Vehicular emission is an important source of air pollutants in urban cities in the Pearl River Delta (PRD) region of South China. In order to study the impact of evaporative loss of vehicular fuel on air quality, several commonly used fuel samples were collected in four main cities in the PRD region - Hong Kong, Guangzhou, Macau and Zhuhai, and analyzed for their volatile organic compounds (VOCs) composition. Source profiles of vapors of the vehicular fuels used in these cities were constructed and are believed to be the first reported for the PRD region. The C-8-C-10 hydrocarbons were the main constituents of diesel. Different from diesel, gasoline used in the PRD region was mainly comprised of lighter C-4-C-7 hydrocarbons, with toluene and i-pentane being the two most abundant species. The toluene content in the Hong Kong and Macau gasoline samples were higher than that in Guangzhou and Zhuhai, while the reverse was true for the benzene content. The benzene levels in Guangzhou and Zhuhai exceeded the maximum allowable benzene levels for Mainland China unleaded gasoline. Liquefied Petroleum Gas (LPG) samples were collected only in Hong Kong and were comprised mainly of n-butane, propane and i-butane. Traffic samples indicated that evaporative loss and vehicular combustion were the primary contributors to elevated VOC levels in roadside atmospheres. Significant i-pentane and toluene concentrations were observed in roadside atmospheres in all four cities. Ratio of i-pentane in gasoline vapors to that in roadside samples were calculated and this showed that the degree of evaporative loss were higher in Guangzhou and Zhuhai than that in Hong Kong and Macau. We suggest the difference is due to the better maintenance and more new cars in Hong Kong and Macau. From tunnel samples collected in Hong Kong in two different years, we found that the relative amount of propane, i-butane, and n-butane increased between 2001 to 2003, consistent with the 40% increase in LPG fueled vehicles. Propane to butanes ratios were calculated for LPG samples and tunnels samples, and the comparable ratios illustrated the LPG leakages from LPG fueled vehicles crossing the tunnel.

Background

Activated factor X (FXa) is a vitamin K-dependent serine protease that plays a pivotal role in blood coagulation by converting prothrombin to thrombin. There are no reports of humans with complete deficiency of FX, and knockout of murine F10 is embryonic or perinatal lethal.

Objective

We sought to generate a viable mouse model of FX deficiency.

Methods

We used a socket-targeting construct to generate F10-knockout mice by eliminating F10 exon 8 (knockout allele termed F10(tm1Ccmt), abbreviated as '-'; wild-type '+'), and a plug-targeting construct to generate mice expressing a FX variant with normal antigen levels but low levels of FX activity [4-9% normal in humans carrying the defect, Pro343-->Ser, termed FX Friuli (mutant allele termed F10(tm2Ccmt), abbreviated as F)].

Results

F10 knockout mice exhibited embryonic or perinatal lethality. In contrast, homozygous Friuli mice [F10 (F/F)] had FX activity levels of approximately 5.5% (sufficient to rescue both embryonic and perinatal lethality), but developed age-dependent iron deposition and cardiac fibrosis. Interestingly, F10 (-/F) mice with FX activity levels of 1-3% also showed complete rescue of lethality. Further study of this model provides evidence supporting a role of maternal FX transfer in the embryonic survival.

Conclusions

We demonstrate that, while complete absence of FX is incompatible with murine survival, minimal FX activity as low as 1-3% is sufficient to rescue the lethal phenotype. This viable low-FX mouse model will facilitate the development of FX-directed therapies as well as investigation of the FX role in embryonic development.

Mice in which lung epithelial cells can be induced to express an oncogenic Kras(G12D) develop lung adenocarcinomas in a manner analogous to humans. A myriad of genetic changes accompany lung adenocarcinomas, many of which are poorly understood. To get a comprehensive understanding of both the transcriptional and post-transcriptional changes that accompany lung adenocarcinomas, we took an omics approach in profiling both the coding genes and the non-coding small RNAs in an induced mouse model of lung adenocarcinoma. RNAseq transcriptome analysis of Kras(G12D) tumors from F1 hybrid mice revealed features specific to tumor samples. This includes the repression of a network of GTPase-related genes (Prkg1, Gnao1 and Rgs9) in tumor samples and an enrichment of Apobec1-mediated cytosine to uridine RNA editing. Furthermore, analysis of known single-nucleotide polymorphisms revealed not only a change in expression of Cd22 but also that its expression became allele specific in tumors. The most salient finding, however, came from small RNA sequencing of the tumor samples, which revealed that a cluster of ∼53 microRNAs and mRNAs at the Dlk1-Dio3 locus on mouse chromosome 12qF1 was markedly and consistently increased in tumors. Activation of this locus occurred specifically in sorted tumor-originating cancer cells. Interestingly, the 12qF1 RNAs were repressed in cultured Kras(G12D) tumor cells but reactivated when transplanted in vivo. These microRNAs have been implicated in stem cell pleuripotency and proteins targeted by these microRNAs are involved in key pathways in cancer as well as embryogenesis. Taken together, our results strongly imply that these microRNAs represent key targets in unraveling the mechanism of lung oncogenesis.