144 research outputs found
How are Green National Accounts Produced in Practice?
No full textDuring the last part of the twentieth century, the effect of human activity upon the environment became an important policy issue. There is now a growing concern about how economic activity affects the environment and it has become more and more recognised that economic growth is dependent upon the provision of environ-mental services. To be able to combine economic growth with a healthy environment in terms of a sustainable use of natural resources, a better understanding of the rela-tionships between economy and ecology needs to be developed.
Costs of Climate Policy when Pollution Affects Health and Labour Productivity. A general Equilibrium Analysis Applied to Sweden
No full textMuch of the debate over global climate change involves estimates of the direct costs of global climate change mitigation. Recently this debate has included the issue of ancillary benefits. These benefits consist mainly of health improvements. Although it is generally acknowledged that air pollution affects respiratory health, and that valuations of these impacts make up a significant proportion of the damage costs of air pollution, these impacts are often neglected when evaluating the costs of climate policy. Since reducing greenhouse gases has the effect of also reducing other pollutants affecting human health and labour productivity these effects should be taken into consideration. The analysis incorporates a linkage between air pollution and health effects into a general equilibrium model for Sweden through a theoretical consistent framework. Results from recent Swedish concentration-response and contingent valuation studies are used to model direct disutility and indirect health effects that negatively affects the productivity of labour. The costs of feedback effects on health and productivity are compared in three different scenarios for attaining the Swedish carbon dioxide target with alternative projected emission levels in the baseline scenario as well as alternative harmful emission levels. Results show that not including feedback effects could mean overstating the costs of climate policy. The magnitude of these effects are, however, very sensitive to projected emission levels and to the judgement of harmful emission levels.air pollution; ancillary benefits; climate policy; general equilibrium; health
Does remediation save lives? On the cost of cleaning up arsenic-contaminated sites in Sweden
No full textSwedish environmental policy is based on 16 environmental quality objectives (Gov. Bill 2000/01:130 and Gov.Bill 2004/05:150).1 One of the most challenging objectives,‘A non toxic environment’, has two interim targets that concern remediation of contaminated sites. In sum, they state that the highest priority should be given to sites posing the highest risks to human health and the environment.2 By eliminating pollutants in soil, groundwater and sediment, the interim targets aim to reduce risks to human health and the environment. In Sweden, 83,000 sites are potentially contaminated due to previous industrial activities. According to the Swedish Environmental Protection Agency (EPA), the administrator of the governmental funds for remediation, approximately 1500 of these sites contain contaminant concentrations that could seriously harm human health and the environment (Swedish EPA, 2008a). To reach the interim targets, all these sites need to be remediated by 2050. Remediation of contaminated sites has so far cost more than SEK 3,000 million.3 The approximated cost to mitigate the potential risks at the most harmful sites is estimated at SEK 60,000 million.4 The Swedish government’s funding for remediation presently comes in the form of a directed grant (sakanslag). The directed grant, administrated by the Swedish EPA, subsidises remediation of contaminated sites that were contaminated prior to modern environmental legislation (in 1969) or for which no liable party can be found. The directed grant amounts to approximately 455 millions annually, which corresponds to about 10 percent of the annual national funds for environmental protection (Gov. Bill 2007/08:1). To make it possible to prioritise among contaminated sites, the Swedish EPA has developed a method for risk assessment called the ‘MIFO’ (i.e. the Method for Inventory of Contaminated Sites). The risk assessment does not take into account the actual exposure at a contaminated site. Risk is instead assessed based on divergence from guideline values for acceptable concentrations given a standardised (i.e. worst case) exposure situation on an individual level. This means that a site can be remediated without any individuals actually being exposed. The expected risk reduction is consequently not quantified. This eliminates the possibility of valuing the risk reduction, which should be weighed against the remediation cost. The purpose of this paper is to analyse how health effects, in the form of cancer risks, from sites contaminated by arsenic are valued implicitly in remediation. By using an environmental medicine approach that takes exposure into account, and without underestimating the potential health consequences of arsenic exposure, our purpose is to place arsenic risk management in the overall picture of live-saving interventions. In the case of cancer prevention, it is necessary to recognise that focus on an environmental carcinogen like arsenic may draw public attention – and funding – away from mental health risks like ambient air pollution and indoor radon. Although environmental pollution accounts for less than ten percent of all cancer cases (Harvard Centre for Cancer Prevention, 1996; Saracci and Vineis, 2007), environmental factors are important to recognize since they may be preventable. We emphasise, however, the inefficiency in becoming overly concerned about small risks while, at the same time, losing sight of the large risks. If society’s spending on lifesaving measures with small effects (i.e. a small number of lives saved) crowds out spending on lifesaving measures with large effects, then remediation can, in fact, even be said to waste lives. By using data on 23 arsenic-contaminated sites in Sweden, we estimate the sitespecific cancer risks and calculate the cost per life saved by using the sites’ remediation costs. Our results show that the cost per life saved through remediation is much higher than that associated with other primary prevention measures, indicating that the ambition level of Swedish remediation may be too high.
Helix pomatia Lectin, an inducer of Drosophila immune response, binds to Hemomucin, a novel surface Mucin
No full textWe describe the isolation and initial characterization of hemomucin, a novel Drosophila surface mucin that is likely to be involved in the induction of antibacterial effector molecules after binding a snail lectin (Helix pomatia A hemagglutinin). Two proteins of 100 and 220 kDa were purified from the membrane fraction of a Drosophila blood cell line using lectin columns. The two proteins are products of the same gene, as demonstrated by peptide sequencing. The corresponding cDNAs code for a product that contains an amino-terminal putative transmembrane domain, a domain related to the plant enzyme strictosidine synthase, and a mucin-like domain in the carboxyl-terminal part of the protein. The gene is expressed throughout development. In adult flies, high expression is found in hemocytes, in specialized regions of the gut, and in the ovary, where the protein is deposited onto the egg surface. In the gut, the mucin co-localizes with the peritrophic membrane. The cytogenetic location of the gene is on the third chromosome in the region 97F-98A.Ulrich Theopold, Christos Samakovlis, Hediye Erdjument-Bromage, Natalie Dillon, Bernt Axelsson, Otto Schmidt, Paul Tempst, and Dan Hultmar
BHLHE40 positively regulates the differentiation of human airway basal cells
No full textAirway basal cells are multipotent stem cell progenitors, which are crucial to maintaining the pseudostratified epithelium. Understanding the molecular mechanisms that regulate their differentiation is essential to unravel how normal and pathological airway epithelial regeneration occurs. With this aim, we performed single-cell RNA sequencing and pseudotime analysis of primary human bronchial epithelial cells (pHBECs) differentiated on air-liquid-interface (ALI) culture, revealing a selective upregulation of the transcription factor BHLHE40 in differentiating intermediate epithelial cells. Using our ALI cultures in combination with lentiviral-based gene transfer, we show that the overexpression of BHLHE40 in human basal cells increased their differentiation into club, goblet, and ciliated cells. Consistent with the overexpression results, the knockdown of BHLHE40 in the ALI cultures reduced basal epithelial cell differentiation. Interestingly, we demonstrate that BHLHE40-mediated loss of basal cell fate through increased differentiation was preceded earlier in the culture by an increase in Notch signaling on day 5. Previous studies have shown that Notch1 signaling activation in basal cells of the murine airway epithelium is associated with the downregulation of basal cell genes and upregulation of luminal differentiation markers. Furthermore, N1ICD overexpression in primary epithelial cells from the human mammary epithelium reduced TP63 expression. Taken together, we propose that BHLHE40-induced loss of basal cells and transition to an intermediate state involves Notch signaling.
To investigate the molecular mechanisms of BHLHE40-induced basal-to-intermediate cell transition and identify its direct transcriptional targets involved in Notch signaling activation driving this transition, we did a 3-step selection by performing a comparative analysis of three datasets: the data from the published BHLHE40 A549 ChIP-sequencing, our differentially expressed transcription factors in the differentiation trajectory of the Submucosal glands (SMGs)-like basal cells toward secretory cells, and our Real-Time qPCR analysis of transduced A549 cells overexpressing GFP or BHLHE40-GFP. We ended up with 8 potential BHLHE40 targets: FOS, HIF1a, MYC, HMGA2, BNC1, ZFP36L1, FOSL1, and SOX9. To confirm that they are transcriptional targets of BHLHE40 in our pHBECs-derived ALI culture, we used CUT&RUN DNA enrichment combined with gene expression analysis of transduced cells overexpressing BHLHE40-GFP from ALI day 14. We show that, although BHLHE40 has bound to HIF1a, BNC1, FOSL1, MYC, HMGA2, and ZFP36L1 genomic regions, it only repressed BNC1 gene expression without affecting the other targets. Consistently, we show that BHLHE40 overexpression reduced the number of BNC1- expressing cells in the basal layer and that BNC1 expression was exclusive to basal cells, further confirming BHLHE40-mediated transcriptional repression of BNC1 in basal cells.
Previous studies showed that BNC1 has a selectively high expression in basal cells of the skin epithelium, which goes down in the Suprabasal and differentiated layers. Consistently, its reduction was associated with the appearance of keratinocytes differentiation marker, suggesting its role in maintaining the undifferentiated basal cell state. In line with our results, we show a correlation between the downregulation of BNC1, the reduction of basal cell markers, and the increase in epithelial cell differentiation following BHLHE40 overexpression on day 14. Taken together, our data indicate that BHLHE40 transcriptionally represses BNC1 expression, which in turn induces the loss of basal cells and their differentiation. We hypothesized that BNC1 is the solely transcriptional target of BHLHE40 that is needed to maintain the undifferentiated basal cell state by negatively regulating Notch signaling in basal cells (e.g., by activating Notch inhibitor). Bulk RNA sequencing of sorted BHLHE40-GFP cells from ALI day 14 identified LFNG, a basal cell-specific Notch inhibitor, as a potential downstream target of BNC1, as its expression decreased following BHLHE40 overexpression. However, it remains unclear whether LFNG or other mediators contribute to the BHLHE40-BNC1-induced transition from basal to intermediate cells.
Additionally, since TP63 expression is regulated by multiple signaling pathways in addition to Notch signaling, further investigation is needed to deepen our understanding of the molecular mechanisms driving BHLHE40-BNC1-mediated loss of TP63+ basal cells, focusing on identifying BNC1 downstream targets, which our findings suggest as a promising starting point for future studies. This will determine how BNC1 maintains TP63 expression in the human airway epithelium and whether Notch signaling is solely involved in BHLHE40-mediated regulation of basal cell differentiation.
Considering our pHBECs-derived ALI culture as a re-generation model, our data suggest a potential of BHLHE40 to enhance the regeneration of the human airway epithelium upon airway injury through increasing differentiation. Also, our single-cell RNA sequencing and pseudotime analysis of differentiating ALI culture suggested the involvement of BHLHE40 in the SMGs-like basal cell differentiation trajectory towards secretory cells. Since basal cells of the SMGs have been shown to contribute to the surface airway epithelium (SAE) regeneration upon injury, we propose a potential role of BHLHE40 in enhancing regeneration via increasing differentiation of basal progenitor cells, both in the SAE and the SMGs. Collectively, we propose that BHLHE40 could serve as a target for therapeutic strategies aimed at enhancing tissue repair and regeneration in the airway epithelium
Author response
No full textDevelopmental potentials of cells are tightly controlled at multiple levels. The embryonic Drosophila airway tree is roughly subdivided into two types of cells with distinct developmental potentials: a proximally located group of multipotent adult precursor cells (P-fate) and a distally located population of more differentiated cells (D-fate). We show that the GATA-family transcription factor (TF) Grain promotes the P-fate and the POU-homeobox TF Ventral veinless (Vvl/Drifter/U-turned) stimulates the D-fate. Hedgehog and receptor tyrosine kinase (RTK) signaling cooperate with Vvl to drive the D-fate at the expense of the P-fate while negative regulators of either of these signaling pathways ensure P-fate specification. Local concentrations of Decapentaplegic/BMP, Wingless/Wnt, and Hedgehog signals differentially regulate the expression of D-factors and P-factors to transform an equipotent primordial field into a concentric pattern of radially different morphogenetic potentials, which gradually gives rise to the distal-proximal organization of distinct cell types in the mature airway.</p
Green Accounting, Air Pollution and Health
No full textHuman capital is an important component of economic growth. The article extends a theoretical model for comprehensive national accounting to the welfare effects of pollution on human capital. The model includes a production externality in the form of a flow of air pollutants that cause both direct disutility and indirect welfare effects by negatively affecting the productivity of labor. We show that defensive medical expenditures or healthcare costs allocated to mitigating the disutility of air pollution should not be deducted from conventional net national product (NNP), whereas the value of the percieved disutility of illness episodes caused by pollution should be subtracted from NNP. We derive a marginal cost-benefit rule for an optimal level of pollution given its negative health effects. The rule can be used for determining an optimal tax on harmful emissions. Finally, we outline a scheme for empirical comprehensive accounting and for estimation of an emissions tax.
Regulation of the Drosophila hypoxia-inducible factor alpha Sima by CRM1-dependent nuclear export
No full textHypoxia-inducible factor alpha (HIF-alpha) proteins are regulated by oxygen levels through several different mechanisms that include protein stability, transcriptional coactivator recruitment, and subcellular localization. It was previously reported that these transcription factors are mainly nuclear in hypoxia and cytoplasmic in normoxia, but so far the molecular basis of this regulation is unclear. We show here that the Drosophila melanogaster HIF-alpha protein Sima shuttles continuously between the nucleus and the cytoplasm. We identified the relevant nuclear localization signal and two functional nuclear export signals (NESs). These NESs are in the Sima basic helix-loop-helix (bHLH) domain and promote CRM1-dependent nuclear export. Site-directed mutagenesis of either NES provoked Sima nuclear retention and increased transcriptional activity, suggesting that nuclear export contributes to Sima regulation. The identified NESs are conserved and probably functional in the bHLH domains of several bHLH-PAS proteins. We propose that rapid nuclear export of Sima regulates the duration of cellular responses to hypoxia.Fil: Romero, Nuria Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Irisarri, Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Roth, Peggy. Stockholms Universitet; SueciaFil: Cauerhff, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Samakovlis, Christos. Stockholms Universitet; SueciaFil: Wappner, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentin
Future Waste Scenarios for Sweden based on a CGE-model
No full textOver the last decades, waste quantities have grown steadily in close relation to economic growth. To tackle the problem of continuing waste growth within the EU, waste prevention was listed among four top priorities in the EU Sixth environment Action Programme. A Computable General Equilibrium (CGE) model is here used for projecting future quantities of hazardous and non-hazardous waste in Sweden to 2030. The effects of driving forces behind waste generation are illustrated by comparing the results of waste projections for a Baseline scenario and four alternative scenarios. The scenarios differ mainly in GDP growth rates and in the assumptions about future waste intensities of the economic activities of firms and households. We use a high-resolution data set on waste flows of 18 various types of non-hazardous waste and 16 various types of hazardous waste attributed to six waste-generating sources for the base year 2006. Waste generated in the scenarios, thus, relate to firms’ material input, output, employees, capital scrapping and fuel combustion as well as households’ consumption. The impact of economic growth in increasing the generation of nonhazardous and hazardous waste is apparent when comparing the growth of waste from 2006 to 2030 in the five scenarios. On the contrary, technological change resulting in less waste intensive production processes and changed behaviour among households, making their activities less waste intensive, have a strong reducing effect, especially on generation of non-hazardous waste relating to firms’ material input.general equilibrium model; waste generation; decoupling; waste intensities waste scenarios.
- …
