Global change phenomena, such as forest disturbance and land-use change, significantly affect elemental balances as well as the structure and function of terrestrial ecosystems. However, the ...importance of shifts in soil nutrient stoichiometry for the regulation of belowground biota and soil food webs have not been intensively studied for tropical ecosystems. In the present account, we examine the effects of land-use change and soil depth on soil and microbial stoichiometry along a land-use sequence (natural forest, pastures of different ages, secondary succession) in the tropical mountain rainforest region of southern Ecuador. Furthermore, we analyzed (PLFA-method) whether shifts in the microbial community structure were related to alterations in soil and microbial stoichiometry. Soil and microbial stoichiometry were affected by both land-use change and soil depth. After forest disturbance, significant decreases of soil C:N:P ratios at the pastures were followed by increases during secondary succession. Microbial C:N ratios varied slightly in response to land-use change, whereas no fixed microbial C:P and N:P ratios were observed. Shifts in microbial community composition were associated with soil and microbial stoichiometry. Strong positive relationships between PLFA-markers 18:2n6,9c (saprotrophic fungi) and 20:4 (animals) and negative associations between 20:4 and microbial N:P point to land-use change affecting the structure of soil food webs. Significant deviations from global soil and microbial C:N:P ratios indicated a major force of land-use change to alter stoichiometric relationships and to structure biological systems. Our results support the idea that soil biotic communities are stoichiometrically flexible in order to adapt to alterations in resource stoichiometry.
Canopy and tree morphology are assumed to play a significant role in modulating the amount of rainfall water during its routing throughout the vegetation and the near‐surface Critical Zone. One ...crucial point of research addresses the spatial extent of stemflow (SF) infiltration, because its concentration over small areas at the trunk base appears to affect the magnitude and timing of water and solutes input to the soil and hence amplify biogeochemical cycling. By a Brilliant Blue tracer experiment, we examined the flow patterns of SF water along the trunk surface of two broadleaved tree species (Fagus sylvatica and Acer pseudoplatanus) and the infiltration area at the trunk base and down to 0.12‐m soil depth following natural rainfall events.
Our results point to highly preferential SF with smaller washed‐off stem areas for sycamore maple (≤15%) compared with European beech (≤39%). The infiltration area is remarkably smaller than the basal area (BA), accounting for only 17% of the BA for beech and for 30% for maple. Differences in decolourized stem areas between the trees do not relate to the magnitude of infiltration areas at the soil surface, suggesting a strong effect of coarse root abundance and run‐off properties on the funnelling of SF water.
In essence, our investigation exhibited that SF routing along bark surfaces and infiltration at the trunk base were spatially more concentrated than commonly assumed. The outcome of this study might contribute to our understanding on hydrological and biogeochemical interlinkages between the plant cover and the near‐surface Critical Zone.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Although clear cell renal cell carcinoma (ccRCC) has been shown to result in widespread aberrant cytosine methylation and loss of 5-hydroxymethylcytosine (5hmC), the prognostic impact and therapeutic ...targeting of this epigenetic aberrancy has not been fully explored. Analysis of 576 primary ccRCC samples demonstrated that loss of 5hmC was strongly associated with aggressive clinicopathologic features and was an independent adverse prognostic factor. Loss of 5hmC also predicted reduced progression-free survival after resection of nonmetastatic disease. The loss of 5hmC in ccRCC was not due to mutational or transcriptional inactivation of ten eleven translocation (TET) enzymes, but to their functional inactivation by l-2-hydroxyglutarate (L2HG), which was overexpressed due to the deletion and underexpression of L2HG dehydrogenase (L2HGDH). Ascorbic acid (AA) reduced methylation and restored genome-wide 5hmC levels via TET activation. Fluorescence quenching of the recombinant TET-2 protein was unaffected by L2HG in the presence of AA. Pharmacologic AA treatment led to reduced growth of ccRCC in vitro and reduced tumor growth in vivo, with increased intratumoral 5hmC. These data demonstrate that reduced 5hmC is associated with reduced survival in ccRCC and provide a preclinical rationale for exploring the therapeutic potential of high-dose AA in ccRCC.
Several ionic liquids have been shown to act as suppressors of protein aggregation and to effectively promote the
in vitro refolding of denatured proteins. In this work, the influence of the anion of ...these organic salts on their performance as refolding enhancers was tested, using a series of N-ethyl-N′-methyl imidazolium (EMIM) salts. Variation of the anion had a profound effect on the renaturation of the recombinant plasminogen activator rPA, which served as a model protein. The effect was roughly correlated with the stability of proteins in the tested aqueous ionic liquid solutions. Strongly destabilizing anions with higher alkyl substitutions like, e.g., hexyl sulfate were unable to promote protein refolding. However, the dimethyl and diethyl phosphate salts, which are known to be quite compatible with protein stability, also effectively suppressed renaturation, while alkylated sulfate anions with the same influence on protein stability did promote
in vitro refolding. Only ionic liquid co-solvent systems with an intermediate capacity for solubilizing the proteinogenic amino acid tryptophan were found to permit effective renaturation of the model protein rPA. The most effective refolding enhancer among the tested ionic liquids was EMIM chloride.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
Background
A molecular basis for von Willebrand factor (VWF) self‐inhibition has been proposed by which the N‐terminal and C‐terminal flanking sequences of the globular A1 domain disulfide loop bind ...to and suppress the conformational dynamics of A1. These flanking sequences are rich in O‐linked glycosylation (OLG), which is known to suppress platelet adhesion to VWF, presumably by steric hindrance. The inhibitory mechanism remains unresolved as to whether inhibition is due to steric exclusion by OLGs or a direct self‐association interaction that stabilizes the domain.
Objectives
The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild‐type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild‐type glycosylated A1 domain (HEK293 cell culture) to decipher the self‐inhibitory mechanism.
Methods
Surface plasmon resonance and analytical rheology are utilized to assess Glycoprotein Ibα (GPIbα) binding at equilibrium and platelet adhesion under shear flow. The conformational stability is assessed through a combination of protein unfolding thermodynamics and hydrogen‐deuterium exchange mass spectrometry (HXMS).
Results
A1 glycosylation inhibits both GPIbα binding and platelet adhesion. Glycosylation increases the hydrodynamic size of A1 and stabilizes the thermal unfolding of A1 without changing its equilibrium stability. Glycosylation does not alter the intrinsic conformational dynamics of the A1 domain.
Conclusions
These studies invalidate the proposed inhibition through conformational suppression since glycosylation within these flanking sequences does not alter the native state stability or the conformational dynamics of A1. Rather, they confirm a mechanism by which glycosylation sterically hinders platelet adhesion to the A1 domain at equilibrium and under rheological shear stress.
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FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Fire can have large effects on ecosystems, with phosphorus being highly important in this regard, especially when considering productivity in burned or adjacent ecosystems after fire. Unfortunately, ...existing data pose contradictions and methodological challenges to assessing P availability. Here, the impact of fire on topsoil available P was estimated using three different types of organic soil layers (raw humus from spruce, humus from beech, and peat) and two fire regimes (obtaining black carbon and ash). Our findings suggest a strong fire impact on P availability, by enhancing available P during burning to black carbon (~10-fold), and to ash (~2- to 7.5-fold) dependent on calcite content. Fire impact on P availability is on a similar order of magnitude as mineral weathering and annual P cycling/uptake in/by ecosystems. Furthermore, the proportion of available P in relation to total P depends on the origin of the organic soil layers. When related to the remaining mass after burning, as is commonly done, P availability can be overestimated by up to 1400%. Results from this study provide a realistic magnitude of shifts in P release and P availability by fire events of different intensity for widely abundant ecosystem conditions. Taking the importance of P for ecosystem processes into account, these results are highly relevant, because fires for fuel reduction are a common application, and for temperate and boreal ecosystems even moderate climate change scenarios predict an increasing appearance of fires in these regions.
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BFBNIB, FZAB, GIS, IJS, INZLJ, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZRSKP
Increasing demands for livelihood resources in tropical rural areas have led to progressive clearing of biodiverse natural forests. Restoration of abandoned farmlands could counter this process. ...However, as aims and modes of restoration differ in their ecological and socio-economic value, the assessment of achievable ecosystem functions and benefits requires holistic investigation. Here we combine the results from multidisciplinary research for a unique assessment based on a normalization of 23 ecological, economic and social indicators for four restoration options in the tropical Andes of Ecuador. A comparison of the outcomes among afforestation with native alder or exotic pine, pasture restoration with either low-input or intense management and the abandoned status quo shows that both variants of afforestation and intense pasture use improve the ecological value, but low-input pasture does not. Economic indicators favour either afforestation or intense pasturing. Both Mestizo and indigenous Saraguro settlers are more inclined to opt for afforestation.
The frequent overexpression of CD46 in malignant tumors has provided a basis to use vaccine-lineage measles virus (MeV) as an oncolytic virotherapy platform. However, widespread measles ...seropositivity limits the systemic deployment of oncolytic MeV for the treatment of metastatic neoplasia. Here, we report the development of MeV-Stealth, a modified vaccine MeV strain that exhibits oncolytic properties and escapes antimeasles antibodies in vivo. We engineered this virus using homologous envelope glycoproteins from the closely-related but serologically non-cross reactive canine distemper virus (CDV). By fusing a high-affinity CD46 specific single-chain antibody fragment (scFv) to the CDV-Hemagglutinin (H), ablating its tropism for human nectin-4 and modifying the CDV-Fusion (F) signal peptide we achieved efficient retargeting to CD46. A receptor binding affinity of ~20 nM was required to trigger CD46-dependent intercellular fusion at levels comparable to the original MeV H/F complex and to achieve similar antitumor efficacy in myeloma and ovarian tumor-bearing mice models. In mice passively immunized with measles-immune serum, treatment of ovarian tumors with MeV-Stealth significantly increased overall survival compared with treatment with vaccine-lineage MeV. Our results show that MeV-Stealth effectively targets and lyses CD46-expressing cancer cells in mouse models of ovarian cancer and myeloma, and evades inhibition by human measles-immune serum. MeV-Stealth could therefore represent a strong alternative to current oncolytic MeV strains for treatment of measles-immune cancer patients.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The frequent von Willebrand factor (VWF) variant p.Phe2561Tyr is located within the C4 domain, which also harbors the platelet GPIIb/IIIa-binding RGD sequence. To investigate its potential effect on ...hemostasis, we genotyped 865 patients with coronary artery disease (CAD), 915 with myocardial infarction (MI), and 417 control patients (Ludwigshafen Risk and Cardiovascular Health Study) and performed functional studies of this variant. A univariate analysis of male and female carriers of the Tyr2561 allele aged 55 years or younger revealed an elevated risk for repeated MI (odds ratio, 2.53; 95% confidence interval CI, 1.07-5.98). The odds ratio was even higher in females aged 55 years or younger, at a value of 5.93 (95% CI, 1.12-31.24). Cone and plate aggregometry showed that compared with Phe2561, Tyr2561 was associated with increased platelet aggregate size both in probands' blood and with the recombinant variants. Microfluidic assays revealed that the critical shear rate for inducing aggregate formation was decreased to 50% by Tyr2561 compared with Phe2561. Differences in C-domain circular dichroism spectra resulting from Tyr2561 suggest an increased shear sensitivity of VWF as a result of altered association of the C domains that disrupts the normal dimer interface. In summary, our data emphasize the functional effect of the VWF C4 domain for VWF-mediated platelet aggregation in a shear-dependent manner and provide the first evidence that a functional variant of VWF plays a role in arterial thromboembolism.
•VWF p.Phe2561Tyr is the first gain-of-function variant, which increases the force sensitivity of VWF interaction with platelets.•VWF p.Phe2561Tyr is associated with repeated myocardial infarction, particularly in younger women.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
(1) Background: Leaf area index (LAI) is an essential structural property of plant canopies and is functionally related to fluxes of energy, water, carbon, and light in ecosystems; coupling the ...biosphere to the geo-, hydro-, and atmosphere. There is an increasing need for more accurate and traceable measurements among several spatial scales of investigation and modelling. We hypothesize that the spatial variability of LAI at the scale of crown sections of a single European beech (Fagus sylvatica L.) tree in a highly structured, mixed European beech-Norway spruce stand can be determined by simultaneous records of precipitation; (2) Methods: Spatially explicit measurements of throughfall were conducted repeatedly below beech and in forest gaps for rain events in leafed and in leafless periods. Subsequent analysis with a new regression approach resulted in estimating leaf and twig water storage capacities (SCleaf/twig) at point level independent of within-crown lateral flow mechanisms. Inverse modelling was used to estimate spatial litterfall (n = 99) distribution and litter production (mass, area, numbers) for single trees, as a function of diameter at breast height; (3) Results: As revealed by a linear mixed-effects model, SCleaf at the center of a beech canopies amounts to 4.9 mm in average and significantly decreases in the direction of the crown edges to an average value of 1.1 mm. Based on diameter-sensitive prediction of litter production, specific leaf area wetting capacity amounts to 0.260 l·m−2. A linear within-canopy dynamic of LAI was found with a mean of 17.6 m2·m−2 in the center and 4.0 m2·m−2 at the edges; and (4) Conclusions: The application of the method provided plausible results and can be extended to further throughfall datasets and tree species. Unravelling the causes and magnitude of spatial- and temporal heterogeneity of forest ecosystem properties contribute to overall progress in geosciences by improving the understanding how the biosphere relates to the hydro- and atmosphere.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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