effect on plant height, whereas small mammalian herbivores increased species diversity by decreasing dominance of the initially dominating plant species. Above‐ or belowground disturbances caused by herbivores were found to play an important role in shaping the vegetation in all locations.
- Synthesis: Based on these results, we conclude that both small and large mammalian herbivores influence vegetation in Scandinavia and Alaska in a similar way, some of which can mitigate effects of climate change. We also see important differences across locations, but these depend rather on local herbivore and plant community composition than large biogeographical differences among continents.
68.
Josef S. Smolen Ronald van Vollenhoven Arthur Kavanaugh Vibeke Strand Jiri Vencovsky Michael Schiff Robert Landewé Boulos Haraoui Catherine Arendt Irina Mountian David Carter Désirée van der Heijde 《Arthritis research & therapy》2015,17(1)
IntroductionAs patients with rheumatoid arthritis (RA) receive treatment with anti-tumour necrosis factors over several years, it is important to evaluate their long-term safety and efficacy. The objective of this study was to examine the safety and benefits of certolizumab pegol (CZP)+methotrexate (MTX) treatment for almost 5 years in patients with RA.MethodsPatients who completed the 24-week Rheumatoid Arthritis Prevention of Structural Damage (RAPID) 2 randomized controlled trial (RCT; ), or who were American College of Rheumatology (ACR) 20 non-responders at Week 16, entered the open-label extension (OLE; NCT00160602). After ≥6 months treatment with CZP 400 mg every two weeks (Q2W), dose was reduced to 200 mg Q2W, the approved maintenance dose. Safety data are presented from all patients who received ≥1 dose CZP (Safety population, n=612). Efficacy data are presented to Week 232 for the intent-to-treat (ITT, n=492) and Week 24 CZP RCT Completer (n=342) populations, and through 192 weeks of dose-reduction for the Dose-reduction population (patients whose CZP dose was reduced to 200 mg, n=369). Radiographic progression (modified total Sharp score change from RCT baseline >0.5) to Week 128 is reported for the Week 24 CZP Completers.ResultsIn the RCT, 619 patients were randomized to CZP+MTX (n=492) or placebo+MTX (n=127). Overall, 567 patients (91.6%) entered the OLE: 447 CZP and 120 placebo patients. Of all randomized patients, 358 (57.8%) were ongoing at Week 232. Annual drop-out rates during the first four years ranged from 8.4–15.0%. Event rates per 100 patient-years were 163.0 for adverse events (AEs) and 15.7 for serious AEs. Nineteen patients (3.1%) had fatal AEs (incidence rate=0.8). Clinical improvements in the RCT were maintained to Week 232 in the CZP Completers: mean Disease Activity Score 28 (Erythrocyte Sedimentation Rate) change from baseline was −3.4 and ACR20/50/70 responses 68.4%/47.1%/25.1% (non-responder imputation). Similar improvements observed in the ITT were maintained following dose-reduction. 73.2% of CZP Completers had no radiographic progression at Week 128.ConclusionsIn patients with active RA despite MTX therapy, CZP was well tolerated, with no new safety signals identified. CZP provided sustained improvements in clinical outcomes for almost 5 years. NCT00160641
Trial registration
ClinicalTrials.gov, and NCT00160602. Registered 8 September 2005. NCT00160641Electronic supplementary material
The online version of this article (doi:10.1186/s13075-015-0767-2) contains supplementary material, which is available to authorized users. 相似文献69.
L.?C.?Coates D.?D.?Gladman P.?Nash O.?FitzGerald A.?Kavanaugh T.?K.?Kvien L.?Gossec V.?Strand L.?Rasouliyan L.?Pricop K.?Ding S.?M.?Jugl C.?Gaillez 《Arthritis research & therapy》2018,20(1):272
Background
Secukinumab has demonstrated sustained improvement in the signs and symptoms of psoriatic arthritis (PsA) over 2?years in the FUTURE 2 study (NCT01752634). This post hoc analysis assessed the ability of secukinumab to achieve Psoriatic Arthritis Disease Activity Score (PASDAS)-based remission or low disease activity (LDA) through 2?years among patients with PsA in the FUTURE 2 study.Methods
PASDAS (cut-off scores: remission ≤?1.9; LDA >?1.9 and?<?3.2; Moderate Disease Activity ≥?3.2 and?<?5.4; and high disease activity [HDA]?≥?5.4) was assessed in the overall population (tumour necrosis factor inhibitor [TNFi]-naïve and TNFi-experienced), in patients stratified by prior TNFi use and by disease duration at weeks 16, 52 and 104. The impact of secukinumab on individual PASDAS core components and on the relationship between PASDAS states and patient-reported outcomes (PROs), including physical function, health-related quality of life (HRQoL) and work productivity, were also assessed. Data for the approved doses of secukinumab (300 and 150?mg) are reported. PASDAS scores and core components were reported as observed, and PROs were analysed using mixed models for repeated measures.Results
In the overall population, PASDAS remission and LDA were achieved in 15.6% and 22.9%, respectively, of patients treated with secukinumab 300?mg and in 15.2% and 19.2%, respectively, in the secukinumab 150?mg group versus 2.3% and 13.8%, respectively, with placebo at week 16. In the TNFi-naïve group, a higher proportion of patients achieved remission?+?LDA at week 16 with secukinumab 300 and 150?mg (46.2% and 42.9%, respectively) versus placebo (17.5%), with corresponding responses in TNFi-experienced patients being 22.6% and 19.4% versus 13.3%. Remission/LDA responses with secukinumab were sustained through 2?years. Patients achieving remission/LDA reported greater improvements in PROs than patients in HDA through 2?years.Conclusions
Secukinumab-treated patients achieved higher PASDAS-defined remissions or LDA compared with placebo at week 16, which were sustained through 2?years. Remission/LDA was achieved by both TNFi-naïve and TNFi-experienced patients treated with secukinumab, with higher rates in TNFi-naïve patients. Secukinumab-treated patients achieving remission/LDA reported significantly greater improvements in PROs, including physical function and different dimensions of health-related quality of life and work, than patients in HDA.Trial registration
ClinicalTrials.gov, NCT01752634. Registered on December 19, 2012.EUDRACT, 2012-004439-22. Registered on December 12, 2012.70.
Kristin Fenton Silje Fismen Annica Hedberg Natalya Seredkina Chris Fenton Elin Synn?ve Mortensen Ole Petter Rekvig 《PloS one》2009,4(12)