Publications by authors named "Deli Liu"

63 Publications

Tumor size and genomic risk in localized prostate cancer.

Urol Oncol 2021 Feb 6. Epub 2021 Feb 6.

Department of Urology, Weill Cornell Medical Center, New York Presbyterian Hospital, New York, NY.

Purpose: Unlike many other cancers, measurement of primary prostate tumor size has no defined role in the management of localized prostate cancer. Here, we assess whether prostate tumor size is associated with aggressive tumor biology using biomarkers of genomic risk.

Materials And Methods: We abstracted or imputed tumor size from the primary pathology reports of prostate cancers incorporated in The Cancer Genome Atlas. We used transcriptomic data to estimate the Cell Cycle Progression Score (CCPS, Prolaris), the Genomic Classifier Score (GCS, Decipher) and the Genomic Prostate Score (GPS, OncotypeDx), SChLaP1 expression, and copy number alteration percentage (%CNA) as well as hallmark gene set enrichment analysis.

Results: Tumor size and gene expression data was available for 267 men. On multivariable regression adjusted for Gleason Grade Group and tumor purity, tumor size was independently associated with the calculated (c)GCS, cGPS, SChLaP1 expression, and %CNA (P< 0.05), but not cCCPS. Gene set enrichment analysis demonstrated that tumors <5 cc, when adjusting for Gleason grade group, were enriched for androgen response genes, while tumors >5 cc were enriched for MYC targets and genes associated with epithelial mesenchymal transition.

Conclusions: Prostate tumor size is independently associated with established markers of genomic risk. This study nominates the size of a primary prostate cancer as candidate for inclusion in future novel risk scores seeking to quantify cancer aggressiveness.
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http://dx.doi.org/10.1016/j.urolonc.2021.01.020DOI Listing
February 2021

Diversity in Androgen Receptor Action Among Treatment-naïve Prostate Cancers Is Reflected in Treatment Response Predictions and Molecular Subtypes.

Eur Urol Open Sci 2020 Dec 6;22:34-44. Epub 2020 Nov 6.

Department of Cancer Biology, Cleveland Clinic, Cleveland, OH, USA.

Background: Metastatic prostate cancer (CaP) treatments are evolving rapidly but without evidence-based biomarkers to predict responses, and to maximize remissions and survival.

Objective: To determine the activity of androgen receptor (AR), the target for default first-line systemic treatment, in localized treatment-naïve CaP and its association with clinical risk factors, molecular markers, CaP subtypes, and predictors of treatment response.

Design Setting And Participants: We examined 452 bona fide AR target genes in clinical-grade expression profiles from 6532 such CaPs collected between 2013 and 2017 by US physicians ordering the Decipher RP test. Results were validated in three independent smaller cohorts ( = 73, 90, and 127) and clinical CaP AR ChIP-Seq data. Association with CaP differentiation and progression was analyzed in independent datasets.

Outcome Measurements And Statistical Analysis: Unsupervised clustering of CaPs based on AR target gene expression was aligned with clinical variables, differentiation scores, molecular subtypes, and predictors of response to hormonal therapy, radiotherapy, and chemotherapy. AR target gene sets were analyzed via Gene Set Enrichment Analysis for differentiation and treatment resistance, Ingenuity Pathway Analysis for associated biology, and Cistrome for genomic AR binding site (ARBS) composition.

Results And Limitations: Expression of eight AR target gene subsignatures gave rise to five CaP clusters, which were preferentially associated with CaP molecular subtypes, differentiation, and predictors of treatment response rather than with clinical variables. Subsignatures differed in contribution to CaP progression, luminal/basal differentiation, CaP biology, and ARBS composition. Validation in prospective trials and optimized quantitation are needed for clinical implementation.

Conclusions: Measurement of AR activity patterns in treatment-naïve CaP may serve as a first branch of an evidence-based decision tree to optimize personalized treatment plans.

Patient Summary: Treatment options for metastatic prostate cancer are increasing without information needed to choose the right treatment for the right patient. We found variation in the behavior of the target for the default first-line therapy before treatment, which may help optimize treatment plans.
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http://dx.doi.org/10.1016/j.euros.2020.10.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723342PMC
December 2020

Electrochemical and spectroscopic characteristics of cytochrome P450 55A3 and its interaction with nitric oxide.

Int J Biol Macromol 2021 Jan 14;167:1406-1413. Epub 2020 Nov 14.

College of Life Science, South Central University for Nationalities, Wuhan 430074, PR China. Electronic address:

Cytochrome P450 55A3 (CYP55A3) is an enzyme with the catalytic activity of nitric oxide (NO) to nitrous oxide using NADH or NADPH as the electron donor. Herein CYP55A3 has been expressed in E. coli and purified by His-tag columns. The electrochemical and spectroscopic characteristic of CYP55A3 and its interaction with NO has been studied. The direct electrochemistry of Fe/Fe redox peaks in CYP55A3 was realized on the pyrolitic graphite electrode with the redox potential of -475 mV in pH 7.0 phosphate buffer. With the addition of NO a ferric nitroxyl complex (Fe-NO) formed with a new reduction peak at -0.78 V. The reduction peak current increased with the concentration of NO and showed typical Michaelis-Menten kinetic characteristics with the apparent Michaelis constant Kmapp 9.78 μM. The binding constant K calculated to be 3.93 × 10 M by UV-vis method. The fluorescence emission spectra of iron porphyrin in CYP55A3 showed with the peak wavelength 633 nm, and its fluorescence intensity increased after binding with NO. The fluorescence analysis demonstrated that NADH can relay electrons to iron porphyrin and reduce NO. The reductive product of NO released and the iron porphyrin in CYP55A3 turned back to the original form.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.11.094DOI Listing
January 2021

Author Correction: FOXA1 mutations alter pioneering activity, differentiation and prostate cancer phenotypes.

Nature 2020 Sep;585(7826):E20

Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41586-020-2678-xDOI Listing
September 2020

Colorimetric determination of DNA using an aptamer and plasmonic nanoplatform.

Mikrochim Acta 2020 06 17;187(7):393. Epub 2020 Jun 17.

School of Marine Science and Technology, Harbin Institute of Technology, Weihai, 264209, People's Republic of China.

A facile plasmonic nanoplatform was developed for rapid and sensitive determination of nucleic acid. Hg-regulated molecular beacon (MB, hairpin) containing rich thymine (T) bases at both ends is used as the probe. A hairpin structure can be formed in the MB probe due to the strong binding of Hg to T. However, in the presence of target DNA, the hairpin structure is opened owing to target DNA-specific hybridization with the aptamer. Simultaneously, the opened MB interacts with poly(diallyldimethylammonium chloride) (PDDA) and hinders PDDA-induced aggregation of AuNPs, accompanied by a color change from blue to red and a decrease in absorption ratio (A/A). Hence, a good linear relationship was observed between the decreased absorption ratio (A/A) and DNA concentration ranging from 0.02 to 2 nmol/L with a low detection limit of 4.42 pmol/L. Moreover, this nanoplatform has been successfully utilized to discriminate between perfect target and mismatch sequences. More importantly, the bioassay is simple, versatile, rapid, and cost-effective compared with other common methods, which holds great promise for clinical diagnosis and biomedical application. Graphical abstract.
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http://dx.doi.org/10.1007/s00604-020-04361-0DOI Listing
June 2020

Integrative multiplatform molecular profiling of benign prostatic hyperplasia identifies distinct subtypes.

Nat Commun 2020 04 24;11(1):1987. Epub 2020 Apr 24.

Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.

Benign prostatic hyperplasia (BPH), a nonmalignant enlargement of the prostate, is among the most common diseases affecting aging men, but the underlying molecular features remain poorly understood, and therapeutic options are limited. Here we employ a comprehensive molecular investigation of BPH, including genomic, transcriptomic and epigenetic profiling. We find no evidence of neoplastic features in BPH: no evidence of driver genomic alterations, including low coding mutation rates, mutational signatures consistent with aging tissues, minimal copy number alterations, and no genomic rearrangements. At the epigenetic level, global hypermethylation is the dominant process. Integrating transcriptional and methylation signatures identifies two BPH subgroups with distinct clinical features and signaling pathways, validated in two independent cohorts. Finally, mTOR inhibitors emerge as a potential subtype-specific therapeutic option, and men exposed to mTOR inhibitors show a significant decrease in prostate size. We conclude that BPH consists of distinct molecular subgroups, with potential for subtype-specific precision therapy.
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http://dx.doi.org/10.1038/s41467-020-15913-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181734PMC
April 2020

Prognostic value of the SPOP mutant genomic subclass in prostate cancer.

Urol Oncol 2020 05 17;38(5):418-422. Epub 2020 Mar 17.

Department of Urology, New York Presbyterian Hospital, Joan and Sanford I. Weill Medical College of Cornell University, New York, NY; Sandra and Edward Meyer Cancer Center, Joan and Sanford I. Weill Medical College of Cornell University, New York, NY. Electronic address:

Background: Speckle-type POZ protein (SPOP) mutation defines one of the dominant prostate cancer genomic subtypes, yet the impact of this mutation on clinical prognosis is unknown.

Methods: We defined SPOP mutation status either by DNA sequencing or by transcriptional signature in a pooled retrospective multi-institutional cohort, the Decipher retrospective cohort, the Decipher Genomics Resource Information Database prospective cohort, and The Cancer Genome Atlas. Kaplan-Meier survival analysis and multivariable Cox models were used to assess the independent impact of SPOP mutation on survival, biochemical recurrence and time to metastasis. The Decipher retrospective cohort was also used to assess the impact of the addition of SPOP mutation status to a model predicting adverse pathology at prostatectomy which was then validated in the Decipher prospective cohort.

Results: A fixed-effect model incorporating results from multivariable Cox regression including 5,811 subjects demonstrated that SPOP mutation was associated with a lower rate of adverse pathology at radical prostatectomy (odds ratios 0.57, 95% confidence interval 0.34-0.93), independent of preoperative prostate-specific antigen, age, and pathologic Gleason score. SPOP was not associated with biochemical recurrence, metastasis-free survival, or cancer-specific survival independent of pathologic information. The addition of SPOP status to prognostic models reclassified a large proportion of patients with the mutation (55%) into a favorable risk group when used to predict adverse pathology.

Conclusion: While the clinical utility of delineating any single molecular alteration in prostate cancer remains unclear, these results illustrates the importance of genomic subtypes in prostate cancer behavior and potential role in prognostic tools.
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http://dx.doi.org/10.1016/j.urolonc.2020.02.011DOI Listing
May 2020

Transcriptome analysis of fungicide-responsive gene expression profiles in two Penicillium italicum strains with different response to the sterol demethylation inhibitor (DMI) fungicide prochloraz.

BMC Genomics 2020 Feb 12;21(1):156. Epub 2020 Feb 12.

Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, 430079, China.

Background: Penicillium italicum (blue mold) is one of citrus pathogens causing undesirable citrus fruit decay even at strictly-controlled low temperatures (< 10 °C) during shipping and storage. P. italicum isolates with considerably high resistance to sterol demethylation inhibitor (DMI) fungicides have emerged; however, mechanism(s) underlying such DMI-resistance remains unclear. In contrast to available elucidation on anti-DMI mechanism for P. digitatum (green mold), how P. italicum DMI-resistance develops has not yet been clarified.

Results: The present study prepared RNA-sequencing (RNA-seq) libraries for two P. italicum strains (highly resistant (Pi-R) versus highly sensitive (Pi-S) to DMI fungicides), with and without prochloraz treatment, to identify prochloraz-responsive genes facilitating DMI-resistance. After 6 h prochloraz-treatment, comparative transcriptome profiling showed more differentially expressed genes (DEGs) in Pi-R than Pi-S. Functional enrichments identified 15 DEGs in the prochloraz-induced Pi-R transcriptome, simultaneously up-regulated in P. italicum resistance. These included ATP-binding cassette (ABC) transporter-encoding genes, major facilitator superfamily (MFS) transporter-encoding genes, ergosterol (ERG) anabolism component genes ERG2, ERG6 and EGR11 (CYP51A), mitogen-activated protein kinase (MAPK) signaling-inducer genes Mkk1 and Hog1, and Ca/calmodulin-dependent kinase (CaMK) signaling-inducer genes CaMK1 and CaMK2. Fragments Per Kilobase per Million mapped reads (FPKM) analysis of Pi-R transcrtiptome showed that prochloraz induced mRNA increase of additional 4 unigenes, including the other two ERG11 isoforms CYP51B and CYP51C and the remaining kinase-encoding genes (i.e., Bck1 and Slt2) required for Slt2-MAPK signaling. The expression patterns of all the 19 prochloraz-responsive genes, obtained in our RNA-seq data sets, have been validated by quantitative real-time PCR (qRT-PCR). These lines of evidence in together draw a general portrait of anti-DMI mechanisms for P. italicum species. Intriguingly, some strategies adopted by the present Pi-R were not observed in the previously documented prochloraz-resistant P. digitatum transcrtiptomes. These included simultaneous induction of all major EGR11 isoforms (CYP51A/B/C), over-expression of ERG2 and ERG6 to modulate ergosterol anabolism, and concurrent mobilization of Slt2-MAPK and CaMK signaling processes to overcome fungicide-induced stresses.

Conclusions: The present findings provided transcriptomic evidence on P. italicum DMI-resistance mechanisms and revealed some diversity in anti-DMI strategies between P. italicum and P. digitatum species, contributing to our knowledge on P. italicum DMI-resistance mechanisms.
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http://dx.doi.org/10.1186/s12864-020-6564-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017498PMC
February 2020

Whole genome bisulfite sequencing of human spermatozoa reveals differentially methylated patterns from type 2 diabetic patients.

J Diabetes Investig 2020 Jul 3;11(4):856-864. Epub 2020 Feb 3.

Department of Scientific Research, Fujian Academy of Medical Sciences, Fuzhou, Fujian, China.

Aims/introduction: The incidence of type 2 diabetes mellitus is increasing worldwide, and it might partly cause metabolic disorder and type 2 diabetes mellitus susceptibility in patients' offspring through epigenetic modification. However, the underlying mechanisms remain largely unclear. Recent studies have shown a potential link between deoxyribonucleic acid methylation in paternal sperm and susceptibility to type 2 diabetes mellitus in offspring, so this article focuses on whether the whole-genome methylation profiles of spermatozoa in type 2 diabetes mellitus patients have changed.

Materials And Methods: We investigated the genome-wide deoxyribonucleic acid methylation profiles in spermatozoa by comparing eight individuals with type 2 diabetes mellitus and nine non-diabetic controls using whole-genome bisulfite sequencing method.

Results: First, we found that the proportion of methylated cytosine in the whole genome of the type 2 diabetes mellitus group was slightly lower than that of the control group. Interestingly, the proportion of methylated cytosines in the CG context decreased, and the proportion of methylated cytosines in the CHG context (H = A, T or C) increased in the type 2 diabetes mellitus group, but the proportion of methylated cytosines in the CHH context (H = A, T or C) barely changed. The methylated cytosines in the CG context were mainly distributed at the high methylated level, whereas methylated cytosines in the CHG context and methylated cytosines in the CHH context were mainly distributed at the low and middle methylated level in both groups. Second, functional enrichment analysis showed that differentially methylated genes played a significant role in nervous system development and cell metabolism. Finally, we identified 10 top type 2 diabetes mellitus-related differentially methylated genes, including IRS1, PRKCE, FTO, PPARGC1A, KCNQ1, ATP10A, GHR, CREB1, PRKAR1A and HNF1B.

Conclusions: Our study provides the first evidence for deoxyribonucleic acid methylation reprogramming in spermatozoa of type 2 diabetes mellitus patients, and provides a new basis for explaining the complex mechanism of type 2 diabetes mellitus susceptibility in offspring.
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http://dx.doi.org/10.1111/jdi.13201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378413PMC
July 2020

Blue-White Colony Selection of Virus-Infected Isogenic Recipients Based on a Chrysovirus Isolated from Penicillium italicum.

Virol Sin 2019 Dec 2;34(6):688-700. Epub 2019 Aug 2.

Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, 430079, China.

Mycoviruses have been found to infect more than 12 species of Penicillium, but have not been isolated from Penicillium italicum (P. italicum). In this study, we isolated and characterized a new double-stranded RNA (dsRNA) virus, designated Penicillium italicum chrysovirus 1 (PiCV1), from the citrus pathogen P. italicum HSPi-YN1. Viral genome sequencing and molecular characterization indicated that PiCV1 was highly homologous to the previously described Penicillium chrysogenum virus. We further constructed the mutant HSPi-YN1ΔpksP defective in the polyketide synthase gene (pksP), which is involved in pigment biosynthesis, and these mutants formed albino (white) colonies. Then we applied hyphal anastomosis method to horizontally transmit PiCV1 from the white virus-donors (i.e., HSPi-YN1 mutants) to wild-type recipients (i.e., P. italicum strains HSPi-CQ54, HSPi-HB4, and HSPi-HN1), and the desirable PiCV1-infected isogenic recipients, a certain part of blue wild-type strains, can be eventually selected and confirmed by viral genomic dsRNA profile analysis. This blue-white colony screening would be an easier method to select virus-infected P. italicum recipients, according to distinguishable color phenotypes between blue virus-recipients and white virus-donors. In summary, the current work newly isolated and characterized PiCV1, verified its horizontal transmission among dually cultured P. italicum isolates, and based on these, established an effective and simplified approach to screen PiCV1-infected isogenic recipients.
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http://dx.doi.org/10.1007/s12250-019-00150-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888793PMC
December 2019

Cooperation between two strains of Enterobacter and Klebsiella in the simultaneous nitrogen removal and phosphate accumulation processes.

Bioresour Technol 2019 Nov 22;291:121854. Epub 2019 Jul 22.

State Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, PR China. Electronic address:

Two strains, Enterobacter sp. Z1 and Klebsiella sp. Z2, were exhibited great capacities for heterotrophic nitrification-aerobic denitrification (HNAD) and intracellular phosphate accumulation. Strikingly, the co-cultured strains enhanced the removal efficiency of total nitrogen and phosphate, with removal efficiencies of ammonia, nitrate, nitrite and soluble phosphate of 99.64%, 99.85%, 96.94% and 66.7% respectively. Furthermore, high removal efficiencies from wastewaters with high concentrations of ammonia (over 1000 mg/L) were achieved by inoculation with the co-strains, which left residual ammonia of less than 1 mg/L within 10 h. To elucidate the mechanism of HNAD in co-strains, quantitative PCR was carried out to examine the expression levels of hydroxylamine oxidase (Hao), nitrate reductase (NapA and NarG), nitrite reductase (NirS) and polyphosphate kinase (Ppk), and the results showed that the napA2, narG and ppk genes in the strains were significantly upregulated under the co-cultured conditions and provided an explanation for the nitrogen and phosphate removal.
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http://dx.doi.org/10.1016/j.biortech.2019.121854DOI Listing
November 2019

FOXA1 mutations alter pioneering activity, differentiation and prostate cancer phenotypes.

Nature 2019 07 26;571(7765):408-412. Epub 2019 Jun 26.

Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Mutations in the transcription factor FOXA1 define a unique subset of prostate cancers but the functional consequences of these mutations and whether they confer gain or loss of function is unknown. Here, by annotating the landscape of FOXA1 mutations from 3,086 human prostate cancers, we define two hotspots in the forkhead domain: Wing2 (around 50% of all mutations) and the highly conserved DNA-contact residue R219 (around 5% of all mutations). Wing2 mutations are detected in adenocarcinomas at all stages, whereas R219 mutations are enriched in metastatic tumours with neuroendocrine histology. Interrogation of the biological properties of wild-type FOXA1 and fourteen FOXA1 mutants reveals gain of function in mouse prostate organoid proliferation assays. Twelve of these mutants, as well as wild-type FOXA1, promoted an exaggerated pro-luminal differentiation program, whereas two different R219 mutants blocked luminal differentiation and activated a mesenchymal and neuroendocrine transcriptional program. Assay for transposase-accessible chromatin using sequencing (ATAC-seq) of wild-type FOXA1 and representative Wing2 and R219 mutants revealed marked, mutant-specific changes in open chromatin at thousands of genomic loci and exposed sites of FOXA1 binding and associated increases in gene expression. Of note, ATAC-seq peaks in cells expressing R219 mutants lacked the canonical core FOXA1-binding motifs (GTAAAC/T) but were enriched for a related, non-canonical motif (GTAAAG/A), which was preferentially activated by R219-mutant FOXA1 in reporter assays. Thus, FOXA1 mutations alter its pioneering function and perturb normal luminal epithelial differentiation programs, providing further support for the role of lineage plasticity in cancer progression.
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http://dx.doi.org/10.1038/s41586-019-1318-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661172PMC
July 2019

Molecular Characterization of a Chrysovirus Isolated From the Citrus Pathogen and Related Fungicide Resistance Analysis.

Front Cell Infect Microbiol 2019 15;9:156. Epub 2019 May 15.

Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, China.

sp. are damaging to a range of foods and fruits including citrus. To date, double-stranded (ds)RNA viruses have been reported in most species but not in citrus pathogen . Here we report a novel dsRNA virus, designated as chrysovirus 1 (PcCV1) and isolated from strain HS-CQ15. PcCV1 genome comprises four dsRNA segments, referred to as dsRNA1, dsRNA2, dsRNA3, and dsRNA4, which are 3600, 3177, 3078, and 2808 bp in length, respectively. Sequence analysis revealed the presence of four open reading frames (ORFs) in the PcCV1 genome. ORF1 in dsRNA1 encodes a putative RNA-dependent RNA polymerase (RdRp) and ORF2 in dsRNA2 encodes a putative coat protein (CP). The two remaining ORFs, ORF3 in dsRNA3 and ORF4 in dsRNA4, encode proteins of unknown function. Phylogenetic analysis based on RdRp sequences showed that PcCV1 clusters with other members of the genus , family . Transmission electron microscope (TEM) analysis revealed that the PcCV1 visions are approximately 40 nm in diameter. Regarding biological effects of PcCV1, HS-CQ15 harboring the chrysovirus exhibited no obvious difference in colony morphology under fungicide-free conditions but decreased resistance to demethylation inhibitor (DMI)-fungicide prochloraz, as compared to PcCV1-cured strain. Here we provide the first evidence of a virus present in citrus pathogenic fungus and the chrysovirus-induced change in fungicide-resistance of its host fungus.
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http://dx.doi.org/10.3389/fcimb.2019.00156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529537PMC
January 2020

CHD1 Loss Alters AR Binding at Lineage-Specific Enhancers and Modulates Distinct Transcriptional Programs to Drive Prostate Tumorigenesis.

Cancer Cell 2019 04 28;35(4):603-617.e8. Epub 2019 Mar 28.

Department of Urology, Weill Cornell Medicine, New York, NY 10065, USA; Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY 10065, USA. Electronic address:

Deletion of the gene encoding the chromatin remodeler CHD1 is among the most common alterations in prostate cancer (PCa); however, the tumor-suppressive functions of CHD1 and reasons for its tissue-specific loss remain undefined. We demonstrated that CHD1 occupied prostate-specific enhancers enriched for the androgen receptor (AR) and lineage-specific cofactors. Upon CHD1 loss, the AR cistrome was redistributed in patterns consistent with the oncogenic AR cistrome in PCa samples and drove tumor formation in the murine prostate. Notably, this cistrome shift was associated with a unique AR transcriptional signature enriched for pro-oncogenic pathways unique to this tumor subclass. Collectively, these data credential CHD1 as a tumor suppressor in the prostate that constrains AR binding/function to limit tumor progression.
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http://dx.doi.org/10.1016/j.ccell.2019.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467783PMC
April 2019

Impact of the SPOP Mutant Subtype on the Interpretation of Clinical Parameters in Prostate Cancer.

JCO Precis Oncol 2018 24;2018. Epub 2018 Jul 24.

Weill Cornell Medicine, NewYork-Presbyterian Hospital, New York, NY.

Purpose: Molecular characterization of prostate cancer, including The Cancer Genome Atlas, has revealed distinct subtypes with underlying genomic alterations. One of these core subtypes, (speckle-type POZ protein) mutant prostate cancer, has previously only been identifiable via DNA sequencing, which has made the impact on prognosis and routinely used risk stratification parameters unclear.

Methods: We have developed a novel gene expression signature, classifier (Subclass Predictor Based on Transcriptional Data), and decision tree to predict the mutant subclass from RNA gene expression data and classify common prostate cancer molecular subtypes. We then validated and further interrogated the association of prostate cancer molecular subtypes with pathologic and clinical outcomes in retrospective and prospective cohorts of 8,158 patients.

Results: The subclass predictor based on transcriptional data model showed high sensitivity and specificity in multiple cohorts across both RNA sequencing and microarray gene expression platforms. We predicted approximately 8% to 9% of cases to be mutant from both retrospective and prospective cohorts. We found that the mutant subclass was associated with lower frequency of positive margins, extraprostatic extension, and seminal vesicle invasion at prostatectomy; however, mutant cancers were associated with higher pretreatment serum prostate-specific antigen (PSA). The association between mutant status and higher PSA level was validated in three independent cohorts. Despite high pretreatment PSA, the SPOP mutant subtype was associated with a favorable prognosis with improved metastasis-free survival, particularly in patients with high-risk preoperative PSA levels.

Conclusion: Using a novel gene expression model and a decision tree algorithm to define prostate cancer molecular subclasses, we found that the mutant subclass is associated with higher preoperative PSA, less adverse pathologic features, and favorable prognosis. These findings suggest a paradigm in which the interpretation of common risk stratification parameters, particularly PSA, may be influenced by the underlying molecular subtype of prostate cancer.
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http://dx.doi.org/10.1200/PO.18.00036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6370327PMC
July 2018

SEG - A Software Program for Finding Somatic Copy Number Alterations in Whole Genome Sequencing Data of Cancer.

Comput Struct Biotechnol J 2018 7;16:335-341. Epub 2018 Sep 7.

Department of Biochemistry and Molecular Biology, Institute of Bioinformatics, University of Georgia, Athens, GA30602-7229, USA.

As next-generation sequencing technology advances and the cost decreases, whole genome sequencing (WGS) has become the preferred platform for the identification of somatic copy number alteration (CNA) events in cancer genomes. To more effectively decipher these massive sequencing data, we developed a software program named SEG, shortened from the word "segment". SEG utilizes mapped read or fragment density for CNA discovery. To reduce CNA artifacts arisen from sequencing and mapping biases, SEG first normalizes the data by taking the log-ratio of each tumor density against its matching normal density. SEG then uses dynamic programming to find change-points among a contiguous log-ratio data series along a chromosome, dividing the chromosome into different segments. SEG finally identifies those segments having CNA. Our analyses with both simulated and real sequencing data indicate that SEG finds more small CNAs than other published software tools.
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http://dx.doi.org/10.1016/j.csbj.2018.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154469PMC
September 2018

Molecular characterization of a new gammapartitivirus isolated from the citrus-pathogenic fungus Penicillium digitatum.

Arch Virol 2018 Nov 4;163(11):3185-3189. Epub 2018 Aug 4.

Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, 430079, People's Republic of China.

To date, partitiviruses, including gammapartitiviruses, have been extensively studied in various fungal hosts but have not been reported in Penicillium digitatum (also called green mold, the pathogenic fungus infecting citrus). In the present work, we isolated and molecularly characterized a double-stranded RNA (dsRNA) partitivirus from citrus green mold, which we have named "Penicillium digitatum gammapartitivirus 1" (PdGV1). The bisegmented genome of PdGV1 contains two dsRNA segments (dsRNA1 and dsRNA2) with a length of 1795 bp and 1622 bp, respectively. Each of the two genomic dsRNAs contains a single open reading frame encoding a putative RNA-dependent RNA polymerase (RdRp) and a coat protein (CP), respectively. Phylogenetic analysis based on RdRp and CP sequences showed that PdGV1 clustered with mycoviruses belonging to the genus Gammapartitivirus, family Partitiviridae, e.g., Penicillium stoloniferum virus S. The 5'- and 3'-untranslated regions (UTRs) of the PdGV1 genomic dsRNAs both contained unique conserved RNA motifs that have never been found in any other partitivirus. This is the first report of a new gammapartitivirus that infects the citrus-pathogenic fungus P. digitatum.
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http://dx.doi.org/10.1007/s00705-018-3951-2DOI Listing
November 2018

Characterization of two novel mycoviruses from Penicillium digitatum and the related fungicide resistance analysis.

Sci Rep 2018 04 3;8(1):5513. Epub 2018 Apr 3.

Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, 430079, P. R. China.

Pathogenic fungi including Penicillium digitatum and Penicillium italicum are the main destructive pathogens in the citrus industry, causing great losses during postharvest process. To our knowledge, only one mycovirus from P. digitatum has been reported, and the prevalence of such mycoviruses against citrus postharvest pathogenic fungi and their genotyping were still under investigation. In the present study, we showed that 39 of 152 Penicillium isolates from main citrus-growing areas in China were infected with various mycoviruses belonging to polymycoviruses, Narna-like viruses, and families Totiviridae, Partitivirdae and Chrysoviridae. The next generation sequencing (NGS) towards virus genome library and the following molecular analysis revealed two novel mycoviruses Penicillium digitatum polymycovirus 1 (PdPmV1) and Penicillium digitatum Narna-like virus 1 (PdNLV1), coexisting in P. digitatum strain HS-RH2. The fungicide-resistant P. digitatum strains HS-F6 and HS-E9 coinfected by PdPmV1 and PdNLV1 exhibited obvious reduction in triazole drug prochloraz resistance by mycelial growth analysis on both PDA plates and citrus fruit epidermis with given prochloraz concentration. This report at the first time characterized two novel mycoviruses from P. digitatum and revealed the mycovirus-induced reduction of fungicide resistance.
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http://dx.doi.org/10.1038/s41598-018-23807-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882929PMC
April 2018

Quantum dots for a high-throughput Pfu polymerase based multi-round polymerase chain reaction (PCR).

Analyst 2018 Feb;143(5):1259-1267

School of Marine Science and Technology, Harbin Institute of Technology, Weihai, 264209, People's Republic of China.

Multi-round PCR is an important technique for obtaining enough target DNA from rare DNA resources, and is commonly used in many fields including forensic science, ancient DNA analysis and cancer research. However, multi-round PCR is often aborted, largely due to the accumulation of non-specific amplification during repeated amplifications. Here, we developed a Pfu polymerase based multi-round PCR technique assisted by quantum dots (QDs). Different PCR assays, DNA polymerases (Pfu and Taq), DNA sizes and GC amounts were compared in this study. In the presence of QDs, PCR specificity could be retained even in the ninth-round amplification. Moreover, the longer and more complex the targets were, the earlier the abortion happened in multi-round PCR. However, no obvious enhancement of specificity was found in multi-round PCR using Taq DNA polymerase. Significantly, the fidelity of Pfu polymerase based multi-round PCR was not sacrificed in the presence of QDs. Besides, pre-incubation at 50 °C for an hour had no impact on multi-round PCR performance, which further authenticated the hot start effect of QDs modulated in multi-round PCR. The findings of this study demonstrated that a cost-effective and promising multi-round PCR technique for large-scale and high-throughput sample analysis could be established with high specificity, sensibility and accuracy.
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http://dx.doi.org/10.1039/c7an01764bDOI Listing
February 2018

PCR-DGGE Analysis on Microbial Community Structure of Rural Household Biogas Digesters in Qinghai Plateau.

Curr Microbiol 2018 May 12;75(5):541-549. Epub 2017 Dec 12.

Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, 430079, Hubei, China.

To investigate contribution of environmental factor(s) to microbial community structure(s) involved in rural household biogas fermentation at Qinghai Plateau, we collected slurry samples from 15 digesters, with low-temperature working conditions (11.1-15.7 °C) and evenly distributed at three counties (Datong, Huangyuan, and Ledu) with cold plateau climate, to perform polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) and further sequencing. The bacterial communities in the total 15 digesters were classified into 38 genera with Mangroviflexus (12.1%) as the first dominant, and the archaeal communities into ten genera with Methanogenium (38.5%) as the most dominant. For each county, the digesters with higher biogas production, designated as HP digesters, exclusively had 1.6-3.1 °C higher fermentation temperature and the unique bacterial structure composition related, i.e., unclassified Clostridiales for all the HP digesters and unclassified Marinilabiliaceae and Proteiniclasticum for Ledu HP digesters. Regarding archaeal structure composition, Methanogenium exhibited significantly higher abundances at all the HP digesters and Thermogymnomonas was the unique species only identified at Ledu HP digesters with higher-temperature conditions. Redundancy analysis also confirmed the most important contribution of temperature to the microbial community structures investigated. This report emphasized the correlation between temperature and specific microbial community structure(s) that would benefit biogas production of rural household digesters at Qinghai Plateau.
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http://dx.doi.org/10.1007/s00284-017-1414-8DOI Listing
May 2018

SPOP mutation drives prostate neoplasia without stabilizing oncogenic transcription factor ERG.

J Clin Invest 2018 01 4;128(1):381-386. Epub 2017 Dec 4.

Department of Urology, New York Presbyterian Hospital.

Nearly 50% of prostate cancers harbor gene fusions that lead to overexpression of the transcription factor ERG, while a mutually exclusive 10% of prostate cancers harbor recurrent mutations in the gene encoding the E3 ubiquitin ligase SPOP. Recent reports suggest that SPOP acts as a ubiquitin ligase for ERG and propose that ERG stabilization is the oncogenic effector of SPOP mutation. Here, we used human prostate cancer samples and showed that the vast majority of human SPOP-mutant cancers do not express ERG. Comparison of SPOP-mutant and ERG-fusion organoid models showed evidence of divergent, rather than common, transcriptional programs. Furthermore, expression of prostate cancer-associated SPOP mutations in genetically engineered mouse models of SPOP-mutant prostate cancer did not result in the expression of ERG protein in histologically normal prostate glands, high-grade prostatic intraepithelial neoplasia, invasive adenocarcinoma, or prostate organoids. In summary, we found no evidence that ERG is an effector of SPOP mutation in human prostate cancer or mouse models.
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http://dx.doi.org/10.1172/JCI96551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749531PMC
January 2018

Microbial community structure and diversity within hypersaline Keke Salt Lake environments.

Can J Microbiol 2017 Nov 29;63(11):895-908. Epub 2017 Aug 29.

c Research Center of Basic Medical Sciences, Qinghai University Medical College, Xining, Qinghai 810016, People's Republic of China.

Keke Salt Lake is located in the Qaidamu Basin of China. It is a unique magnesium sulfate-subtype hypersaline lake that exhibits a halite domain ecosystem, yet its microbial diversity has remained unstudied. Here, the microbial community structure and diversity was investigated via high-throughput sequencing of the V3-V5 regions of 16S rRNA genes. A high diversity of operational taxonomic units was detected for Bacteria and Archaea (734 and 747, respectively), comprising 21 phyla, 43 classes, and 201 genera of Bacteria and 4 phyla, 4 classes, and 39 genera of Archaea. Salt-saturated samples were dominated by the bacterial genera Bacillus (51.52%-58.35% relative abundance), Lactococcus (9.52%-10.51%), and Oceanobacillus (8.82%-9.88%) within the Firmicutes phylum (74.81%-80.99%), contrasting with other hypersaline lakes. The dominant Archaea belonged to the Halobacteriaceae family, and in particular, the genera (with an abundance of >10% of communities) Halonotius, Halorubellus, Halapricum, Halorubrum, and Natronomonas. Additionally, we report the presence of Nanohaloarchaeota and Woesearchaeota in Qinghai-Tibet Plateau lakes, which has not been previously documented. Total salinity (especially Mg, Cl, Na, and K) mostly correlated with taxonomic distribution across samples. These results expand our understanding of microbial resource utilization within hypersaline lakes and the potential adaptations of dominant microorganisms that allow them to inhabit such environments.
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http://dx.doi.org/10.1139/cjm-2016-0773DOI Listing
November 2017

Identification of novel prostate cancer drivers using RegNetDriver: a framework for integration of genetic and epigenetic alterations with tissue-specific regulatory network.

Genome Biol 2017 07 27;18(1):141. Epub 2017 Jul 27.

Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York, 10065, USA.

We report a novel computational method, RegNetDriver, to identify tumorigenic drivers using the combined effects of coding and non-coding single nucleotide variants, structural variants, and DNA methylation changes in the DNase I hypersensitivity based regulatory network. Integration of multi-omics data from 521 prostate tumor samples indicated a stronger regulatory impact of structural variants, as they affect more transcription factor hubs in the tissue-specific network. Moreover, crosstalk between transcription factor hub expression modulated by structural variants and methylation levels likely leads to the differential expression of target genes. We report known prostate tumor regulatory drivers and nominate novel transcription factors (ERF, CREB3L1, and POU2F2), which are supported by functional validation.
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http://dx.doi.org/10.1186/s13059-017-1266-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5530464PMC
July 2017

Co-clinical Analysis of a Genetically Engineered Mouse Model and Human Prostate Cancer Reveals Significance of NKX3.1 Expression for Response to 5α-reductase Inhibition.

Eur Urol 2017 10 4;72(4):499-506. Epub 2017 Apr 4.

Departments of Urology, Medicine, Pathology & Cell Biology, and Systems Biology, Institute of Cancer Genetics, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA. Electronic address:

Background: Although men on active surveillance for prostate cancer (PCa) may benefit from intervention with 5α-reductase inhibitors (5-ARIs), it has not been resolved whether 5-ARIs are effective for delaying disease progression and, if so, whether specific patients are more likely to benefit.

Objective: To identify molecular features predictive of patient response to 5-ARIs.

Design, Setting, And Participants: Nkx3.1 mutant mice, a model of early-stage PCa, were treated with the 5-ARI finasteride, and histopathological and molecular analyses were performed. Cross-species computational analyses were used to compare expression profiles for treated mice with those of patients who had received 5-ARIs before prostatectomy.

Intervention: Finasteride administered to Nkx3.1 mutant mice. 5-ARI-treated patient specimens obtained retrospectively.

Outcome Measurements And Statistical Analysis: Endpoints in mice included histopathology, immunohistochemistry, and molecular profiling. GraphPad Prism software, R-studio, and Matlab were used for statistical and data analyses.

Results And Limitations: Finasteride treatment of Nkx3.1 mutant mice resulted in a significant reduction in prostatic intraepithelial neoplasia (PIN), as evident from histopathological and expression profiling analyses. Cross-species computational analysis comparing finasteride-treated mice with two independent 5-ARI-treated patient cohorts showed that reduced NKX3.1 expression is predictive of response to 5-ARI. A limitation of the study is that these retrospective human cohorts have relatively few patients with limited clinical outcome data. Future prospective clinical trials are needed to validate whether stratifying patients on the basis of NKX3.1 expression improves the benefit of 5-ARIs during active surveillance.

Conclusions: This co-clinical study implicates NKX3.1 status as a predictor of response to 5-ARIs, and suggests that molecular features, including NKX3.1 expression, may help to identify PCa patients most likely to benefit from 5-ARIs during active surveillance.

Patient Summary: The aim of precision cancer prevention is to tailor interventions on the basis of individualized patient characteristics. We propose that patients with low NKX3.1 expression are optimal candidates for intervention with 5α-reductase inhibitors as an adjunct to active surveillance.
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http://dx.doi.org/10.1016/j.eururo.2017.03.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5600823PMC
October 2017

Pharmacophore-Based Virtual Screening of Novel Inhibitors and Docking Analysis for CYP51A from Penicillium italicum.

Mar Drugs 2017 Apr 5;15(4). Epub 2017 Apr 5.

Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Science, Central China Normal University, Wuhan 430079, China.

Sterol 14α-demethylases from Cytochrome P450 family (CYP51s) are essential enzymes in sterol biosynthesis and well-known as the target of antifungal drugs. The 3D structure of CYP51A from (PiCYP51A) was constructed through homology modeling based on the crystal structure of human CYP51A (PDB: 3LD6). Molecular dynamics (MD) simulation was operated to relax the initial model and followed by quality assessment using PROCHECK program. On the basis of the docking information on the currently available CYP51s with the patent demethylase inhibitors (DMIs), pharmacophore-based virtual screening combined with docking analysis was performed to pick out twelve new compounds from ZINC database. Six hits revealed in the ligand database suggested potential ability to inhibit PiCYP51A. Compared to patent fungicide triazolone, the top three lead compounds had similar or higher affinity with the target enzyme, and accordingly, exhibited comparable or lower EC values to isolates. The results could provide references for de novo antifungal drug design.
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http://dx.doi.org/10.3390/md15040107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5408253PMC
April 2017

SPOP Mutation Drives Prostate Tumorigenesis In Vivo through Coordinate Regulation of PI3K/mTOR and AR Signaling.

Cancer Cell 2017 03;31(3):436-451

Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA; Department of Urology, Weill Cornell Medicine, New York, NY 10065, USA. Electronic address:

Recurrent point mutations in SPOP define a distinct molecular subclass of prostate cancer. Here, we describe a mouse model showing that mutant SPOP drives prostate tumorigenesis in vivo. Conditional expression of mutant SPOP in the prostate dramatically altered phenotypes in the setting of Pten loss, with early neoplastic lesions (high-grade prostatic intraepithelial neoplasia) with striking nuclear atypia and invasive, poorly differentiated carcinoma. In mouse prostate organoids, mutant SPOP drove increased proliferation and a transcriptional signature consistent with human prostate cancer. Using these models and human prostate cancer samples, we show that SPOP mutation activates both PI3K/mTOR and androgen receptor signaling, effectively uncoupling the normal negative feedback between these two pathways.
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http://dx.doi.org/10.1016/j.ccell.2017.02.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384998PMC
March 2017

Aminoalcohol-Induced Activation of Organophosphorus Hydrolase (OPH) towards Diisopropylfluorophosphate (DFP).

PLoS One 2017 13;12(1):e0169937. Epub 2017 Jan 13.

Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, Hubei, P. R. China.

Aminoalcohols have been addressed as activating buffers for alkaline phosphatase. However, there is no record on the buffer activation regarding organophosphorus hydrolase (OPH). Here we reported the activating effects of aminoalcohols on OPH-catalyzed hydrolysis of diisopropylfluorophosphate (DFP), an analog molecule of G-type warfare agents. The kinetic parametors kcat, Vmax and kcat/Km in the OPH reaction were remarkably increased in the buffers (pH 8.0, 25°C) containing aminoalcohols with C2 between nitrogen (N) and oxygen (O) in their structures, including triethanolamine (TEA), diethanolamine, monoethanolamine, 1-amino-2-propanol, 2-amino-2-methyl-1-propanol, and triisopropanolamine. In contrast, much lower or no rate-enhancing effects were observed in the adding of amines, alcohols, amine/alcohol mixtures, or 3-amino-1-propanol (C3 between N and O). The 300 mM TEA further increased DFP-degrading activities of OPH mutants F132Y and L140Y, the previously reported OPH mutants with desirable activities towards DFP. However, the treatment of ethylenediaminetetraacetate (EDTA) markedly abolished the TEA-induced activation of OPH. The product fluoride effectively inhibited OPH-catalyzed hydrolysis of DFP by a linear mixed inhibition (inhibition constant Ki ~ 3.21 mM), which was partially released by TEA adding at initial or later reaction stage. The obtained results indicate the activation of OPH by aminoalcohol buffers could be attributed to the reduction of fluoride inhibition, which would be beneficial to the hydrolase-based detoxification of organophosphofluoridate.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0169937PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5234802PMC
August 2017

A novel major facilitator superfamily transporter in Penicillium digitatum (PdMFS2) is required for prochloraz resistance, conidiation and full virulence.

Biotechnol Lett 2016 Aug 5;38(8):1349-57. Epub 2016 May 5.

Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Science, Central China Normal University, 152 Luoyu Road, Wuhan, 430079, Hubei, People's Republic of China.

Objectives: To clone a novel major facilitator superfamily (MFS, a large protein family with diverse physiological functions in all kingdoms) transporter gene, Pdmfs2, and characterize its function in Penicillium digitatum.

Results: A novel MFS transporter gene, Pdmfs2, was isolated from P. digitatum. The full-length DNA of Pdmfs2 had a 1590 bp ORF encoding a full-size MFS transporter with 529 amino acids. In a prochloraz-resistant strain (PdHS-F6), Pdmfs2 transcript level was up-regulated compared with the prochloraz-sensitive strain (PdHS-E3) and could be induced by 7 μg prochloraz/ml. The deletion of Pdmfs2 (ΔPdmfs2) in PdHS-F6 led to increased susceptibility to prochloraz and lower EC50 value (the concentration of prochloraz producing 50 % growth inhibition) compared with the PdHS-F6 or complementation strain (COPdmfs2). The ΔPdmfs2 strain was defective in conidia yield and virulence towards citrus fruits, while the complementation of Pdmfs2 could restore the phenotypic features to a large extent.

Conclusions: Pdmfs2 is the second MFS transporter gene in P. digitatum and is required for prochloraz resistance, conidiation and full virulence.
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http://dx.doi.org/10.1007/s10529-016-2113-4DOI Listing
August 2016

Isolation and characterization of a novel mycovirus from Penicillium digitatum.

Virology 2016 07 7;494:15-22. Epub 2016 Apr 7.

Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Science, Central China Normal University, Wuhan 430079, China. Electronic address:

A novel double-stranded RNA virus designated Penicillium digitatum virus 1 (PdV1) was isolated from the citrus fruit rot pathogen P. digitatum (HS-RH1). The full-length cDNA sequence of the dsRNA/PdV1 (5211bp) possesses two partially overlapping open reading frames, which encode a coat protein (CP) and a putative RNA-dependent RNA polymerase (RdRp), respectively. Phylogenetic analysis based on multiple alignments of the amino acid sequences of the RdRp and CP indicated that PdV1 tentatively belongs to the genus Victorivirus in the Totiviridae family. Electron micrographs of negatively stained viral particles purified from the peak fraction of sucrose density gradient centrifugation showed spherical particles ~35nm in diameter. Transfection experiments with purified virions indicated that PdV1 could reduce the vegetative growth and virulence of P. digitatum strain HS-F6. In summary, we report the first isolation and characterization of a mycovirus from P. digitatum that contributes to the hypovirulence phenotypes of the host strain.
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http://dx.doi.org/10.1016/j.virol.2016.04.004DOI Listing
July 2016