Born to be green: new insights into the economics and management of green entrepreneurship

While the number of green start-ups has steadily increased around the world in response to the environmental problems demanding immediate solutions, there are several unresolved questions on the behaviour and performance of such ventures. The papers in this special issue shed light on these issues by underscoring the role of several factors, such as industry life cycles, knowledge spillovers, institutions, and availability of external finance, in shaping decision-making and firm behaviour in green start-ups. This paper highlights the state-of-the art developments in the literature, discusses the key contributions of the papers put together in this special issue and presents a future research agenda for scholars interested in green entrepreneurship

Citizens Show Strong Support for Climate Policy, But Are They Also Willing to Pay?

To what extent citizens are willing not only to support ambitious climate policy, but also willing to pay for such policy remains subject to debate. Our analysis addresses three issues in this regard: whether, as is widely assumed but not empirically established, willingness to support (WTS) is higher than willingness to pay (WTP); whether the determinants of the two are similar; and what accounts for within-subject similarity between WTS and WTP. We address these issues based on data from an original nationally representative survey (N=2500) on forest conservation in Brazil, arguably the key climate policy issue in the country. The findings reveal that WTP is much lower than WTS. The determinants differ to some extent as well; regarding the effects of age, gender, and trust in government. The analysis also provides insights into factors influencing how much WTS and WTP line up within individuals, with respect to age, education, political ideology, salience of the deforestation issue, and trust in government. Our findings provide a more nuanced picture of how strong public support for climate change policy is, and a starting point for more targeted climate policy communication

Protein destabilization and loss of protein‐protein interaction are fundamental mechanisms in cblA

Mutations in the human MMAA gene cause the metabolic disorder cblA-type methylmalonic aciduria (MMA), although knowledge of the mechanism of dysfunction remains lacking. MMAA regulates the incorporation of the cofactor adenosylcobalamin, generated from the MMAB adenosyltransferase, into the destination enzyme methylmalonyl-CoA mutase (MUT). This function of MMAA depends on its GTPase activity, which is stimulated by an interaction with MUT. Here, we present 67 new patients with cblA-type MMA, identifying 19 novel mutations. We investigated biochemically how 22 patient missense mutations in MMAA lead to disease. About a third confer instability to the recombinant protein in bacterial and human expression systems. All 15 purified mutant proteins demonstrated wild-type like intrinsic GTPase activity and only one (p.Asp292Val), where the mutation is in the GTP binding domain, revealed decreased GTP binding. However, all mutations strongly decreased functional association with MUT by reducing GTPase activity stimulation upon incubation with MUT, while 9 mutant proteins additionally lost the ability to physically bind MUT. Finally, all mutations interfered with gating the transfer of adenosylcobalamin from MMAB to MUT. This work suggests loss of functional interaction between MMAA and MUT as a disease causing mechanism that impacts processing and assembly of a cofactor to its destination enzyme. This article is protected by copyright. All rights reserved

Protein destabilization and loss of protein-protein interaction are fundamental mechanisms in cblA-type methylmalonic aciduria

Mutations in the human MMAA gene cause the metabolic disorder cblA-type methylmalonic aciduria (MMA), although knowledge of the mechanism of dysfunction remains lacking. MMAA regulates the incorporation of the cofactor adenosylcobalamin, generated from the MMAB adenosyltransferase, into the destination enzyme methylmalonyl-CoA mutase (MUT). This function of MMAA depends on its GTPase activity, which is stimulated by an interaction with MUT. Here, we present 67 new patients with cblA-type MMA, identifying 19 novel mutations. We investigated biochemically how 22 patient missense mutations in MMAA lead to disease. About a third confer instability to the recombinant protein in bacterial and human expression systems. All 15 purified mutant proteins demonstrated wild-type like intrinsic GTPase activity and only one (p.Asp292Val), where the mutation is in the GTP binding domain, revealed decreased GTP binding. However, all mutations strongly decreased functional association with MUT by reducing GTPase activity stimulation upon incubation with MUT, while 9 mutant proteins additionally lost the ability to physically bind MUT. Finally, all mutations interfered with gating the transfer of adenosylcobalamin from MMAB to MUT. This work suggests loss of functional interaction between MMAA and MUT as a disease causing mechanism that impacts processing and assembly of a cofactor to its destination enzyme. This article is protected by copyright. All rights reserved

Protein destabilization and loss of protein-protein interaction are fundamental mechanisms in cblA-type methylmalonic aciduria

Mutations in the human MMAA gene cause the metabolic disorder cblA-type methylmalonic aciduria (MMA), although knowledge of the mechanism of dysfunction remains lacking. MMAA regulates the incorporation of the cofactor adenosylcobalamin, generated from the MMAB adenosyltransferase, into the destination enzyme methylmalonyl-CoA mutase (MUT). This function of MMAA depends on its GTPase activity, which is stimulated by an interaction with MUT. Here, we present 67 new patients with cblA-type MMA, identifying 19 novel mutations. We investigated biochemically how 22 patient missense mutations in MMAA lead to disease. About a third confer instability to the recombinant protein in bacterial and human expression systems. All 15 purified mutant proteins demonstrated wild-type like intrinsic GTPase activity and only one (p.Asp292Val), where the mutation is in the GTP binding domain, revealed decreased GTP binding. However, all mutations strongly decreased functional association with MUT by reducing GTPase activity stimulation upon incubation with MUT, while 9 mutant proteins additionally lost the ability to physically bind MUT. Finally, all mutations interfered with gating the transfer of adenosylcobalamin from MMAB to MUT. This work suggests loss of functional interaction between MMAA and MUT as a disease causing mechanism that impacts processing and assembly of a cofactor to its destination enzyme. This article is protected by copyright. All rights reserved

Assessment of the current thermal performance level of the Swiss residential building stock ::statistical analysis of energy performance certificates

The reduction of energy consumption in the existing building stock is a crucial element of the Swiss Energy Strategy 2050 in view of the fact that the built environment accounts for more than 44% of the final energy use in Switzerland. It is therefore necessary to characterise the Swiss building stock and in particular the residential sector at an appropriate degree of detail, distinguishing between various types of buildings (archetypes) and building elements in order to identify the untapped potential for energy retrofit. In this paper, the current thermal performance and retrofit state of the Swiss residential building stock is examined based on approximately 10,400 Cantonal Building Energy Certificates issued for individual buildings across the country. The statistical analysis of the certificates allows to estimate a thermal performance level of archetype buildings and their respective building elements as well as of the heating systems. For this purpose, we develop a method allowing to obtain typical U-Values for original and retrofitted buildings from the total U-Value distributions. Our results indicate that approximately 75% of all building elements do not yet reach the thermal performance of buildings constructed in the last 15 years. In order to reach current low-energy building standards (MINERGIE P), the U-Values of building elements constructed prior to 1990 would have to be reduced by a factor of three to more than six, from 0.5–1 W/(m²K) to 0.15 W/(m²K); windows would require an improvement by at least a factor of two, from 2.5–2 to 0.9 W/(m²K). With regard to heat supply, 50% of the surface area is still heated by inefficient and CO2-intensive oil-fired boilers. The results of this study hence confirm the high potential for thermal retrofit in the Swiss residential building stock

A single mutation in MCCC1 or MCCC2 as a potential cause of positive screening for 3-methylcrotonyl-CoA carboxylase deficiency

Isolated 3-Methylcrotonyl-CoA carboxylase deficiency (MCC deficiency) is an organic aciduria presenting with a highly variable phenotype and has been part of newborn screening programs in various countries, in particular in the US. Here we present enzymatic and genetic characterisation of 22 individuals with increased 3-hydroxyisovalerylcarnitine and/or 3-methylcrotonylglycine suggesting MCC deficiency, but only partially reduced 3-methylcrotonyl-CoA carboxylase activity. Among these, 21 carried a single mutant allele in either MCCC1 (n=20) or MCCC2 (n=1). Our results suggest that heterozygosity for such a single deleterious mutation may lead to misdiagnosis of MCC deficiency

Genetic, structural, and functional analysis of pathogenic variations causing methylmalonyl-CoA epimerase deficiency

Human methylmalonyl-CoA epimerase (MCEE) catalyzes the interconversion of d-methylmalonyl-CoA and l-methylmalonyl-CoA in propionate catabolism. Autosomal recessive pathogenic variations in MCEE reportedly cause methylmalonic aciduria (MMAuria) in eleven patients. We investigated a cohort of 150 individuals suffering from MMAuria of unknown origin, identifying ten new patients with pathogenic variations in MCEE. Nine patients were homozygous for the known nonsense variation p.Arg47* (c.139C > T), and one for the novel missense variation p.Ile53Arg (c.158T > G). To understand better the molecular basis of MCEE deficiency, we mapped p.Ile53Arg, and two previously described pathogenic variations p.Lys60Gln and p.Arg143Cys, onto our 1.8 Å structure of wild-type (wt) human MCEE. This revealed potential dimeric assembly disruption by p.Ile53Arg, but no clear defects from p.Lys60Gln or p.Arg143Cys. We solved the structure of MCEE-Arg143Cys to 1.9 Å and found significant disruption of two important loop structures, potentially impacting surface features as well as the active-site pocket. Functional analysis of MCEE-Ile53Arg expressed in a bacterial recombinant system as well as patient-derived fibroblasts revealed nearly undetectable soluble protein levels, defective globular protein behavior, and using a newly developed assay, lack of enzymatic activity - consistent with misfolded protein. By contrast, soluble protein levels, unfolding characteristics and activity of MCEE-Lys60Gln were comparable to wt, leaving unclear how this variation may cause disease. MCEE-Arg143Cys was detectable at comparable levels to wt MCEE, but had slightly altered unfolding kinetics and greatly reduced activity. These studies reveal ten new patients with MCEE deficiency and rationalize misfolding and loss of activity as molecular defects in MCEE-type MMAuria

Genetic, structural, and functional analysis of pathogenic variations causing methylmalonyl-CoA epimerase deficiency

Human methylmalonyl-CoA epimerase (MCEE) catalyzes the interconversion of d-methylmalonyl-CoA and l-methylmalonyl-CoA in propionate catabolism. Autosomal recessive pathogenic variations in MCEE reportedly cause methylmalonic aciduria (MMAuria) in eleven patients. We investigated a cohort of 150 individuals suffering from MMAuria of unknown origin, identifying ten new patients with pathogenic variations in MCEE. Nine patients were homozygous for the known nonsense variation p.Arg47* (c.139C > T), and one for the novel missense variation p.Ile53Arg (c.158T > G). To understand better the molecular basis of MCEE deficiency, we mapped p.Ile53Arg, and two previously described pathogenic variations p.Lys60Gln and p.Arg143Cys, onto our 1.8 Å structure of wild-type (wt) human MCEE. This revealed potential dimeric assembly disruption by p.Ile53Arg, but no clear defects from p.Lys60Gln or p.Arg143Cys. We solved the structure of MCEE-Arg143Cys to 1.9 Å and found significant disruption of two important loop structures, potentially impacting surface features as well as the active-site pocket. Functional analysis of MCEE-Ile53Arg expressed in a bacterial recombinant system as well as patient-derived fibroblasts revealed nearly undetectable soluble protein levels, defective globular protein behavior, and using a newly developed assay, lack of enzymatic activity - consistent with misfolded protein. By contrast, soluble protein levels, unfolding characteristics and activity of MCEE-Lys60Gln were comparable to wt, leaving unclear how this variation may cause disease. MCEE-Arg143Cys was detectable at comparable levels to wt MCEE, but had slightly altered unfolding kinetics and greatly reduced activity. These studies reveal ten new patients with MCEE deficiency and rationalize misfolding and loss of activity as molecular defects in MCEE-type MMAuria