Influence of human impact and bedrock differences on the vegetational history of the Insubrian Southern Alps

Vegetation history for the study region is reconstructed on the basis of pollen, charcoal and AMS14C investigations of lake sediments from Lago del Segrino (calcareous bedrock) and Lago di Muzzano (siliceous bedrock). Late-glacial forests were characterised byBetula andPinus sylvestris. At the beginning of the Holocene they were replaced by temperate continental forest and shrub communities. A special type of temperate lowland forest, withAbies alba as the most important tree, was present in the period 8300 to 4500 B.P. Subsequently,Fagus, Quercus andAlnus glutinosa were the main forest components andA. alba ceased to be of importance.Castanea sativa andJuglans regia were probably introduced after forest clearance by fire during the first century A.D. On soils derived from siliceous bedrock,C. sativa was already dominant at ca. A.D. 200 (A.D. dates are in calendar years). In limestone areas, however,C. sativa failed to achieve a dominant role. After the introduction ofC. sativa, the main trees were initially oak (Quercus spp.) and later the walnut (Juglans regia). Ostrya carpinifolia became the dominant tree around Lago del Segrino only in the last 100–200 years though it had spread into the area at ca. 5000 cal. B.C. This recent expansion ofOstrya is confirmed at other sites and appears to be controlled by human disturbances involving especially clearance. It is argued that these forests should not be regarded as climax communities. It is suggested that under undisturbed succession they would develop into mixed deciduous forests consisting ofFraxinus excelsior, Tilia, Ulmus, Quercus and Acer.

Human Capital and New Venture Performance: The Moderating Role of Social Relations

With whom should entrepreneurs create their firms in order to enhance nascent venture performance? Conventional wisdom suggests that the stronger human capital and social relations in nascent venture teams are, the better the nascent venture’s performance. We draw from social embeddedness literature, however, and argue that the positive effect of team members’ human capital on three different dimensions of nascent venture performance is weaker when team members exhibit strong social relations. Our analysis of 488 nascent venture teams in the PSED II dataset confirms our predictions, showing that nascent ventures of teams with strong human capital but weaker social relations exhibit the best performance. The study thus offers valuable contributions particularly to literature on entrepreneurial teams the determinants of new venture performance.

Fetuin-A and cystatin C are endogenous inhibitors of human meprin metalloproteases

Meprin and , zinc metalloproteinases, play significant roles in inflammation, including inflammatory bowel disease (IBD), possibly by activating cytokines, like interleukin 1 , interleukin 18, or tumor growth factor . Although a number of potential activators for meprins are known, no endogenous inhibitors have been identified. In this work, we analyzed the inhibitory potential of human plasma and identified bovine fetuin-A as an endogenous meprin inhibitor with a K(i) (inhibition constant) of 4.2 × 10(-5) M for meprin and a K(i) of 1.1 × 10(-6) M meprin . This correlated with data obtained for a fetuin-A homologue from carp (nephrosin inhibitor) that revealed a potent meprin and inhibition (residual activities of 27 and 22%, respectively) at a carp fetuin concentration of 1.5 × 10(-6) M. Human fetuin-A is a negative acute phase protein involved in inflammatory diseases, thus being a potential physiological regulator of meprin activity. We report kinetic studies of fetuin-A with the proteolytic enzymes astacin, LAST, LAST_MAM, trypsin, and chymotrypsin, indeed demonstrating that fetuin-A is a broad-range protease inhibitor. Fetuin-A inhibition of meprin activity was 40 times weaker than that of meprin activity. Therefore, we tested cystatin C, a protein structurally closely related to fetuin-A. Indeed, cystatin C was an inhibitor for human meprin (K(i) = 8.5 × 10(-6) M) but, interestingly, not for meprin . Thus, the identification of fetuin-A and cystatin C as endogenous proteolytic regulators of meprin activity broadens our understanding of the proteolytic network in plasma.

The complement inhibitor low molecular weight dextran sulfate prevents TLR4-induced phenotypic and functional maturation of human dendritic cells

Low molecular weight dextran sulfate (DXS) has been reported to inhibit the classical, alternative pathway as well as the mannan-binding lectin pathway of the complement system. Furthermore, it acts as an endothelial cell protectant inhibiting complement-mediated endothelial cell damage. Endothelial cells are covered with a layer of heparan sulfate (HS), which is rapidly released under conditions of inflammation and tissue injury. Soluble HS induces maturation of dendritic cells (DC) via TLR4. In this study, we show the inhibitory effect of DXS on human DC maturation. DXS significantly prevents phenotypic maturation of monocyte-derived DC and peripheral myeloid DC by inhibiting the up-regulation of CD40, CD80, CD83, CD86, ICAM-1, and HLA-DR and down-regulates DC-SIGN in response to HS or exogenous TLR ligands. DXS also inhibits the functional maturation of DC as demonstrated by reduced T cell proliferation, and strongly impairs secretion of the proinflammatory mediators IL-1beta, IL-6, IL-12p70, and TNF-alpha. Exposure to DXS leads to a reduced production of the complement component C1q and a decreased phagocytic activity, whereas C3 secretion is increased. Moreover, DXS was found to inhibit phosphorylation of IkappaB-alpha and activation of NF-kappaB. These findings suggest that DXS prevents TLR-induced maturation of human DC and may therefore be a useful reagent to impede the link between innate and adaptive immunity.

Quantitative 1H-magnetic resonance spectroscopy of human brain: Influence of composition and parameterization of the basis set in linear combination model-fitting

Localized short-echo-time (1)H-MR spectra of human brain contain contributions of many low-molecular-weight metabolites and baseline contributions of macromolecules. Two approaches to model such spectra are compared and the data acquisition sequence, optimized for reproducibility, is presented. Modeling relies on prior knowledge constraints and linear combination of metabolite spectra. Investigated was what can be gained by basis parameterization, i.e., description of basis spectra as sums of parametric lineshapes. Effects of basis composition and addition of experimentally measured macromolecular baselines were investigated also. Both fitting methods yielded quantitatively similar values, model deviations, error estimates, and reproducibility in the evaluation of 64 spectra of human gray and white matter from 40 subjects. Major advantages of parameterized basis functions are the possibilities to evaluate fitting parameters separately, to treat subgroup spectra as independent moieties, and to incorporate deviations from straightforward metabolite models. It was found that most of the 22 basis metabolites used may provide meaningful data when comparing patient cohorts. In individual spectra, sums of closely related metabolites are often more meaningful. Inclusion of a macromolecular basis component leads to relatively small, but significantly different tissue content for most metabolites. It provides a means to quantitate baseline contributions that may contain crucial clinical information.

Local formation of varved sediments in a karstic collapse depression of Lake Banyoles (NE Spain)

Banyoles is the largest and deepest lake of karstic-tectonic origin in the Iberian Peninsula. The lake comprises several circular sub-basins characteri- zed by different oxygenation conditions at their hypolimnions. The multiproxy analysis of a > 5 m long sediment core combined with high resolution seis- mic stratigraphy (3.5 kHz pinger and multi-frequency Chirp surveys), allow a precise reconstruction of the evolution of a karstic depression (named B3) until present times. Local meromictic conditions in this sub-basin have been conducive to deposition and preservation of ca. 85 cm of varved sediments since the late 19th century. The onset of these conditions is likely related to lake waters eutrophication caused by increasing farming activities in the wa- tershed. Increasing clastic input and organic productivity during the second half of the 20th century have also been recorded within the laminated sedi- ments, revealing an intensification of human impact and warmer water tem- peratures.

Land Management in the Central Highlands of Eritrea: A Participatory Appraisal of Conservation Measures and Soils in Afdeyu and its Vicinity

A comprehensive inventory of local and introduced soil and water conservation (SWC) measures presented in standardized fact sheets and completed with a special focus on the underlying reasons (problems) of acceptance / rejection. Different approaches are analysed and measures identified which are adapted to the specific local context. Second part of the study: soil assessment resulting in a consistent local classification of soil types and soil fertility, comparison with scientific classifications. Different topical maps show the spatial distribution of SWC measures, their condition, degradation hotspots, soil types, soil fertility and interrelations between these parameters. Based on the conclusions and the outcome of a stakeholder workshop recommendations are given for further activities in research and implementation of SWC in the Central Highlands of Eritrea.

Stable transduction of bovine TLR4 and bovine MD-2 into LPS-nonresponsive cells and soluble CD14 promote the ability to respond to LPS

The interaction of bovine cells with lipopolysaccharide (LPS) was explored using human embryo kidney (HEK) 293 cell line stably transduced with bovine toll-like receptor-4 (TLR4) alone or in combination with bovine MD-2. These lines and mock-transduced HEK293 cells were tested by flow cytometry for LPS-fluorescein isothiocyanate (LPS-FITC) binding, nuclear factor kappa B (NFkappaB) activation, interleukin-8 (IL-8) production and interferon-beta mRNA expression/interferon (IFN) type I production. Whereas bovine TLR4 was sufficient to promote binding of high concentrations of LPS-FITC, both bovine TLR4 and MD-2 were required for activation by LPS, as assessed by NFkappaB activation and IL-8 production. Induction of IFN bioactivity was not observed in doubly transduced HEK293 cells, and no evidence for IFN-beta mRNA induction in response to LPS was obtained, although cells responded by IFN-beta mRNA expression to stimulation by Sendai virus and poly-inosinic acid-poly-cytidylic acid (poly(I:C)). Cells stably transduced with both bovine TLR4 and bovine MD-2 responded to LPS by IL-8 production, in decreasing order, in the presence of fetal bovine serum (FCS), of human serum, and of human serum albumin (HSA). The reduced activity in the presence of HSA could be restored by the addition of soluble CD14 (sCD14) but not of LPS binding protein (LBP). This is in contrast to macrophages which show a superior response to LPS in the presence of HSA when compared with macrophages stimulated by LPS in the presence of FCS. This suggests that macrophages but not HEK293 cells express factors rendering LPS stimulation serum-independent. Stably double-transduced cells reacted, in decreasing order, to LPS from Rhodobacter sphaeroides, to LPS from Escherichia coli, to synthetic lipd-IVa (compound 406), to diphosphoryl-lipid-A (S. minnesota) and to monophosphoryl-lipid-A (S. minnesota). They failed to react to the murine MD-2/TLR4 ligand taxol. This resembles the reactivity of bovine macrophages with regard to sensitivity (ED(50)) and order of potency but is distinct from the reactivity pattern of other species. This formally establishes that in order to react to LPS, cattle cells require serum factors (e.g. sCD14) and cell-expressed factors such as MD-2 and TLR4. The cell lines described are the first of a series expressing defined pattern recognition receptors (PRR) of bovine origin. They will be useful in the study of the interaction of the bovine TLR4-MD-2 complex and Gram-negative bovine pathogens, e.g. the agents causing Gram-negative bovine mastitis.

Regulation of human liver delta-aminolevulinic acid synthase by bile acids

Aminolevulinic acid synthase 1 (ALAS1) is the rate-limiting enzyme of heme synthesis in the liver and is highly regulated to adapt to the metabolic demand of the hepatocyte. In the present study, we describe human hepatic ALAS1 as a new direct target of the bile acid-activated nuclear receptor farnesoid X receptor (FXR). Experiments in primary human hepatocytes and in human liver slices showed that ALAS1 messenger RNA (mRNA) and activity is increased upon exposure to chenodeoxycholic acid (CDCA), the most potent natural FXR ligand, or the synthetic FXR-specific agonist GW4064. Moreover, overexpression of a constitutively active form of FXR further increased ALAS1 mRNA expression. In agreement with these observations, an FXR response element was identified in the 5' flanking region of human ALAS1 and characterized in reporter gene assays. A highly conserved FXR binding site (IR1) within a 175-bp fragment at -13 kilobases upstream of the transcriptional start site was able to trigger an FXR-specific increase in luciferase activity upon CDCA treatment. Site-directed mutagenesis of IR1 abolished this effect. Binding of FXR/retinoid acid X receptor heterodimers was demonstrated by mobility gel shift experiments. Conclusion: These data strongly support a role of bile acid-activated FXR in the regulation of human ALAS1 and, consequently, hepatic porphyrin and heme synthesis. These data also suggest that elevated endogenous bile acids may precipitate neuropsychiatric attacks in patients with acute hepatic porphyrias.

A novel enzyme immunoassay specific for ABCA1 protein quantification in human tissues and cells

ATP-binding cassette transporter A1 (ABCA1) mediates the transport of cholesterol and phospholipids from cells to lipid-poor HDL and maintains cellular lipid homeostasis. Impaired ABCA1 function plays a role in lipid disorders, cardiovascular disease, atherosclerosis, and metabolic disorders. Despite the clinical importance of ABCA1, no method is available for quantifying ABCA1 protein. We developed a sensitive indirect competitive ELISA for measuring ABCA1 protein in human tissues using a commercial ABCA1 peptide and a polyclonal anti-ABCA1 antibody. The ELISA has a detection limit of 8 ng/well (0.08 mg/l) with a working range of 9-1000 ng/well (0.09-10 mg/l). Intra- and interassay coefficient of variations (CVs) were 6.4% and 9.6%, respectively. Good linearity (r = 0.97-0.99) was recorded in serial dilutions of human arterial and placental crude membrane preparations, and fibroblast lysates. The ELISA measurements for ABCA1 quantification in reference arterial tissues corresponded well with immunoblot analysis. The assay performance and clinical utility was evaluated with arterial tissues obtained from 15 controls and 44 patients with atherosclerotic plaques. ABCA1 protein concentrations in tissue lysates were significantly lower in patients (n = 24) as compared with controls (n = 5; 9.37 +/- 0.82 vs. 17.03 +/- 4.25 microg/g tissue; P < 0.01). The novel ELISA enables the quantification of ABCA1 protein in human tissues and confirms previous semiquantitative immunoblot results.

Expression of human heteromeric amino acid transporters in the yeast Pichia pastoris

Human heteromeric amino acid transporters (HATs) play key roles in renal and intestinal re-absorption, cell redox balance and tumor growth. These transporters are composed of a heavy and a light subunit, which are connected by a disulphide bridge. Heavy subunits are the two type II membrane N-glycoproteins rBAT and 4F2hc, while L-type amino acid transporters (LATs) are the light and catalytic subunits of HATs. We tested the expression of human 4F2hc and rBAT as well as seven light subunits in the methylotrophic yeast Pichia pastoris. 4F2hc and the light subunit LAT2 showed the highest expression levels and yields after detergent solubilization. Co-transformation of both subunits in Pichia cells resulted in overexpression of the disulphide bridge-linked 4F2hc/LAT2 heterodimer. Two sequential affinity chromatography steps were applied to purify detergent-solubilized heterodimers yielding ~1mg of HAT from 2l of cell culture. Our results indicate that P. pastoris is a convenient system for the expression and purification of human 4F2hc/LAT2 for structural studies.

At the Interface of Culture, Development, and Forests: Insights from Bolivia and Kenya

The first part summarises the origins, definitions and debates around the general notions of development, culture and associated more specific concepts such as identity, tradition, exogenous and endogenous knowledge, institutions, governance or territoriality. A second part highlights how culture and development got related to the debates around sustainable governance of natural resources and forests. The third part illustrates on the basis of a case study from Kenya and Bolivia how culture as a transversal element of forest governance is expressed in empirical terms. Moreover it is shown how the cultural dimension affects positively or negatively the outcomes of culturally shaped forest governance outcomes and the role these effects play in shaping the sustainability of the socio-ecological systems of forests in Africa and South America.

Assessment of soil erosion and soil conservation practices in Angereb watershed, Ethiopia: Technological and land user context

Soil conservation technologies that fit well to local scale and are acceptable to land users are increasingly needed. To achieve this at small-holder farm level, there is a need for an understanding of specific erosion processes and indicators, the land users’ knowledge and their willingness, ability and possibilities to respond to the respective problems to decide on control options. This study was carried out to assess local erosion and performance of earlier introduced conservation terraces from both technological and land users’ points of view. The study was conducted during July to August 2008 at Angereb watershed on 58 farm plots from three selected case-study catchments. Participatory erosion assessment and evaluation were implemented along with direct field measurement procedures. Our focus was to involve the land users in the action research to explore with them the effectiveness of existing conservation measures against the erosion hazard. Terrace characteristics measured and evaluated against the terrace implementation guideline of Hurni (1986). The long-term consequences of seasonal erosion indicators had often not been known and noticed by farmers. The cause and effect relationships of the erosion indicators and conservation measures have shown the limitations and gaps to be addressed towards sustainable erosion control strategies. Less effective erosion control has been observed and participants have believed the gaps are to be the result of lack of landusers’ genuine participation. The results of both local erosion observation and assessment of conservation efficacy using different aspects show the need to promote approaches for erosion evaluation and planning of interventions by the farmers themselves. This paper describes the importance of human factor involving in the empirical erosion assessment methods towards sustainable soil conservation.