This study investigates the environmental and economic impacts of the Kyoto Protocol on Annex I parties through an impact assessment by combining the propensity score matching and the difference-in-difference methods. We establish a country-level panel data set including CO₂ emissions, gross domestic product (GDP), and other socioeconomic data for 1997–2008 and 2005–2008. Based on the impact evaluation, we conduct the simulation predicting the impacts of the Protocol to capture the differences of marginal damage cost of carbon emissions between the actual and counterfactual situations. The results suggest that participating as an Annex I party has a significant positive impact on CO₂ emission reductions, but a negative impact on the GDP of the participants in the long run. The predicted marginal benefit of the Protocol based on the marginal damage cost of carbon emissions shows that the marginal benefit of emission reductions mitigates a limited portion of the GDP loss. Future global climate change frameworks should focus on balancing the impact on economic and environmental performance in order to ensure sustainable development, especially for developing countries that have low capacity to mitigate emissions.

KIF1A is a brain-specific anterograde motor protein that transports cargoes towards the plus-ends of microtubules. Many variants of the KIF1A gene have been associated with neurodegenerative diseases and developmental delay. Homozygous mutations of KIF1A have been identified in a recessive subtype of hereditary spastic paraplegia (HSP), SPG30. In addition, KIF1A mutations have been found in pure HSP with autosomal dominant inheritance. Here we report the first case of familial complicated HSP with a KIF1A mutation transmitted in autosomal dominant inheritance. A heterozygous p.T258M mutation in KIF1A was found in a Korean family through targeted exome sequencing. They displayed phenotypes of mild intellectual disability with language delay, epilepsy, optic nerve atrophy, thinning of corpus callosum, periventricular white matter lesion, and microcephaly. A structural modeling revealed that the p.T258M mutation disrupted the binding of KIF1A motor domain to microtubules and its movement along microtubules. Assays of peripheral accumulation and proximal distribution of KIF1A motor indicated that the KIF1A motor domain with p.T258M mutation has reduced motor activity and exerts a dominant negative effect on wild-type KIF1A. These results suggest that the p.T258M mutation suppresses KIF1A motor activity and induces complicated HSP accompanying intellectual disability transmitted in autosomal dominant inheritance.

Background/Aims: This study aimed to clarify the frequency, phenotypes, and molecular spectrum of DUOX2, TPO, TSHR, and TG mutations in patients with congenital hypothyroidism (CH) with enlarged or normal-sized eutopic thyroid glands. Methods: The study cohort included 43 subjects from 41 unrelated families who had CH with eutopic thyroid glands. Mutation analyses of DUOX2, TPO, and TSHR were performed. The functional capacities of novel missense variants of DUOX2 were verified by measuring H2O2 generation in vitro. Results: Of the 43 subjects, 23 (53.5%) had sequence variants in at least one gene. Twelve different DUOX2 variants, including seven novel variants, were identified in 20 subjects. A functional analysis of the DUOX2 variants revealed that most variants, other than p.G206V and p.H678R, caused a significant reduction in H2O2 generation. Therefore, 15 subjects harbored functionally deleterious DUOX2 variants. Of these, 5 subjects had transient CH, and 10 were found to have permanent CH. Sequence variants in TSHR were identified in 5 subjects. One of the 43 subjects (2.3%) had sequence variants in two different genes. Conclusions:DUOX2 variants are a relatively common cause of CH with normal-sized or enlarged eutopic thyroid glands. Variable phenotypes were associated with partial loss of the functional activity of DUOX2 variants.