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41.
This paper provides an overview of the plethora of approaches that are available to measure welfare and sustainable development. Many methods exist but there is no consensus on the ‘correct’ approach. Furthermore, we also show that the wide variety of sustainable development indictor (SDI) sets which have been adopted also show significant differences. We argue that this is mostly because many of these studies do not use a theoretical approach. We argue that the ‘capital approach’, which is used in the sustainability debate, is the most promising method to enhance international harmonization. Support is mounting in the scientific, policy and statistical communities for this approach in which economic capital, human capital, natural capital and social capital are distinguished. Many applications of this method express these capital stocks in monetary units (the ‘monetary capital approach’). This paper argues that the ‘hybrid capital approach’, in which the capital stocks can also be measured in non-monetary units, is probably more likely to achieve consensus over a large number of countries and institutes. Also a number of challenges remain for the capital approach. We argue that ideally the indicators should be based on satellite accounts of the national accounting framework. Also the capital approach could be further expanded to current welfare, progress of societies, inequality, and the international dimension of sustainability. We conclude that if the hybrid capital approach is adopted it may become easier to make consistent, theoretically sound and policy relevant comparisons between countries. 相似文献
42.
Smisterová J Wagenaar A Stuart MC Polushkin E ten Brinke G Hulst R Engberts JB Hoekstra D 《The Journal of biological chemistry》2001,276(50):47615-47622
Pyridinium amphiphiles, abbreviated as SAINT, are highly efficient vectors for delivery of DNA into cells. Within a group of structurally related compounds that differ in transfection capacity, we have investigated the role of the shape and structure of the pyridinium molecule on the stability of bilayers formed from a given SAINT and dioleoylphosphatidylethanolamine (DOPE) and on the polymorphism of SAINT/DOPE-DNA complexes. Using electron microscopy and small angle x-ray scattering, a relationship was established between the structure, stability, and morphology of the lipoplexes and their transfection efficiency. The structure with the lowest ratio of the cross-sectional area occupied by polar over hydrophobic domains (SAINT-2) formed the most unstable bilayers when mixed with DOPE and tended to convert into the hexagonal structure. In SAINT-2-containing lipoplexes, a hexagonal topology was apparent, provided that DOPE was present and complex assembly occurred in 150 mm NaCl. If not, a lamellar phase was obtained, as for lipoplexes prepared from geometrically more balanced SAINT structures. The hexagonal topology strongly promotes transfection efficiency, whereas a strongly reduced activity is seen for complexes displaying the lamellar topology. We conclude that in the DOPE-containing complexes the molecular shape and the nonbilayer preferences of the cationic lipid control the topology of the lipoplex and thereby the transfection efficiency. 相似文献
43.
Kingsolver JG Hoekstra HE Hoekstra JM Berrigan D Vignieri SN Hill CE Hoang A Gibert P Beerli P 《The American naturalist》2001,157(3):245-261
How strong is phenotypic selection on quantitative traits in the wild? We reviewed the literature from 1984 through 1997 for studies that estimated the strength of linear and quadratic selection in terms of standardized selection gradients or differentials on natural variation in quantitative traits for field populations. We tabulated 63 published studies of 62 species that reported over 2,500 estimates of linear or quadratic selection. More than 80% of the estimates were for morphological traits; there is very little data for behavioral or physiological traits. Most published selection studies were unreplicated and had sample sizes below 135 individuals, resulting in low statistical power to detect selection of the magnitude typically reported for natural populations. The absolute values of linear selection gradients |beta| were exponentially distributed with an overall median of 0.16, suggesting that strong directional selection was uncommon. The values of |beta| for selection on morphological and on life-history/phenological traits were significantly different: on average, selection on morphology was stronger than selection on phenology/life history. Similarly, the values of |beta| for selection via aspects of survival, fecundity, and mating success were significantly different: on average, selection on mating success was stronger than on survival. Comparisons of estimated linear selection gradients and differentials suggest that indirect components of phenotypic selection were usually modest relative to direct components. The absolute values of quadratic selection gradients |gamma| were exponentially distributed with an overall median of only 0.10, suggesting that quadratic selection is typically quite weak. The distribution of gamma values was symmetric about 0, providing no evidence that stabilizing selection is stronger or more common than disruptive selection in nature. 相似文献
44.
Otter-Nilsson M Hendriks R Pecheur-Huet EI Hoekstra D Nilsson T 《The EMBO journal》1999,18(8):2074-2083
Much recent work has focussed on the role of membrane-bound components in fusion. We show here that p97 and NSF are sufficient to mediate rapid membrane fusion. Fractionation of cytosol revealed that p97 and its co-factor, p47, constitutes the major fusion activity. This was confirmed by depleting p97 from the cytosol, which resulted in an 80% decrease in fusion. Using purified protein, p97 or NSF was found to be sufficient to mediate rapid fusion in an ATP-dependent manner. A regulatory role was observed for their corresponding co-factors, p47 and alpha-SNAP. When present at a molar ratio half of that of the ATPase, both co-factors increased fusion activity significantly. Intriguingly, at this ratio the ATPase activity of the complex measured in solution was at its lowest, suggesting that the co-factor stabilizes the ATP state. The fusion event involved mixing of both leaflets of the opposing membranes and contents of liposomes. We conclude from these data that p97, NSF and perhaps other related ATPases catalyse rapid and complete fusion between lipid bilayers on opposing membranes. This highlights a new role for p97 and NSF and prompts a re-evaluation of current fusion models. 相似文献
45.
Dyatkin AB Hoekstra WJ Kinney WA Kontoyianni M Santulli RJ Kimball ES Fisher MC Carolyn Fisher M Prouty SM Abraham WM de Garavilla L Andrade-Gordon P Hlasta DJ He W Hornby PJ Damiano BP Maryanoff BE 《Bioorganic & medicinal chemistry letters》2004,14(3):591-596
The design, synthesis, and biological activity of novel alpha(4)beta(1) and alpha(4)beta(7) integrin antagonists, containing a bridged azabicyclic nucleus, are reported. Conformational analysis of targets containing an azabicyclo[2.2.2]octane carboxylic acid and known integrin antagonists indicated that this azabicycle would be a suitable molecular scaffold. Variation of substituents on the pendant arylsulfonamide and phenylalanine groups resulted in potent alpha(4)beta(1)-selective and dual alpha(4)beta(1)/alpha(4)beta(7) antagonists. Potent compounds 11i, 11h, and 14 were effective in the antigen-sensitized sheep model of asthma. 相似文献
46.
Oncostatin M-stimulated apical plasma membrane biogenesis requires p27(Kip1)-regulated cell cycle dynamics 下载免费PDF全文
Van IJzendoorn SC Théard D Van Der Wouden JM Visser W Wojtal KA Hoekstra D 《Molecular biology of the cell》2004,15(9):4105-4114
Oncostatin M regulates membrane traffic and stimulates apicalization of the cell surface in hepatoma cells in a protein kinase A-dependent manner. Here, we show that oncostatin M enhances the expression of the cyclin-dependent kinase (cdk)2 inhibitor p27(Kip1), which inhibits G(1)-S phase progression. Forced G(1)-S-phase transition effectively renders presynchronized cells insensitive to the apicalization-stimulating effect of oncostatin M. G(1)-S-phase transition prevents oncostatin M-mediated recruitment of protein kinase A to the centrosomal region and precludes the oncostatin M-mediated activation of a protein kinase A-dependent transport route to the apical surface, which exits the subapical compartment (SAC). This transport route has previously been shown to be crucial for apical plasma membrane biogenesis. Together, our data indicate that oncostatin M-stimulated apicalization of the cell surface is critically dependent on the ability of oncostatin M to control p27(Kip1)/cdk2-mediated G(1)-S-phase progression and suggest that the regulation of apical plasma membrane-directed traffic from SAC is coupled to centrosome-associated signaling pathways. 相似文献
47.
Polarized membrane traffic and cell polarity development is dependent on dihydroceramide synthase-regulated sphinganine turnover 下载免费PDF全文
Van IJzendoorn SC Van Der Wouden JM Liebisch G Schmitz G Hoekstra D 《Molecular biology of the cell》2004,15(9):4115-4124
Sphingoid bases have been implicated in various cellular processes including cell growth, apoptosis and cell differentiation. Here, we show that the regulated turnover of sphingoid bases is crucial for cell polarity development, i.e., the biogenesis of apical plasma membrane domains, in well-differentiated hepatic cells. Thus, inhibition of dihydroceramide synthase or sphinganine kinase activity with fumonisin B1 or N,N-dimethylsphingosine, respectively, dramatically perturbs cell polarity development, which is due to increased levels of sphinganine. Consistently, reduction of free sphinganine levels stimulates cell polarity development. Moreover, dihydroceramide synthase, the predominant enzyme responsible for sphinganine turnover, is a target for cell polarity stimulating cAMP/protein kinase A (PKA) signaling cascades. Indeed, electrospray ionization tandem mass spectrometry analyses revealed a significant reduction in sphinganine levels in cAMP/PKA-stimulated cells. These data suggest that sphinganine turnover is critical for and is actively regulated during HepG2 cell polarity development. Previously, we have identified an apical plasma membrane-directed trafficking pathway from the subapical compartment. This transport pathway, which is part of the basolateral-to-apical transcytotic itinerary, plays a crucial role in apical plasma membrane biogenesis. Here, we show that, as a part of the underlying mechanism, the inhibition of dihydroceramide synthase activity and ensuing increased sphinganine levels specifically perturb the activation of this particular pathway in the de novo apical membrane biogenesis. 相似文献
48.
Identifying the genes responsible for adaptation has been an elusive goal in evolutionary biology. Rock pocket mice (Chaetodipus intermedius) provide a useful system for studying the genetics of adaptation: most C. intermedius are light-coloured and live on light-coloured rocks, but in several different geographical regions, C. intermedius are melanic and live on dark-coloured basalt lava, presumably as an adaptation for crypsis. Previous work demonstrated that mutations at the melanocortin-1 receptor gene (Mc1r) are responsible for the dark/light difference in mice from one population in Arizona. Here, we investigate whether melanism has evolved independently in populations of dark C. intermedius from New Mexico, and whether the same or different genes underlie the dark phenotype in mice from these populations compared with the dark mice from Arizona. Seventy-six mice were collected from pairs of dark and light localities representing four different lava flows and adjacent light-coloured rocks; lava flows were separated by 70-750 km. Spectrophotometric analysis of mouse pelage and of rock samples revealed a strong positive association between coat colour and substrate colour. No significant differences were observed in the colour of rocks among the four lava flows, suggesting that mice in these separate populations have experienced similar selection for crypsis. Despite this similarity in environment, melanic mice from the three New Mexico populations were slightly, but significantly, darker than melanic mice from Arizona. The entire Mc1r gene was sequenced in all mice. The previously identified mutations responsible for the light/dark difference in mice from Arizona were absent in all melanic mice from three different populations in New Mexico. Five new Mc1r polymorphisms were observed among mice from New Mexico, but none showed any association with coat colour. These results indicate that adaptive melanism has arisen at least twice in C. intermedius and that these similar phenotypic changes have a different genetic basis. 相似文献
49.
The Slc11a1 (Nramp1) gene controls efficacy of mycobacterial treatment of allergic asthma 总被引:2,自引:0,他引:2
Smit JJ Van Loveren H Hoekstra MO Karimi K Folkerts G Nijkamp FP 《Journal of immunology (Baltimore, Md. : 1950)》2003,171(2):754-760
Genes controlling antibacterial resistance may be important in the hygiene hypothesis, which states that lack of bacterial infections during childhood would favor development of allergic disease. We, therefore, studied whether Nramp1 (Slc11a1) alleles, which determine susceptibility (Nramp1(s)) or resistance (Nramp1(r)) to intracellular bacteria, affect the efficacy of heat-killed Mycobacterium vaccae in the treatment of allergic asthma in a mouse model. Treatment of OVA-sensitized Nramp1(s) mice with M. vaccae suppressed airway hyperresponsiveness, airway eosinophilia, Ag-specific IgE, and IL-4 and IL-5 production after OVA aerosol challenge. In contrast, M. vaccae hardly affected these parameters in Nramp1(r) mice. In addition, The Nramp1 gene affected both T cell-mediated responses to M. vaccae in vivo and the level of macrophage activation after stimulation with M. vaccae in vitro. In conclusion, the efficacy of M. vaccae in preventing allergic and asthmatic manifestations in a mouse model is strongly affected by Nramp1 alleles. These findings could have important implications for the future use of mycobacteria and their components in the prevention or treatment of allergic asthma. A new link is described between genes, the environment, and the development of allergy, in which the Nramp1 gene fine tunes the hygiene hypothesis. 相似文献
50.
In stony corals it is often observed that specimens collected from a sheltered growth site have more open and more thinly branched growth forms than specimens of the same species from more exposed growth sites, where stronger water currents are found. This observation was explained using an abiotic computational model inspired by coral growth, in which the growth velocity depended locally on the absorption of a resource dispersed by advection and diffusion (Kaandorp and Sloot, J. Theor. Biol 209 (2001) 257). In that model a morphological range was found; as the Péclet-number (indicating the relative importance of advective and diffusive nutrient transport) was increased, more compact and spherical growth forms were found. Two unsatisfactory items have remained in this model, which we address in the present paper. First, an explicit curvature rule was responsible for branching. In this work we show that the curvature rule is not needed: the model exhibits spontaneous branching, provided that the resource field is computed with enough precision. Second, previously no explanation was given for the morphological range found in the simulations. Here we show that such an explanation is given by the conditions under which spontaneous branching occurs in our model, in which the compactness of the growth forms depends on the ratio of the rates of growth and nutrient transport. We did not find an effect of flow. This suggests that the computational evidence that hydrodynamics influences the compactness of corals in laminar flows may not be conclusive. The applicability of the Laplacian growth paradigm to understand coral growth is discussed. 相似文献