Publications by authors named "Xiangzhou Meng"

26 Publications

  • Page 1 of 1

Multi- and trans-generational effects of N-butylpyridium chloride on reproduction, lifespan, and pro/antioxidant status in Caenorhabditis elegans.

Sci Total Environ 2021 Jul 10;778:146371. Epub 2021 Mar 10.

College of Ecological Technology and Engineering, Shanghai Institute of Technology, Shanghai, 201418, PR China. Electronic address:

Ionic liquids (ILs) became emerging pollutants. Their poor degradation and accumulation in organisms urged studies on the long-term effects and also the underlying mechanisms. Currently, 1-butylpyrinium chloride ([bpyr]Cl) was chosen to represent the pyridine-based ILs. Its multi-generational effects were measured on C. elegans for 14 consecutive generations (F1 to F14), and the trans-generational effects were also measured in the great-grand-children (T3 and T3') of F1 and F14. The multi-generational results from F1 to F14 showed that the effects of [bpyr]Cl on the initial and total reproduction and lifespan showed oscillation between inhibition and stimulation. Notably, hormetic effects on reproduction were observed in F7 to F10. The trans-generational effects in T3 and T3' showed different residual consequences between one generational exposure (F1) and multiple generational exposure (F14). Further biochemical analysis showed that the pro/antioxidant status also showed oscillation between inhibition and stimulation. The oscillation levels were greater in superoxide dismutase (SOD), catalase (CAT) and protein carbonyl content (PC) than those in glutathione peroxidase (GSH-Px), reactive oxygen species (ROS) and hydroxyl radical (OH). The pro/antioxidant status contributed to both multi- and trans-generational effects of [bpyr]Cl. Future studies should pay attentions to the long-term influence of ILs and also epigenetic explanations.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146371DOI Listing
July 2021

Tumor cell membrane-based peptide delivery system targeting the tumor microenvironment for cancer immunotherapy and diagnosis.

Acta Biomater 2021 06 2;127:266-275. Epub 2021 Apr 2.

Key Laboratory of Nano-Bio Interface Research, Division of Nano biomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China. Electronic address:

The development of an effective delivery system for peptides targeting the tumor microenvironment has always been a hot topic of research in the field of cancer diagnosis and therapy. In this study, superparamagnetic iron oxide nanoparticles (SPIO NPs) were encapsulated with H460 lung cancer cell membranes (SPIO [email protected]), and two peptides, namely PD-L1 inhibitory peptide (TPP1) and MMP2 substrate peptide (PLGLLG), were conjugated to the H460 membrane (SPIO [email protected]). Homologous targeting, cytotoxicity, and pharmacokinetics of SPIO [email protected] were evaluated. The TPP1 peptide was delivered and released to the tumor microenvironment through the homotypic effect of tumor cell membrane and specific digestion by the tumor-specific enzyme MMP2. The newly developed delivery system (SPIO [email protected]) for the PD-L1 inhibitory peptide could effectively extend the half-life of the peptides (60 times longer than that for peptides alone) and could maintain the ability to reactivate T cells and inhibit the tumor growth both in vitro and in vivo. Furthermore, SPIO NPs in the system could be used as a tumor imaging agent and thus show the effect of peptide treatment. The SPIO [email protected] might serve as a promising theranostic platform for therapeutic application of peptides in cancer therapy. STATEMENT OF SIGNIFICANCE: A multifunctional delivery system (SPIO [email protected]) was constructed for effectively delivering therapeutic peptides into the tumor microenvironment for cancer diagnosis and therapy. In this paper, the TPP-1 peptide inhibiting the binding of PD-L1 and PD-1 was delivered and released into the tumor microenvironment by the homotypic targeting of H460 cell membrane and specific digestion by the MMP2 enzyme. SPIO NPs in this system were aggregated effectively at the tumor sites and were used for magnetic resonance imaging of tumors. The SPIO [email protected] delivery system could effectively extend the half-life of the TPP-1 peptide (60 times longer than that of the free peptide) and could maintain the ability to re-activate T cells and inhibit tumor growth in vitro and in vivo. In conclusion, the SPIO [email protected] system coated with lung cancer cell membrane and loaded with the PD-L1-blocking TPP-1 peptide could be a promising integrated platform for tumor diagnosis and treatment.
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http://dx.doi.org/10.1016/j.actbio.2021.03.056DOI Listing
June 2021

Distribution of eight organophosphorus pesticides and their oxides in surface water of the East China Sea based on high volume solid phase extraction method.

Environ Pollut 2021 Jun 9;279:116886. Epub 2021 Mar 9.

Ministry of Natural Resources Key Laboratory for Polar Science, Polar Research Institute of China, Shanghai, 200136, China. Electronic address:

In this study, we reported the occurrence of eight organophosphorus pesticides (OPPs) in the East China Sea. Forty samples were collected and analysed with a high volume solid phase extraction method (Hi-throat/Hi-volume SPE) in the early summer of 2020. All the target OPPs were detected in the surface water at one or more stations in the East China Sea, and the concentrations of ΣOPPs were in the range 0.0775-3.09 ng/L (mean: 0.862 ± 0.624 ng/L). Terbufos sulfone and fenthion were the main pollutants in this area, probably resulting from pesticide use in China and other countries. The off-shore input from coastal regions was suggested to be a major source of OPP pollution in the East China Sea, and the movement of ocean currents played an important role in their transportation because around 0.86 t OPPs passed through the Tsushima Strait from the East China Sea each month. An ecological risk assessment showed that these OPPs presented a high risk to species in the East China Sea, whereas they posed no health risk to humans under both the median and high exposure scenario.
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http://dx.doi.org/10.1016/j.envpol.2021.116886DOI Listing
June 2021

The Srs2 helicase dampens DNA damage checkpoint by recycling RPA from chromatin.

Proc Natl Acad Sci U S A 2021 02;118(8)

Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065;

The DNA damage checkpoint induces many cellular changes to cope with genotoxic stress. However, persistent checkpoint signaling can be detrimental to growth partly due to blockage of cell cycle resumption. Checkpoint dampening is essential to counter such harmful effects, but its mechanisms remain to be understood. Here, we show that the DNA helicase Srs2 removes a key checkpoint sensor complex, RPA, from chromatin to down-regulate checkpoint signaling in budding yeast. The Srs2 and RPA antagonism is supported by their numerous suppressive genetic interactions. Importantly, moderate reduction of RPA binding to single-strand DNA (ssDNA) rescues hypercheckpoint signaling caused by the loss of Srs2 or its helicase activity. This rescue correlates with a reduction in the accumulated RPA and the associated checkpoint kinase on chromatin in mutants. Moreover, our data suggest that Srs2 regulation of RPA is separable from its roles in recombinational repair and critically contributes to genotoxin resistance. We conclude that dampening checkpoint by Srs2-mediated RPA recycling from chromatin aids cellular survival of genotoxic stress and has potential implications in other types of DNA transactions.
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http://dx.doi.org/10.1073/pnas.2020185118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923681PMC
February 2021

DNA polymerase ε relies on a unique domain for efficient replisome assembly and strand synthesis.

Nat Commun 2020 05 15;11(1):2437. Epub 2020 May 15.

Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.

DNA polymerase epsilon (Pol ε) is required for genome duplication and tumor suppression. It supports both replisome assembly and leading strand synthesis; however, the underlying mechanisms remain to be elucidated. Here we report that a conserved domain within the Pol ε catalytic core influences both of these replication steps in budding yeast. Modeling cancer-associated mutations in this domain reveals its unexpected effect on incorporating Pol ε into the four-member pre-loading complex during replisome assembly. In addition, genetic and biochemical data suggest that the examined domain supports Pol ε catalytic activity and symmetric movement of replication forks. Contrary to previously characterized Pol ε cancer variants, the examined mutants cause genome hyper-rearrangement rather than hyper-mutation. Our work thus suggests a role of the Pol ε catalytic core in replisome formation, a reliance of Pol ε strand synthesis on a unique domain, and a potential tumor-suppressive effect of Pol ε in curbing genome re-arrangements.
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http://dx.doi.org/10.1038/s41467-020-16095-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228970PMC
May 2020

Sources apportionment and carcinogenic risk of polycyclic aromatic hydrocarbons in gas phase of urban Shanghai: Based on high volume solid phase extraction (Hi-volume SPE).

Ecotoxicol Environ Saf 2020 Jun 19;195:110398. Epub 2020 Mar 19.

Ministry of Natural Resources Key Laboratory for Polar Science, Polar Research Institute of China, Shanghai, 200136, China.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants, posing potentially serious threats to human health. This study analyzed compositional characteristics, sources, and carcinogenic risks of PAHs in the atmospheric gas phase at an urban site in Shanghai, East China. Seventy-four gas phase samples were collected during the warm months of May-October 2018 using a high-volume solid phase extraction (Hi-volume SPE) technique. The total concentration of sixteen priority PAHs (ΣPAHs) was in the range of 5.54-182.05 ng m (average 34.47 ng m) and the total of seven carcinogenic PAHs (ΣCPAHs) was in range of 0.03-1.49 ng m (average 0.48 ng m), accounting for 1.47% of ΣPAHs and indicating low carcinogenic potential. Redundancy analyses indicated positive correlations between ΣPAHs and air quality, and ΣCPAHs and average high temperature, and a negative correlation between ΣPAHs and wind speed. Four possible sources, namely petroleum and petrogenic sources, traffic emissions, coal combustion, and mixed gasoline and coal combustion sources, were identified by positive matrix factorization (PMF), accounting for 62.84%, 19.31%, 10.15%, and 7.69% of ΣPAHs, respectively. The overall lifetime lung cancer risk (LLCR) through inhalation of PAHs was estimated to be at a low risk level of 1.61 × 10. The LLCR based on PMF apportionment decreased in the order of mixed gasoline and coal combustion sources (47.07%) > traffic emissions (35.10%) > petroleum and petrogenic sources (11.06%) > coal combustion (6.74%). This study demonstrates the effectiveness of Hi-volume SPE in collecting and analyzing atmospheric gas phase PAHs.
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http://dx.doi.org/10.1016/j.ecoenv.2020.110398DOI Listing
June 2020

Sumoylation of the DNA polymerase ε by the Smc5/6 complex contributes to DNA replication.

PLoS Genet 2019 11 25;15(11):e1008426. Epub 2019 Nov 25.

Molecular Biology Department, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.

DNA polymerase epsilon (Pol ε) is critical for genome duplication, but little is known about how post-translational modification regulates its function. Here we report that the Pol ε catalytic subunit Pol2 in yeast is sumoylated at a single lysine within a catalytic domain insertion uniquely possessed by Pol2 family members. We found that Pol2 sumoylation occurs specifically in S phase and is increased under conditions of replication fork blockade. Analyses of the genetic requirements of this modification indicate that Pol2 sumoylation is associated with replication fork progression and dependent on the Smc5/6 SUMO ligase known to promote DNA synthesis. Consistently, the pol2 sumoylation mutant phenotype suggests impaired replication progression and increased levels of gross chromosomal rearrangements. Our findings thus indicate a direct role for SUMO in Pol2-mediated DNA synthesis and a molecular basis for Smc5/6-mediated regulation of genome stability.
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http://dx.doi.org/10.1371/journal.pgen.1008426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6876774PMC
November 2019

Molecular Basis for Control of Diverse Genome Stability Factors by the Multi-BRCT Scaffold Rtt107.

Mol Cell 2019 07 16;75(2):238-251.e5. Epub 2019 Jul 16.

Molecular Biology Department, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address:

BRCT domains support myriad protein-protein interactions involved in genome maintenance. Although di-BRCT recognition of phospho-proteins is well known to support the genotoxic response, whether multi-BRCT domains can acquire distinct structures and functions is unclear. Here we present the tetra-BRCT structures from the conserved yeast protein Rtt107 in free and ligand-bound forms. The four BRCT repeats fold into a tetrahedral structure that recognizes unmodified ligands using a bi-partite mechanism, suggesting repeat origami enabling function acquisition. Functional studies show that Rtt107 binding of partner proteins of diverse activities promotes genome replication and stability in both distinct and concerted manners. A unified theme is that tetra- and di-BRCT domains of Rtt107 collaborate to recruit partner proteins to chromatin. Our work thus illustrates how a master regulator uses two types of BRCT domains to recognize distinct genome factors and direct them to chromatin for constitutive genome protection.
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http://dx.doi.org/10.1016/j.molcel.2019.05.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745058PMC
July 2019

Cyclic RGD functionalized liposomes encapsulating urokinase for thrombolysis.

Acta Biomater 2018 04 9;70:227-236. Epub 2018 Feb 9.

CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China. Electronic address:

Thrombosis, a critical event in blood vessels, not only is associated with myocardial infarction and stroke, but also accounts for considerable morbidity and mortality. Thrombolytic drugs are usually applied to the treatment of acute myocardial infarction, acute cerebral infarction and pulmonary embolism. However, thrombolytic drugs show limited efficacy in clinical practice because of the short half-life in plasma and systemic side effects. In this study, the cyclic RGD (cRGD) functionalized liposomes were prepared to encapsulate urokinase, a cheap and widely used thrombolytic drug in clinic and better thrombolysis efficacy was achieved. The flow cytometry analysis showed that the cRGD liposomes could bind to the activated platelets while not to the resting platelets. In vitro release study revealed that the release percentage reached plateau in about 5 h with 60% urokinase being released from liposomes. Results from the in vitro thrombolysis experiments demonstrated a good thrombolysis potential of the cRGD urokinase liposomes. The in vivo thrombolysis study demonstrated that the cRGD liposomes could significantly reduce the dose of urokinase by 75% while achieving the equivalent thrombolysis effect as the free urokinase in mouse mesenteric thrombosis model. In conclusion, the cRGD liposomes encapsulating urokinase hold great promise in clinic for better thrombolytic efficacy.

Statement Of Significance: In this paper, the cRGD liposomes were prepared to encapsulate urokinase for targeted thrombolysis therapy. The cRGD liposomes could specifically bind to the activated platelets and could stably and continuously release its loaded urokinase. The mouse mesenteric thrombosis model was established to evaluate the thrombolysis effect of the cRGD urokinase liposomes. The results demonstrated that the cRGD liposomes could improve the thrombolytic efficacy by almost 4-fold over free urokinase. In conclusion, the cRGD liposomes encapsulating urokinase had great potential for the clinical treatment of thrombosis.
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http://dx.doi.org/10.1016/j.actbio.2018.01.038DOI Listing
April 2018

Environmental Risk Implications of Metals in Sludges from Waste Water Treatment Plants: The Discovery of Vast Stores of Metal-Containing Nanoparticles.

Environ Sci Technol 2017 May 14;51(9):4831-4840. Epub 2017 Apr 14.

The Center for NanoBioEarth, Department of Geosciences, Virginia Tech , Blacksburg, Virginia 24061, United States.

Nanoparticle (NP) assessment in sludge materials, although of growing importance in eco- and biotoxicity studies, is commonly overlooked and, at best, understudied. In the present study, sewage sludge samples from across the mega-city of Shanghai, China were investigated for the first time using a sequential extraction method coupled with single particle inductively coupled plasma mass spectrometry (SP-ICP-MS) to quantify the abundance of metal-containing NPs in the extraction fractions and transmission electron microscopy to specifically identify the nanophases present. In general, most sludges observed showed high concentrations of Cr, Cu, Cd, Ni, Zn, and Pb, exceeding the maximum permitted values in the national application standard of acid soil in China. NPs in these sludges contribute little to the volume and mass but account for about half of the total particle number. Based on electron microscopy techniques, various NPs were further identified, including Ti-, Fe-, Zn-, Sn-, and Pb-containing NPs. All NPs, ignored by traditional metal risk evaluation methods, were observed at a concentration of 10 -10 particles/g within the bioavailable fraction of metals. These results indicate the underestimate or misestimation in evaluating the environmental risks of metals based on traditional sequential extraction methods. A new approach for the environmental risk assessment of metals, including NPs, is urgently needed.
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http://dx.doi.org/10.1021/acs.est.6b05931DOI Listing
May 2017

Spatiotemporal distribution and potential sources of perfluoroalkyl acids in Huangpu River, Shanghai, China.

Chemosphere 2017 May 27;174:127-135. Epub 2017 Jan 27.

State Key Laboratory of Pollution Control and Resources Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China.

Perfluoroalkyl acids (PFAAs) have been found to be ubiquitously disseminated in the environment due to their widespread use in recent decades. In this study, the occurrence and spatiotemporal distribution of PFAAs in the surface water of Huangpu River, Shanghai, China were investigated from 2012 to 2014. The total concentration of 14 PFAAs (ΣPFAAs) ranged from 39.8 to 596.2 ng L, with a mean value of 226.3 ng L. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) were dominant, with their mean concentrations of 139.6 and 46.5 ng L, respectively. The concentration of ΣPFAAs increased greatly downstream especially in the lower reach of an industrial and urbanized area. Samples collected in different seasons were used to analyze the seasonal variation. The results showed that higher concentration of ΣPFAAs occurred in the wet season, especially downstream. Therefore, industrial discharges, municipal wastewater and surface runoff were identified as major potential sources. The annual discharge load of ΣPFAAs from Huangpu River to Yangtze River was estimated to be 2263.4 kg yr. The hazard assessment suggested that the contamination of PFAAs in Huangpu River could pose risks to the aquatic environment and drinking water safety, which should draw more attention.
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http://dx.doi.org/10.1016/j.chemosphere.2017.01.122DOI Listing
May 2017

Replication fork regression and its regulation.

FEMS Yeast Res 2017 01;17(1)

One major challenge during genome duplication is the stalling of DNA replication forks by various forms of template blockages. As these barriers can lead to incomplete replication, multiple mechanisms have to act concertedly to correct and rescue stalled replication forks. Among these mechanisms, replication fork regression entails simultaneous annealing of nascent and template strands, which leads to regression of replication forks and formation of four-way DNA junctions. In principle, this process can lead to either positive outcomes, such as DNA repair and replication resumption, or less desirable outcomes, such as misalignment between nascent and template DNA and DNA cleavage. While our understanding of replication fork regression and its various possible outcomes is still at an early stage, recent studies using combinational approaches in multiple organisms have begun to identify the enzymes that catalyze this DNA transaction and how these enzymes are regulated, as well as the specific manners by which fork regression can influence replication. This review summarizes these recent progresses. In keeping with the theme of this series of reviews, we focus on studies in yeast and compare to findings in higher eukaryotes. It is anticipated that these findings will form the basis for future endeavors to further elucidate replication fork remodeling and its implications for genome maintenance.
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http://dx.doi.org/10.1093/femsyr/fow110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5976033PMC
January 2017

Umbilical cord blood PBDEs concentrations are associated with placental DNA methylation.

Environ Int 2016 Dec 18;97:1-6. Epub 2016 Oct 18.

Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai, China. Electronic address:

Background: In utero polybrominated diphenyl ethers (PBDEs) exposure has been associated with adverse fetal growth. Alterations in placental DNA methylation might mediate those adverse effects.

Objectives: To examine the associations between in utero PBDEs exposure and DNA methylation in human placenta.

Methods: Eighty apparently healthy mother-newborn pairs delivering at the Second Affiliated Hospital of Wenzhou Medical College were enrolled in this study. Placental DNA methylation of LINE1, NR3C1 and IGF2 was measured by quantitative polymerase chain reaction-pyrosequencing. In utero PBDEs exposure was assessed by measuring umbilical cord blood PBDEs concentrations.

Results: For LINE-1, higher levels of BDE-66 exposure were associated with decreased DNA methylation (β=-0.9, 95% CI, -1.8 to -0.1); For NR3C1, BDE-153 concentrations was significantly inversely associated with DNA methylation (β=-2.0, 95% CI, -3.7 to -0.2); For IGF2, elevated concentrations of both BDE-153 (β=-1.7; 95% CI, -3.0 to -0.4) and BDE-209 (β=-1.0; 95% CI, -1. 9 to -0.1) were significantly associated with decreased DNA methylation.

Conclusions: We found that placental DNA methylation is associated with in utero PBDEs exposure. Changes in placental DNA methylation might be part of the underlying biological pathway between in utero PBDEs exposure and adverse fetal growth.
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http://dx.doi.org/10.1016/j.envint.2016.10.014DOI Listing
December 2016

Breeding signatures of rice improvement revealed by a genomic variation map from a large germplasm collection.

Proc Natl Acad Sci U S A 2015 Sep 10;112(39):E5411-9. Epub 2015 Sep 10.

National Key Laboratory of Crop Genetic Improvement and National Center of Plant Gene Research (Wuhan), Huazhong Agricultural University, Wuhan 430070, China

Intensive rice breeding over the past 50 y has dramatically increased productivity especially in the indica subspecies, but our knowledge of the genomic changes associated with such improvement has been limited. In this study, we analyzed low-coverage sequencing data of 1,479 rice accessions from 73 countries, including landraces and modern cultivars. We identified two major subpopulations, indica I (IndI) and indica II (IndII), in the indica subspecies, which corresponded to the two putative heterotic groups resulting from independent breeding efforts. We detected 200 regions spanning 7.8% of the rice genome that had been differentially selected between IndI and IndII, and thus referred to as breeding signatures. These regions included large numbers of known functional genes and loci associated with important agronomic traits revealed by genome-wide association studies. Grain yield was positively correlated with the number of breeding signatures in a variety, suggesting that the number of breeding signatures in a line may be useful for predicting agronomic potential and the selected loci may provide targets for rice improvement.
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http://dx.doi.org/10.1073/pnas.1515919112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4593105PMC
September 2015

Checkpoint Activation of an Unconventional DNA Replication Program in Tetrahymena.

PLoS Genet 2015 Jul 28;11(7):e1005405. Epub 2015 Jul 28.

Interdisciplinary Program in Genetics, Texas A&M University, College Station, Texas, United States of America; Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center, College Station, Texas, United States of America; Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas, United States of America.

The intra-S phase checkpoint kinase of metazoa and yeast, ATR/MEC1, protects chromosomes from DNA damage and replication stress by phosphorylating subunits of the replicative helicase, MCM2-7. Here we describe an unprecedented ATR-dependent pathway in Tetrahymena thermophila in which the essential pre-replicative complex proteins, Orc1p, Orc2p and Mcm6p are degraded in hydroxyurea-treated S phase cells. Chromosomes undergo global changes during HU-arrest, including phosphorylation of histone H2A.X, deacetylation of histone H3, and an apparent diminution in DNA content that can be blocked by the deacetylase inhibitor sodium butyrate. Most remarkably, the cell cycle rapidly resumes upon hydroxyurea removal, and the entire genome is replicated prior to replenishment of ORC and MCMs. While stalled replication forks are elongated under these conditions, DNA fiber imaging revealed that most replicating molecules are produced by new initiation events. Furthermore, the sole origin in the ribosomal DNA minichromosome is inactive and replication appears to initiate near the rRNA promoter. The collective data raise the possibility that replication initiation occurs by an ORC-independent mechanism during the recovery from HU-induced replication stress.
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http://dx.doi.org/10.1371/journal.pgen.1005405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4517752PMC
July 2015

Genetic Architecture of Natural Variation in Rice Chlorophyll Content Revealed by a Genome-Wide Association Study.

Mol Plant 2015 Jun 5;8(6):946-57. Epub 2015 Mar 5.

National Key Laboratory of Crop Genetic Improvement and National Center of Plant Gene Research (Wuhan), Huazhong Agricultural University, Wuhan 430070, China. Electronic address:

Chlorophyll content is one of the most important physiological traits as it is closely related to leaf photosynthesis and crop yield potential. So far, few genes have been reported to be involved in natural variation of chlorophyll content in rice (Oryza sativa) and the extent of variations explored is very limited. We conducted a genome-wide association study (GWAS) using a diverse worldwide collection of 529 O. sativa accessions. A total of 46 significant association loci were identified. Three F2 mapping populations with parents selected from the association panel were tested for validation of GWAS signals. We clearly demonstrated that Grain number, plant height, and heading date7 (Ghd7) was a major locus for natural variation of chlorophyll content at the heading stage by combining evidence from near-isogenic lines and transgenic plants. The enhanced expression of Ghd7 decreased the chlorophyll content, mainly through down-regulating the expression of genes involved in the biosynthesis of chlorophyll and chloroplast. In addition, Narrow leaf1 (NAL1) corresponded to one significant association region repeatedly detected over two years. We revealed a high degree of polymorphism in the 5' UTR and four non-synonymous SNPs in the coding region of NAL1, and observed diverse effects of the major haplotypes. The loci or candidate genes identified would help to fine-tune and optimize the antenna size of canopies in rice breeding.
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http://dx.doi.org/10.1016/j.molp.2015.02.014DOI Listing
June 2015

Developmental regulation of the Tetrahymena thermophila origin recognition complex.

PLoS Genet 2015 Jan 8;11(1):e1004875. Epub 2015 Jan 8.

Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center, College Station, Texas, United States of America; Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas, United States of America.

The Tetrahymena thermophila DNA replication machinery faces unique demands due to the compartmentalization of two functionally distinct nuclei within a single cytoplasm, and complex developmental program. Here we present evidence for programmed changes in ORC and MCM abundance that are not consistent with conventional models for DNA replication. As a starting point, we show that ORC dosage is critical during the vegetative cell cycle and development. A moderate reduction in Orc1p induces genome instability in the diploid micronucleus, aberrant division of the polyploid macronucleus, and failure to generate a robust intra-S phase checkpoint response. In contrast to yeast ORC2 mutants, replication initiation is unaffected; instead, replication forks elongation is perturbed, as Mcm6p levels decline in parallel with Orc1p. Experimentally induced down-regulation of ORC and MCMs also impairs endoreplication and gene amplification, consistent with essential roles during development. Unexpectedly Orc1p and Mcm6p levels fluctuate dramatically in developing wild type conjugants, increasing for early cycles of conventional micronuclear DNA replication and macronuclear anlagen replication (endoreplication phase I, rDNA gene amplification). This increase does not reflect the DNA replication load, as much less DNA is synthesized during this developmental window compared to vegetative S phase. Furthermore, although Orc1p levels transiently increase prior to endoreplication phase II, Orc1p and Mcm6p levels decline when the replication load increases and unconventional DNA replication intermediates are produced. We propose that replication initiation is re-programmed to meet different requirements or challenges during the successive stages of Tetrahymena development.
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http://dx.doi.org/10.1371/journal.pgen.1004875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287346PMC
January 2015

Age and sex-specific relationships between phthalate exposures and obesity in Chinese children at puberty.

PLoS One 2014 14;9(8):e104852. Epub 2014 Aug 14.

Department of Maternal, Child and Adolescent Health, School of Public Health/Key Laboratory of Public Health Safety of Chinese Ministry of Education, Fudan University, Shanghai, China.

Objective: To examine the age and sex-specific associations of urine levels of six mono-phthalates with body size and fat distribution in Chinese children at puberty.

Materials And Methods: Four hundred and ninety-three school-aged children (247 boys, 246 girls) were recruited. Obesity related anthropometric indices were measured and body fat proportion (BF%) was calculated. Spot urine samples were collected and phthalate monoesters were detected by an API 2000 electrospray triple quadrupole mass spectrometer (ESI-MS/MS). Associations between phthalate exposure and overweight/obesity measures and their trends were examined by multiple linear regression and Logistic regression analyses, respectively.

Results: Di-2-ethylhexyl phthalate (DEHP) metabolites and monobutyl phthalate (MBP) were found to be the most detectable chemicals. In 8-10 years (yrs) group, concentrations of MEHP and MBP were significantly higher in girls than those in boys. However, concentrations of all phthalate monoesters, except for MEP and MEHP, in 11-13 yrs boys were significantly higher than those in girls. After adjusting for confounders including puberty onset, urinary concentrations of MBP and sum of low molecular-weight phthalate metabolites (∑LMP) were positively associated with boys' obesity in a concentration-effect manner, while concentrations of MEHP, MEHHP and sum of DEHP metabolites (∑MEHP) were negatively associated with girls' obesity. Associations between phthalate exposure levels and BMI z-score changes were age- and sex-specific in school-age children.

Conclusion: There are age and sex-specific concentration-effect associations between phthalate exposure and fat distribution in Chinese children. Urinary phthalate levels in 11-13 yrs boys were about 30 percent higher than those in girls, and ∑MEHP levels in younger boys (<10 yrs) were significantly higher than those in elder boys (>10 yrs). Associations were positive for MBP and ∑LMP with both BMI z-score and fat distribution in boys >10 years of age, and negative for ∑MEHP with fat distribution in girls <10 years of age.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0104852PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133266PMC
March 2016

New insight into the effects of Ca(II) on cake layer structure in submerged membrane bioreactors.

Biofouling 2014 10;30(5):571-8. Epub 2014 Apr 10.

a State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering , Tongji University , Shanghai , PR China.

The effects of Ca(II) on the structure of the cake layer in submerged membrane bioreactors (SMBRs) were investigated in this study. Three parallel laboratory-scale SMBRs were operated with synthetic municipal wastewater with three Ca(II) levels (82, 208 and 410 mg l(-1)). As the Ca(II) concentration increased, the sludge floc size increased and the molecular weight of the soluble microbial products (SMP) in the bulk liquid decreased. These observations were attributed to the neutralization and bridging function of Ca(II). Furthermore, Ca(II) addition did not change the thickness of the cake layer, but inhibited the deposition of other elements, such as Al, Si, Mg, and Fe. As a result of Ca(II) addition, the cake layer became less compact and more porous. The interspaces among the flocs in the cake layer helped to reduce the membrane fouling potential.
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http://dx.doi.org/10.1080/08927014.2014.905546DOI Listing
January 2015

Application of a sewage-based approach to assess the use of ten illicit drugs in four Chinese megacities.

Sci Total Environ 2014 Jul 31;487:710-21. Epub 2014 Jan 31.

Toxicological Centre, University of Antwerp, Antwerp, Belgium. Electronic address:

Sewage-based epidemiology was applied for the first time to a number of mainland Chinese megacities. The application monitored influents to 9 sewage treatment plants (STPs) to estimate the use of illicit drugs in Beijing, Guangzhou, Shenzhen, and Shanghai. Altogether, 11.4 million inhabitants were covered during September-October 2012. 24-h composite raw sewage samples were collected for 4 consecutive days at each STP. Each collected sample was analyzed for cocaine, benzoylecgonine, ecgonine methylester, methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, 6-monoacetylmorphine, amphetamine, methamphetamine, ecstasy, mephedrone, methylenedioxypyrovalerone, 11-nor-9-carboxy-delta-9-tetrahydrocannabinol, ketamine, and norketamine. Through the analysis of these chemical residues, the use of amphetamine, cannabis, cocaine, ecstasy, heroin, mephedrone, methadone, methamphetamine, methylenedioxypyrovalerone and ketamine among Chinese urban inhabitants was monitored. The results obtained demonstrated in a quantitative way that the drug use patterns of Chinese are different from their European counterparts. Abuse of methamphetamine and ketamine was particularly noteworthy in China, while consumption of cocaine and ecstasy, the most popular drugs in Europe, was very low among the sampled Chinese inhabitants. Further, the use of most drugs demonstrated a geographical trend, since their use was much higher in the southern cities of Shenzhen and Guangzhou than it was in Beijing and Shanghai. Interestingly, the exclusive, but minor, metabolite of heroin, 6-monoacetylmorphine, was detected only sporadically. This would suggest that the use of heroin among Chinese urban users sampled in the study was low. Further, the patterns of drug use observed during the study are largely consistent with trends reported by the United Nations Office on Drugs and Crime. Overall, our study suggests that sewage-based epidemiology can readily be used to monitor the use of illicit drugs in those countries/regions where traditional means to monitor drug use patterns have only yielded limited or information of questionable reliability.
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http://dx.doi.org/10.1016/j.scitotenv.2014.01.043DOI Listing
July 2014

Effects of suspended titanium dioxide nanoparticles on cake layer formation in submerged membrane bioreactor.

Bioresour Technol 2014 12;152:101-6. Epub 2013 Nov 12.

State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China.

Effects of the suspended titanium dioxide nanoparticles (TiO2 NPs, 50 mg/L) on the cake layer formation in a submerged MBR were systematically investigated. With nanometer sizes, TiO2 NPs were found to aggravate membrane pore blocking but postpone cake layer fouling. TiO2 NPs showed obvious effects on the structure and the distribution of the organic and the inorganic compounds in cake layer. Concentrations of fatty acids and cholesterol in the cake layer increased due to the acute response of bacteria to the toxicity of TiO2 NPs. Line-analysis and dot map of energy-dispersive X-ray were also carried out. Since TiO2 NPs inhibited the interactions between the inorganic and the organic compounds, the inorganic compounds (especially SiO2) were prevented from depositing onto the membrane surface. Thus, the postponed cake layer fouling was due to the changing features of the complexes on the membrane surface caused by TiO2 NPs.
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http://dx.doi.org/10.1016/j.biortech.2013.11.006DOI Listing
August 2014

Effects of low-concentration Cr(VI) on the performance and the membrane fouling of a submerged membrane bioreactor in the treatment of municipal wastewater.

Biofouling 2014 Jan 25;30(1):105-14. Epub 2013 Nov 25.

a State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering , Tongji University , Shanghai , China ;

The effects of low-concentration Cr(VI) (0.4 mg l(-1)) on the performance of a submerged membrane bioreactor (SMBR) in the treatment of municipal wastewater, as well as membrane fouling were investigated. Compared with the SMBR for control municipal wastewater, the SMBR for Cr(VI)-containing municipal wastewater had a higher concentration of soluble microbial products (SMP) with lower molecular weights, and smaller sludge particle sizes. Furthermore, low-concentration Cr(VI) induced membrane fouling, especially irreversible membrane pore blocking, which markedly shortened the service life of the membrane.
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http://dx.doi.org/10.1080/08927014.2013.847925DOI Listing
January 2014

Contamination by persistent toxic substances in surface sediment of urban rivers in Chaohu City, China.

J Environ Sci (China) 2012 ;24(11):1934-41

College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China.

The concentration and spatial distribution of persistent toxic substances (PTS) in the river sediment in Chaohu City, China were investigated. A total of nine surface sediments were collected and the selected PTS pollutants including six heavy metals and nineteen polybrominated diphenyl ethers (PBDEs) were analyzed. The mean heavy metal concentrations (in mg/kg, dry weight) ranged within 0.18-1.53 (Hg), 50.08-200.18 (Cu), 118.70-313.65 (Zn), 50.77-310.85 (Cr), 37.12-92.72 (Pb) and 13.29-197.24 (As), and Cu, Zn and As have been regarded as the main metal pollutants. The levels of PBDEs (1.2-12.1 ng/g) and BDE-209 (2.4-30.5 ng/g) were at the middle level of the global range. BDE-209 was the predominant congener (67.0%-85.7%), which agrees with the fact that technical deca-BDE mixtures are the dominant PBDE formulation in China. The relative high level of PTS pollutants in the western part of the city is probably owing to the intensive agricultural activities and lack of sewerage system there. The ecological risk assessment with the sediment quality guidelines (SOGs) indicates that the urban river sediments in the city have been heavily contaminated by heavy metals with probable ecotoxicological impacts on freshwater organisms and the main toxic pollutants are Hg and As. The results of current study imply that the city, and perhaps many other small cities in China as well, requires immediate pollution control measures with emphasis on not only conventional organic pollutants but also on PTS such as heavy metals and PBDEs.
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http://dx.doi.org/10.1016/s1001-0742(11)61033-4DOI Listing
May 2013

A novel NADH-dependent and FAD-containing hydroxylase is crucial for nicotine degradation by Pseudomonas putida.

J Biol Chem 2011 Nov 23;286(45):39179-87. Epub 2011 Sep 23.

State Key Laboratory of Microbial Metabolism & School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.

Nicotine, the main alkaloid produced by Nicotiana tabacum and other Solanaceae, is very toxic and may be a leading toxicant causing preventable disease and death, with the rise in global tobacco consumption. Several different microbial pathways of nicotine metabolism have been reported: Arthrobacter uses the pyridine pathway, and Pseudomonas, like mammals, uses the pyrrolidine pathway. We identified and characterized a novel 6-hydroxy-3-succinoyl-pyridine (HSP) hydroxylase (HspB) using enzyme purification, peptide sequencing, and sequencing of the Pseudomonas putida S16 genome. The HSP hydroxylase has no known orthologs and converts HSP to 2,5-dihydroxy-pyridine and succinic semialdehyde, using NADH. (18)O(2) labeling experiments provided direct evidence for the incorporation of oxygen from O(2) into 2,5-dihydroxy-pyridine. The hspB gene deletion showed that this enzyme is essential for nicotine degradation, and site-directed mutagenesis identified an FAD-binding domain. This study demonstrates the importance of the newly discovered enzyme HspB, which is crucial for nicotine degradation by the Pseudomonas strain.
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http://dx.doi.org/10.1074/jbc.M111.283929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3234743PMC
November 2011

Novel nicotine oxidoreductase-encoding gene involved in nicotine degradation by Pseudomonas putida strain S16.

Appl Environ Microbiol 2009 Feb 5;75(3):772-8. Epub 2008 Dec 5.

Key Laboratory of Microbial Metabolism, Ministry of Education, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, People's Republic of China.

There are quite a few ongoing biochemical investigations of nicotine degradation in different organisms. In this work, we identified and sequenced a gene (designated nicA) involved in nicotine degradation by Pseudomonas putida strain S16. The gene product, NicA, was heterologously expressed and characterized as a nicotine oxidoreductase catalyzing the initial steps of nicotine metabolism. Biochemical analyses using resting cells and the purified enzyme suggested that nicA encodes an oxidoreductase, which converts nicotine to 3-succinoylpyridine through pseudooxynicotine. Based on enzymatic reactions and direct evidence obtained using H(2)(18)O labeling, the process may consist of enzyme-catalyzed dehydrogenation, followed by spontaneous hydrolysis and then repetition of the dehydrogenation and hydrolysis steps. Sequence comparisons revealed that the gene showed 40% similarity to genes encoding NADH dehydrogenase subunit I and cytochrome c oxidase subunit I in eukaryotes. Our findings demonstrate that the molecular mechanism for nicotine degradation in strain S16 involves the pyrrolidine pathway and is similar to the mechanism in mammals, in which pseudooxynicotine, the direct precursor of a potent tobacco-specific lung carcinogen, is produced.
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http://dx.doi.org/10.1128/AEM.02300-08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2632140PMC
February 2009

A novel gene, encoding 6-hydroxy-3-succinoylpyridine hydroxylase, involved in nicotine degradation by Pseudomonas putida strain S16.

Appl Environ Microbiol 2008 Mar 18;74(5):1567-74. Epub 2008 Jan 18.

State Key Laboratory of Microbial Technology, Shandong University, Jinan 250100, People's Republic of China.

Previous research suggested that Pseudomonas spp. may attack the pyrrolidine ring of nicotine in a way similar to mammalian metabolism, resulting in the formation of pseudooxynicotine, the direct precursor of a potent tobacco-specific lung carcinogen. In addition, the subsequent intermediates, 6-hydroxy-3-succinoylpyridine (HSP) and 2,5-dihydroxypyridine (DHP) in the Pseudomonas nicotine degradation pathway are two important precursors for drug syntheses. However, there is little information on the molecular mechanism for nicotine degradation via the pyrrolidine pathway until now. In this study we cloned and sequenced a 4,879-bp gene cluster involved in nicotine degradation. Intermediates N-methylmyosmine, pseudooxynicotine, 3-succinoylpyridine, HSP, and DHP were identified from resting cell reactions of the transformant containing the gene cluster and shown to be identical to those of the pyrrolidine pathway reported in wild-type strain Pseudomonas putida S16. The gene for 6-hydroxy-3-succinoylpyridine hydroxylase (HSP hydroxylase) catalyzing HSP directly to DHP was cloned, sequenced, and expressed in Escherichia coli, and the purified HSP hydroxylase (38 kDa) is NADH dependent. DNA sequence analysis of this 936-bp fragment reveals that the deduced amino acid shows no similarity with any protein of known function.
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http://dx.doi.org/10.1128/AEM.02529-07DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2258644PMC
March 2008
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