Observation of the Exotic 0_{2}

We report here the first observation of the 0_{2}^{+} state of ^{8}He, which has been predicted to feature the condensatelike α+^{2}n+^{2}n cluster structure. We show that this state is characterized by a spin parity of 0^{+}, a large isoscalar monopole transition strength, and the emission of a strongly correlated neutron pair, in line with theoretical predictions. Our finding is further supported by the state-of-the-art microscopic α+4n model calculations. The present results may lead to new insights into clustering in neutron-rich nuclear systems and the pair correlation and condensation in quantum many-body systems under strong interactions.

The effect of anticoagulants on oral squamous cell carcinoma: A systematic review.

Tumour progression allows for aberrant angiogenesis. Consequently, cancer-associated thrombosis is a prevalent complication that is coupled with poor prognosis. Anticoagulants have therefore been prescribed with chemotherapeutic agents to target potential thrombo-embolic risk. A systematic review was carried out to summarise existing evidence on the interactions between anticoagulants and oral cancer. This treatment paradigm has demonstrated beneficial results in some oncology patients, thus associating anticoagulants with anticancer effects. Increasing prevalence of oral cancer presents a need to source alternative therapeutic means to prevent disease progression, and thus the use of anticoagulants in these patients may provide an avenue for this to occur. The paucity of evidence regarding the interactions between oral squamous cell carcinoma and anticoagulants emphasises the urgency with which further research should be conducted.

Genome-wide association studies for growth-related traits in a crossbreed pig population.

Growth-related traits are important economic traits in the pig industry that directly influence pork production efficiency. To detect quantitative trait loci and candidate genes affecting growth traits, genome-wide association studies were performed for backfat thickness (BF) and loin muscle depth (LMD) in 370 Chuying-black pigs using Illumina PorcineSNP50 BeadChip array. We totally identified 14 BF-associated SNPs, which included 11 genome-wide SNPs (P < 1.39E-06) and 3 chromosome-wide suggestive SNPs (P < 2.79E-05) and for LMD, 9 SNPs surpassed the genome-wide significant threshold (P < 1.39E-06). These SNPs explained 30.33 and 27.51% phenotypic variance for BF and LMD respectively. Furthermore, 14 and 9 genes nearest to the significant SNPs were selected to be candidate genes, including MAGED1, GPHN, CCSER1, and GUCY2D for BF and PARM1, COL18A1, HSF5, and SCML2 genes for LMD. One significant SNP, which explained 6.07% of phenotypic variance for BF, mapped to a pleiotropic quantitative trait locus with a 494-kb interval. Together, the SNPs and candidate genes identified in this study will advance our understanding of the complex genetic architecture of BF and LMD traits, and they will also provide important clues for future implementation of a genomic selection program in Chuying-black pigs.

Population structure and genetic diversity of four Henan pig populations.

To investigate the population structure and genetic diversity of Henan indigenous pig breeds, samples from a total of 78 pigs of 11 breeds were collected, including four pig populations from Henan Province, three Western commercial breeds, three Chinese native pig breeds from other provinces and one Asian wild boar. The genotyping datasets were obtained by genotyping-by-sequencing technology. We found a high degree of polymorphism and rapid linkage disequilibrium decay in Henan pigs. A neighbor-joining tree, principal component analysis and structure analysis revealed that the Huainan and Erhualian pigs were clustered together and that the Queshan black pigs were clearly grouped together but that the Nanyang and Yuxi pigs were extensively admixed with Western pigs. In addition, heterozygosity values might indicate that Henan indigenous pigs, especially the Queshan black and Huainan pigs, were subjected to little selection during domestication. The results presented here indicate that Henan pig breeds were admixed from Western breeds, especially Nanyang and Yuxi pigs. Therefore, establishment of purification and rejuvenation systems to implement conservation strategies is urgent. In addition, it is also necessary to accelerate genetic resources improvement and utilization using modern breeding technologies, such as genomic selection and genome-wide association studies.

Genome-wide association study identifies variants in the CAPN9 gene associated with umbilical hernia in pigs.

Pig umbilical hernia (UH) affects pig welfare and brings considerable economic loss to the pig industry. To date, the molecular mechanisms underlying pig UH are still poorly understood. To identify potential loci for susceptibility to this disease, we performed a genome-wide association study in an Erhualian × Shaziling F2 intercross population. A total of 45 animals were genotyped using Illumina Porcine SNP60 BeadChips. We observed a SNP (rs80993347) located in the calpain-9 (CAPN9) gene on Sus scrofa chromosome 14 that was significantly associated with UH (P = 1.97 × 10-10 ). Then, we identified a synonymous mutation rs321865883 (g.20164T>C) in exon 10 of the CAPN9 gene that distinguished two affected individuals (CC) from their normal full-sibs (TC). Finally, quantitative polymerase chain reaction was explored to investigate the mRNA expression profile of the CAPN9 gene in 12 tissues in Yorkshire pigs at different developmental stages (3, 90 and 180 days). CAPN9 showed high expression levels in the gastrointestinal tract at these three growth stages. The results of this study indicate that the CAPN9 gene might be implicated in UH. Further studies are required to establish a role of CAPN9 in pig UH.

An Isolated Method and Assignment for Critical Impurities in Semi-Synthetic Process of Arbekacin Sulfate.

Four potential process related impurities were detected during the impurity profiling study of a semi-synthetic aminoglycoside antibiotic, arbekacin. The current preparation process from 3',4'-didehydro-dibekacin easily generates the specific impurities with similar structures to arbekacin that makes hard to separate and identify the residues. HPLC-ELSD and column chromatography loading weakly acidic cation exchange resin were used for the detection and isolation of these process impurities. Based on the synthesis and spectral data (ESI-MS/MS, 1H NMR, 13C NMR and 2D-NMR), the structures of these impurities were characterized as dibekacin, 3-N-γ-aminohydroxybutyric (AHB)-dibekacin, 3''-N-AHB-dibekacin and 1,3-N,N-di-AHB-dibekacin. The characterization of these impurities is discussed in detail and our current efforts may help to develop a general strategy for isolation and identification of aminoglycoside products.

Effect of ligand sequence-specific modification on DNA hybrid catalysis.

Development of a stereoselective asymmetric catalytic system with high conversion is the key to success for acquiring chiral materials. In recent years, DNA hybrid catalysts have attracted significant interest due to their excellent abilities in accelerating reactions and achieving high enantioselectivity. We report here that bipyridine linked with polyamide as a sequence-specific catalytic ligand was designed to perform a DNA hybrid asymmetric reaction. The products presented different stereoselectivities compared to the results of reactions catalyzed by bipyridine. Comparing catalytic experiments based on alternative oligonucleotides verified that sequence-locating of the ligand affected the catalytic microenvironment. Circular dichroism spectra, combined with singular value decomposition, proposed that different binding modes could exist somewhere between the ligand and alternative sequences. The current work provides a strategy to extend the chemical range of DNA-based catalysis.

Observation of enhanced monopole strength and clustering in (12)Be.

In a recent breakup-reaction experiment using a Be12 beam at 29 MeV/nucleon, the 0+ band head of the expected He4+He8 molecular rotation was clearly identified at about 10.3 MeV, from which a large monopole matrix element of 7.0±1.0 fm2 and a large cluster-decay width were determined for the first time. These findings support the picture of strong clustering in Be12, which has been a subject of intense investigations over the past decade. The results were obtained thanks to a specially arranged detection system around zero degrees, which is essential in determining the newly emphasized monopole strengths to signal the cluster formation in a nucleus.

Resonant soft-X-ray emission as a bulk probe of correlated electron behavior in metallic SrxCa1-xVO3.

The evolution of electron correlation in SrxCa1-xVO3 has been studied using a combination of bulk-sensitive resonant soft x-ray emission spectroscopy, surface-sensitive photoemission spectroscopy, and ab initio band structure calculations. We show that the effect of electron correlation is enhanced at the surface. Strong incoherent Hubbard subbands are found to lie ∼20% closer in energy to the coherent quasiparticle features in surface-sensitive photoemission spectroscopy measurements compared with those from bulk-sensitive resonant soft x-ray emission spectroscopy, and a ∼10% narrowing of the overall bandwidth at the surface is also observed.

[Peripheral blood KCNMA1 methylation level is associated with the occurrence and progression of lung cancer].

OBJECTIVE: To explore the association of KCNMA1 gene methylation levels in peripheral blood with lung cancer. METHODS: The methylation levels of 4 CpG sites in KCNMA1 gene were quantitatively detected in 285 patients with lung cancer, 186 age- and sex-matched patients with benign pulmonary nodules and 278 matched healthy control subjects using mass spectrometry (MALDI-TOF-MS). The association of KCNMA1 methylation levels with lung cancer was analyzed using logistic regression models adjusted for covariates. The KCNMA1 methylation levels in different subgroups of lung cancer patients were compared using Mann-Whitney U test. RESULTS: In subjects over 55 years and in female subjects, the highest quartile (Q4) vs the lowest quartile (Q1) of KCNMA1_CpG_5 methylation levels were significantly correlated with lung cancer (for subjects over 55 years: OR=2.60, 95% CI: 1.25-5.41, P=0.011; for female subjects: OR=2.09, 95% CI: 1.03?4.26, P=0.042). From Q2 to Q4 of KCNMA1_CpG_5 methylation levels, their correlation with lung cancer became gradually stronger (P=0.003 and 0.038, respectively). In male subjects, the OR of Q4 of KCNMA1_CpG_5 methylation levels was 0.35 in patients with lung cancer as compared with patients with benign nodules (95% CI: 0.16-0.79, P=0.012). KCNMA1_CpG_3 methylation level was significantly lower in invasive adenocarcinoma than in noninvasive adenocarcinoma (P=0.028), and that of KCNMA1_CpG_1 was significantly higher in patients with larger tumors (T2-4) than in those with smaller tumors (T1) (P=0.021). CONCLUSION: The change of peripheral blood KCNMA1 methylation level is correlated with the occurrence and development of lung cancer.

Commonly Prescribed Anticoagulants Exert Anticancer Effects in Oral Squamous Cell Carcinoma Cells In Vitro.

Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer. With anticoagulant usage on the rise, it is important to elucidate their potential effects on tumour biology and interactions with chemotherapeutics. The aim of the present study was to investigate the effects of anticoagulants on OSCC cell lines and their interactions with the drug 5-fluorouracil (5-FU). Cell proliferation was assessed using an MTS in vitro assay in two human OSCC cell lines (H357/H400) and in normal oral keratinocytes (OKF6) treated with the 5-FU (0.2/1/5/10 µg/mL), conventional anticoagulants warfarin (1/5/10/20 µM) and heparin (5/20/80 U), as well as four new oral anticoagulants, dabigatran (5/10/20 µM), rivaroxaban (5/10/20 µM), apixaban (0.1/1/5 µg/mL), and edoxaban (5/10/20 µM). Cell migration was assessed at 3 h intervals up to18 h using a wound healing assay. Our results clearly demonstrate, for the first time, that commonly prescribed anticoagulants exert in vitro antiproliferative effects on OSCC cells. Furthermore, treatment with some anticoagulants reduced the migration of OSCC cell lines. Nevertheless, most of the anticoagulants tested reduced the effectiveness of the chemotherapeutic agent tested, 5-FU, highlighting potential flaws in the current pharmacological management of these patients. Our findings showed the need for the immediate translation of this research to preclinical animal models.

Validation of a paternally imprinted QTL affecting pH24h distinct from PRKAG3 on SSC15.

We previously performed a genome scan in a White Duroc × Erhualian F(2) population and identified a QTL on SSC15 with strong effect on pH24h in M. Longissimus dorsi and M. Semimembranous muscle tissue. At that time, the mode of inheritance of this QTL was not clarified, and it was also unclear whether the observed QTL effect was completely or partially caused by mutations in the PRKAG3 gene, which is the only major gene on SSC15 so far known to influence pH24h. In this study, effects of the PRKAG3 gene on meat quality traits were estimated by association analyses. Two substitutions in PRKAG3, p.Ile199Val (p.I199V) and p.Thr30Asn (p.T30N), were found to be segregating in the F(2) population and to significantly affect pH24h and total glycogen in meat, respectively. However, we excluded PRKAG3 as a causative gene for the detected QTL based on the following reasons: (i) the gene was located outside of the QTL confidence interval; (ii) when the PRKAG3 substitution was included as a fixed effect in the QTL model, the F-ratio for the QTL increased rather than decreased; (iii) favourable alleles for pH24h at the QTL and at the PRKAG3 p.I199V locus originated from Erhualian and White Duroc founders, respectively; (iv) more importantly, this QTL showed exclusive maternal expression, differing from the Mendelian expression of PRKAG3. In conclusion, this study is the first to report a maternally-expressed QTL for pH24h on SSC15, which is distinct from PRKAG3.

The Combined Effect of Hearing Impairment and Cognitive Impairment with Health-Related Outcomes in Chinese Older People.

OBJECTIVES: To determine the risk of poor health-related outcomes in older adults with cooccurring hearing impairment and cognitive impairment, and to compare the risk of hearing impairment only, cognitive impairment only, and multiple morbidities. DESIGN: Cross-sectional study. SETTING: Community-dwelling older adults aged 60 years and older were included. PARTICIPANTS: The data of missing hearing and cognitive status were excluded, and 3770 older people participated in the study. MEASUREMENTS: The hearing function evaluation was conducted by questionnaire survey. Assessment of cognitive function was completed using the SPMSQ scale. The subjects were divided into hearing impairment and cognitive impairment group, hearing impairment only group, cognitive impairment only group and neither group. Multiple logistic regression was used to analyze the risks of hearing and cognitive impairment and health-related condition. RESULTS: The prevalence of hearing impairment and cognitive impairment, hearing impairment only, cognitive impairment only, and neither were 9.4%, 8.3%, 29.9% and 52.4%, respectively. Compared with the control group, the individuals with hearing impairment and cognitive impairment were associated with depression (OR=3.48, 95% CI=2.66, 4.56), anxiety (OR=2.35, 95% CI=1.92, 3.33), frailty (OR=4.30, 95% CI=2.89, 6.40), and ADL impairment (OR=2.77, 95% CI=2.03, 3.77). CONCLUSION: The studies shows that hearing impairment combined with cognitive impairment is significantly associated with anxiety, depression, frailty, and ADL impairment. Comprehensive management and intervention should be provided for older people to reduce the occurrence of adverse health consequences.

[Study on the damage of the tight junctions of nasal mucosal epithelial cells by artemisia annua pollen].

Objective: To investigate the damage and mechanism of artemisia annua pollen on tight junction of human nasal mucosa epithelial cells (HNEpC). Methods: HNEpC were cultured in vitro. Different concentrations of artemisia annua pollen (0, 20, 40, 80, 100, 160, 200 µg/ml) were used to intervene the cells for 24 h, and the cell proliferation activity was detected by the CCK-8 method. The expression and phosphorylation of p38MAPK signaling pathway were detected by Western Blot before and after the intervention of SB203580, a p38MAPK inhibitor in HNEpC. Immunofluorescence chemical staining, Western Blot and quantitative real-time PCR (qPCR) were used to observe the expression and distribution of tight junctions Occludin and Claudin-1. SPSS 21.1 software was used for statistical analysis. Results: CCK-8 results showed that, compared with the control group, the proliferation activity of HNEpC increased after 6 h intervention with different concentrations of artemisia annua pollen (all P<0.05). After 12 h of intervention, the proliferation activity of HNEpC in the 20, 40, 80, 100 and 160 µg/ml groups was not significantly changed (all P>0.05), while that in the 200 µg/ml group was decreased (P<0.05). After the intervention for 24 h, the proliferation activity of cells in the 20 and 40 µg/ml groups was not significantly changed (all P>0.05), while that in the 80, 100, 160 and 200 µg/ml groups was decreased (all P<0.05). Immunofluorescence staining showed that the Occludin and Claudin-1 proteins in the normal control group were localized on the cell membrane and expressed more and formed a ring structure around the cell membrane. However, under the intervention of high concentration artemisia annua pollen, its expression level decreased, appeared broken, fuzzy, and nonuniform distribution. Western Blot and qPCR results showed that after 24 h of intervention, the expression levels of HNEpC Claudin-1 protein and its mRNA in the pollen groups (40, 80, 100, 160, 200 µg/ml) of artemisia annua decreased compared with those of those of the control group (mRNA expression levels were 0.567±0.214, 0.443±0.109, 0.462±0.160, 0.497±0.134, 0.388±0.076 compared with 1.001±0.067, respectively, all P<0.05). However, the mRNA of Occludin protein and its mRNA only decreased in the 200 µg/ml treatment group (mRNA expression level was 0.631±0.109 compared with 1.016±0.026, P<0.05), while all the other treatment groups increased (mRNA expression levels were 1.258±0.134, 1.827±0.103, 2.429±0.077, 1.707±0.085, 1.477±0.066 compared with 1.016±0.026, respectively, all P<0.05). Western Blot showed that p-p38MAPK expression increased after intervention with 100, 160, 200 µg/ml artemisia annua pollen for 24 h. SB203580 could inhibit the decreasing expression of Occludin caused by artemisinin pollen (mRNA expression was 1.255±0.179 compared with 0.631±0.109, P<0.05), but had no effect on Claudin-1 protein expression. Conclusion: Pollen from artemisia annua may activate p38MAPK signaling pathway and destroy the close connection of HNEpC.

Exogenous expression of N-cadherin in breast cancer cells induces cell migration, invasion, and metastasis.

E- and N-cadherin are calcium-dependent cell adhesion molecules that mediate cell-cell adhesion and also modulate cell migration and tumor invasiveness. The loss of E-cadherin-mediated adhesion has been shown to play an important role in the transition of epithelial tumors from a benign to an invasive state. However, recent evidence indicates that another member of the cadherin family, N-cadherin, is expressed in highly invasive tumor cell lines that lacked E-cadherin expression. These findings have raised the possibility that N-cadherin contributes to the invasive phenotype. To determine whether N-cadherin promotes invasion and metastasis, we transfected a weakly metastatic and E-cadherin-expressing breast cancer cell line, MCF-7, with N-cadherin and analyzed the effects on cell migration, invasion, and metastasis. Transfected cells expressed both E- and N-cadherin and exhibited homotypic cell adhesion from both molecules. In vitro, N-cadherin-expressing cells migrated more efficiently, showed an increased invasion of Matrigel, and adhered more efficiently to monolayers of endothelial cells. All cells produced low levels of the matrix metalloproteinase MMP-9, which was dramatically upregulated by treatment with FGF-2 only in N-cadherin-expressing cells. Migration and invasion of Matrigel were also greatly enhanced by this treatment. When injected into the mammary fat pad of nude mice, N-cadherin-expressing cells, but not control MCF-7 cells, metastasized widely to the liver, pancreas, salivary gland, omentum, lung, lymph nodes, and lumbar spinal muscle. The expression of both E- and N-cadherin was maintained both in the primary tumors and metastatic lesions. These results demonstrate that N-cadherin promotes motility, invasion, and metastasis even in the presence of the normally suppressive E-cadherin. The increase in MMP-9 production by N-cadherin-expressing cells in response to a growth factor may endow them with a greater ability to penetrate matrix protein barriers, while the increase in their adherence to endothelium may improve their ability to enter and exit the vasculature, two properties that may be responsible for metastasis of N-cadherin-expressing cells.

A genome scan for quantitative trait loci affecting three ear traits in a White Duroc x Chinese Erhualian resource population.

Chinese Erhualian pigs have larger and floppier ears compared with White Duroc pigs (small, half- or fully-pricked ears). To identify quantitative trait loci (QTL) for ear weight and area as well as erectness, a genome-wide scan with 194 microsatellites was performed in a White Duroc x Chinese Erhualian resource population (>1000 F(2) animals). Twenty-three genome-wide significant QTL and 12 suggestive QTL were identified. All QTL for ear erectness and size detected in two previous studies, bar two on SSC6 and 9, were confirmed here. The 1% genome-wide significant QTL at 70 cM on SSC5 and at 58 cM on SSC7 have profound and pleiotropic effects on the three ear traits, with Erhualian alleles increasing weight and area but decreasing erectness. Notably, the 95% confidence interval of the QTL for weight and area on SSC7 spanned only 3 cM. New QTL reaching 1% genome-wide significance were found on SSC8 (at 37 cM) for all three ear traits, on SSC4 and 16 for weight and area, and on SSCX for area. Unexpectedly, Erhualian alleles at these loci were associated with lighter and smaller or erect ear. Some new suggestive QTL were also found on other chromosome regions. Almost all the QTL for weight and area had essentially additive effects, while the QTL for erectness on SSC2, 5 and 7 showed not only additive effects but also partial dominance effects of Erhualian alleles. The two most significant QTL on SSC7 and SSC5 could be promising targets for fine mapping and identification of the causative mutations.

A single fast radio burst localized to a massive galaxy at cosmological distance.

Fast radio bursts (FRBs) are brief radio emissions from distant astronomical sources. Some are known to repeat, but most are single bursts. Nonrepeating FRB observations have had insufficient positional accuracy to localize them to an individual host galaxy. We report the interferometric localization of the single-pulse FRB 180924 to a position 4 kiloparsecs from the center of a luminous galaxy at redshift 0.3214. The burst has not been observed to repeat. The properties of the burst and its host are markedly different from those of the only other accurately localized FRB source. The integrated electron column density along the line of sight closely matches models of the intergalactic medium, indicating that some FRBs are clean probes of the baryonic component of the cosmic web.

[Associations between maternal exposure to chemical fertilizers during pregnancy and the risk of offspring's low birth weights].

Objective: To explore the association between the consumption of chemical fertilizers and the risk of low birth weight (LBW), to provide references for prevention programs on LBW and to improve the birth outcomes. Methods: Stratified multivariate logistic regression method was used in this study involving 153 preterm LBW infants, 179 term LBW infants and 204 normal control infants that were randomly selected from the birth monitoring data between October 2007 and September 2012 in Pingding county, Shanxi province. Associations between the risk of LBW and maternal exposure to chemical fertilizers during pregnancy were identified. A normal control group was set up to compare results between preterm and term LBW groups. Results: Totally, 18 749 infants were born between 2007 and 2012, with the total incidence rates of LBW as 48.5‰, preterm LBW as 19.4‰, and term LBW as 29.1‰. Concerning the case control study on preterm LBW, after adjustment for confounding factors, the risk of preterm LBW appeared 2.51 (95%CI: 1.05-5.99) times higher in villages with annual consumption of chemical fertilizer ≥100 tons than those villages that using chemical fertilizer less than 50 tons. No significant statistical associations were found between the amounts of household chemical fertilizer consumption and the risks of preterm LBW. Regarding the case control study on term LBW, after adjustment for confounding factors, in villages with ≥100 tons annual consumption of chemical fertilizers, the risk of term LBW was 4.03 (95%CI: 1.63-9.92) times of the risk in villages where the annal use of chemical fertilizers was less than 50 tons. There was no significant association between household consumption of chemical fertilizers and the risk of term LBW. Conclusions: Maternal exposure to chemical fertilizers during pregnancy was associated with the risk of LBW. Our findings suggested that the amount of chemical fertilizer consumption in rural areas seemed also associated with the risks of other adverse pregnancy outcomes. Women should avoid the chance of exposure to chemical fertilizers during pregnancy and the consumption of chemical fertilizers should be carefully managed.

Increased circulating microparticles in women with preeclampsia.

INTRODUCTION: Preeclampsia (PE) is associated with hypercoagulability, endothelial dysfunction and inflammation, which generate microparticles (MPs). Therefore, MPs may be important for PE. METHODS: We established a verified MP measurement procedure to detect MPs in nonpregnant women (n = 25), healthy pregnant women (n = 29) and PE women (n = 73) and compared their MP levels. RESULTS: Microparticles prepared from platelets (PMPs), endothelial cells (EMPs) and leucocytes (LMPs) were confirmed by transmission electron microscopy and were analysed by our established flow cytofluorimetric approach, which showed good specificity for determining the cell origin and level of MPs. The levels of total MPs (tMPs) and PMPs in the healthy pregnant group were significantly higher than those in the nonpregnant group (158.78 vs 93.00 and 45.04 vs 17.41, P = .004 and P = .007, respectively) but were not significantly different from those of the PE group. However, EMPs and LMPs were significantly higher in the PE group than in the healthy pregnant group (14.62 vs 11.48 and 8.94 vs 5.03, P = .015 and P < .001, respectively). Furthermore, the area under the receiver operating characteristic curves (AUC) for EMPs, LMPs and the combined sum of EMPs and LMPs were 0.661, 0.746 and 0.718, respectively (P < . 05); at their optimal cut-off values, the sensitivities were 50.68%, 87.67% and 46.58%, respectively, and the specificities were 80.77%, 58.33% and 95.65%, respectively. CONCLUSION: Determining the MP level, especially that of EMPs and LMPs, by a specificity-verified method may reflect the endothelial dysfunction and inflammation involved in PE pathogenesis.

A mouse model of arterial gene transfer: antigen-specific immunity is a minor determinant of the early loss of adenovirus-mediated transgene expression.

We developed a murine model of arterial gene transfer and used it to test the role of antigen-specific immunity in the loss of adenovirus-mediated transgene expression. Adenoviral vectors encoding either beta-galactosidase (beta-gal) or green fluorescent protein were infused to the lumen of normal common carotids of CD-1 and C57BL/6 mice and atherosclerotic carotids of Apoe(-/-) mice. At 3 days after gene transfer, significant reporter gene expression was detected in all strains. Transgene expression was transient, with expression undetectable at 14 days. Next, a beta-gal-expressing vector was infused into carotids of ROSA26 mice (transgenic for, and therefore tolerant of, beta-gal) and RAG-2(-/-) mice (deficient in recombinase-activating gene [RAG]-2 and therefore lacking in antigen-specific immunity). beta-Gal expression was again high at 3 days but declined substantially (>90%) by 14 days. In vivo labeling with bromodeoxyuridine revealed that carotid endothelial proliferation was increased dramatically by the gene-transfer procedure alone, likely leading to the loss of episomal adenoviral DNA. Gene transfer to normal and atherosclerotic mouse carotids can be accomplished; however, elimination of antigen-specific immune responses does not prevent the early loss of adenovirus-mediated transgene expression. Efforts to prolong adenovirus-mediated transgene expression in the artery wall must be redirected. These efforts will likely include strategies to avoid the consequences of increased cell turnover. Nevertheless, despite the brevity of expression, this mouse model of gene transfer to normal and severely atherosclerotic arteries will likely be useful for investigating the genetic basis of vascular disease and for developing gene therapies.