Publications by authors named "Yanhui Peng"

43 Publications

Rare primary hepatic carcinosarcoma composed of hepatocellular carcinoma, cholangiocarcinoma, and sarcoma: a case report.

J Int Med Res 2021 Oct;49(10):3000605211050539

Department of Hepatobiliary, Pancreatic, and Splenic Surgery, 117872Hebei General Hospital, Hebei General Hospital, Shijiazhuang, China.

Primary hepatic carcinosarcoma (HCS) is an extremely rare malignant tumor of the liver that contains carcinomatous and sarcomatous components. The diagnosis, treatment, and prognosis of HCS pose great challenges to clinicians. Herein, we present a case of HCS in a 67-year-old man with unique pathological manifestation. Preoperative magnetic resonance imaging showed a malignant lesion in the right liver and a small sub-focus in the left liver. Radical treatment was performed, including excision of the right posterior lobe of the liver, thrombectomy of the right posterior portal vein, and radiofrequency ablation of lesions in the left liver. The specimens were confirmed to be HCS by pathological examinations, which revealed a combination of poorly differentiated hepatocellular carcinoma, moderately differentiated cholangiocellular carcinoma, and spindle cell sarcoma. Transhepatic arterial chemotherapy and embolization was performed after surgery. Unfortunately, pulmonary metastasis occurred 1.5 months later, which meant a poor prognosis. In this report, we discuss the clinicopathological characteristics of this case and factors that affected surgical outcomes, which may add some ideas for the future diagnosis and treatment of HCS patients.
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http://dx.doi.org/10.1177/03000605211050539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516393PMC
October 2021

Reg3A (regenerating family member 3 alpha) acts as a tumor suppressor by targeting DMBT1 (deleted in malignant brain tumors 1) in gastric cancer.

Bioengineered 2021 Dec;12(1):7644-7655

Department of Surgery, Hebei Medical University, Shijiazhuang, China.

Regenerating family member 3 alpha (Reg3A) encodes a pancreatic secretory protein that may be involved in cell proliferation or differentiation. However, the function and downstream regulatory mechanism of Reg3A in gastric cancer (GC) remains elusive. This study aimed to clarify the function and mechanism of Reg3A regulating cell proliferation in GC. The expression levels of Reg3A were confirmed in GC patients and cells using qRT-PCR and western blotting. TCGA datasets and clinical samples were used to explore the correlation between Reg3A and clinicopathologic features in GC. Cell viability, colony formation, and xenograft tumorigenesis assays were performed to detect the function of Reg3A on cell proliferation. Besides, we predicted the correlated genes of Reg3A by analyzing TCGA datasets, and further investigated the downstream regulatory mechanism of Reg3A in GC. Our results demonstrated that Reg3A is down-regulated in and (P < 0.05). Reg3A expression are negatively correlated with TNM classification ( < 0.001), lymph node ( < 0.001) in GC. Reg3A significantly suppresses cell proliferation in GC (P < 0.05). Bioinformatic analysis and experimental results confirmed that Reg3A positively regulates the expression of deleted in malignant brain tumor 1 (DMBT1, < 0.05). Besides, Reg3A and DMBT1 all prolong the overall survival (OS, < 0.01), post-progression survival (PPS, < 0.05), and first progression survival (FP, < 0.01). The function of Reg3A inhibiting cell proliferation is abolished by DMBT1 siRNA in GC ( < 0.05). In conclusion, Reg3A may act as a novel tumor suppressor by promoting DMBT1 expression, which may be a potential therapeutic target in patients with GC.
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http://dx.doi.org/10.1080/21655979.2021.1981800DOI Listing
December 2021

The Application of ASSRs, P50, and MMN in the Exploration of Cognitive Dysfunction Involving Inputs and Processing in Insomnia Patients.

Front Hum Neurosci 2021 3;15:714302. Epub 2021 Sep 3.

Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Changchun, China.

Objective cognitive dysfunction has been commonly found in patients with insomnia, such as attention, memory, speed of information processing, and executive functions. Auditory steady-state responses (ASSRs), P50, mismatch negativity (MMN) can meet varied need and estimate such different cognitive dysfunction. Thus, we can examine whether insomnia is associated with different cognitive dysfunction by such multiple event-related potential (ERP) tasks. Methods we used polysomnography (PSG) to record such objective PSG parameters. ASSR, P50, and MMN were performed in sequence, different ERP components have been analyzed such as latency or amplitude between insomnia group and control group. And we chosed person correlation to make correlation analysis between different ERP components and gender, education, and sleep characteristics. Results there is a significant gender difference of ASSR latency found in insomnia group, and the similar result has been found in suppression ratio of amplitudes (S2:S1) for P50. Additionally, a significant correlation between sleep characteristics and ASSR, P50 has been found. Furthermore, there was a significant difference of MMN latency between insomnia and control group, and between sleep characteristics and varied MMN parameters as latency and amplitude. Discussion our results suggested robust electrophysiological abnormalities as ASSR, P50, and MMN in insomnia patients. Such abnormalities included gender difference, education difference, difference in depressive tendency, and difference in sleep parameters. That results revealed varied cognitive dysfunction involving inputs and processing in insomnia patients. And at the same time, we have also explored the neuropsychological mechanisms underlying the cognitive dysfunction with such different ERP tasks.
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http://dx.doi.org/10.3389/fnhum.2021.714302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8454545PMC
September 2021

Current perspectives on exosomes in the diagnosis and treatment of hepatocellular carcinoma (review).

Cancer Biol Ther 2021 04 13;22(4):279-290. Epub 2021 Apr 13.

Department of Hepatobiliary Surgery, General Hospital, Shijiazhuang, Hebei, P. R. China.

The prognosis of hepatocellular carcinoma (HCC), a malignant tumor, is poor. Tumor recurrence and metastasis are the major challenges for the treatment of HCC. Various studies have demonstrated that exosomes, which are loaded with various biomolecules including nucleic acids, lipids, and proteins are involved in the recurrence and metastasis of HCC. Additionally, exosomes mediate various biological processes, such as immune response, cell apoptosis, angiogenesis, thrombosis, autophagy, and intercellular signal transduction. In cancer, exosomes regulate cancer cell differentiation, development, and drug resistance. Circular RNAs, microRNAs, and proteins in the exosomes can serve as early diagnostic and prognostic markers for HCC. As exosomes are characterized by low immunogenicity and high stability in the tissues and circulation, they can be used to deliver the drugs in cancer therapies.
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http://dx.doi.org/10.1080/15384047.2021.1898728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183537PMC
April 2021

Gallbladder gangrene after percutaneous vertebroplasty, an uncommon presentation of vascular complication: a case report and analysis of the causes.

J Int Med Res 2021 Mar;49(3):3000605211001720

Department of Hepatobiliary, Pancreatic, and Splenic Surgery, 117872Hebei General Hospital, Shijiazhuang, China.

We present a case of an 81-year-old man with gallbladder gangrene after percutaneous vertebroplasty (PV) that was successfully treated via laparoscopic cholecystectomy (LC). The patient underwent multilevel, thoracic PV for painful osteoporotic compression fractures. PV performed at the T6 level was complicated by severe abdominal pain owing to direct embolization of the right T6 segmental artery with penetration of bone cement into the radicular artery beneath the pedicle. Cement leakage, especially arterial embolization of cement into the general circulation, is a known potential complication following PV. Serious complications related to PV augmentation procedures, such as vertebroplasty and kyphoplasty, are rare and most often result from local cement leakage or venous embolization. Combined with this case report, we reviewed the literature regarding the unusual occurrence of direct arterial cement embolization during PV and analyzed the causes to alert clinicians to this potentially rare vascular complication.
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http://dx.doi.org/10.1177/03000605211001720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020101PMC
March 2021

Role of chemokines in hepatocellular carcinoma (Review).

Oncol Rep 2021 03 22;45(3):809-823. Epub 2020 Dec 22.

Department of Hepatobiliary Surgery, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China.

Hepatocellular carcinoma (HCC) is a prevalent malignant tumor worldwide, with an unsatisfactory prognosis, although treatments are improving. One of the main challenges for the treatment of HCC is the prevention or management of recurrence and metastasis of HCC. It has been found that chemokines and their receptors serve a pivotal role in HCC progression. In the present review, the literature on the multifactorial roles of exosomes in HCC from PubMed, Cochrane library and Embase were obtained, with a specific focus on the functions and mechanisms of chemokines in HCC. To date, >50 chemokines have been found, which can be divided into four families: CXC, CX3C, CC and XC, according to the different positions of the conserved N‑terminal cysteine residues. Chemokines are involved in the inflammatory response, tumor immune response, proliferation, invasion and metastasis via modulation of various signaling pathways. Thus, chemokines and their receptors directly or indirectly shape the tumor cell microenvironment, and regulate the biological behavior of the tumor. In addition, the potential application of chemokines in chemotaxis of exosomes as drug vehicles is discussed. Exosomes containing chemokines or expressing receptors for chemokines may improve chemotaxis to HCC and may thus be exploited for targeted drug delivery.
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http://dx.doi.org/10.3892/or.2020.7906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859922PMC
March 2021

Genomic Surveillance and Improved Molecular Typing of Bordetella pertussis Using wgMLST.

J Clin Microbiol 2021 04 20;59(5). Epub 2021 Apr 20.

Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Multilocus sequence typing (MLST) provides allele-based characterization of bacterial pathogens in a standardized framework. However, classical MLST schemes for , the causative agent of whooping cough, seldom reveal diversity among the small number of gene targets and thereby fail to delineate population structure. To improve the discriminatory power of allele-based molecular typing of , we have developed a whole-genome MLST (wgMLST) scheme from 225 reference-quality genome assemblies. Iterative refinement and allele curation resulted in a scheme of 3,506 coding sequences and covering 81.4% of the genome. This wgMLST scheme was further evaluated with data from a convenience sample of 2,389 isolates sequenced on Illumina instruments, including isolates from known outbreaks and epidemics previously characterized by existing molecular assays, as well as replicates collected from individual patients. wgMLST demonstrated concordance with whole-genome single nucleotide polymorphism (SNP) profiles, accurately resolved outbreak and sporadic cases in a retrospective comparison, and clustered replicate isolates collected from individual patients during diagnostic confirmation. Additionally, a reanalysis of isolates from two statewide epidemics using wgMLST reconstructed the population structures of circulating strains with increased resolution, revealing new clusters of related cases. Comparison with an existing core genome (cgMLST) scheme highlights the stable gene content of this bacterium and forms the initial foundation for necessary standardization. These results demonstrate the utility of wgMLST for improving characterization and genomic surveillance during the current pertussis disease resurgence.
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http://dx.doi.org/10.1128/JCM.02726-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091836PMC
April 2021

Genomic epidemiology of nontoxigenic from King County, Washington State, USA between July 2018 and May 2019.

Microb Genom 2020 12 4;6(12). Epub 2020 Dec 4.

Division of Bacterial Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.

Between July 2018 and May 2019, was isolated from eight patients with non-respiratory infections, seven of whom experienced homelessness and had stayed at shelters in King County, WA, USA. All isolates were microbiologically identified as nontoxigenic biovar mitis. Whole-genome sequencing confirmed that all case isolates were genetically related, associated with sequence type 445 and differing by fewer than 24 single-nucleotide polymorphisms (SNPs). Compared to publicly available genomic data, these WA isolates formed a discrete cluster with SNP variation consistent with previously reported outbreaks. Virulence-related gene content variation within the highly related WA cluster isolates was also observed. These results indicated that genome characterization can readily support epidemiology of nontoxigenic .
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http://dx.doi.org/10.1099/mgen.0.000467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116682PMC
December 2020

Detection and Characterization of Diphtheria Toxin Gene-Bearing Species through a New Real-Time PCR Assay.

J Clin Microbiol 2020 09 22;58(10). Epub 2020 Sep 22.

Pertussis and Diphtheria Laboratory, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Respiratory diphtheria, characterized by a firmly adherent pseudomembrane, is caused by toxin-producing strains of , with similar illness produced occasionally by toxigenic or, rarely, While diphtheria laboratory confirmation requires culture methods to determine toxigenicity, real-time PCR (RT-PCR) provides a faster method to detect the toxin gene (). Nontoxigenic -bearing (NTTB) isolates have been described, but impact of these isolates on the accuracy of molecular diagnostics is not well characterized. Here, we describe a new triplex RT-PCR assay to detect and distinguish from the closely related species and Analytical sensitivity and specificity of the assay were assessed in comparison to culture using 690 previously characterized microbial isolates. The new triplex assay characterized isolates accurately, with 100% analytical sensitivity for all targets. Analytical specificity with isolates was 94.1%, 100%, and 99.5% for , Diph_, and CUP_ targets, respectively. Twenty-nine NTTB isolates, representing 5.9% of 494 nontoxigenic isolates tested, were detected by RT-PCR. Whole-genome sequencing of NTTB isolates revealed varied mutations putatively underlying their lack of toxin production, as well as eight isolates with no mutation in or the promoter region. This new RT-PCR method provides a rapid tool to screen isolates and identify probable diphtheria cases directly from specimens. However, the sporadic occurrence of NTTB isolates reinforces the viewpoint that diphtheria culture diagnostics continue to provide the most accurate case confirmation.
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http://dx.doi.org/10.1128/JCM.00639-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7512153PMC
September 2020

Conserved Patterns of Symmetric Inversion in the Genome Evolution of Respiratory Pathogens.

mSystems 2019 Nov 19;4(6). Epub 2019 Nov 19.

Division of Bacterial Disease, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Whooping cough (pertussis), primarily caused by , has resurged in the United States, and circulating strains exhibit considerable chromosome structural fluidity in the form of rearrangement and deletion. The genus includes additional pathogenic species infecting various animals, some even causing pertussis-like respiratory disease in humans; however, investigation of their genome evolution has been limited. We studied chromosome structure in complete genome sequences from 167 species isolates, as well as 469 isolates, to gain a generalized understanding of rearrangement patterns among these related pathogens. Observed changes in gene order primarily resulted from large inversions and were only detected in species with genomes harboring multicopy insertion sequence (IS) elements, most notably and While genomes of contain >240 copies of IS, IS elements appear less numerous in other species and yield less chromosome structural diversity through rearrangement. These data were further used to predict all possible rearrangements between IS element copies present in genomes, revealing that only a subset is observed among circulating strains. Therefore, while it appears that rearrangement occurs less frequently in other species than in , these clinically relevant respiratory pathogens likely experience similar mutation of gene order. The resulting chromosome structural fluidity presents both challenges and opportunity for the study of respiratory pathogens. is the primary agent of whooping cough (pertussis). The genus includes additional pathogens of animals and humans, including some that cause pertussis-like respiratory illness. The chromosome of has previously been shown to exhibit considerable structural rearrangement, but insufficient data have prevented comparable investigation in related species. In this study, we analyze chromosome structure variation in several species to gain a generalized understanding of rearrangement patterns in this genus. Just as in , we observed inversions in other species that likely result from common mutational processes. We used these data to further predict additional, unobserved inversions, suggesting that specific genome structures may be preferred in each species.
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http://dx.doi.org/10.1128/mSystems.00702-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6867878PMC
November 2019

Genomic Survey of Bordetella pertussis Diversity, United States, 2000-2013.

Emerg Infect Dis 2019 04;25(4):780-783

We characterized 170 complete genome assemblies from clinical Bordetella pertussis isolates representing geographic and temporal diversity in the United States. These data capture genotypic shifts, including increased pertactin deficiency, occurring amid the current pertussis disease resurgence and provide a foundation for needed research to direct future public health control strategies.
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http://dx.doi.org/10.3201/eid2504.180812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433035PMC
April 2019

Effect of electroacupuncture at homotopic and heterotopic acupoints on abdominal pain in patients with irritable bowel syndrome: study protocol for a randomized controlled trial.

Trials 2018 Oct 16;19(1):559. Epub 2018 Oct 16.

The Secondary Medical College, Guangzhou University of Traditional Chinese Medicine, 111 Dade Road, Guangzhou, 510120, People's Republic of China.

Background: Acupuncture has been widely applied in the clinic to treat irritable bowel syndrome (IBS), but the underlying mechanism remains unknown. Diffuse noxious inhibitory control (DNIC) is deficient in patients with IBS, which attenuates the systemic analgesic effect elicited by noxious stimulation that is remote from pain areas. Therefore, the aim of this study is to investigate the analgesic effect of electroacupuncture (EA) at homotopic or heterotopic acupoints on abdominal pain in patients with IBS.

Methods/design: This study is a randomized, single-blinded, controlled, four-arm parallel trial. A total of 144 patients will be randomly assigned to four groups: a homotopic noxious stimulation group (group A), a homotopic innocuous stimulation group (group B), a heterotopic noxious stimulation group (group C), and a heterotopic innocuous stimulation group (group D). Each patient will receive 14 sessions of treatment, twice per week for 7 weeks. The primary outcome will be pain intensity measured with the visual analog scale. The secondary outcomes will include the IBS Symptom Severity Scale, IBS Quality of Life questionnaire, pain threshold (PT), and the Symptom Checklist-90 for psychological distress. The PT will be measured before and after every treatment. All other outcomes will be evaluated before the 1st treatment, after 7th and 14th treatment, and 3 months later during follow-up.

Discussion: The aim of this study is to assess the analgesic effect of EA at homotopic (abdomen) acupoints and heterotopic (lower limb) acupoints on abdominal pain in patients with IBS, as well as the difference in analgesic effects between noxious and innocuous stimulation.

Trial Registration: Chinese Clinical Trial Registry, ChiCTR-IPR-15006879 . Registered on 5 August 2015.
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http://dx.doi.org/10.1186/s13063-018-2948-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192074PMC
October 2018

Switchgrass ( L.) promoters for green tissue-specific expression of the transcription factor for reduced-recalcitrance transgenic switchgrass.

Biotechnol Biofuels 2018 24;11:122. Epub 2018 Apr 24.

1Department of Plant Sciences, University of Tennessee, Knoxville, TN USA.

Background: Genetic engineering of switchgrass ( L.) for reduced cell wall recalcitrance and improved biofuel production has been a long pursued goal. Up to now, constitutive promoters have been used to direct the expression of cell wall biosynthesis genes toward attaining that goal. While generally sufficient to gauge a transgene's effects in the heterologous host, constitutive overexpression often leads to undesirable plant phenotypic effects. Green tissue-specific promoters from switchgrass are potentially valuable to directly alter cell wall traits exclusively in harvestable aboveground biomass while not changing root phenotypes.

Results: We identified and functionally characterized three switchgrass green tissue-specific promoters and assessed marker gene expression patterns and intensity in stably transformed rice ( L.), and then used them to direct the expression of the switchgrass () transcription factor gene in transgenic switchgrass to endow reduced recalcitrance in aboveground biomass. These promoters correspond to photosynthesis-related light-harvesting complex II chlorophyll-a/b binding gene (), phosphoenolpyruvate carboxylase (), and the photosystem II 10 kDa R subunit (). Real-time RT-PCR analysis detected their strong expression in the aboveground tissues including leaf blades, leaf sheaths, internodes, inflorescences, and nodes of switchgrass, which was tightly up-regulated by light. Stable transgenic rice expressing the reporter under the control of each promoter (756-2005 bp in length) further confirmed their strong expression patterns in leaves and stems. With the exception of the serial promoter deletions of , all marker patterns under the control of each 5'-end serial promoter deletion were not different from that conveyed by their respective promoters. All of the shortest promoter fragments (199-275 bp in length) conveyed strong green tissue-specific expression in transgenic rice. is a master repressor of lignin biosynthesis. The green tissue-specific expression of via each promoter in transgenic switchgrass led to significant gains in saccharification efficiency, decreased lignin, and decreased S/G lignin ratios. In contrast to constitutive overexpression of , which negatively impacts switchgrass root growth, plant growth was not compromised in green tissue-expressed switchgrass plants in the current study.

Conclusions: Each of the newly described green tissue-specific promoters from switchgrass has utility to change cell wall biosynthesis exclusively in aboveground harvestable biomass without altering root systems. The truncated green tissue promoters are very short and should be useful for targeted expression in a number of monocots to improve shoot traits while restricting gene expression from roots. Green tissue-specific expression of is an effective strategy for improvement of transgenic feedstocks.
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http://dx.doi.org/10.1186/s13068-018-1119-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5914048PMC
April 2018

Screening and Genomic Characterization of Filamentous Hemagglutinin-Deficient Bordetella pertussis.

Infect Immun 2018 04 22;86(4). Epub 2018 Mar 22.

Division of Bacterial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Despite high vaccine coverage, pertussis cases in the United States have increased over the last decade. Growing evidence suggests that disease resurgence results, in part, from genetic divergence of circulating strain populations away from vaccine references. The United States employs acellular vaccines exclusively, and current isolates are predominantly deficient in at least one immunogen, pertactin (Prn). First detected in the United States retrospectively in a 1994 isolate, the rapid spread of Prn deficiency is likely vaccine driven, raising concerns about whether other acellular vaccine immunogens experience similar pressures, as further antigenic changes could potentially threaten vaccine efficacy. We developed an electrochemiluminescent antibody capture assay to monitor the production of the acellular vaccine immunogen filamentous hemagglutinin (Fha). Screening 722 U.S. surveillance isolates collected from 2010 to 2016 identified two that were both Prn and Fha deficient. Three additional Fha-deficient laboratory strains were also identified from a historic collection of 65 isolates dating back to 1935. Whole-genome sequencing of deficient isolates revealed putative, underlying genetic changes. Only four isolates harbored mutations to known genes involved in Fha production, highlighting the complexity of its regulation. The chromosomes of two Fha-deficient isolates included unexpected structural variation that did not appear to influence Fha production. Furthermore, insertion sequence disruption of was also detected in a previously identified pertussis toxin-deficient isolate that still produced normal levels of Fha. These results demonstrate the genetic potential for additional vaccine immunogen deficiency and underscore the importance of continued surveillance of circulating evolution in response to vaccine pressure.
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http://dx.doi.org/10.1128/IAI.00869-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865017PMC
April 2018

Complete Genome Sequences of Isolates with Novel Pertactin-Deficient Deletions.

Genome Announc 2017 Sep 14;5(37). Epub 2017 Sep 14.

Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Clinical isolates of the respiratory pathogen in the United States have become predominantly deficient for the acellular vaccine immunogen pertactin through various independent mutations. Here, we report the complete genome sequences for four isolates that harbor novel deletions responsible for pertactin deficiency.
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http://dx.doi.org/10.1128/genomeA.00973-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5597764PMC
September 2017

Definitions for sepsis in pediatrics should be different from the adults.

J Crit Care 2017 06 9;39:288. Epub 2017 Feb 9.

Department of Emergency, Guangdong Provincial Hospital of Chinese Medicine, 111 Dade Road, Yuexiu District, Guangzhou, 510120. Electronic address:

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http://dx.doi.org/10.1016/j.jcrc.2017.02.004DOI Listing
June 2017

The History of Bordetella pertussis Genome Evolution Includes Structural Rearrangement.

J Bacteriol 2017 04 28;199(8). Epub 2017 Mar 28.

Division of Bacterial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Despite high pertussis vaccine coverage, reported cases of whooping cough (pertussis) have increased over the last decade in the United States and other developed countries. Although is well known for its limited gene sequence variation, recent advances in long-read sequencing technology have begun to reveal genomic structural heterogeneity among otherwise indistinguishable isolates, even within geographically or temporally defined epidemics. We have compared rearrangements among complete genome assemblies from 257 isolates to examine the potential evolution of the chromosomal structure in a pathogen with minimal gene nucleotide sequence diversity. Discrete changes in gene order were identified that differentiated genomes from vaccine reference strains and clinical isolates of various genotypes, frequently along phylogenetic boundaries defined by single nucleotide polymorphisms. The observed rearrangements were primarily large inversions centered on the replication origin or terminus and flanked by IS, a mobile genetic element with >240 copies per genome and previously suspected to mediate rearrangements and deletions by homologous recombination. These data illustrate that structural genome evolution in is not limited to reduction but also includes rearrangement. Therefore, although genomes of clinical isolates are structurally diverse, specific changes in gene order are conserved, perhaps due to positive selection, providing novel information for investigating disease resurgence and molecular epidemiology. Whooping cough, primarily caused by , has resurged in the United States even though the coverage with pertussis-containing vaccines remains high. The rise in reported cases has included increased disease rates among all vaccinated age groups, provoking questions about the pathogen's evolution. The chromosome of includes a large number of repetitive mobile genetic elements that obstruct genome analysis. However, these mobile elements facilitate large rearrangements that alter the order and orientation of essential protein-encoding genes, which otherwise exhibit little nucleotide sequence diversity. By comparing the complete genome assemblies from 257 isolates, we show that specific rearrangements have been conserved throughout recent evolutionary history, perhaps by eliciting changes in gene expression, which may also provide useful information for molecular epidemiology.
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http://dx.doi.org/10.1128/JB.00806-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5370423PMC
April 2017

Complete Genome Sequences of Four Bordetella pertussis Vaccine Reference Strains from Serum Institute of India.

Genome Announc 2016 Dec 22;4(6). Epub 2016 Dec 22.

Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Serum Institute of India is among the world's largest vaccine producers. Here, we report the complete genome sequences for four Bordetella pertussis strains used by Serum Institute of India in the production of whole-cell pertussis vaccines.
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http://dx.doi.org/10.1128/genomeA.01404-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5180383PMC
December 2016

Complete Genome Sequences of Four Different Bordetella sp. Isolates Causing Human Respiratory Infections.

Genome Announc 2016 Oct 6;4(5). Epub 2016 Oct 6.

Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Species of the genus Bordetella associate with various animal hosts, frequently causing respiratory disease. Bordetella pertussis is the primary agent of whooping cough and other Bordetella species can cause similar cough illness. Here, we report four complete genome sequences from isolates of different Bordetella species recovered from human respiratory infections.
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http://dx.doi.org/10.1128/genomeA.01080-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5054321PMC
October 2016

Complete Genome Sequences of Bordetella pertussis Vaccine Reference Strains 134 and 10536.

Genome Announc 2016 Sep 15;4(5). Epub 2016 Sep 15.

Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Vaccine formulations and vaccination programs against whooping cough (pertussis) vary worldwide. Here, we report the complete genome sequences of two divergent Bordetella pertussis reference strains used in the production of pertussis vaccines.
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http://dx.doi.org/10.1128/genomeA.00979-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5026441PMC
September 2016

Genome Structural Diversity among 31 Bordetella pertussis Isolates from Two Recent U.S. Whooping Cough Statewide Epidemics.

mSphere 2016 May-Jun;1(3). Epub 2016 May 11.

Division of Bacterial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

During 2010 and 2012, California and Vermont, respectively, experienced statewide epidemics of pertussis with differences seen in the demographic affected, case clinical presentation, and molecular epidemiology of the circulating strains. To overcome limitations of the current molecular typing methods for pertussis, we utilized whole-genome sequencing to gain a broader understanding of how current circulating strains are causing large epidemics. Through the use of combined next-generation sequencing technologies, this study compared de novo, single-contig genome assemblies from 31 out of 33 Bordetella pertussis isolates collected during two separate pertussis statewide epidemics and 2 resequenced vaccine strains. Final genome architecture assemblies were verified with whole-genome optical mapping. Sixteen distinct genome rearrangement profiles were observed in epidemic isolate genomes, all of which were distinct from the genome structures of the two resequenced vaccine strains. These rearrangements appear to be mediated by repetitive sequence elements, such as high-copy-number mobile genetic elements and rRNA operons. Additionally, novel and previously identified single nucleotide polymorphisms were detected in 10 virulence-related genes in the epidemic isolates. Whole-genome variation analysis identified state-specific variants, and coding regions bearing nonsynonymous mutations were classified into functional annotated orthologous groups. Comprehensive studies on whole genomes are needed to understand the resurgence of pertussis and develop novel tools to better characterize the molecular epidemiology of evolving B. pertussis populations. IMPORTANCE Pertussis, or whooping cough, is the most poorly controlled vaccine-preventable bacterial disease in the United States, which has experienced a resurgence for more than a decade. Once viewed as a monomorphic pathogen, B. pertussis strains circulating during epidemics exhibit diversity visible on a genome structural level, previously undetectable by traditional sequence analysis using short-read technologies. For the first time, we combine short- and long-read sequencing platforms with restriction optical mapping for single-contig, de novo assembly of 31 isolates to investigate two geographically and temporally independent U.S. pertussis epidemics. These complete genomes reshape our understanding of B. pertussis evolution and strengthen molecular epidemiology toward one day understanding the resurgence of pertussis.
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http://dx.doi.org/10.1128/mSphere.00036-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4888882PMC
June 2016

Diversity of ABC transporter genes across the plant kingdom and their potential utility in biotechnology.

BMC Biotechnol 2016 05 31;16(1):47. Epub 2016 May 31.

The Graduate School of Genome Science and Technology, University of Tennessee, Knoxville, TN, 37996, USA.

Background: The ATP-binding cassette (ABC) transporter gene superfamily is ubiquitous among extant organisms and prominently represented in plants. ABC transporters act to transport compounds across cellular membranes and are involved in a diverse range of biological processes. Thus, the applicability to biotechnology is vast, including cancer resistance in humans, drug resistance among vertebrates, and herbicide and other xenobiotic resistance in plants. In addition, plants appear to harbor the highest diversity of ABC transporter genes compared with any other group of organisms. This study applied transcriptome analysis to survey the kingdom-wide ABC transporter diversity in plants and suggest biotechnology applications of this diversity.

Results: We utilized sequence similarity-based informatics techniques to infer the identity of ABC transporter gene candidates from 1295 phylogenetically-diverse plant transcriptomes. A total of 97,149 putative (approximately 25 % were full-length) ABC transporter gene members were identified; each RNA-Seq library (plant sample) had 88 ± 30 gene members. As expected, simpler organisms, such as algae, had fewer unique members than vascular land plants. Differences were also noted in the richness of certain ABC transporter subfamilies. Land plants had more unique ABCB, ABCC, and ABCG transporter gene members on average (p < 0.005), and green algae, red algae, and bryophytes had significantly more ABCF transporter gene members (p < 0.005). Ferns had significantly fewer ABCA transporter gene members than all other plant groups (p < 0.005).

Conclusions: We present a transcriptomic overview of ABC transporter gene members across all major plant groups. An increase in the number of gene family members present in the ABCB, ABCC, and ABCD transporter subfamilies may indicate an expansion of the ABC transporter superfamily among green land plants, which include all crop species. The striking difference between the number of ABCA subfamily transporter gene members between ferns and other plant taxa is surprising and merits further investigation. Discussed is the potential exploitation of ABC transporters in plant biotechnology, with an emphasis on crops.
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http://dx.doi.org/10.1186/s12896-016-0277-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886425PMC
May 2016

What role does transactional sex play in the HIV/STI and reproductive health risk behaviour among high-tier entertainment centre workers in China?

Glob Public Health 2015 ;10(8):947-67

a HIV Center for Clinical and Behavioral Studies , New York State Psychiatric Institute and Columbia University , New York , NY , USA.

China's rapid economic growth over the last three decades has led to increased population wealth and the proliferation of entertainment centres where people can conduct business, relax and meet new people. Little is known about the sexual risk behaviours of employees at high-tier entertainment centres. This paper addresses this gap in knowledge by comparing HIV risk perception and sexual and reproductive health behaviours among female and male employees at three high-tier entertainment centres in two cities in China, comparing those who report a history of transactional sex to those who do not. In both cities, participants who reported a history of transactional sex were more likely than those without a history of transactional sex to report multiple sexual partnerships, more lifetime sexual partners, a history of sexually transmitted infections (STIs), having anal sex and/or recent abortions, and were more likely to perceive themselves to be at risk for STIs/HIV. However, risk behaviour was also high among those with no history of transactional sex. These findings highlight the need for targeted sexual and reproductive health initiatives for employees in these work settings.
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http://dx.doi.org/10.1080/17441692.2015.1045918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4575811PMC
June 2016

Multiple polyploidy events in the early radiation of nodulating and nonnodulating legumes.

Mol Biol Evol 2015 Jan 27;32(1):193-210. Epub 2014 Oct 27.

Department of Plant Biology, University of Georgia.

Unresolved questions about evolution of the large and diverse legume family include the timing of polyploidy (whole-genome duplication; WGDs) relative to the origin of the major lineages within the Fabaceae and to the origin of symbiotic nitrogen fixation. Previous work has established that a WGD affects most lineages in the Papilionoideae and occurred sometime after the divergence of the papilionoid and mimosoid clades, but the exact timing has been unknown. The history of WGD has also not been established for legume lineages outside the Papilionoideae. We investigated the presence and timing of WGDs in the legumes by querying thousands of phylogenetic trees constructed from transcriptome and genome data from 20 diverse legumes and 17 outgroup species. The timing of duplications in the gene trees indicates that the papilionoid WGD occurred in the common ancestor of all papilionoids. The earliest diverging lineages of the Papilionoideae include both nodulating taxa, such as the genistoids (e.g., lupin), dalbergioids (e.g., peanut), phaseoloids (e.g., beans), and galegoids (=Hologalegina, e.g., clovers), and clades with nonnodulating taxa including Xanthocercis and Cladrastis (evaluated in this study). We also found evidence for several independent WGDs near the base of other major legume lineages, including the Mimosoideae-Cassiinae-Caesalpinieae (MCC), Detarieae, and Cercideae clades. Nodulation is found in the MCC and papilionoid clades, both of which experienced ancestral WGDs. However, there are numerous nonnodulating lineages in both clades, making it unclear whether the phylogenetic distribution of nodulation is due to independent gains or a single origin followed by multiple losses.
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http://dx.doi.org/10.1093/molbev/msu296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4271530PMC
January 2015

De novo genome assembly of the economically important weed horseweed using integrated data from multiple sequencing platforms.

Plant Physiol 2014 Nov 10;166(3):1241-54. Epub 2014 Sep 10.

Department of Plant Science, University of Tennessee, Knoxville, Tennessee 37996 (Y.P., T.L., M.N.-R., C.N.S.);Department of Biology, Indiana University, Bloomington, Indiana 47405 (Z.L., L.H.R.);Department of Plant Sciences (M.O., M.J.) and Genome Center (H.O., R.W.K.), University of California, Davis, California 95616;Monsanto, Inc., St. Louis, Missouri 63130 (R.D.S.); andDepartment of Botany, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4 (L.H.R.)

Horseweed (Conyza canadensis), a member of the Compositae (Asteraceae) family, was the first broadleaf weed to evolve resistance to glyphosate. Horseweed, one of the most problematic weeds in the world, is a true diploid (2n = 2x = 18), with the smallest genome of any known agricultural weed (335 Mb). Thus, it is an appropriate candidate to help us understand the genetic and genomic bases of weediness. We undertook a draft de novo genome assembly of horseweed by combining data from multiple sequencing platforms (454 GS-FLX, Illumina HiSeq 2000, and PacBio RS) using various libraries with different insertion sizes (approximately 350 bp, 600 bp, 3 kb, and 10 kb) of a Tennessee-accessed, glyphosate-resistant horseweed biotype. From 116.3 Gb (approximately 350× coverage) of data, the genome was assembled into 13,966 scaffolds with 50% of the assembly = 33,561 bp. The assembly covered 92.3% of the genome, including the complete chloroplast genome (approximately 153 kb) and a nearly complete mitochondrial genome (approximately 450 kb in 120 scaffolds). The nuclear genome is composed of 44,592 protein-coding genes. Genome resequencing of seven additional horseweed biotypes was performed. These sequence data were assembled and used to analyze genome variation. Simple sequence repeat and single-nucleotide polymorphisms were surveyed. Genomic patterns were detected that associated with glyphosate-resistant or -susceptible biotypes. The draft genome will be useful to better understand weediness and the evolution of herbicide resistance and to devise new management strategies. The genome will also be useful as another reference genome in the Compositae. To our knowledge, this article represents the first published draft genome of an agricultural weed.
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http://dx.doi.org/10.1104/pp.114.247668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226366PMC
November 2014

'Fukusensor:' a genetically engineered plant for reporting DNA damage in response to gamma radiation.

Plant Biotechnol J 2014 Dec 4;12(9):1329-32. Epub 2014 Sep 4.

Department of Plant Sciences, University of Tennessee, Knoxville, TN, USA.

Transgenic plants can be designed to be 'phytosensors' for detection of environmental contaminants and pathogens. In this study, we describe the design and testing of a radiation phytosensor in the form of green fluorescence protein (GFP)-transgenic Arabidopsis plant utilizing a DNA repair deficiency mutant background as a host. Mutant lines of Arabidopsis AtATM (At3g48190), which are hypersensitive to gamma irradiation, were used to generate stable GFP transgenic plants in which a gfp gene was under the control of a strong constitutive CaMV 35S promoter. Mutant and nonmutant genetic background transgenic plants were treated with 0, 1, 5, 10 and 100 Gy radiation doses, respectively, using a Co-60 source. After 1 week, the GFP expression levels were drastically reduced in young leaves of mutant background plants (treated by 10 and 100 Gy), whereas there were scant visible differences in the fluorescence of the nonmutant background plants. These early results indicate that transgenic plants could serve in a relevant sensor system to report radiation dose and the biological effects to organisms in response to radionuclide contamination.
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http://dx.doi.org/10.1111/pbi.12247DOI Listing
December 2014

ATP-dependent binding cassette transporter G family member 16 increases plant tolerance to abscisic acid and assists in basal resistance against Pseudomonas syringae DC3000.

Plant Physiol 2014 Oct 21;166(2):879-88. Epub 2014 Aug 21.

Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260 (H.J., N.M., M.B.T.); andDepartment of Plant Sciences, University of Tennessee, Knoxville, Tennessee 37996 (Y.P., S.A., C.N.S.)

Plants have been shown previously to perceive bacteria on the leaf surface and respond by closing their stomata. The virulent bacterial pathogen Pseudomonas syringae pv tomato DC3000 (PstDC3000) responds by secreting a virulence factor, coronatine, which blocks the functioning of guard cells and forces stomata to reopen. After it is inside the leaf, PstDC3000 has been shown to up-regulate abscisic acid (ABA) signaling and thereby suppress salicylic acid-dependent resistance. Some wild plants exhibit resistance to PstDC3000, but the mechanisms by which they achieve this resistance remain unknown. Here, we used genome-wide association mapping to identify an ATP-dependent binding cassette transporter gene (ATP-dependent binding cassette transporter G family member16) in Arabidopsis (Arabidopsis thaliana) that contributes to wild plant resistance to PstDC3000. Through microarray analysis and β-glucuronidase reporter lines, we showed that the gene is up-regulated by ABA, bacterial infection, and coronatine. We also used a green fluorescent protein fusion protein and found that transporter is more likely to localize on plasma membranes than in cell walls. Transferred DNA insertion lines exhibited consistent defective tolerance of exogenous ABA and reduced resistance to infection by PstDC3000. Our conclusion is that ATP-dependent binding cassette transporter G family member16 is involved in ABA tolerance and contributes to plant resistance against PstDC3000. This is one of the first examples, to our knowledge, of ATP-dependent binding cassette transporter involvement in plant resistance to infection by a bacterial pathogen. It also suggests a possible mechanism by which plants reduce the deleterious effects of ABA hijacking during pathogen attack. Collectively, these results improve our understanding of basal resistance in Arabidopsis and offer unique ABA-related targets for improving the innate resistance of plants to bacterial infection.
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http://dx.doi.org/10.1104/pp.114.248153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4213115PMC
October 2014

Computational discovery of soybean promoter cis-regulatory elements for the construction of soybean cyst nematode-inducible synthetic promoters.

Plant Biotechnol J 2014 Oct 3;12(8):1015-26. Epub 2014 Jun 3.

Department of Plant Sciences, The University of Tennessee, Knoxville, TN, USA.

Computational methods offer great hope but limited accuracy in the prediction of functional cis-regulatory elements; improvements are needed to enable synthetic promoter design. We applied an ensemble strategy for de novo soybean cyst nematode (SCN)-inducible motif discovery among promoters of 18 co-expressed soybean genes that were selected from six reported microarray studies involving a compatible soybean-SCN interaction. A total of 116 overlapping motif regions (OMRs) were discovered bioinformatically that were identified by at least four out of seven bioinformatic tools. Using synthetic promoters, the inducibility of each OMR or motif itself was evaluated by co-localization of gain of function of an orange fluorescent protein reporter and the presence of SCN in transgenic soybean hairy roots. Among 16 OMRs detected from two experimentally confirmed SCN-inducible promoters, 11 OMRs (i.e. 68.75%) were experimentally confirmed to be SCN-inducible, leading to the discovery of 23 core motifs of 5- to 7-bp length, of which 14 are novel in plants. We found that a combination of the three best tools (i.e. SCOPE, W-AlignACE and Weeder) could detect all 23 core motifs. Thus, this strategy is a high-throughput approach for de novo motif discovery in soybean and offers great potential for novel motif discovery and synthetic promoter engineering for any plant and trait in crop biotechnology.
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http://dx.doi.org/10.1111/pbi.12206DOI Listing
October 2014

Physiological and transcriptional responses of Baccharis halimifolia to the explosive "composition B" (RDX/TNT) in amended soil.

Environ Sci Pollut Res Int 2014 1;21(13):8261-70. Epub 2014 Apr 1.

Department of Life Science, Dongguk University-Seoul, Seoul, 100-715, South Korea.

Unexploded explosives that include royal demolition explosive (RDX) and trinitrotoluene (TNT) cause environmental concerns for surrounding ecosystems. Baccharis halimifolia is a plant species in the sunflower family that grows naturally near munitions sites on contaminated soils, indicating that it might have tolerance to explosives. B. halimifolia plants were grown on 100, 300, and 750 mg kg(-1) of soil amended with composition B (Comp B) explosive, a mixture of royal demolition explosive and trinitrotoluene. These concentrations are environmentally relevant to such munitions sites. The purpose of the experiment was to mimic contaminated sites to assess the plant's physiological response and uptake of explosives and to identify upregulated genes in response to explosives in order to better understand how this species copes with explosives. Stomatal conductance was not significantly reduced in any treatments. However, net photosynthesis, absorbed photons, and chlorophyll were significantly reduced in all treatments relative to the control plants. The dark-adapted parameter of photosynthesis was reduced only in the 750 mg kg(-1) Comp B treatment. Thus, we observed partial physiological tolerance to Comp B in B. halimifolia plants. We identified and cloned 11 B. halimifolia gene candidates that were orthologous to explosive-responsive genes previously identified in Arabidopsis and poplar. Nine of those genes showed more than 90% similarity to Conyza canadensis (horseweed), which is the closest relative with significant available genomics resources. The expression patterns of these genes were studied using quantitative real-time PCR. Three genes were transcriptionally upregulated in Comp B treatments, and the Cytb6f gene was found to be highly active in all the tested concentrations of Comp B. These three newly identified candidate genes of this explosives-tolerant plant species can be potentially exploited for uses in phytoremediation by overexpressing these genes in transgenic plants and, similarly, by using promoters or variants of promoters from these genes fused to reporter genes in transgenic plants for making phytosensors to report the localized presence of explosives in contaminated soils.
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http://dx.doi.org/10.1007/s11356-014-2764-4DOI Listing
May 2015

Synthetic TAL effectors for targeted enhancement of transgene expression in plants.

Plant Biotechnol J 2014 May 23;12(4):436-46. Epub 2013 Dec 23.

Department of Plant Sciences, The University of Tennessee, Knoxville, TN, USA.

Transcription activator-like effectors (TALEs), secreted by the pathogenic bacteria Xanthomonas, specifically activate expression of targeted genes in plants. Here, we designed synthetic TALEs that bind to the flanking regions of the TATA-box motif on the CaMV 35S promoter for the purpose of understanding the engineerable 'hot-spots' for increasing transgene expression. We demonstrated that transient expression of de novo-engineered TALEs using agroinfiltration could significantly increase reporter gene expression in stable transgenic tobacco expressing the orange fluorescent protein reporter gene pporRFP under the control of synthetic inducible, minimal or full-length 35S promoters. Moreover, the additive effects of a combination of two different synthetic TALEs could significantly enhance the activation effects of TALEs on reporter gene expression more than when each TALE was used individually. We also studied the effects of the C-terminal domain and the activation domain of synthetic TALEs, as well as the best 'hot-spots' on the 35S promoter on targeted transgene activation. Furthermore, TALE activation of the Arabidopsis MYB transcription factor AtPAP1 (PRODUCTION OF ANTHOCYANIN PIGMENT 1) in stable transgenic tobacco gave rise to a dark purple colour on infiltrated leaves when driven by four copies of cis-regulatory elements of pathogenesis-related gene (PR1) with enhancer motifs B and A1 from the 35S promoter. These results provide novel insights into the potential applications of synthetic TALEs for targeted gene activation of transgenes in plants.
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http://dx.doi.org/10.1111/pbi.12150DOI Listing
May 2014
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