Publications by authors named "Yanping Guo"

43 Publications

Fixed-time consensus of nonlinear multi-agent system with uncertain disturbances based on event-triggered strategy.

ISA Trans 2021 Aug 3. Epub 2021 Aug 3.

School of Sciences, Hebei University of Science and Technology, Shijiazhuang, 050018, Hebei, PR China.

This paper presents a fixed-time consensus problem for multi-agent systems (MASs) with nonlinear dynamics and uncertain disturbances, the event-triggered strategy is proposed to address this issue. Firstly, based on event-triggered control theory, a fixed-time consensus protocol is proposed, which can avoid continuous communication and greatly reduces the power consumption of proposed protocols. Secondly, based on graph topology, fixed-time control method and Lyapunov theory, the novel fixed-time consensus criteria of MASs with nonlinearity under Lipschitz condition and uncertain disturbances bounds is derived via the designed protocols. Furthermore, the consensus can be guaranteed by setting the proper parameters, it should be pointed out that for any given initial state, the MASs can reach consensus within the setting time. Thirdly, by utilizing the above control strategy, the MASs have no Zeno behavior. Finally, two simulation examples and the practical application of unmanned air vehicles (UAVs) verify the reliability of proposed control scheme.
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http://dx.doi.org/10.1016/j.isatra.2021.07.044DOI Listing
August 2021

Using Fecal DNA Metabarcoding to Investigate Foraging Reveals the Effects of Specific Herbage on the Improved n-3 Fatty Acid (PUFA) Composition in the Longissimus Dorsi Muscle of Grazing Tan Sheep.

J Agric Food Chem 2021 Aug 11;69(33):9725-9734. Epub 2021 Aug 11.

State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.

Understanding the natural diet of grazing sheep can help fulfill their nutritional requirements and positively affect the quality of their meat. Emerging fecal DNA (fDNA) metabarcoding technology can provide more accurate estimates for the dietary composition of free-ranging animals. This study has shown that pasture feeding can promote deposition of n-3 polyunsaturated fatty acids (PUFAs) in Tan lambs' muscle and decrease the ratio of n-6/n-3 fatty acids (FAs), and thus, we investigated the dietary composition of grazing lambs using fDNA metabarcoding to assess the prevalence of medicinal herbage plants in their diet. Herein, based on the full-time natural pasture grazing and 4-h natural pasture grazing with indoor feeding patterns, the herbage taxa (, , , and sp.) most correlated to n-3 PUFAs were highlighted to elucidate how diversification in dietary components was associated with the muscle FA profile of lambs. Our findings provide experimental evidence for future feeding research.
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http://dx.doi.org/10.1021/acs.jafc.1c03788DOI Listing
August 2021

Defining the Role of Cellular Immune Signatures in Diagnostic Evaluation of Suspected Tuberculosis.

J Infect Dis 2021 Jul 31. Epub 2021 Jul 31.

TB Research Centre, National Heart and Lung Institute, Imperial College London, London, United Kingdom.

Background: Diagnosis of paucibacillary tuberculosis (TB) including extrapulmonary TB is a significant challenge, particularly in high-income, low-incidence settings. Measurement of Mycobacterium tuberculosis (Mtb)-specific cellular immune signatures by flow cytometry discriminates active TB from latent TB infection (LTBI) in case-control studies; however, their diagnostic accuracy and clinical utility in routine clinical practice is unknown.

Methods: Using a nested case-control study design within a prospective multicenter cohort of patients presenting with suspected TB in England, we assessed diagnostic accuracy of signatures in 134 patients who tested interferon-gamma release assay (IGRA)-positive and had final diagnoses of TB or non-TB diseases with coincident LTBI. Cellular signatures were measured using flow cytometry.

Results: All signatures performed less well than previously reported. Only signatures incorporating measurement of phenotypic markers on functional Mtb-specific CD4 T cells discriminated active TB from non-TB diseases with LTBI. The signatures measuring HLA-DR+IFNγ + CD4 T cells and CD45RA-CCR7-CD127- IFNγ -IL-2-TNFα + CD4 T cells performed best with 95% positive predictive value (95% confidence interval, 90-97) in the clinically challenging subpopulation of IGRA-positive but acid-fast bacillus (AFB) smear-negative TB suspects.

Conclusions: Two cellular immune signatures could improve and accelerate diagnosis in the challenging group of patients who are IGRA-positive, AFB smear-negative, and have paucibacillary TB.
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http://dx.doi.org/10.1093/infdis/jiab311DOI Listing
July 2021

Precise Tuning of Band Structures and Electron Correlations by van der Waals Stacking of One-dimensional WTe Wires.

Nano Lett 2020 Dec 23;20(12):8866-8873. Epub 2020 Nov 23.

School of Physics and Technology, and Key Laboratory of Artificial Micro- and Nano-structures of Ministry of Education, Wuhan University, Wuhan 430072, China.

Stacking of two-dimensional (2D) van der Waals (vdW) atomic sheets has been established as a powerful approach to fabricating new materials with broad versatilities and emergent functionalities. Here we demonstrate a bottom-up approach to fabricating isolated single WTe wires and their lateral assemblies, offering a unique platform for investigating the elegant role of vdW coupling in 1D systems with atomic precision. We find experimentally and theoretically a single WTe wire is a 1D semiconductor with a band gap of ∼60 meV, and a semiconductor-to-metal transition takes place upon interwire vdW stacking. The metallic multiwires exhibit strong Tomonaga-Luttinger liquid characteristics with the correlation parameter varying from = 0.086 for biwire to = 0.136 for six-wire assemblies, all much reduced from the Fermi liquid regime ( = 1). The present study demonstrates wire-by-wire vdW stacking is a versatile means for fabrication of 1D systems with tunable electronic properties.
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http://dx.doi.org/10.1021/acs.nanolett.0c03897DOI Listing
December 2020

Human Papillomavirus E7 Oncoprotein Promotes Proliferation and Migration through the Transcription Factor E2F1 in Cervical Cancer Cells.

Anticancer Agents Med Chem 2021 ;21(13):1689-1696

Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Background: High-Risk Human Papillomavirus (HR-HPV) persistent infection is the main cause of cervical cancer and its precancerous lesions. A previous study showed that HPV16 and HPV58 infections were the most common infection types in the local region. Some studies also declared that HPV58 E7 variants increased the risk of cervical cancer among Asian populations.

Objective: This study aimed to determine whether the HPV58 E7 T20I (C632T) variant promotes the malignant behavior of cervical cancer cells and the underlying mechanism of the HR-HPV E7 oncoprotein involved in the development of cervical cancer.

Methods: CCK-8 and clone formation assays were used to detect cell proliferation ability. Transwell assays and cell wound healing assays were used to evaluate cell migration ability. Targeted knockdown of E2F1 expression using specific siRNA, RT-qPCR and Western blot were performed to assess gene expression changes. A chromatin immunoprecipitation assay was used to verify that E2F1 interacted with the TOP2A promoter region.

Results: HPV58 E7 and HPV58 E7M oncoproteins increased the proliferation and migration ability of cervical cancer cells. However, the HPV58 E7 T20I variant did not promote malignant behaviors compared with wildtype HPV58 E7. HPV E7 and E7M oncoproteins increased the expression of TOP2A, BIRC5 and E2F1, and knockdown of HPV E7 decreased their expression. Low E2F1 expression reduced the expression of TOP2A and BIRC5 and inhibited the proliferation and migration ability of cervical cancer cells. E2F1 interacted with the TOP2A gene promoter region to promote its transcriptional expression.

Conclusion: The HPV58 E7 T20I variant did not promote malignant behaviors compared with wild-type HPV58 E7. The HR-HPV E7 oncoprotein enhanced the proliferation and migration of cervical cancer cells, which was considered to be due to the HPV E7 oncoprotein, increasing the expression of BIRC5 and TOP2A by upregulating the transcription factor E2F1.
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http://dx.doi.org/10.2174/1871520620666201106085227DOI Listing
January 2021

Isolating Pathogen-Specific Human Monoclonal Antibodies (hmAbs) Using Bacterial Whole Cells as Molecular Probes.

Methods Mol Biol 2021 ;2183:9-18

Section of Paediatric Infectious Disease, Department of Infectious Disease, Imperial College London, London, UK.

The immunoglobulin capture assay (ICA) enables the enrichment for pathogen-specific plasmablasts from individuals with a confirmed adaptive immune response to vaccination or disseminated infection. Only single recombinant antigens have been used previously as probes in this ICA and it was unclear whether the method was applicable to complex probes such as whole bacterial cells. Here, we describe the enrichment of plasmablasts specific for polysaccharide and protein antigens of both Streptococcus pneumoniae and Neisseria meningitidis using whole formalin-fixed bacterial cells as probes. The modified ICA protocol described here allowed for a pathogen-specific hmAb cloning efficiency of >80%.
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http://dx.doi.org/10.1007/978-1-0716-0795-4_2DOI Listing
March 2021

Decomplexation of heterogeneous catalytic ozonation assisted with heavy metal chelation for advanced treatment of coordination complexes of Ni.

Sci Total Environ 2020 Aug 8;732:139223. Epub 2020 May 8.

Guangzhou Key Laboratory Environmental Catalysis and Pollution Control, Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, School of Environmental Science and Engineering, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou 510006, China.

Following the conventional physicochemical treatment of electroless nickel (Ni) plating wastewater (ENPW) in electroplating wastewater treatment plants, highly stable and recalcitrant coordination complexes of Ni (CCN) still remain. This results in various technical problems, leading to the treatment difficulty, poor wastewater biochemistry, and failure to meet effluent standards. Therefore, an efficient decomplexation system involving heterogeneous catalytic ozonation assisted with heavy metal chelation (O/SAO3II-MDCR) was proposed in this study for the advanced treatment of CCN. The catalyst SAO3II was characterized by various methods, which revealed the mechanism of catalytic ozonation. Hydroxyl radicals (OH) and other reactive oxygen species (ROS) groups were detected, proving that catalytic ozonation was a complicated reaction process and also a foundation process of the entire system. These ROS are vital for decomplexation via heterogeneous catalytic ozonation of the system. During the catalytic decomplexation process via ozonation, CCN first underwent gradual decomposition from a highly stable macromolecular state to a volatile micromolecular state (or even completely mineralized state). Then Ni was chelated to form an insoluble and stable chelate via competitive coordination. The optimum conditions for the O/SAO3II-MDCR system were determined by single factor static experiments. After treatment with the O/SAO3II-MDCR system, the effluent concentration of total Ni was found to be <0.1 mg L, exhibiting a removal rate of up to 95.6% and achieving effective removal of total Ni from ENPW and stably meeting the discharge standard. O/SAO3II-MDCR system can easily and hopefully be extended to practical engineering applications.
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http://dx.doi.org/10.1016/j.scitotenv.2020.139223DOI Listing
August 2020

Evaluation of Risk Factors for Venous Thromboembolism in Patients Who Underwent Gynecological Surgery and Validation of a Fast-Rating Assessment Table.

Med Sci Monit 2019 Nov 21;25:8814-8819. Epub 2019 Nov 21.

Department of Gynecology and Obstetrics, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland).

BACKGROUND The aim of this study was to retrospectively analyze the risk factors for venous thromboembolism (VTE) in gynecological patients and verify the validity of a fast-rating assessment table. MATERIAL AND METHODS From October 2015 to October 2017, 53 patients complicated with VTE after gynecological operations were analyzed, and a total of 106 patients with 2 adjacent operations were selected as the control group. Factors such as age, body mass index (BMI), and tumor type were analyzed by univariate and multivariate analysis. A fast-rating assessment table of VTE risk factors was constructed. This fast-rating assessment table and the Caprini score table were used to compare the scores of all patients. RESULTS In the univariate analysis, there were significant differences in BMI, tumor type, operation duration, blood loss, blood transfusion, bed rest time, and thrombus-related history between the 2 groups. In the multiple factor analysis, age >60 years old, BMI >28 kg/m², malignant tumors, operation duration ≥3 hours, laparoscopic surgery and thrombus-related history were independent risk factors for VTE in patients. Both the fast-rating assessment table and the Caprini score table identified 90% of VTE patients as high-risk and very high-risk, and there was no significant difference between the tables. CONCLUSIONS Patients with older age, high BMI, malignant tumors, longer operation duration, laparoscopic surgery, or history of thrombosis may be more prone to VTE after gynecologic surgery. The fast-rating assessment table is easy to operate and has a high recognition level for VTE. It can be applied widely.
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http://dx.doi.org/10.12659/MSM.920198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882298PMC
November 2019

Responses to Quadrivalent Influenza Vaccine Reveal Distinct Circulating CD4+CXCR5+ T Cell Subsets in Men Living with HIV.

Sci Rep 2019 10 30;9(1):15650. Epub 2019 Oct 30.

Section of Virology, Department of Infectious Disease, Imperial College London, London, UK.

T cell help for B cells may be perturbed in people living with HIV (PLWH), even when HIV is suppressed, as evidenced by reports of suboptimal responses to influenza vaccination. We investigated cT responses to the 2017-18 inactivated quadrivalent influenza vaccine (QIV) in men living with antiretroviral therapy (ART)-suppressed HIV infection who were treated in the early or chronic phase of infection, and control subjects. Here we show that seroprotective antibody responses in serum and oral fluid correlated with cT activation and were equivalent in all three groups, irrespective of when ART was started. These responses were attenuated in those reporting immunisation with influenza vaccine in the preceding three years, independent of HIV infection. Measurement of influenza-specific IgG in oral fluid was closely correlated with haemagglutination inhibition titre. T-SNE and two-dimensional analysis revealed a subset of CD4CXCR3CXCR5 cT activated at one week after vaccination. This was distinguishable from cTFH not activated by vaccination, and a rare, effector memory CD4CXCR5CD32 T cell subset. The data support the use of QIV for immunisation of PLWH, reveal distinct circulating CD4CXCR5 T cell subsets and demonstrate oral fluid sampling for influenza-specific IgG is an alternative to phlebotomy.
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http://dx.doi.org/10.1038/s41598-019-51961-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821795PMC
October 2019

Adaptive neural network based position tracking control for Dual-master/Single-slave teleoperation system under communication constant time delays.

ISA Trans 2019 Oct 20;93:80-92. Epub 2019 Mar 20.

School of Electrical Engineering, Hebei University of Science and Technology, Shijiazhuang, 050018, Hebei, PR China.

The novel trajectory tracking control strategies for trilateral teleoperation systems with Dual-master/Single-slave robot manipulators under communication constant time delays are proposed in this article. By incorporating this design technique into the neural network (NN) based adaptive control framework, two controllers are designed for the trilateral teleoperation systems in free motion. First, with acceleration measurements, an adaptive controller under the synchronization variables containing the position and velocity error is constructed to guarantee the position and velocity tracking errors between the trilateral teleoperation systems asymptotically converge to zero. Second, without acceleration measurements, an adaptive controller under the new synchronization variables is presented such that the trilateral teleoperation systems can obtain the same trajectory tracking performance as the first controller. Third, in term of establishing suitable Lyapunov-Krasovskii functionals, the asymptotic tracking performances of the trilateral teleoperation systems can be derived independent of the communication constant time delays. Moreover, these two controllers are obtained without the knowledge of upper bounds of the NN approximation errors, respectively. Finally, simulation results are presented to demonstrate the validity of the proposed methods.
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http://dx.doi.org/10.1016/j.isatra.2019.03.019DOI Listing
October 2019

Therapeutic evaluation of acupoint stimulation with needle-scapelon on rat model of degenerative cervical intervertebral discs.

Biomed Pharmacother 2019 Feb 12;110:677-684. Epub 2018 Dec 12.

Department of Acupuncture, Qianfo Shan Hospital, Jinan, Shandong Province, 250014, China.

Cervical spondylosis (CS), which is resulted from degeneration of cervical intervertebral disc, is a common disease seriously threatening human health and quality of life. However, there is still no effective clinic strategies for the treatment of this disease. The acupoint stimulation with needle-scalpel is a widely used approach to treat orthopedic diseases. In the present study, we evaluated the therapeutic effects of acupoint stimulation around neck with needle-scalpel on delaying the degeneration of cervical intervertebral discs and hopefully provided an approach for the precaution and early intervention of CS. We firstly established a rat model of CS by cervical static-dynamic imbalance to mimics disc degeneration and then stimulated the acupoints around neck with needle-scalpel. The cervical intervertebral disc samples were collected to measure type I and II collagen by quantitative PCR (qPCR), immunohistochemistry, and western blot. The changes in micro-structure and ultra-structure of nucleus pulposus were analyzed under the optical microscope and electron microscope respectively. Acupoint stimulation with needle-scapelon increased type I collagen production and decreased type II collagen production, and improved the micro-structure and ultra-structure of nucleus pulposus. Our results suggest that acupoint stimulation around neck with needle-scapelon could inhibit intervertebral disc degeneration through modulating the extracellular matrix collagen system and improving the changed structure of nucleus pulposus.
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http://dx.doi.org/10.1016/j.biopha.2018.11.070DOI Listing
February 2019

Potassium fertilization arrests malate accumulation and alters soluble sugar metabolism in apple fruit.

Biol Open 2018 Dec 14;7(12). Epub 2018 Dec 14.

Shaanxi Engineering Research Center for Apple, Northwest A&F University, Yangling 712100, Shaanxi, China.

Effects of different potassium (K) levels, which were K0 (no fertilizer), K1 (71.5 g KCl plant year), K2 (286.7 g KCl plant year), and K3 (434 g KCl plant year), were evaluated based on sugar and organic acid metabolism levels from 70-126 days after bloom (DAB) in the developing fruit of potted five-year-old apple (, Borkh.) trees. The results indicate that K fertilization promoted greater fruit mass, higher Ca and soluble solid levels, and lower titratable acid levels, as well as increased pH values at harvest. With the application of different levels of K fertilizer, fructose, sorbitol, glucose and sucrose accumulation rates significantly changed during fruit development. Fruit in the K2 group had higher fructose, sucrose and glucose levels than those in other treatment groups at 126 DAB. These changes in soluble sugar are related to the activity of metabolic enzymes. Sucrose synthase (SS) and sorbitol dehydrogenase (SDH) activity in the K2 treated fruit was significantly higher than those in other treatment groups from 70-126 DAB. Malate levels in K-supplemented fruit were notably lower than those in non K-supplemented fruit, and K3 treated fruit had the lowest malate levels during fruit development. Cytosolic malic enzyme (ME) and phosphoenolpyruvate carboxykinase (PEPCK) activity significantly increased in fruit under the K2 treatment during 112-126 DAB and 98-126 DAB, respectively. In addition, Ca concentration increased with increasing K fertilization levels, which promoted a maximum of 11.72 mg g dry weight in apple fruit. These results show that K levels can alter soluble sugar and malate levels due to the interaction between sugars and acid-metabolic enzymes in fruit.
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http://dx.doi.org/10.1242/bio.024745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310881PMC
December 2018

Validating the RedMIT/GFP-LC3 Mouse Model by Studying Mitophagy in Autosomal Dominant Optic Atrophy Due to the OPA1Q285STOP Mutation.

Front Cell Dev Biol 2018 19;6:103. Epub 2018 Sep 19.

Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, United Kingdom.

Autosomal dominant optic atrophy (ADOA) is usually caused by mutations in the essential gene, OPA1. This encodes a ubiquitous protein involved in mitochondrial dynamics, hence tissue specificity is not understood. Dysregulated mitophagy (mitochondria recycling) is implicated in ADOA, being increased in OPA1 patient fibroblasts. Furthermore, autophagy may be increased in retinal ganglion cells (RGCs) of the OPA1 mouse model. We developed a mouse model for studying mitochondrial dynamics in order to investigate mitophagy in ADOA. We crossed the OPA1 mouse with our RedMIT/GFP-LC3 mouse, harboring red fluorescent mitochondria and green fluorescent autophagosomes. Colocalization between mitochondria and autophagosomes, the hallmark of mitophagy, was quantified in fluorescently labeled organelles in primary cell cultures, using two high throughput imaging methods Imagestream (Amnis) and IN Cell Analyzer 1000 (GE Healthcare Life Sciences). We studied colocalization between mitochondria and autophagosomes in fixed sections using confocal microscopy. We validated our imaging methods for RedMIT/GFP-LC3 mouse cells, showing that colocalization of red fluorescent mitochondria and green fluorescent autophagosomes is a useful indicator of mitophagy. We showed that colocalization increases when lysosomal processing is impaired. Further, colocalization of mitochondrial fragments and autophagosomes is increased in cultures from the OPA1/RedMIT/GFP-LC3 mice compared to RedMIT/GFP-LC3 control mouse cells that were wild type for OPA1. This was apparent in both mouse embryonic fibroblasts (MEFs) using IN Cell 1000 and in splenocytes using ImageStream imaging flow cytometer (Amnis). We confirmed that this represents increased mitophagic flux using lysosomal inhibitors. We also used microscopy to investigate the level of mitophagy in the retina from the OPA1/RedMIT/GFP-LC3 mice and the RedMIT/GFP-LC3 control mice. However, the expression levels of fluorescent proteins and the image signal-to-background ratios precluded the detection of colocalization so we were unable to show any difference in colocalization between these mice. We show that colocalization of fluorescent mitochondria and autophagosomes in cell cultures, but not fixed tissues from the RedMIT/GFP-LC3, can be used to detect mitophagy. We used this model to confirm that mitophagy is increased in a mouse model of ADOA. It will be useful for cell based studies of diseases caused by impaired mitochondrial dynamics.
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http://dx.doi.org/10.3389/fcell.2018.00103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156146PMC
September 2018

Herbivore-Diet Analysis Based on Illumina MiSeq Sequencing: The Potential Use of an ITS2-Barcoding Approach to Establish Qualitative and Quantitative Predictions of Diet Composition of Mongolian Sheep.

J Agric Food Chem 2018 Sep 10;66(37):9858-9867. Epub 2018 Sep 10.

Key Laboratory of Grassland Management and Utilization, Ministry of Agriculture; Department of Grassland Science, College of Animal Science and Technology , China Agricultural University , Beijing 100193 , China.

DNA-barcoding approaches to estimate the diet compositions of grazing animals have received significant attention, and particularly when combined with next-generation sequencing, these techniques have substantially improved in recent years. In this study, the identity and species composition of plant material ingested by Mongolian sheep were estimated through the use of 350 bp ITS2 gene sequences of the vegetation found in fecal samples. Four diets were formulated using varying amounts of eight plant species that are common in the grasslands of northern China. Sixteen Mongolian sheep were taken from pastures and randomly assigned to four groups, and each group received one of four diets. Each sheep was randomly assigned to one of 16 confinement pens and fed its respective diet for 12 consecutive days. Fecal samples were removed from each pen from days 7-12, preserved, and composited for each pen. All herbage species included in the daily diets were detected in each fecal sample, with the exception of Phragmites australis. Moreover, 12 additional different plant species were retrieved from feces of the experimental sheep. The obtained data provided preliminary support for the use of the ITS2 barcode to determine which plants were consumed. Moreover, the proportions of the herbage DNA sequences recovered from sheep feces and those of the herbage masses in the daily diets did not completely match. These results indicate that the non-Gramineae DNA sequences amplified with ITS2 primers (including those of Chenopodium album, Artemisia scoparia, Artemisia tanacetifolia, and Medicago sativa) far exceeded those of the Gramineae species (including Leymus chinensis and Puccinellia distans), which constitute the largest share of the experimental diets. A significant positive correlation (Spearman's ρ = 0.376, P = 0.003) between the actual herbage mass proportions in the experimental diets and the herbage-DNA-sequence proportions provided sufficiently favorable support for the further investigation of DNA barcoding for the quantification of plants in feces. A significant regression coefficient was found between the relative DNA-sequence proportions of L. chinensis ( R = 0.82, P < 0.0001), P. distans ( R = 0.64, P = 0.0017), and C. album ( R = 0.98, P < 0.0001) and their respective herbage mass proportions. The quantitative relationship can be expressed by the linear-regression equations y = 0.90 x - 0.22, y = 0.98 x - 0.03, and y = 5.00 x - 0.25, respectively. Thus, these results demonstrate that dietary-DNA-barcoding methods exhibited potential in providing valuable quantitative information regarding food-item components. However, it should be noted that this explorative data needs to be further improved by using additional genes and by creating a sophisticated reference database, thus enhancing both quality and accuracy of the obtained results.
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http://dx.doi.org/10.1021/acs.jafc.8b02814DOI Listing
September 2018

Effects of drought stress on photosynthesis and photosynthetic electron transport chain in young apple tree leaves.

Biol Open 2018 Nov 22;7(11). Epub 2018 Nov 22.

College of Horticulture, Northwest A&F University, Yangling, Shaanxi 712100, China.

In our study, the effects of water stress on photosynthesis and photosynthetic electron transport chain (PETC) were studied in several ways, including monitoring the change of gas exchange parameters, modulated chlorophyll fluorescence, rapid fluorescence induction kinetics, reactive oxygen species (ROS), antioxidant enzyme activities and D1 protein levels in apple leaves. Our results show that when leaf water potential ( ) is above -1.5 MPa, the stomatal limitation should be the main reason for a drop of photosynthesis. In this period, photosynthetic rate ( ), stomatal conductance ( ), transpiration rate () and intercellular CO concentration ( ) all showed a strong positive correlation with Modulated chlorophyll fluorescence parameters related to photosynthetic biochemistry activity including maximum photochemical efficiency (F/F), actual photochemical efficiency of PSII (Φ), photochemical quenching coefficient ( ) and coefficient of photochemical fluorescence quenching assuming interconnected PSII antennae ( ) also showed a strong positive correlation as gradually decreased. On the other hand, in this period, Stern-Volmer type non-photochemical quenching coefficient (NPQ) and quantum yield of light-induced non-photochemical fluorescence quenching [ ] kept going up, which shows an attempt to dissipate excess energy to avoid damage to plants. When was below -1.5 MPa, continued to decrease linearly, while increased and a 'V' model presents the correlation between and by polynomial regression. This implies that, in this period, the drop in photosynthesis activity might be caused by non-stomatal limitation. F/F, Φ, and in apple leaves treated with water stress were much lower than in control, while NPQ and started to go down. This demonstrates that excess energy might exceed the tolerance ability of apple leaves. Consistent with changes of these parameters, excess energy led to an increase in the production of ROS including HO and O Although the activities of antioxidant enzymes like catalase (CAT), superoxide dismutase (SOD) and peroxidase (POD) increased dramatically and ascorbate peroxidase (APX) decreased in apple leaves with drought stress, it was still not sufficient to scavenge ROS. Consequently, the accumulation of ROS triggered a reduction of net D1 protein content, a core protein in the PSII reaction center. As D1 is responsible for the photosynthetic electron transport from plastoquinone A (Q) to plastoquinone B (Q), the capacity of PETC between Q and Q was considerably downregulated. The decline of photosynthesis and activity of PETC may result in the shortage of adenosine triphosphate (ATP) and limitation the regeneration of RuBP ( ), a key enzyme in CO assimilation. These are all non-stomatal factors and together contributed to decreased CO assimilation under severe water stress.
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http://dx.doi.org/10.1242/bio.035279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262865PMC
November 2018

miR-5591-5p regulates the effect of ADSCs in repairing diabetic wound via targeting AGEs/AGER/JNK signaling axis.

Cell Death Dis 2018 05 1;9(5):566. Epub 2018 May 1.

Department of Plastic Surgery, Affiliated Hospital of Xuzhou Medical University, Jiangsu, Xuzhou, China.

Advanced glycation end products/advanced glycation end products receptor (AGEs/AGER) interaction triggers reactive oxygen species (ROS) generation and activates downstream signal pathways and induces apoptosis in endothelial progenitor cells. A number of studies have revealed the involvement of microRNAs (miRNAs) in regulating intracellular ROS production and apoptosis. However, few studies explore the role of miRNAs in regulating the effect of adipose tissue-derived stem cells (ADSCs) in repairing diabetic wound and the associated cellular mechanisms remain unclear. In this study, ADSCs were exposed to AGEs, then siRNA for AGER was transfected into ADSCs. We found that AGEs/AGER axis induced ROS generation and apoptosis in ADSCs. AGEs treatment downregulated miR-5591-5p in ADSCs, which directly targeted AGER. miR-5591-5p suppressed AGEs/AGER axis-mediated ROS generation and apoptosis in ADSCs in vitro. In addition, miR-5591-5p promoted cell survival and enhanced the ability of ADSCs for repairing cutaneous wound in vivo. Furthermore, we confirmed that c-jun kinase (JNK) signal was involved in the inhibitory effect of miR-5591-5p on AGEs/AGER axis-induced ROS generation and apoptosis in ADSCs. Thus, these results indicated that miR-5591-5p targeting AGEs/AGER/JNK signaling axis possibly regulates the effect of ADSCs in repairing diabetic wound.
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http://dx.doi.org/10.1038/s41419-018-0615-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5948214PMC
May 2018

Isolation and Characterization of Antigen-Specific Plasmablasts Using a Novel Flow Cytometry-Based Ig Capture Assay.

J Immunol 2017 12 8;199(12):4180-4188. Epub 2017 Nov 8.

Division of Medicine, Department of Infectious Diseases, Imperial College London, London W2 1PG, United Kingdom; and

We report the development of a novel flow cytometry-based Ig capture assay (ICA) for the identification and sorting of individual Ab-secreting cells based on their Ag reactivity. The ICA represents a fast and versatile tool for single-cell sorting of peripheral plasmablasts, streamlining subsequent Ab analysis, and cloning. We demonstrate the utility of the assay by isolating Ag-reactive plasmablasts from cryopreserved PBMC obtained from volunteers vaccinated with a recombinant HIV envelope protein. To show the specificity of the ICA, we produced Ag-specific Abs from these cells and subsequently verified their Ag reactivity via ELISA. Furthermore, we used the ICA to track Ag-specific plasmablast responses in HIV-vaccine recipients over a period of 42 d and performed a head-to-head comparison with a conventional B cell ELISpot. Results were highly comparable, highlighting that this assay is a viable alternative for monitoring Ag-specific plasmablast responses at early time points after infection or vaccination. The ICA provides important added benefits in that phenotypic information can be obtained from the identified Ag-specific cells that can then be captured for downstream applications such as B cell sequencing and/or Ab cloning. We envisage the ICA as being a useful tool in Ab repertoire analysis for future clinical trials.
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http://dx.doi.org/10.4049/jimmunol.1701253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5720343PMC
December 2017

Negative immune factors might predominate local tumor immune status and promote carcinogenesis in cervical carcinoma.

Virol J 2017 01 13;14(1). Epub 2017 Jan 13.

Department of Obstetrics and Gynecology, First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, China.

Background: The disequilibrium of local immune microenvironment is an essential element during tumorigenesis.

Method: By conducting real-time polymerase chain reaction, we identified the mRNA level of immune factors, FoxP3 (forkhead box protein P3), CCL22/CCR4 (chemokine (C-C motif) ligand 22/CC chemokine receptor 4), OX40L/OX40 (tumor necrosis factor superfamily member 4/tumor necrosis factor receptor superfamily member 4) and Smad3 (SMAD family member 3) in neoplastic foci and its periphery tissues from 30 cases of squamous cervical carcinoma and 20 cases of normal cervix.

Result: The FoxP3, CCL22 and CCR4 mRNA level in local immune microenvironment of normal cervix was lower than that in cervical cancer. While OX40L, OX40 and Smad3 mRNA level profile in normal cervix was higher than that in cervical cancer. Beyond individual effect, the pairwise positive correlations were demonstrated among the mRNA level of FoxP3, CCL22 and CCR4. The mRNA level of OX40 negatively correlated with CCL22, but positively correlated with Smad3. Moreover, the mRNA level of FoxP3 and CCL22 was increased while Smad3 was decreased in cervical tissue with HPV (human papilloma virus) infection.

Conclusion: Our data yields insight into the roles of these immune factors in cervical carcinogenesis. It may therefore be that, in microenvironment of cervical squamous cell carcinoma, along with the context of HPV infection, negative immune regulators FoxP3, CCL22 and CCR4 might overwhelm positive immune factors OX40L, OX40 and Smad3, giving rise to an immunosuppressive status and promote the progression of cervical carcinogenesis.

Trial Registration: Not applicable.
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http://dx.doi.org/10.1186/s12985-016-0670-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5237320PMC
January 2017

Trehalose 6-phosphate signal is closely related to sorbitol in apple ( Borkh. cv. Gala).

Biol Open 2017 Feb 15;6(2):260-268. Epub 2017 Feb 15.

College of Horticulture, Northwest A&F University, Yangling, Shaanxi 712100, China.

Trehalose-6-phosphate (Tre6P) is a precursor of trehalose, which is widespread in nature and greatly influences plant growth and development. Tre6P acts as a signal of carbon availability in many plants, but little is known about the function of Tre6P in rosaceous plants, which have specific sorbitol biosynthesis and transportation pathways. In the present study, Tre6P levels and Sorbitol:Tre6P ratios were analyzed in apple (, Borkh. cv. Gala). Tre6P levels were positively correlated with sorbitol content but negatively correlated with sucrose, glucose, and fructose content in developing fruit. However, under sorbitol-limited conditions, Tre6P levels were positively correlated with both sorbitol and sucrose. In the presence of different exogenous sugar supply, Tre6P levels increased corresponding with sorbitol, but this was not the case with sucrose. In addition, Tre6P content and sorbitol:Tre6P ratios were more highly correlated with ADP-glucose levels under sorbitol-limited conditions and fruit development stages, respectively. These results suggest that Tre6P is more closely related to sorbitol than other soluble sugars and has an important role in influencing carbon metabolism in apple.
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http://dx.doi.org/10.1242/bio.022301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312103PMC
February 2017

Stromal cell-derived factor-1 promotes human adipose tissue-derived stem cell survival and chronic wound healing.

Exp Ther Med 2016 Jul 4;12(1):45-50. Epub 2016 May 4.

Plastic Surgery Department, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.

Adipose tissue-derived stem cells (ADSCs) hold great potential for the stem cell-based therapy of cutaneous wound healing. Stromal cell-derived factor-1 (SDF-1) activates CXC chemokine receptor (CXCR)4 and CXCR7 cells and plays an important role in wound healing. Increasing evidence suggests a critical role for SDF-1 in cell apoptosis and the survival of mesenchymal stem cells. However, the function of SDF-1 in the apoptosis and wound healing ability of ADSCs is not well understood. The aim of this study was to analyze the effect of SDF-1 on the apoptosis and therapeutic effect of ADSCs in cutaneous chronic wounds and s. By flow cytometric analysis, it was found that hypoxia and serum free promoted the apoptosis of ADSCs. When pretreated with SDF-1, the apoptosis of ADSCs induced by hypoxia and serum depletion was partly recovered. Furthermore, experiments established that the post-implantation cell survival and chronic wound healing ability of ADSCs were increased following pretreatment with SDF-1 in a diabetic mouse model of chronic wound healing. To explore the potential mechanism underlying the effect of SDF-1 on ADSC apoptosis, western blot analysis was employed and the results indicate that SDF-1 may protect against cell apoptosis in hypoxic and serum-free conditions through activation of the caspase signaling pathway in ADSCs. This study provides evidence that SDF-1 pretreatment can increase the therapeutic effect of ADSCs in cutaneous chronic wounds and .
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http://dx.doi.org/10.3892/etm.2016.3309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4906949PMC
July 2016

Macrophage-Induced Blood Vessels Guide Schwann Cell-Mediated Regeneration of Peripheral Nerves.

Cell 2015 Aug 13;162(5):1127-39. Epub 2015 Aug 13.

MRC Laboratory for Molecular Cell Biology, UCL, Gower Street, London WC1E 6BT, UK; UCL Cancer Institute, UCL, 72 Huntley Street, London WC1E 6DD, UK. Electronic address:

The peripheral nervous system has remarkable regenerative capacities in that it can repair a fully cut nerve. This requires Schwann cells to migrate collectively to guide regrowing axons across a 'bridge' of new tissue, which forms to reconnect a severed nerve. Here we show that blood vessels direct the migrating cords of Schwann cells. This multicellular process is initiated by hypoxia, selectively sensed by macrophages within the bridge, which via VEGF-A secretion induce a polarized vasculature that relieves the hypoxia. Schwann cells then use the blood vessels as "tracks" to cross the bridge taking regrowing axons with them. Importantly, disrupting the organization of the newly formed blood vessels in vivo, either by inhibiting the angiogenic signal or by re-orienting them, compromises Schwann cell directionality resulting in defective nerve repair. This study provides important insights into how the choreography of multiple cell-types is required for the regeneration of an adult tissue.
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http://dx.doi.org/10.1016/j.cell.2015.07.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4553238PMC
August 2015

Single-Cell Network Analysis Identifies DDIT3 as a Nodal Lineage Regulator in Hematopoiesis.

Cell Rep 2015 Jun 4;11(10):1503-10. Epub 2015 Jun 4.

Stem Cell Laboratory, UCL Cancer Institute, University College London, London W1CE 6BT, UK. Electronic address:

We explore cell heterogeneity during spontaneous and transcription-factor-driven commitment for network inference in hematopoiesis. Since individual genes display discrete OFF states or a distribution of ON levels, we compute and combine pairwise gene associations from binary and continuous components of gene expression in single cells. Ddit3 emerges as a regulatory node with positive linkage to erythroid regulators and negative association with myeloid determinants. Ddit3 loss impairs erythroid colony output from multipotent cells, while forcing Ddit3 in granulo-monocytic progenitors (GMPs) enhances self-renewal and impedes differentiation. Network analysis of Ddit3-transduced GMPs reveals uncoupling of myeloid networks and strengthening of erythroid linkages. RNA sequencing suggests that Ddit3 acts through development or stabilization of a precursor upstream of GMPs with inherent Meg-E potential. The enrichment of Gata2 target genes in Ddit3-dependent transcriptional responses suggests that Ddit3 functions in an erythroid transcriptional network nucleated by Gata2.
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http://dx.doi.org/10.1016/j.celrep.2015.05.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528262PMC
June 2015

Genetic diversity of male and female Chinese bayberry (Myrica rubra) populations and identification of sex-associated markers.

BMC Genomics 2015 May 19;16:394. Epub 2015 May 19.

Department of Horticulture, College of Agriculture and Biotechnology, Zhejiang University, 310058, Hangzhou, Zhejiang, China.

Background: Chinese bayberry (Myrica rubra Sieb. & Zucc.) is an important subtropical evergreen fruit tree in southern China. Generally dioecious, the female plants are cultivated for fruit and have been studied extensively, but male plants have received very little attention. Knowledge of males may have a major impact on conservation and genetic improvement as well as on breeding. Using 84 polymorphic SSRs, we genotyped 213 M. rubra individuals (99 male individuals, 113 female varieties and 1 monoecious) and compared the difference in genetic diversity between the female and the male populations.

Results: Neighbour-joining cluster analysis separated M. rubra from three related species, and the male from female populations within M. rubra. By structure analysis, 178 M. rubra accessions were assigned to two subpopulations: Male dominated (98) and Female dominated (80). The well-known cultivars 'Biqi' and 'Dongkui', and the landraces 'Fenhong' are derived from three different gene pools. Female population had a slightly higher values of genetic diversity parameters (such as number of alleles and heterozygosity) than the male population, but not significantly different. The SSR loci ZJU062 and ZJU130 showed an empirical Fst value of 0.455 and 0.333, respectively, which are significantly above the 95 % confidence level, indicating that they are outlier loci related to sex separation.

Conclusion: The male and female populations of Chinese bayberry have similar genetic diversity in terms of average number of alleles and level of heterozygosity, but were clearly separated by genetic structure analysis due to two markers associated with sex type, ZJU062 and ZJU130. Zhejiang Province China could be the centre of diversity of M. rubra in China, with wide genetic diversity coverage; and the two representative cultivars 'Biqi' and 'Dongkui', and one landrace 'Fenhong' in three female subpopulations. This research provides genetic information on male and female Chinese bayberry and will act as a reference for breeding programs.
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http://dx.doi.org/10.1186/s12864-015-1602-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436740PMC
May 2015

[The risk factors of chronic obstructive pulmonary disease in Heilongjiang province].

Zhonghua Jie He He Hu Xi Za Zhi 2015 Feb;38(2):93-8

Email:

Objective: To study the prevalence and risk factors of chronic obstructive pulmonary disease (COPD) in Heilongjiang province.

Methods: This was a population-based and cross-sectional survey on prevalence of COPD in Heilongjiang province from September 2013 to March 2014. The stratified-cluster-random sampling method was performed to collect the data from 4 478 people in 5 cities (Jixi, Daqing, Suihua, Yichun and Jiagedaqi). The subjects were interviewed with questionnaires and tested with spirometry. A post-bronchodilator FEV1/FVC<70% was defined as diagnostic of COPD.

Results: Completed and qualified data were obtained from 4 059 participants. The average prevalence of COPD was 7.3% (urban 6.0%; rural 8.8%; men 8.6%; women 6.5%). When using SPSS18.0 for the single factors logistic regression analysis, results indicated that sex (OR = 0.700, 95%CI:0.540-0.907), age ≥ 50 (OR = 1.236, 95%CI:0.758-2.017), lower education level (OR = 1.551, 95%CI:0.929-2.590), biomass for cooking (compared with electricity, OR = 2.744, 95%CI:1.429-5.271), biomass (compared with centralized heat supply, OR = 1.229, 95%CI:0.120-12.546)and coal (compared with centralized heat supply, OR = 4.661, 95%CI:0.474-45.840) for heating, respiratory diseases (OR = 3.594, 95%CI:2.738-4.716), combined with cardiovascular disease (OR = 1.370, 95%CI:1.058-1.776) were the risk factors of COPD in Heilongjiang province.

Conclusion: Higher risk for COPD was related with sex, age, education level, cooking fuel, heating methods, respiratory diseases and combined with cardiovascular disease.
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February 2015

The histone demethylase Jarid1b is required for hematopoietic stem cell self-renewal in mice.

Blood 2015 Mar 5;125(13):2075-8. Epub 2015 Feb 5.

Stem Cell Group, University College London Cancer Institute, University College London, London, United Kingdom.

Jarid1b/KDM5b is a histone demethylase that regulates self-renewal and differentiation in stem cells and cancer; however, its function in hematopoiesis is unclear. Here, we find that Jarid1b is highly expressed in primitive hematopoietic compartments and is overexpressed in acute myeloid leukemias. Constitutive genetic deletion of Jarid1b did not impact steady-state hematopoiesis. In contrast, acute deletion of Jarid1b from bone marrow increased peripheral blood T cells and, following secondary transplantation, resulted in loss of bone marrow reconstitution. Our results reveal that deletion of Jarid1b compromises hematopoietic stem cell (HSC) self-renewal capacity and suggest that Jarid1b is a positive regulator of HSC potential.
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http://dx.doi.org/10.1182/blood-2014-08-596734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467872PMC
March 2015

Dynamic analysis of gene expression and genome-wide transcription factor binding during lineage specification of multipotent progenitors.

Cell Stem Cell 2013 Dec 10;13(6):754-68. Epub 2013 Oct 10.

Stem Cell Group, UCL Cancer Institute, University College London, London WC1E 6BT, UK; Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.

We used the paradigmatic GATA-PU.1 axis to explore, at the systems level, dynamic relationships between transcription factor (TF) binding and global gene expression programs as multipotent cells differentiate. We combined global ChIP-seq of GATA1, GATA2, and PU.1 with expression profiling during differentiation to erythroid and neutrophil lineages. Our analysis reveals (1) differential complexity of sequence motifs bound by GATA1, GATA2, and PU.1; (2) the scope and interplay of GATA1 and GATA2 programs within, and during transitions between, different cell compartments, and the extent of their hard-wiring by DNA motifs; (3) the potential to predict gene expression trajectories based on global associations between TF-binding data and target gene expression; and (4) how dynamic modeling of DNA-binding and gene expression data can be used to infer regulatory logic of TF circuitry. This rubric exemplifies the utility of this cross-platform resource for deconvoluting the complexity of transcriptional programs controlling stem/progenitor cell fate in hematopoiesis.
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http://dx.doi.org/10.1016/j.stem.2013.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3878573PMC
December 2013

The tetraspanin CD9 affords high-purity capture of all murine hematopoietic stem cells.

Cell Rep 2013 Aug 15;4(4):642-8. Epub 2013 Aug 15.

Stem Cell Laboratory, University College London Cancer Institute, London WC1E 6BT, UK.

Prospective isolation is critical for understanding the cellular and molecular aspects of stem cell heterogeneity. Here, we identify the cell surface antigen CD9 as a positive marker that provides a simple alternative for hematopoietic stem cell isolation at high purity. Crucially, CD9 affords the capture of all hematopoietic stem cells in murine bone marrow in the absence of contaminating populations that lack authentic stem cell function. Using CD9 as a tool to subdivide hematopoietic stem-cell-containing populations, we provide evidence for heterogeneity at the cellular, functional, and molecular levels.
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http://dx.doi.org/10.1016/j.celrep.2013.07.020DOI Listing
August 2013

Genetic variegation of clonal architecture and propagating cells in leukaemia.

Nature 2011 Jan 15;469(7330):356-61. Epub 2010 Dec 15.

Section of Haemato-Oncology, The Institute of Cancer Research, Sutton SM2 5NG, UK.

Little is known of the genetic architecture of cancer at the subclonal and single-cell level or in the cells responsible for cancer clone maintenance and propagation. Here we have examined this issue in childhood acute lymphoblastic leukaemia in which the ETV6-RUNX1 gene fusion is an early or initiating genetic lesion followed by a modest number of recurrent or 'driver' copy number alterations. By multiplexing fluorescence in situ hybridization probes for these mutations, up to eight genetic abnormalities can be detected in single cells, a genetic signature of subclones identified and a composite picture of subclonal architecture and putative ancestral trees assembled. Subclones in acute lymphoblastic leukaemia have variegated genetics and complex, nonlinear or branching evolutionary histories. Copy number alterations are independently and reiteratively acquired in subclones of individual patients, and in no preferential order. Clonal architecture is dynamic and is subject to change in the lead-up to a diagnosis and in relapse. Leukaemia propagating cells, assayed by serial transplantation in NOD/SCID IL2Rγ(null) mice, are also genetically variegated, mirroring subclonal patterns, and vary in competitive regenerative capacity in vivo. These data have implications for cancer genomics and for the targeted therapy of cancer.
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http://dx.doi.org/10.1038/nature09650DOI Listing
January 2011

Expression of ABCC-type nucleotide exporters in blasts of adult acute myeloid leukemia: relation to long-term survival.

Clin Cancer Res 2009 Mar 24;15(5):1762-9. Epub 2009 Feb 24.

Medical Science Division, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.

Purpose: Successful treatment of acute myeloid leukemia (AML) remains a therapeutic challenge, with a high percentage of patients suffering from persistent or relapsed disease. Resistance to drug therapy can develop from increased drug export and/or altered intracellular signaling. Both mechanisms are mediated by the efflux transporters ABCC4 (MRP4), ABCC5 (MRP5), and ABCC11 (MRP8), which are involved in cellular efflux of endogenous signaling molecules (e.g., cyclic adenosine 3', 5'-monophosphate and cyclic guanosine 3',5'-monophosphate) and nucleoside analogues. The nucleoside analogue cytosine arabinoside (AraC) is administered to all patients with AML.

Experimental Design: Expression of ABCC transporters MRP4, MRP5, and MRP8 in blast samples from 50 AML patients was investigated by real-time reverse transcription-PCR analysis and correlated with clinical outcome measures. Accumulation of radiolabeled AraC, transport of AraC metabolites, and AraC cytotoxicity were analyzed in MRP8-transfected LLC-PK1 cells.

Results: Regression analysis revealed that high expression of MRP8 is associated with a low probability of overall survival assessed over 4 years (P<0.03). MRP8-transfected LLC-PK1 cells accumulated reduced intracellular levels of AraC (63% of the parental vector-transfected LLC-PK1 control cells) as well as AraC metabolites. Furthermore, AraC monophosphate was transported by MRP8-enriched membrane vesicles (116+/-6 versus 65+/-13 pmol/mg/10 minutes by control vesicles), and MRP8-transfected cells were resistant to AraC.

Conclusion: These data suggest that MRP8 is differentially expressed in AML blasts, that expression of MRP8 serves as a predictive marker for treatment outcome in AML, and that efflux of AraC metabolites by MRP8 is a mechanism that contributes to resistance of AML blasts.
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http://dx.doi.org/10.1158/1078-0432.CCR-08-0442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5744661PMC
March 2009
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