Sex Differences in the Risk of Coronary Heart Disease Associated With Type 2 Diabetes: A Mendelian Randomization Analysis

OBJECTIVE: Observational studies have demonstrated that type 2 diabetes is a stronger risk factor for coronary heart disease (CHD) in women compared with men. However, it is not clear whether this reflects a sex differential in the causal effect of diabetes on CHD risk or results from sex-specific residual confounding. RESEARCH DESIGN AND METHODS: Using 270 single nucleotide polymorphisms (SNPs) for type 2 diabetes identified in a type 2 diabetes genome-wide association study, we performed a sex-stratified Mendelian randomization (MR) study of type 2 diabetes and CHD using individual participant data in UK Biobank (251,420 women and 212,049 men). Weighted median, MR-Egger, MR-pleiotropy residual sum and outlier, and radial MR from summary-level analyses were used for pleiotropy assessment. RESULTS: MR analyses showed that genetic risk of type 2 diabetes increased the odds of CHD for women (odds ratio 1.13 [95% CI 1.08–1.18] per 1-log unit increase in odds of type 2 diabetes) and men (1.21 [1.17–1.26] per 1-log unit increase in odds of type 2 diabetes). Sensitivity analyses showed some evidence of directional pleiotropy; however, results were similar after correction for outlier SNPs. CONCLUSIONS: This MR analysis supports a causal effect of genetic liability to type 2 diabetes on risk of CHD that is not stronger for women than men. Assuming a lack of bias, these findings suggest that the prevention and management of type 2 diabetes for CHD risk reduction is of equal priority in both sexes

Consumption-based emission accounting for Chinese cities

Most of China’s CO2 emissions are related to energy consumption in its cities. Thus, cities are critical for implementing China’s carbon emissions mitigation policies. In this study, we employ an input-output model to calculate consumption-based CO2 emissions for thirteen Chinese cities and find substantial differences between production- and consumption-based accounting in terms of both overall and per capita carbon emissions. Urban consumption not only leads to carbon emissions within a city’s own boundaries but also induces emissions in other regions via interregional trade. In megacities such as Shanghai, Beijing and Tianjin, approximately 70% of consumption-based emissions are imported from other regions. Annual per capita consumption-based emissions in the three megacities are 14, 12 and 10 tonnes of CO2 per person, respectively. Some medium-sized cities, such as Shenyang, Dalian and Ningbo, exhibit per capita emissions that resemble those in Tianjin. From the perspective of final use, capital formation is the largest contributor to consumption-based emissions at 32–65%. All thirteen cities are categorized by their trading patterns: five are production-based cities in which production-based emissions exceed consumption-based emissions, whereas eight are consumption-based cities, with the opposite emissions pattern. Moreover, production-based cities tend to become consumption-based as they undergo socioeconomic development

Temporal change in India’s imbalance of carbon emissions embodied in international trade

In India, rapid industrialization and reorganization of the global supply chain are driving economic growth, accompanied by increasing exports and carbon emissions. India is poised to succeed China as the next world manufactory, which will lead to huge emissions in the country. To formulate appropriate emission mitigation measures, it is necessary to further understand the temporal change in India’s emissions at the sectoral level from both the production and consumption perspectives. However, existing studies that have estimated emissions in India have paid less attention to the link among original emitters, final producers and final consumers and to its temporal change. Based on an emission inventory compiled in this study, we trace emission flows from original emitters to final producers and then to final consumers through the international supply chain by using an environmentally extended multi-regional input-output model. This study finds that both production-based and consumption-based emissions in India increased constantly from 2000 to 2014, and production-based emissions had higher growth rates due to the increased coal share. The major receivers of India’s exported emissions were developed countries (e.g., the European Union and the United States), while the main sources of India’s imported emissions were developing countries (e.g., China and Russia). From 2011 to 2014, India’s net exported emissions increased by 29.2% because of the decrease of imported emissions. Moreover, intermediate products (63% and 73.7%) were the major contributors to exported and imported emissions, most of which were embodied in manufacturing products (48.8% and 65.7%, respectively). Therefore, international cooperation to optimize the energy and trade structure and to improve energy efficiency can be effective in mitigating carbon emissions in India

Inferring the Tree of Life: chopping a phylogenomic problem down to size?

The combination of molecular sequence data and bioinformatics has revolutionized phylogenetic inference over the past decade, vastly increasing the scope of the evolutionary trees that we are able to infer. A recent paper in BMC Biology describing a new phylogenomic pipeline to help automate the inference of evolutionary trees from public sequence databases provides another important tool in our efforts to derive the Tree of Life

Efficacy, pharmacokinetic and pharmacodynamic evaluation of Apaziquone in the treatment of non- muscle invasive bladder cancer

Introduction: Apaziquone (also known as EO9 and Qapzola) is a prodrug that is activated to DNA damaging species by oxidoreductases (particularly NQO1) and has the ability to kill aerobic and/or hypoxic cancer cells. Areas covered: Whilst its poor pharmacokinetic properties contributed to its failure in phase II clinical trials when administered intravenously, these properties were ideal for loco-regional therapies. Apaziquone demonstrated good anti-cancer activity against non-muscle invasive bladder cancer (NMIBC) when administered intravesically to marker lesions and was well tolerated with no systemic side effects. However, phase III clinical trials did not reach statistical significance for the primary endpoint of 2-year recurrence in apaziquone over placebo although improvements were observed. Post-hoc analysis of the combined study data did indicate a significant benefit for patients treated with apaziquone, especially when the instillation of apaziquone was given 30 minutes or more after surgery. A further phase III study is ongoing to test the hypotheses generated in the unsuccessful phase III studies conducted to date. Expert opinion: Because of its specific pharmacological properties, Apaziquone is excellently suited for local therapy such as NMIBC. Future studies should include proper biomarkers

Construction of a \u3cem\u3eSonchus Yellow Net Virus\u3c/em\u3e Minireplicon: A Step Toward Reverse Genetic Analysis of Plant Negative-Strand RNA Viruses

Reverse genetic analyses of negative-strand RNA (NSR) viruses have provided enormous advances in our understanding of animal viruses over the past 20 years, but technical difficulties have hampered application to plant NSR viruses. To develop a reverse genetic approach for analysis of plant NSR viruses, we have engineered Sonchus yellow net nucleorhabdovirus (SYNV) minireplicon (MR) reporter cassettes for Agrobacterium tumefaciens expression in Nicotiana benthamiana leaves. Fluorescent reporter genes substituted for the SYNV N and P protein open reading frames (ORFs) exhibited intense single-cell foci throughout regions of infiltrated leaves expressing the SYNV MR derivatives and the SYNV nucleocapsid (N), phosphoprotein (P), and polymerase (L) proteins. Genomic RNA and mRNA transcription was detected for reporter genes substituted for both the SYNV N and P ORFs. These activities required expression of the N, P, and L core proteins in trans and were enhanced by codelivery of viral suppressor proteins that interfere with host RNA silencing. As is the case with other members of the Mononegavirales, we detected polar expression of fluorescent proteins and chloramphenicol acetyltransferase substitutions for the N and P protein ORFs. We also demonstrated the utility of the SYNV MR system for functional analysis of SYNV core proteins in trans and the cis-acting leader and trailer sequence requirements for transcription and replication. This work provides a platform for construction of more complex SYNV reverse genetic derivatives and presents a general strategy for reverse genetic applications with other plant NSR viruses