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Background: Breast cancer (BC) is a common malignant tumor that threatens the health of women worldwide. Hsa_circ_0005273 has been identified as a carcinogenic factor in some solid tumors, including BC. However, the molecular mechanism of circ_0005273 in BC is poorly defined. Methods: The expression of circ_0005273, miR‐509‐3p, and hyaluronan‐mediated motility receptor (HMMR) mRNA in BC was detected by quantitative real‐time polymerase chain reaction. Cell proliferation, migration, invasion, and apoptosis were detected by 5‐ethynyl‐2′‐deoxyuridine, transwell, and flow cytometry assays. The glycolysis level was detected via specific kits. Western blot was used to detect protein expression. Binding between miR‐509‐3p and circ_0005273 or HMMR was also verified by dual‐luciferase reporter, RNA pull‐down, and RNA immunoprecipitation assays. Xenograft tumor model was used to detect tumor changes in mice, and immunohistochemistry assay was employed to detect Ki‐67 abundance. Results: Circ_0005273 was increased in BC tissues and cells. Circ_0005273 knockdown might inhibit BC cell proliferation, migration, invasion, glutamine metabolism, and induce apoptosis. Circ_0005273 was a miR‐509‐3p, and the repression role of circ_0005273 absence on BC cell development was weakened by miR‐509‐3p inhibitor or HMMR overexpression. Circ_0005273 up‐regulated the expression of HMMR by sponging miR‐509‐3p. Additionally, circ_0005273 silencing might hinder tumor growth in vivo. Conclusion: Circ_0005273 knockdown might repress BC cell malignant behaviors by regulating the miR‐509‐3p/HMMR axis, which might provide a potential therapeutic target for BC. [ABSTRACT FROM AUTHOR]

Odorant binding proteins (OBPs) and chemosensory proteins (CSPs) play important roles in transporting semiochemicals through the sensillar lymph to olfactory receptors in insect antennae. In the present study, twenty OBPs and three CSPs were identified from the antennal transcriptome of Microplitis mediator. Ten OBPs (MmedOBP11–20) and two CSPs (MmedCSP2–3) were newly identified. The expression patterns of these new genes in olfactory and non-olfactory tissues were investigated by real-time quantitative PCR (qPCR) measurement. The results indicated that MmedOBP14, MmedOBP18, MmedCSP2 and MmedCSP3 were primarily expressed in antennae suggesting potential olfactory roles in M. mediator. However, other genes including MmedOBP11–13, 15–17, 19–20 appeared to be expressed at higher levels in body parts than in antennae. Focusing on the functional characterization of MmedCSP3, immunocytochemistry and fluorescent competitive binding assays were conducted indoors. It was found that MmedCSP3 was specifically located in the sensillum lymph of olfactory sensilla basiconca type 2. The recombinant MmedCSP3 could bind several types of host insects odors and plant volatiles. Interestingly, three sex pheromone components of Noctuidae insects, cis-11-hexadecenyl aldehyde (Z11-16: Ald), cis-11-hexadecanol (Z11-16: OH), and trans-11-tetradecenyl acetate (E11-14: Ac), showed high binding affinities (Ki = 17.24–18.77 μM). The MmedCSP3 may be involved in locating host insects. Our data provide a base for further investigating the physiological roles of OBPs and CSPs in M. mediator, and extend the function of MmedCSP3 in chemoreception of M. mediator. [ABSTRACT FROM AUTHOR]

Objective To study the influence of the methylation level of UGT1A1 gene related to CPT-11 metabolic enzymes in colorectal cancer cells on the sensitivity of chemotherapy drugs. Methods Test the changes in sensitivity of seven colorectal cancer cell strains that have been/not been subject to DAC treatment to CPT-11, analyze its correlation with CES2 , UGT1A1 and GUSB mRNA expression according to IC 50 ; screen the effective interference sequence of UGT1A1 siRNA, test the changes in cytotoxicity of CPT-11 after UGT1A1 siRNA is transfected, select RK0 cells and make them transfected with the chemosynthetic UGT1A1 siRNA after their UGT1A1 expression is restored with or without demethylation treatment. Results The sensitivity of different colorectal cancer cell strains to CPT-11 showed difference ( P < 0.05), UGT1A1 expression in colorectal cell lines had a negative correlation with the IC 50 ( r = 0.790648, P < 0.05), the interference efficiency of the screened UGT1A1 siRNA was up to 78%. The IC 50 value of siRNA decreased by nearly one time after transfected with HT-29 ( P < 0.01); which of methylated RK0 cells of UGT1A1 gene increased instead after the demethylation treatment. However, the IC 50 value of the demethylation treatment group increased compared with the non-demethylation treatment group after UGT1A1 siRNA was transfected. Conclusions The cytotoxicity of CPT-11 to colorectal cancer cells has a negative correlation with UGT1A1 expression, and positive correlation with CES2 and GUSB . The specific silencing UGT1A1 gene of siRNA could significantly increase the sensitivity of CPT-11 to the chemotherapy of colorectal cancer cells. UGT1A1 methylation was an important factor affecting the chemosensitivity of CPT-11. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate the aberrant methylation gene expression related to the irinotecan (CPT-11) metabolic enzymes in different colorectal cancer cell strains; provide new thoughts and measures for reverse of tumor drug resistance. Methods: Studied the aberrant methylation state of CES2, UGT1A1 and GUSB in eight colorectal cancer cell strains through MSP method; and analyze the expression of the target gene after being dealt with DAC. Results: UGT1A1 showed methylation in five cell strains, while CES2 and GUSB respectively showed consistent unmethylation or hemimethylation. After being dealt with DAC, CES2 and GUSB mRNA showed different expressions but not significant. The expression quantity of UGT1A1mRNA in the low-expression cell strains increased significantly. The expression of UGT1A1 protein where POSITIVE presented low expression was up-regulated to different degrees. Negative tropism was found in CES2 and UGT1A1. Conclusion: Methylation in UGT1A1 gene expression silencing as an important mechanism; methylation could provide an effective target for methylation regulation intervening in the treatment of CPT-11. Meanwhile, studies found that the changes in expressions of CES2 and GUSB might be resulted from some unknown target that still existed during the regulation, or from the influence of methylation in the non-core zone of promoters on the gene transcription. [Copyright &y& Elsevier]

Transcriptomic and epigenetic alterations during early embryo development have been proven to play essential roles in regulating the cell fate. Nowadays, advances in single-cell transcriptomics and epigenomics profiling techniques provide large volumes of data for understanding the molecular regulatory mechanisms in early embryos and facilitate the investigation of assisted reproductive technology as well as preimplantation genetic testing. However, the lack of integrated data collection and unified analytic procedures greatly limits their usage in scientific research and clinical application. Hence, it is necessary to establish a database integrating the regulatory information of human and mouse early embryos with unified analytic procedures. Here, we introduce DevOmics (http://devomics.cn/), which contains normalized gene expression, DNA methylation, histone modifications (H3K4me3, H3K9me3, H3K27me3, H3K27ac), chromatin accessibility and 3D chromatin architecture profiles of human and mouse early embryos spanning six developmental stages (zygote, 2cell, 4cell, 8cell, morula and blastocyst (ICM, TE)). The current version of DevOmics provides Search and Advanced Search for retrieving genes a researcher is interested in, Analysis Tools including the differentially expressed genes (DEGs) analysis for acquiring DEGs between different types of samples, allelic explorer for displaying allele-specific gene expression as well as epigenetic modifications and correlation analysis for showing the dynamic changes in different layers of data across developmental stages, as well as Genome Browser and Ortholog for visualization. DevOmics offers a user-friendly website for biologists and clinicians to decipher molecular regulatory mechanisms of human and mouse early embryos. [ABSTRACT FROM AUTHOR]

Enhancers are cis-acting DNA segments with the ability to increase target gene expression. They show high sensitivity to DNase and contain specific DNA elements in an open chromatin state that allows the binding of transcription factors (TFs). While numerous enhancers are annotated in the maize genome, few have been characterized genetically. KERNEL ROW NUMBER4 (KRN4), an intergenic quantitative trait locus for kernel row number, is assumed to be a cis-regulatory element of UNBRANCHED3 (UB3), a key inflorescence gene. However, the mechanism by which KRN4 controls UB3 expression remains unclear. Here, we found that KRN4 exhibits an open chromatin state, harboring sequences that showed high enhancer activity toward the 35S and UB3 promoters. KRN4 is bound by UB2-centered transcription complexes and interacts with the UB3 promoter by three duplex interactions to affect UB3 expression. Sequence variation at KRN4 enhances ub2 and ub3 mutant ear fasciation. Therefore, we suggest that KRN4 functions as a distal enhancer of the UB3 promoter via chromatin interactions and recruitment of UB2-centered transcription complexes for the fine-tuning of UB3 expression in meristems of ear inflorescences. These results provide evidence that an intergenic region helps to finely tune gene expression, providing a new perspective on the genetic control of quantitative traits. Author summary: With the completion of increasing numbers of plant genome sequences and continuous accumulation of multiomics data, numerous regulatory elements are annotated in those intergenic regions containing open chromatin. Enhancers are cis-acting DNA elements with the ability to increase target gene expression. They show high sensitivity to DNase and contain specific DNA elements in an open chromatin state that allows the binding of transcription factors. KERNEL ROW NUMBER4 (KRN4) is an intergenic region located downstream of a key inflorescence gene UNBRANCHED3 (UB3). However, the mechanism by which KRN4 regulates UB3 expression remains unknown. Here, we showed the genetic interactions between KRN4 and UB3 as well as UNBRANCHED2 (UB2) in controlling inflorescence architecture, enhancer activity of KRN4 toward UB3 promoters, and KRN4- recruited UB2-centered transcription complex for UB3 transcription. These results provide evidence that an intergenic region helps to finely tune gene expression and quantitative traits. [ABSTRACT FROM AUTHOR]

Euphorbia helioscopiaL. is an herbaceous species ofEuphorbia(Euphorbiaceae). As an ancient folk herbal medicine, the most effective medicinal component is terpenoid. Diphosphomevalonate decarboxylase (MDC) is the last rate-limiting enzyme of generating the isopentenyl pyrophosphate precursor of terpenoid in MVA pathway. The gene of MDC was cloned successfully fromE. helioscopia, and namedEhMDC(accession number: KP995936). The full length cDNA ofEhMDCwas 1653 bp, and it contained an open reading frame of 1245 bp, a 5′ untranslated region of 184 bp and a 3′ untranslated region of 224 bp. EhMDC contained 415 amino acids. Homologous sequence analysis showed that amino acid sequence of EhMDC had the highest identity of 88% withRicinus communisMDC. Phylogenetic analysis of EhMDC indicatedE. helioscopia,Hevea brasiliensis,R. communis, andJatropha carcaswhich all belonged to Euphorbiaceae were classified into one class. Real-time PCR assay demonstratedEhMDCwas constitutively expressed in roots, stems and leaves with a similar transcription level. Furthermore, in combination with immunoblot analysis and transmission electron microscopy immunogold labeling after anti-EhMDC antibody preparation, the EhMDC was found to be located in the cisternae of the endoplasmic reticulum, small vacuoles from endoplasmic reticulum and cytoplasm of laticifers. As a result, terpenoid biosynthesis site and accumulation ofE. helioscopialaticifers were speculated. [ABSTRACT FROM PUBLISHER]

Although small cell lung cancer (SCLC) is highly responsive to chemotherapies (e.g., cisplatin-etoposide doublet), virtually almost all responsive SCLC patients experience disease recurrence characterized by drug resistance. The mechanisms underlying cisplatin resistance remain elusive. Here we report that cell-intrinsic expression of PD1 and PD-L1, two immune checkpoints, is required for sustained expansion of SCLC cells under cisplatin selection. Indeed, PD1 and PD-L1 were expressed at a higher level in lung cancer cell lines, tumor tissues, and importantly, in SCLC cells resistant to cisplatin (H69R, H82R), when compared to respective controls. Genetic abrogation of PD1 and PD-L1 in H69R and H82R cells decreased their proliferation rate, and restored their sensitivity to cisplatin. Mechanistically, PD-L1 upregulation in H69R and H82R cells was attributed to the overexpression of DNA methyltransferase 1 (DNMT1) or receptor tyrosine kinase KIT, as knockdown of DNMT1 or KIT in H69R and H82R cells led to PD-L1 downregulation. Consequently, combined knockdown of PD-L1 with KIT or DNMT1 resulted in more pronounced inhibition of H69R and H82R cell growth. Thus, cell intrinsic PD1/PD-L1 signaling may be a predictor for poor efficacy of cisplatin treatment, and targeting the cellular PD1/PD-L1 axis may improve chemosensitization of aggressive SCLC. [ABSTRACT FROM AUTHOR]

The complexity of the epigenome landscape and transcriptional regulation is significantly increased during plant polyploidization, which drives genome evolution and contributes to the increased adaptability to diverse environments. However, a comprehensive epigenome map of Brassica napus is still unavailable. In this study, we performed integrative analysis of five histone modifications, RNA polymerase II occupancy, DNA methylation, and transcriptomes in two B. napus lines (2063A and B409), and established global maps of regulatory elements, chromatin states, and their dynamics for the whole genome (including the An and Cn subgenomes) in four tissue types (young leaf, flower bud, silique, and root) of these two lines. Approximately 65.8% of the genome was annotated with different epigenomic signals. Compared with the Cn subgenome, the An subgenome possesses a higher level of active epigenetic marks and lower level of repressive epigenetic marks. Genes from subgenome-unique regions contribute to the major differences between the An and Cn subgenomes. Asymmetric histone modifications between homeologous gene pairs reflect their biased expression patterns. We identified a novel bivalent chromatin state (with H3K4me1 and H3K27me3) in B. napus that is associated with tissue-specific gene expression. Furthermore, we observed that different types of duplicated genes have discrepant patterns of histone modification and DNA methylation levels. Collectively, our findings provide a valuable epigenetic resource for allopolyploid plants. Comprehensive epigenomic maps of Brassica napus are still unavailable. In this study, the authors established comprehensive reference epigenomic maps, annotated over 65.8% of the genome with different epigenome properties, and identified a novel bivalent chromatin state (H3K4me1/H3K27me3), providing the epigenomic basis for the asymmetric expression between the An and Cn subgenomes in Brassica napus. [ABSTRACT FROM AUTHOR]

Abstract: Acetyl-CoA carboxylase α (ACC1), the major regulatory enzyme of fatty acid biosynthesis, catalyzes the conversion of acetyl-CoA to malonyl-CoA. The full-length cDNA coding ACC1 isoform was cloned from liver of grass carp. The cDNA obtained was 7515bp with a 7173bp open reading frame encoding 2389 amino acids. The ACC1 protein has a calculated molecular weight of 269.2kDa and isoelectric point of 6.23. Tissue distribution of ACC1 mRNA in brain, mesenteric adipose, spleen, white muscle and liver of grass carp was analyzed by real-time PCR method using β-actin as an internal control for cDNA normalization. The results showed that the expressions of ACC1 mRNA were detected in all examined tissues. Relative expression profile of ACC1 mRNA in liver normalized with β-actin level was 15, 92, 135 and 165-fold compared with the level in brain, white muscle, mesenteric adipose and spleen, respectively. In addition, we present evidence for the presence of two isoforms of ACC1 (265.7kDa and 267.2kDa) in grass carp liver that differ from the 269.2kDa ACC1 by the absence of 34 and 15 amino acids. In conclusion, the liver is one of the main ACC1 producing tissues in grass carp and ACC1 gene was highly homologous to that of mammals. [Copyright &y& Elsevier]

Abstract: A full-length cDNA coding lipoprotein lipase (LPL) was cloned from liver of adult Pengze crucian carp (Carassius auratus var. Pengze) by RT-PCR and rapid amplification of cDNA ends (RACE) approaches. The cDNA obtained was 1877 bp long with a 1524 bp open reading frame (ORF) encoding 507 amino acids, including a putative signal peptide of 23 amino acids long. The deduced amino acid sequence has a high similarity and shows similar structural features to LPL of other species. The LPL protein has a calculated molecular mass of 57.7 kDa and isolectric point of 7.85. Tissue distribution of LPL mRNA in mesenteric adipose tissue, liver, heart, head kidney and white muscle of adult Pengze crucian carp was analyzed by semi-quantitative RT-PCR method using β-actin gene as internal control, the result showed that this gene was ubiquitously expressed in all tissues tested with the highest abundance in mesenteric adipose tissue, following in head kidney and liver, and the lowest expression was found in heart and white muscle. [Copyright &y& Elsevier]

Brucellosis is one of the most common zoonotic epidemics worldwide. Vaccination against brucellosis is an important control strategy to prevent the disease in many high-prevalence regions. At present, Brucella vaccine strain S2 is the most widely used vaccine in China. To uncover the mechanisms underlying virulence attenuation of S2, in this study we characterized the transcriptional profile of S2 and 1330 infected macrophages by transcriptome analysis. The results revealed that expressions of 440 genes were significantly different between macrophages infected by 1330 and S2. Data analysis showed that in the gene ontology term, the different expressed genes involved in innate immune response, phagoctyosis, recognition, and inflammatory response were significantly enriched. Pathway enrichment analysis indicated that the genes involved in transcriptional misregulation in cancer, staphylococcus aureus infection pathways and NF-kappa B signaling pathway were significantly affected. To reveal the molecular mechanisms related to different expression profiles of infected macrophages, the transcription levels of the different genes between the two bacterial genomes were detected. In total, the transcription of 29 different genes was significantly changed in either culture medium or infected microphages. The results of this study can be conducive to the promotion of better understanding of the related mechanisms underlying virulence attenuation of S2 and interactions between host cells and Brucella strains. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) function as critical regulators to participate in tumor progression and metastasis. However, their roles in non-small cell lung cancer (NSCLC) are poorly understood. In this study, we found that the expression of the lncRNA linc00460 is significantly upregulated in NSCLC tumors and associated with poor prognosis for NSCLC patients, implying that linc00460 is important for lung cancer development. The accurate transcription initiation and termination sites of linc00460 were then identified by rapid-amplification of cDNA ends (RACE) technologies, and the sequencing data demonstrated that linc00460, predominantly located in the cytoplasm of lung cancer cells, is a novel transcript variant. Functional studies through gain- and loss-of-function strategies showed that linc00460 promotes cell migration and invasion through inducing epithelial-mesenchymal transition in lung cancer cells, whereas it has no effect on cell proliferation. The mechanism investigations through RNA pull-down assay and mass spectrometry identified that hnRNP K physically interacts with linc00460, and it also participates in cell migration and invasion. Therefore, our findings suggest that linc00460 acts as an oncogene in NSCLC to promote cell migration and highlight the potential prognostic and therapeutic values of linc00460 for NSCLC patients. [ABSTRACT FROM AUTHOR]

Besides attending protein synthesis, transfer RNA (tRNA) is an important regulatory non-coding RNA (ncRNA) that participates in various cellular processes, including cellular metabolism and cell death. Fragments generated from pre- or mature tRNAs by specific endonucleases cleavage (tRNA-derived small non-coding RNA [tsncRNAs]), rather than random degradation products, are newly defined functional small non-coding RNAs (sncRNAs). They can be regulated in bacteria, yeast, plants and animals to respond to stress conditions, resulting in regulation of gene expressions at both transcriptional and post-transcriptional level. Increasing evidence showed that the dysregulation of a series of tsncRNAs is associated with several types of human disease. In this review, we summarize the diversity and biogenesis of tsncRNAs in mammals and highlight the functions and mechanisms of different sub-classes of tsncRNAs in human disease. [ABSTRACT FROM AUTHOR]

Background: Platinum based therapy is commonly used in the treatment of advanced gastric cancer. However, resistance to chemotherapy is a major challenge that causes marked variation in individual response rate and survival rate. In this study, we aimed to identify the expression of GTSE1 and its correlation with cisplatin resistance in gastric cancer cells. Methods: Methylation profiling was carried out in tissue samples from gastric cancer patients before undergoing neoadjuvent therapy using docetaxel, cisplatin and 5FU (DCX) and in gastric cancer cell lines. The correlation between GTSE1 expression and methylation in gastric cancer cells was determined by RT-PCR and MSP respectively. GTSE1 expression was knocked-down using shRNA's and its effects on cisplatin cytotoxicity and cell survival were detected by MTS, proliferation and clonogenic survival assays. Additionally, the effect of GTSE1 knock down in drug induced apoptosis was determined by western blotting and apoptosis assays. Results: GTSE1 exhibited a differential methylation index in gastric cancer patients and in cell lines that correlated with DCX treatment response and cisplatin sensitivity, respectively. In-vitro, GTSE1 expression showed a direct correlation with hypomethylation. Interestingly, Cisplatin treatment induced a dose dependent up regulation as well as nuclear translocation of GTSE1 expression in gastric cancer cells. Knock down of GTSE1 enhanced cisplatin cytotoxity and led to a significant reduction in cell proliferation and clonogenic survival. Also, loss of GTSE1 expression caused a significant increase in P53 mediated apoptosis in cisplatin treated cells. Conclusion: Our study identifies GTSE1 as a biomarker for cisplatin resistance in gastric cancer cells. This study also suggests the repressive role of GTSE1 in cisplatin induced apoptosis and signifies its potential utility as a therapeutic target for better clinical management of gastric cancer patients. [ABSTRACT FROM AUTHOR]

R-loop, a three-stranded RNA/DNA structure, plays important roles in modulating genome stability and gene expression, but the molecular mechanism of R-loops in cell reprogramming remains elusive. Here, we comprehensively profiled the genome-wide landscape of R-loops during cell reprogramming. The results showed that the R-loop formation on most different types of repetitive elements is stage-specific in cell reprogramming. We unveiled that the cumulative deposition of an R-loop subset is positively correlated with gene expression during reprogramming. More importantly, the dynamic turnover of this R-loop subset is accompanied by the activation of the pluripotent transcriptional regulatory network (TRN). Moreover, the large accumulation of the active histone marker H3K4me3 and the reduction in H3K27me3 were also observed in these R-loop regions. Finally, we characterized the dynamic network of R-loops that facilitates cell fate transitions in reprogramming. Together, our study provides a new clue for deciphering the interplay mechanism between R-loops and HMs to control cell reprogramming. [ABSTRACT FROM AUTHOR]

Objective Cisplatin is a widely used gastric cancer (GC) chemotherapy; however, genetic factors regulating GC responses to cisplatin remain obscure. Identifying genes regulating cisplatin resistance could aid clinicians in tailoring treatments, by distinguishing cisplatin sensitive patients from those who might benefit from alternative platinum therapies, and highlight novel targeted strategies for overcoming cisplatin resistance. Here integrated epigenomics is applied to identify genes associated with GC cisplatin resistance Design 20 GC cell lines were subjected to gene expression profiling, DNA methylation profiling and drug response assays. The molecular data were integrated to identify genes highly expressed and unmethylated specifically in cisplatin-resistant lines. Candidate genes were functionally tested by several in vitro and in vivo assays. Clinical impact of candidate genes was also assessed in a cohort of 197 GC patients. Results Epigenomic analysis identified bone morphogenetic protein 4 (BMP4) as an epigenetically regulated gene highly expressed in cisplatin-resistant lines. Functional assays confirmed that BMP4 is necessary and sufficient for the expression of several prooncogenic traits, likely mediated through stimulation of the epithelial-mesenchymal transition. In primary tumours, BMP4 promoter methylation levels were inversely correlated with BMP4 expression, and patients with high BMP4-expressing tumours exhibited significantly worse prognosis. Therapeutically, targeted genetic inhibition of BMP4 caused significant sensitisation of GC cells to cisplatin. Notably, BMP4- expressing GCs also did not exhibit cross resistance to oxaliplatin. Conclusions BMP4 epigenetic and expression status may represent promising biomarkers for GC cisplatin resistance. Targeting BMP4 may sensitise GC cells to cisplatin. Oxaliplatin, a clinically acceptable cisplatin alternative, may represent a potential therapeutic option for BMP4-positive GCs. [ABSTRACT FROM AUTHOR]

Abstract: Background: Cytochrome P450 (CYP)2C19 is expressed in vascular endothelium and metabolizes arachidonic acid to biologically active epoxyeicosatrienoic acids, which play a key role in regulating vascular tone. The aim of this study was to investigate whether the genetic functional variant 681G>A (*2) of cytochrome CYP2C19 is associated with adverse cardiovascular outcomes in Chinese patients with coronary artery disease (CAD). Methods: Between July 2008 and September 2009, 654 consecutive patients with CAD were enrolled in this study. All participants underwent CYP2C19 genotyping. The primary study endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. Secondary endpoints included the components of the primary endpoint, death from any cause, and recurrent revascularization. Results: The baseline characteristics were well-balanced between carriers (heterozygous *1/*2, n =291; homozygous *2/*2, n =57) and non-carriers (n =306) of the CYP2C19*2 variant. During the follow-up period (11.42±4.23 months), the primary endpoint occurred more frequently in homozygous *2/*2 than in non-carriers (n =306) of CYP2C19*2 variant (12.28% versus 3.27%; adjusted hazard ratio [HR]=5.191; 95% confidence interval [CI]=1.936–13.917; P =0.001); however, no such increase was evident in heterozygous *1/*2 patients (4.12% versus 3.27%; adjusted HR=1.208; 95% CI 0.517–2.822; P =0.662). Conclusions: The homozygous CYP2C19*2/*2 genotype is an independent determinant of adverse vascular events in Chinese patients with CAD. [Copyright &y& Elsevier]

Abstract: The nucleus accumbens (NAc) is involved in contextual drug associations, which might be particularly important for environmental cue-induced relapse to drug seeking. In the present study, rats were first administered repeated morphine for 5 days (5mg/kg, i.p.) in a contextually paired and unpaired design. After reexposure to the morphine-associated environment, which induced conditioned locomotor activity in the morphine-paired group, we performed a rat 27k 70-mer oligo array to profile gene expression in the NAc. One hundred fifty-five upregulated and 88 downregulated genes were found in the paired group compared with the unpaired group. Eight gene transcripts were then selected to confirm their alterations by quantitative real-time polymerase chain reaction (qRT-PCR). The identified genes generally play important roles in neuroactive receptor–ligand interactions, synapse plasticity, ion transport, and protein phosphorylation. Furthermore, the expression of the eight selected genes that were identified and confirmed to show significant fold changes in the first microarray experiment were again measured with qRT-PCR after morphine challenge (2mg/kg, i.p.). As expected, 2mg/kg morphine-induced context-specific sensitization. Meanwhile, mRNA expression of the selected genes showed marked upregulation in the morphine-paired group compared with the unpaired and acute groups. These results suggest that alterations in the expression of the identified genes in the NAc may contribute to the neuroplasticity underlying contextual cue-induced relapse to drug use. [Copyright &y& Elsevier]

Abstract: The conserved DPY-30 is an essential component of the dosage compensation complex that balances the X-linked gene expression by regulation of the complex formation in Caenorhabditis elegans. The human DPY-30-like protein (DPY-30L) homolog is a conserved member of certain histone methyltransferase (HMT) complexes. In the human MLL1 (mixed-lineage leukemia-1) HMT complex, DPY-30L binds to the BRE2 homolog ASH2L in order to regulate histone 3–lysine 4 trimethylation. We have determined the 1.2-Å crystal structure of the human DPY-30L C-terminal domain (DPY-30LC). The DPY-30LC structure, harboring the conserved DPY-30 motif, is composed of two α-helices linked by a sharp loop and forms a typical X-type four-helix bundle required for dimer formation. DPY-30LC dimer formation is largely mediated by an extensive hydrophobic interface with some additional polar interactions. The oligomerization of DPY-30LC in solution, together with its reported binding to ASH2L, leads us to propose that the hydrophobic surface of the dimer may provide a platform for interaction with ASH2L in the MLL1 HMT complex. [Copyright &y& Elsevier]

Cell-wall invertase plays an important role in sucrose partitioning between source and sink organs in higher plants. To investigate the role of cell-wall invertases for seed development in rice ( Oryza sativa L.), cDNAs of three putative cell-wall invertase genes OsCIN1, OsCIN2 and OsCIN3 were isolated. Semi-quantitative reverse transcription-polymerase chain reaction analysis revealed different expression patterns of the three genes in various rice tissues/organs. In developing caryopses, they exhibited similar temporal expression patterns, expressed highly at the early and middle grain filling stages and gradually declined to low levels afterward. However, the spatial expression patterns of them were very different, with OsCIN1 primarily expressed in the caryopsis coat, OsCIN2 in embryo and endosperm, and OsCIN3 in embryo. Further RNA in situ hybridization analysis revealed that a strong signal of OsCIN2 mRNA was detected in the vascular parenchyma surrounding the xylem of the chalazal vein and the aleurone layer, whereas OsCIN3 transcript was strongly detected in the vascular parenchyma surrounding the phloem of the chalazal vein, cross-cells, the aleurone layer and the nucellar tissue. These data indicate that the three cell-wall invertase genes play complementary/synergetic roles in assimilate unloading during the grain filling stage. In addition, the cell type-specific expression patterns of OsCIN3 in source leaf blades and anthers were also investigated, and its corresponding physiological roles were discussed. [ABSTRACT FROM AUTHOR]