AIM: To investigate Helicobacter pylori (H. pylori) CagA diversity and to evaluate the association between protein polymorphisms and the occurrence of gastric pathologies. METHODS: One hundred and twenty-two clinical ...AIM: To investigate Helicobacter pylori (H. pylori) CagA diversity and to evaluate the association between protein polymorphisms and the occurrence of gastric pathologies. METHODS: One hundred and twenty-two clinical isolates of H. pylori cultured from gastric biopsies obtained from Colombian patients with dyspepsia were included as study material. DNA extracted from isolates was used to determine cagA status, amplifying the C-terminal cagA gene region by polymerase chain reaction. One hundred and six strains with a single amplicon were sequenced and results were used to characterize the 3' variable region of the cagA gene. To establish the number and type of tyrosine phosphorylation motifs Glutamine acid-Proline-Isoleucine-Tyrosine-Alanine (EPI-YA) bioinformatic analysis using Amino Acid Sequence Analyzer-Amino Acid Sequence Analyzer software was conducted. Analysis of the association between the number of EPIYA motifs and the gastric pathology was performed using χ2 test and analysis of the presence of EPIYA-C motifs in relation to the pathology was made by logistic regression odds ratios. Comparisons among EPIYA types found and those reported in GenBank were performed using a proportion test in Statistix Analytical Software version 8.0. RESULTS: After amplification of the 3' of the cagA gene, 106 from 122 isolates presented a single amplicon and 16 showed multiple amplicons. As expected, diversity in the size of the cagA unique fragments among isolates was observed. The 106 strains that presented a single amplicon after 3' cagA amplification came from patients with gastritis (19 patients), atrophic gastritis (21), intestinal metaplasia (26), duodenal ulcer (22) and gastric cancer. DNA sequence analysis showed that the differences in size of 3' cagA unique fragments was attributable to the number of EPIYA motifs: 1.9% had two EPIYA motifs, 62.3% had three, 33.0% had four and 2.8% had five motifs. The majority of tested clinical strains (62.3%) were found to harbor the ABC combination of EPIYA motifs and a significant statistical difference was observed between the frequencies of ABCC tyrosine phosphorylation motifs and Western strains sequences deposited in GenBank. CONCLUSION: The present report describes a lack of association between H. pylori CagA-protein polymorphisms and pathogenesis. ABCC high frequency variations compared with Western-strains sequences deposited in GenBank require more investigation.展开更多
AIM: To investigate the influence of the CagA diversity in Helicobacter pylori (H. pylori ) strains from Colombia on the host cell biology. METHODS: Eighty-four H. pylori-cagA positive strains with different Glu-Pro-I...AIM: To investigate the influence of the CagA diversity in Helicobacter pylori (H. pylori ) strains from Colombia on the host cell biology. METHODS: Eighty-four H. pylori-cagA positive strains with different Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs patterns, isolated from patients with gastritis (n=17), atrophic gastritis (n=17), duodenal ulcer (n=16), intestinal metaplasia (n=16) and gastric cancer (n=18), were included. To determine the integrity of the cag pathogenicity island (cag PAI) we evaluated the presence of cagA, cagT, cagE, and cag10 genes by polymerase chain reaction. AGS gastric epithelial cellswere infected with each strain and assayed for translo-cation and tyrosine phosphorylation of CagA by western blot, secretion of interleukin-8 (IL-8) by enzyme-linked immuno sorbent assay after taking supernatants from cocultures and cell elongation induction. For cell elongation quantification, coculture photographs were taken and the proportion of "hummingbird" cells (>15 μm) was determined. RESULTS: Overall 72% (60/84) of the strains were found to harbor a functional cag PAI. Levels of phos-phorylated CagA were significantly higher for isolates from duodenal ulcer than the ones in strains from gas-tritis, atrophic gastritis, intestinal metaplasia and gastric cancer (49.1% ± 23.1% vs 21.1% ± 19.5%, P < 0.02; 49.1% ± 23.1% vs 26.2%±14.8%, P<0.045; 49.1% ± 23.1% vs 21.5% ± 19.5%, P<0.043 and 49.1% ± 23.1% vs 29.5% ± 27.1%, P < 0.047 respectively). We observed variable IL-8 expression levels ranging from 0 to 810 pg/mL and from 8.8 to 1442 pg/mL at 6 h and 30 h post-infection, respectively. cagPAI-defective strains did not induce detectable levels of IL-8 at 6 h post-infection. At 30 h post-infection all strains induced IL-8 expression in AGS cells, although cagPAI-defective strains induced significantly lower levels of IL-8 than strains with a functional cagPAI (57.1 ± 56.6 pg/mL vs 513.6 ± 338.6 pg/mL,P < 0.0001). We did not observe differences in the extent of cell elongation induction between strains with a functional or a defective cagPAI in 6 h cocultures. At 24 h post infection strains with functionalcagPAI showed high diversity in the extent of hummingbird phenotype induction ranging from 7% to 34%. cag PAI defective strains induced significantly lower levels of elongation than strains with functional cag-PAI with one or more than one EPIYA-C motif (15.1% ± 5.2%vs 18.9% ± 4.7%,P < 0.03; and 15.1% ± 5.2% vs 20.0% ± 5.1%, P < 0.003 respectively). No differences were observed in cellular elongation inductionor IL-8 expression among H. pylori strains bearing one and more than one EPIYA-C motifs, neither at 6 h nor at 24 h of coculture. There were no associations between the levels of induction of cell elongation or IL-8 expression and number of EPIYA motifs or pathology. CONCLUSION: The present work describes a lack of association between H. pylori CagA protein EPIYA motifs variations from Colombian isolates and disease-associated cellular responses.展开更多
BACKGROUND Probiotics are a promising solution for managing irritable bowel syndrome(IBS).Saccharomyces cerevisiae(S.cerevisiae)I-3856 has already demonstrated beneficial effects in IBS subjects,particularly in IBS wi...BACKGROUND Probiotics are a promising solution for managing irritable bowel syndrome(IBS).Saccharomyces cerevisiae(S.cerevisiae)I-3856 has already demonstrated beneficial effects in IBS subjects,particularly in IBS with predominant constipation(IBS-C).AIM To confirm the efficacy of S.cerevisiae I-3856 in the management of gastrointestinal symptoms in IBS-C.METHODS A randomized,double-blind,placebo-controlled clinical study was performed in a total of 456 subjects.After a run-in period,subjects were randomly assigned to the group receiving S.cerevisiae I-3856(8×109 CFU daily)or the placebo for 8 wk,and they performed daily self-evaluations of gastrointestinal symptoms.The primary objective was to assess the effect of the probiotic on abdominal pain.The secondary objectives were the evaluation of other gastrointestinal symptoms,bowel movement frequency and consistency,and quality of life(QOL).RESULTS A significantly higher proportion of abdominal pain responders was reported in the Probiotic group(45.1%vs 33.9%,P=0.017).A nonsignificant difference in the area under the curve for abdominal pain over the second month of supplementation was observed in subjects receiving probiotic vs placebo[P=0.073,95%CI:-0.59(-1.23;0.05)].No statistically significant differences were reported in the evolution of bowel movement frequency and stool consistency between the groups.After 8 wk of supplementation,the overall QOL score was significantly higher in the Probiotic group than in the Placebo group[P=0.047,95%CI:3.86(0.52;7.20)].Furthermore,exploratory analyses showed statistically significant and clinically relevant improvements in QOL scores in abdominal pain responders vs nonresponders.CONCLUSION The results of this clinical study confirmed the abdominal pain alleviation properties of S.cerevisiae I-3856 in IBS-C.Abdominal pain relief was associated with improved QOL.ClinicalTrials.gov identifier:NCT03150212.展开更多
Sclerotinia stem rot(SSR) caused by Sclerotinia sclerotiorum(Lib.) de Bary is one of the most devastating diseases of Brassica napus worldwide. Both SSR resistance and flowering time(FT) adaptation are major breeding ...Sclerotinia stem rot(SSR) caused by Sclerotinia sclerotiorum(Lib.) de Bary is one of the most devastating diseases of Brassica napus worldwide. Both SSR resistance and flowering time(FT) adaptation are major breeding goals in B. napus. However, early maturing rapeseed varieties, which are important for rice-rapeseed rotation in China, are often highly susceptible to SSR. Here, we found that SSR resistance was significantly negatively correlated with FT in a natural population containing 521 rapeseed inbred lines and a double haploid(DH) population with 150 individual lines, both of which had great variation in FT. Four chromosomal regions on A2, A6, C2, and C8 affecting both SSR resistance and FT were identified using quantitative trait loci(QTL) mapping after constructing a high-density genetic map based on single nucleotide polymorphism markers in the DH population.Furthermore, we aligned QTL for the two traits identified in the present and previous studies to the B. napus reference genome, and identified four colocalized QTL hotspots of SSR resistance and FT on A2(0–7.7 Mb), A3(0.8–7.5 Mb), C2(0–15.2 Mb), and C6(20.2–36.6 Mb). Our results revealed a genetic link between SSR resistance and FT in B.napus, which should facilitate the development of effective strategies in both early maturing and SSR resistance breeding and in map-based cloning of SSR resistance QTL.展开更多
In this work, we analyzed only the patients of the NSTEMI (non ST-segment elevation myocardial infarction) who arrived at the hospital within 12 h after symptoms started. Using NSTEMI follow-up data within, the charac...In this work, we analyzed only the patients of the NSTEMI (non ST-segment elevation myocardial infarction) who arrived at the hospital within 12 h after symptoms started. Using NSTEMI follow-up data within, the characteristics of the clinical data, the risk factor, and the blood tested in the hospital visit were analyzed for MACE (major adverse cardiac events) patients. MACE includes cardiac death, MI (myocardial infarction), Re-PCI, and CABG (coronary artery bypass graft). As a result, from the NSTEMI patients which can be followed up for over 12 m, NT-ProBNP (p=0.014) and age (p=0.045) are found to be the independent risk factors related to MACE. Accordingly, they can be useful for the diagnosis and prognosis for NSTEMI patients as a biomarker.展开更多
We successfully conduct the label-free and real-time detection of the interactions between epoxy groups and rabbit IgG and 5＇ CTT CAG GTC ATG AGC CTG AT 3＇ oligonucleotide, and between the hybridization of 5＇ CTT C...We successfully conduct the label-free and real-time detection of the interactions between epoxy groups and rabbit IgG and 5＇ CTT CAG GTC ATG AGC CTG AT 3＇ oligonucleotide, and between the hybridization of 5＇ CTT CAG GTC ATG AGC CTG AT 3＇ and its complementary 3＇ GAA GTC CAC TAC TCG GAC TA 5＇ oligonucleotide, by the oblique-incidence reflectivity difference （OI-RD） method. The dynamic curves of OI-RD signals, corresponding to the kinetic processes of biomolecular combination or hybridization, are acquired. In our case, the combination of epoxy groups with rabbit IgG and 5＇ CTT CAC CTC ATG AGC CTG AT 3＇ oligonucleotide need almost one and a half hours and about two hundred seconds, respectively; and the hybridization of the two oligonucleotides needs about five hundred seconds. The experimental results show that the OI-RD is a promising method for the real-time and label-free detection of biomolecular interactions.展开更多
Rice panicle phenotyping is required in rice breeding for high yield and grain quality.To fully evaluate spikelet and kernel traits without threshing and hulling,using X-ray and RGB scanning,we developed an integrated...Rice panicle phenotyping is required in rice breeding for high yield and grain quality.To fully evaluate spikelet and kernel traits without threshing and hulling,using X-ray and RGB scanning,we developed an integrated rice panicle phenotyping system and a corresponding image analysis pipeline.We compared five methods of counting spikelets and found that Faster R-CNN achieved high accuracy(R~2 of 0.99)and speed.Faster R-CNN was also applied to indica and japonica classification and achieved 91%accuracy.The proposed integrated panicle phenotyping method offers benefit for rice functional genetics and breeding.展开更多
Skeletal stem and progenitor cells(SSPCs) perform bone maintenance and repair. With age, they produce fewer osteoblasts and more adipocytes leading to a loss of skeletal integrity. The molecular mechanisms that underl...Skeletal stem and progenitor cells(SSPCs) perform bone maintenance and repair. With age, they produce fewer osteoblasts and more adipocytes leading to a loss of skeletal integrity. The molecular mechanisms that underlie this detrimental transformation are largely unknown. Single-cell RNA sequencing revealed that Notch signaling becomes elevated in SSPCs during aging. To examine the role of increased Notch activity, we deleted Nicastrin, an essential Notch pathway component, in SSPCs in vivo. Middle-aged conditional knockout mice displayed elevated SSPC osteo-lineage gene expression, increased trabecular bone mass, reduced bone marrow adiposity, and enhanced bone repair. Thus, Notch regulates SSPC cell fate decisions, and moderating Notch signaling ameliorates the skeletal aging phenotype, increasing bone mass even beyond that of young mice. Finally, we identified the transcription factor Ebf3 as a downstream mediator of Notch signaling in SSPCs that is dysregulated with aging, highlighting it as a promising therapeutic target to rejuvenate the aged skeleton.展开更多
Background The clinical significance of complete revascularization for ST segment elevation myocardial infarction （STEMI） pa- tients during admission is still debatable. Methods A total of 1406 STEMI patients from t...Background The clinical significance of complete revascularization for ST segment elevation myocardial infarction （STEMI） pa- tients during admission is still debatable. Methods A total of 1406 STEMI patients from the Korean Myocardial Infarction Registry with multivessel diseases without cardiogenic shock who underwent primary percutaneous coronary intervention （PPCI） were analyzed. We used propensity score matching （PSM） to control differences of baseline characteristics between culprit only intervention （CP） and multivessel percutaneous coronary interventions （MP）, and between double vessel disease （DVD） and triple vessel disease （TVD）. The major adverse cardiac event （MACE） was analyzed for one year after discharge. Results TVD patients showed higher incidence of MACE （14.2% vs. 8.6%, P = 0.01）, any cause of revascularization （10.6% vs. 5.9%, P - 0.01）, and repeated PCI （9.5% vs. 5.7%, P = 0.02）, as compared to DVD patients during one year after discharge. MP reduced MACE effectively （7.3% vs. 13.8%, P = 0.03）, as compared to CP for one year, but all cause of death （1.6% vs. 3.2%, P= 0.38）, Ml （0.4% vs. 0.8%, P = 1.00）, and any cause ofrevascularization （5.3% vs. 9.7%, P = 0.09） were comparable in the two treatment groups. Conclusions STEMI patients with TVD showed higher rate of MACE, as compared to DVD MP performed during PPCI or ad hoc during admission for STEMI patients without cardiogenic shock showed lower rate of MACE in this large scaled database. Therefore, MP could be considered as an effective treatment option for STEMI patients without cardiogenic shock.展开更多
The present study is concerned with the isolation and screening of different strains of Aspergillus oryzae for the production of alpha amylase. Ninety strains were isolated from soil and tested for the production of a...The present study is concerned with the isolation and screening of different strains of Aspergillus oryzae for the production of alpha amylase. Ninety strains were isolated from soil and tested for the production of alpha amylase in shake flasks. Of all the strains tested, Aspergillus oryzae GCB-32 and Aspergillus oryzae GCB-35 gave maximum production of alpha amylase. Different culture media were screened for the production of alpha amylase by these two strains. M1 medium containing starch, yeast extract, NH4Cl, MgSO4·7H2O and CaCl2 gave the maximum production of alpha amylase by both the strains Aspergillus oryzae GCB-32 and Aspergillus oryzae GCB-35.Kinetic analysis revealed that the values of product yield coefficient（Y p/x ） and specific product yield coefficient（qp） were found highly significant（p≤0.05） when medium M1 was used for the enzyme production.展开更多
Objective:To explore natural compounds as potential inhibitors against main protease(Mpro)of SARS-CoV-2.Methods:In the current study,systematic molecular docking analysis was conducted using AutoDock 4.2 to determine ...Objective:To explore natural compounds as potential inhibitors against main protease(Mpro)of SARS-CoV-2.Methods:In the current study,systematic molecular docking analysis was conducted using AutoDock 4.2 to determine the binding affinities and interactions between natural compounds and Mpro.Selected natural compounds were further validated using a combination of molecular dynamic(MD)simulations and molecular mechanic Poisson-Boltzmann surface area(MM/PBSA)free energy c alculation s.Results:Out of twenty natural compounds,four natural metabolites namely,amentoflavone,guggulsterone,puerarin,and piperine were found to have strong interaction with Mpro of SARS-CoV-2 based on docking analysis.During MD simulations,all four natural compounds bound to Mpro at 50 ns and MM/G/P/BSA free energy calculations showed that all four shortlisted ligands had stable and favorable energies with strong binding to Mpro protein.Conclusions:Guggulsterone is a potential inhibitor of COVID-19 main protease Mpro.Further in vitro and pre-clinical studies are needed.展开更多
Gene transcriptional regulation （TR） processes are often described by coupled nonlinear ordinary differential equations （ODEs）. When the dimension of TR circuits is high （e.g. n≥3） the motions of the correspond...Gene transcriptional regulation （TR） processes are often described by coupled nonlinear ordinary differential equations （ODEs）. When the dimension of TR circuits is high （e.g. n≥3） the motions of the corresponding ODEs may, very probably, show self-sustained oscillations and chaos. On the other hand, chaoticity may be harmful for the normal biological functions of TR processes. In this letter we numerically study the dynamics of 3-gene TR ODEs in great detail, and investigate many 4-, 5-, and lO-gene TR systems by randomly choosing figures and parameters in the conventionally accepted ranges. And we find that oscillations are very seldom and no chaotic motion is observed, even if the dimension of systems is sufficiently high （n≥3）. It is argued that the observation of nonchaoticity of these ODEs agrees with normal functions of actual TR processes.展开更多
Chromatin interactions functionally affect genome architecture and gene regulation,but to date,only fresh samples must be used in High-through chromosome conformation capture(Hi-C)to keep natural chromatin conformatio...Chromatin interactions functionally affect genome architecture and gene regulation,but to date,only fresh samples must be used in High-through chromosome conformation capture(Hi-C)to keep natural chromatin conformation intact.This requirement has impeded the advancement of 3 D genome research by limiting sample collection and storage options for researchers and severely limiting the number of samples that can be processed in a short time.Here,we develop a freeze substitution Hi-C(FS-Hi-C)technique that overcomes the need for fresh samples.FS-Hi-C can be used with samples stored in liquid nitrogen(LN2):the water in a vitreous form in the sample cells is replaced with ethanol via automated freeze substitution.After confirming that the FS step preserves the natural chromosome conformation during sample thawing,we tested the performance of FS-Hi-C with Drosophila melanogaster and Gossypium hirsutum.Beyond allowing the use of frozen samples and confirming that FS-Hi-C delivers robust data for generating contact heat maps and delineating A/B compartments and topologically associating domains,we found that FS-HiC outperforms the in situ Hi-C in terms of library quality,reproducibility,and valid interactions.Thus,FS-HiC will probably extend the application of 3D genome structure analysis to the vast number of experimental contexts in biological and medical research for which Hi-C methods have been unfeasible to date.展开更多
Integration of human papillomavirus(HPV)DNA into the human genome is a reputed key driver of cervical cancer.However,the effects of HPV integration on chromatin structural organization and gene expression are largely ...Integration of human papillomavirus(HPV)DNA into the human genome is a reputed key driver of cervical cancer.However,the effects of HPV integration on chromatin structural organization and gene expression are largely unknown.We studied a cohort of 61 samples and identified an integration hot spot in the CCDC106 gene on chromosome 19.We then selected fresh cancer tissue that contained the unique integration loci at CCDC106 with no HPV episomal DNA and performed whole-genome,RNA,chromatin immunoprecipitation and high-throughput chromosome conformation capture(Hi-C)sequencing to identify the mechanisms of HPV integration in cervical carcinogenesis.Molecular analyses indicated that chromosome 19 exhibited significant genomic variation and differential expression densities,with correlation found between three-dimensional(3D)structural change and gene expression.Importantly,HPV integration divided one topologically associated domain(TAD)into two smaller TADs and hijacked an enhancer from PEG3 to CCDC106,with a decrease in PEG3 expression and an increase in CCDC106 expression.This expression dysregulation was further confirmed using 10 samples from our cohort,which exhibited the same HPV-CCDC106 integration.In summary,we found that HPV-CCDC106 integration altered local chromosome architecture and hijacked an enhancer via 3D genome structure remodeling.Thus,this study provides insight into the 3D structural mechanism underlying HPV integration in cervical carcinogenesis.展开更多
Objective:To investigate the renoprotective effects of luteolin on diabetes in rats.Methods:One week after administration of streptozotocin 55 mg/kg intraperitoneally,rats were given 25,50,and 75 mg/kg/day of luteolin...Objective:To investigate the renoprotective effects of luteolin on diabetes in rats.Methods:One week after administration of streptozotocin 55 mg/kg intraperitoneally,rats were given 25,50,and 75 mg/kg/day of luteolin orally for another eight weeks.At the end of the experiment,body weight,blood glucose level,biochemical parameters for renal function(serum creatinine,blood urea nitrogen,uric acid,serum albumin,and total protein),kidney histology,matrix metalloproteinase(MMP)-2,MMP-9,and histone deacetylase 2(HDAC-2)expression,and malondialdehyde,myeloperoxidase,and hydroxyproline content in renal tissue were evaluated.High glucose-induced damage using NRK-52E cell line was studied to evaluate cell viability and metalloenzyme expression.Additionally,in silico studies including docking and molecular dynamics simulations were conducted.Results:MMP-2,MMP-9,and HDAC-2 expressions were significantly increased in high glucose-induced NRK-52E cells and the renal tissue of diabetic rats.However,these changes were reversed by luteolin at the administered doses.Additionally,luteolin significantly reduced oxidative stress,inflammation,and fibrosis,as well as improved biochemical parameters in diabetic rats.Furthermore,luteolin at the examined doses markedly alleviated diabetes-induced histopathological changes in renal tissues.Conclusions:Luteolin effectively attenuates streptozotocin-induced diabetic nephropathy in rats by inhibiting MMP-2,MMP-9,and HDAC-2 expression,and reducing oxidative stress and inflammation.展开更多
Understanding the genetic architecture of indi-vidual taxa of medical importance is the first step for designing disease preventive strategies. To understand the genetic details and evolu-tionary perspective of the mo...Understanding the genetic architecture of indi-vidual taxa of medical importance is the first step for designing disease preventive strategies. To understand the genetic details and evolu-tionary perspective of the model malaria vector, Anopheles gambiae and to use the information in other species of local importance, we scanned the published X-chromosome se-quence for detail characterization and obtain evolutionary status of different genes. The te-locentric X-chromosome contains 106 genes of known functions and 982 novel genes. Majori-ties of both the known and novel genes are with introns. The known genes are strictly biased towards less number of introns;about half of the total known genes have only one or two in-trons. The extreme sized (either long or short) genes were found to be most prevalent (58% short and 23% large). Statistically significant positive correlations between gene length and intron length as well as with intron number and intron length were obtained signifying the role of introns in contributing to the overall size of the known genes of X-chromosome in An. gam-biae. We compared each individual gene of An. gambiae with 33 other taxa having whole ge-nome sequence information. In general, the mosquito Aedes aegypti was found to be ge-netically closest and the yeast Saccharomyces cerevisiae as most distant taxa to An. gambiae. Further, only about a quarter of the known genes of X-chromosome were unique to An. gambiae and majorities have orthologs in dif-ferent taxa. A phylogenetic tree was constructed based on a single gene found to be highly orthologous across all the 34 taxa. Evolutionary relationships among 13 different taxa were in-ferred which corroborate the previous and pre-sent findings on genetic relationships across various taxa.展开更多
Although only about 2%of the human genome has proved to be protein-coding genes,recent advances in genome wide analysis have revealed that the majority of the genome is transcribed,mainly from noncoding segments that ...Although only about 2%of the human genome has proved to be protein-coding genes,recent advances in genome wide analysis have revealed that the majority of the genome is transcribed,mainly from noncoding segments that were once considered＂junk sequences＂or＂dark matters＂（Liu et al.,2011a;Zhang et al.,2014b）. In addition to the well-characterized housekeeping non- coding RNAs （ncRNAs） （tRNA, rRNA, small nuclear RNA and small nucleolar RNAs） and some small regulatory ncRNAs （microRNAs and small interfering RNAs）, the transcriptome of mammals could also pervasively have been transcribed long noncoding RNAs （lncRNAs, at least 200 nt） （Rinn and Chang, 2012; Xie et al., 2012）.展开更多
Cancer is a leading cause of death globally, claiming about 9.6 million lives and approximately 420 million new cases of cancer will be diagnosed in the world by the year 2025. The aim of this study was to synthesize ...Cancer is a leading cause of death globally, claiming about 9.6 million lives and approximately 420 million new cases of cancer will be diagnosed in the world by the year 2025. The aim of this study was to synthesize and computationally evaluate pharmacological potential of some derivatives of 9-amino-3-phenylacridone, as topoisomerase II (Topo II) inhibitors. In this study, 10 derivatives of 3-phenyl-9-aminoacridone were chemically synthesized and characterized, and the potential pharmacological indications of these compounds were computationally predicted by methods such as ADMET prediction, molecular target prediction and molecular docking. The results showed that two derivatives (58e and 58j) were non-permeant of blood-brain barrier, and this property was found similar to that of amsacrine and etoposide. The results of molecular docking of the ten derivatives of 3-phenyl-9-aminoacridone that were synthesized in this work showed that the synthetic compounds (58a-j) and the standard drugs have overall best binding affinities for human acetylcholine esterase than butyrylcholinesterase, and overall best binding affinities for human topo IIα than human topo IIβ. Overall, the results of this study suggest that the synthetic compounds 58a, 58c, 58f, 58g, and 58i could probably inhibit topo IIα by catalytic inhibition as seen with amsacrine, but only 58b and 58e possessed DNA non-intercalation properties as seen with etoposide, serving as topo II poison. In conclusion, this study showed that 3-phenyl-9-aminoacridone derivatives are potential inhibitor of topo IIα/β both by catalytic inhibition and poison as non-intercalator of DNA.展开更多
The human genome contains around 20,000 protein-coding genes and a vast of transcriptional regulatory elements(ENCODE Project Consortium,2012;Roadmap Epigenomics Consortium et al.,2015;Stunnenberg and Hirst,2016).It s...The human genome contains around 20,000 protein-coding genes and a vast of transcriptional regulatory elements(ENCODE Project Consortium,2012;Roadmap Epigenomics Consortium et al.,2015;Stunnenberg and Hirst,2016).It still remains elusive how these regulatory elements regulate their target genes across genomic distances of millions of bases.展开更多
Dear Editor,Oryza sativa subsp, indica and japonica are two subspecies of Asian cultivated rice, among which indica rice is much more widely grown and genetically diverse. Over the past years, the Rice Annotation Proj...Dear Editor,Oryza sativa subsp, indica and japonica are two subspecies of Asian cultivated rice, among which indica rice is much more widely grown and genetically diverse. Over the past years, the Rice Annotation Project Database （RAP-DB） （Ohyanagi et al., 2006） and Michigan State University Rice Genome Annotation Project （MSU-RGAP） （Ouyang et al., 2007） are two popular databases that have been developed to manage rice genomic and transcriptomic data based on the unified reference genome of japonica cultivar Nipponbare （International Rice Genome Sequencing Project, 2005）. Beijing Genomics Institute Rice Information System （BGI-RIS） （Zhao et ai., 2004） is an available resource for indica rice cultivar 93-11;展开更多
基金Supported by Sciences Faculty,Los Andes University,Bogotá,Colombia and National Cancer Institute,Bogotá,Colombia,Grant No.41030310-28 (to Bravo MM)
文摘AIM: To investigate Helicobacter pylori (H. pylori) CagA diversity and to evaluate the association between protein polymorphisms and the occurrence of gastric pathologies. METHODS: One hundred and twenty-two clinical isolates of H. pylori cultured from gastric biopsies obtained from Colombian patients with dyspepsia were included as study material. DNA extracted from isolates was used to determine cagA status, amplifying the C-terminal cagA gene region by polymerase chain reaction. One hundred and six strains with a single amplicon were sequenced and results were used to characterize the 3' variable region of the cagA gene. To establish the number and type of tyrosine phosphorylation motifs Glutamine acid-Proline-Isoleucine-Tyrosine-Alanine (EPI-YA) bioinformatic analysis using Amino Acid Sequence Analyzer-Amino Acid Sequence Analyzer software was conducted. Analysis of the association between the number of EPIYA motifs and the gastric pathology was performed using χ2 test and analysis of the presence of EPIYA-C motifs in relation to the pathology was made by logistic regression odds ratios. Comparisons among EPIYA types found and those reported in GenBank were performed using a proportion test in Statistix Analytical Software version 8.0. RESULTS: After amplification of the 3' of the cagA gene, 106 from 122 isolates presented a single amplicon and 16 showed multiple amplicons. As expected, diversity in the size of the cagA unique fragments among isolates was observed. The 106 strains that presented a single amplicon after 3' cagA amplification came from patients with gastritis (19 patients), atrophic gastritis (21), intestinal metaplasia (26), duodenal ulcer (22) and gastric cancer. DNA sequence analysis showed that the differences in size of 3' cagA unique fragments was attributable to the number of EPIYA motifs: 1.9% had two EPIYA motifs, 62.3% had three, 33.0% had four and 2.8% had five motifs. The majority of tested clinical strains (62.3%) were found to harbor the ABC combination of EPIYA motifs and a significant statistical difference was observed between the frequencies of ABCC tyrosine phosphorylation motifs and Western strains sequences deposited in GenBank. CONCLUSION: The present report describes a lack of association between H. pylori CagA-protein polymorphisms and pathogenesis. ABCC high frequency variations compared with Western-strains sequences deposited in GenBank require more investigation.
基金Supported by National Cancer Institute, Bogotá, Colombia,Grant No. 41030310 to Bravo MM and Sciences Faculty, LosAndes University, Bogotá, Colombia
文摘AIM: To investigate the influence of the CagA diversity in Helicobacter pylori (H. pylori ) strains from Colombia on the host cell biology. METHODS: Eighty-four H. pylori-cagA positive strains with different Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs patterns, isolated from patients with gastritis (n=17), atrophic gastritis (n=17), duodenal ulcer (n=16), intestinal metaplasia (n=16) and gastric cancer (n=18), were included. To determine the integrity of the cag pathogenicity island (cag PAI) we evaluated the presence of cagA, cagT, cagE, and cag10 genes by polymerase chain reaction. AGS gastric epithelial cellswere infected with each strain and assayed for translo-cation and tyrosine phosphorylation of CagA by western blot, secretion of interleukin-8 (IL-8) by enzyme-linked immuno sorbent assay after taking supernatants from cocultures and cell elongation induction. For cell elongation quantification, coculture photographs were taken and the proportion of "hummingbird" cells (>15 μm) was determined. RESULTS: Overall 72% (60/84) of the strains were found to harbor a functional cag PAI. Levels of phos-phorylated CagA were significantly higher for isolates from duodenal ulcer than the ones in strains from gas-tritis, atrophic gastritis, intestinal metaplasia and gastric cancer (49.1% ± 23.1% vs 21.1% ± 19.5%, P < 0.02; 49.1% ± 23.1% vs 26.2%±14.8%, P<0.045; 49.1% ± 23.1% vs 21.5% ± 19.5%, P<0.043 and 49.1% ± 23.1% vs 29.5% ± 27.1%, P < 0.047 respectively). We observed variable IL-8 expression levels ranging from 0 to 810 pg/mL and from 8.8 to 1442 pg/mL at 6 h and 30 h post-infection, respectively. cagPAI-defective strains did not induce detectable levels of IL-8 at 6 h post-infection. At 30 h post-infection all strains induced IL-8 expression in AGS cells, although cagPAI-defective strains induced significantly lower levels of IL-8 than strains with a functional cagPAI (57.1 ± 56.6 pg/mL vs 513.6 ± 338.6 pg/mL,P < 0.0001). We did not observe differences in the extent of cell elongation induction between strains with a functional or a defective cagPAI in 6 h cocultures. At 24 h post infection strains with functionalcagPAI showed high diversity in the extent of hummingbird phenotype induction ranging from 7% to 34%. cag PAI defective strains induced significantly lower levels of elongation than strains with functional cag-PAI with one or more than one EPIYA-C motif (15.1% ± 5.2%vs 18.9% ± 4.7%,P < 0.03; and 15.1% ± 5.2% vs 20.0% ± 5.1%, P < 0.003 respectively). No differences were observed in cellular elongation inductionor IL-8 expression among H. pylori strains bearing one and more than one EPIYA-C motifs, neither at 6 h nor at 24 h of coculture. There were no associations between the levels of induction of cell elongation or IL-8 expression and number of EPIYA motifs or pathology. CONCLUSION: The present work describes a lack of association between H. pylori CagA protein EPIYA motifs variations from Colombian isolates and disease-associated cellular responses.
文摘BACKGROUND Probiotics are a promising solution for managing irritable bowel syndrome(IBS).Saccharomyces cerevisiae(S.cerevisiae)I-3856 has already demonstrated beneficial effects in IBS subjects,particularly in IBS with predominant constipation(IBS-C).AIM To confirm the efficacy of S.cerevisiae I-3856 in the management of gastrointestinal symptoms in IBS-C.METHODS A randomized,double-blind,placebo-controlled clinical study was performed in a total of 456 subjects.After a run-in period,subjects were randomly assigned to the group receiving S.cerevisiae I-3856(8×109 CFU daily)or the placebo for 8 wk,and they performed daily self-evaluations of gastrointestinal symptoms.The primary objective was to assess the effect of the probiotic on abdominal pain.The secondary objectives were the evaluation of other gastrointestinal symptoms,bowel movement frequency and consistency,and quality of life(QOL).RESULTS A significantly higher proportion of abdominal pain responders was reported in the Probiotic group(45.1%vs 33.9%,P=0.017).A nonsignificant difference in the area under the curve for abdominal pain over the second month of supplementation was observed in subjects receiving probiotic vs placebo[P=0.073,95%CI:-0.59(-1.23;0.05)].No statistically significant differences were reported in the evolution of bowel movement frequency and stool consistency between the groups.After 8 wk of supplementation,the overall QOL score was significantly higher in the Probiotic group than in the Placebo group[P=0.047,95%CI:3.86(0.52;7.20)].Furthermore,exploratory analyses showed statistically significant and clinically relevant improvements in QOL scores in abdominal pain responders vs nonresponders.CONCLUSION The results of this clinical study confirmed the abdominal pain alleviation properties of S.cerevisiae I-3856 in IBS-C.Abdominal pain relief was associated with improved QOL.ClinicalTrials.gov identifier:NCT03150212.
基金supported by the National Natural Science Foundation of China(31671725,31601330,31330057)the National Key Basic Research Program of China(2015CB150201)+1 种基金Science&Technology Special Project of Guizhou Academy of Agricultural Sciences([2014] 014,[2017] 08)the China Postdoctoral Science Foundation(2015M581867,2016T90514)
文摘Sclerotinia stem rot(SSR) caused by Sclerotinia sclerotiorum(Lib.) de Bary is one of the most devastating diseases of Brassica napus worldwide. Both SSR resistance and flowering time(FT) adaptation are major breeding goals in B. napus. However, early maturing rapeseed varieties, which are important for rice-rapeseed rotation in China, are often highly susceptible to SSR. Here, we found that SSR resistance was significantly negatively correlated with FT in a natural population containing 521 rapeseed inbred lines and a double haploid(DH) population with 150 individual lines, both of which had great variation in FT. Four chromosomal regions on A2, A6, C2, and C8 affecting both SSR resistance and FT were identified using quantitative trait loci(QTL) mapping after constructing a high-density genetic map based on single nucleotide polymorphism markers in the DH population.Furthermore, we aligned QTL for the two traits identified in the present and previous studies to the B. napus reference genome, and identified four colocalized QTL hotspots of SSR resistance and FT on A2(0–7.7 Mb), A3(0.8–7.5 Mb), C2(0–15.2 Mb), and C6(20.2–36.6 Mb). Our results revealed a genetic link between SSR resistance and FT in B.napus, which should facilitate the development of effective strategies in both early maturing and SSR resistance breeding and in map-based cloning of SSR resistance QTL.
基金Project(2012-0000478) supported by the National Research Foundation of Korea (NRF) grant funded by the Korea Government (MEST)
文摘In this work, we analyzed only the patients of the NSTEMI (non ST-segment elevation myocardial infarction) who arrived at the hospital within 12 h after symptoms started. Using NSTEMI follow-up data within, the characteristics of the clinical data, the risk factor, and the blood tested in the hospital visit were analyzed for MACE (major adverse cardiac events) patients. MACE includes cardiac death, MI (myocardial infarction), Re-PCI, and CABG (coronary artery bypass graft). As a result, from the NSTEMI patients which can be followed up for over 12 m, NT-ProBNP (p=0.014) and age (p=0.045) are found to be the independent risk factors related to MACE. Accordingly, they can be useful for the diagnosis and prognosis for NSTEMI patients as a biomarker.
基金Project supported by the National Basic Research Program in China(Grant No.2007CB935700)
文摘We successfully conduct the label-free and real-time detection of the interactions between epoxy groups and rabbit IgG and 5＇ CTT CAG GTC ATG AGC CTG AT 3＇ oligonucleotide, and between the hybridization of 5＇ CTT CAG GTC ATG AGC CTG AT 3＇ and its complementary 3＇ GAA GTC CAC TAC TCG GAC TA 5＇ oligonucleotide, by the oblique-incidence reflectivity difference （OI-RD） method. The dynamic curves of OI-RD signals, corresponding to the kinetic processes of biomolecular combination or hybridization, are acquired. In our case, the combination of epoxy groups with rabbit IgG and 5＇ CTT CAC CTC ATG AGC CTG AT 3＇ oligonucleotide need almost one and a half hours and about two hundred seconds, respectively; and the hybridization of the two oligonucleotides needs about five hundred seconds. The experimental results show that the OI-RD is a promising method for the real-time and label-free detection of biomolecular interactions.
基金supported by the National Key Research and Development Program of China(2016YFD0100101-18)the National Natural Science Foundation of China(31770397,31701317)the Fundamental Research Funds for the Central Universities(2662017PY058)。
文摘Rice panicle phenotyping is required in rice breeding for high yield and grain quality.To fully evaluate spikelet and kernel traits without threshing and hulling,using X-ray and RGB scanning,we developed an integrated rice panicle phenotyping system and a corresponding image analysis pipeline.We compared five methods of counting spikelets and found that Faster R-CNN achieved high accuracy(R~2 of 0.99)and speed.Faster R-CNN was also applied to indica and japonica classification and achieved 91%accuracy.The proposed integrated panicle phenotyping method offers benefit for rice functional genetics and breeding.
基金supported by a K08AR069099 (P.L.) from the National Institutes of Health/ National Institute of Arthritis and Musculoskeletal and Skinsupported by an R01AG056169 and a gift by the Patricia and Frank Zarb Family+5 种基金supported by an F30AG072834 from the National Institutes of Health/National Institute on Agingfunded through NIH Grant S10OD010751 and the Preclinical Imaging Laboratorypartially supported by the Laura and Isaac Perlmutter Cancer Center Support Grant NIH/NCI 5P30CA016087NIBIB Biomedical Technology Resource Center Grant NIH P41 EB017183supported in part by grant P30CA016087 from the National Institutes of Health/National Cancer Institutepartially supported by the Cancer Center Support Grant P30CA016087 at the Laura and Isaac Perlmutter Cancer Center。
文摘Skeletal stem and progenitor cells(SSPCs) perform bone maintenance and repair. With age, they produce fewer osteoblasts and more adipocytes leading to a loss of skeletal integrity. The molecular mechanisms that underlie this detrimental transformation are largely unknown. Single-cell RNA sequencing revealed that Notch signaling becomes elevated in SSPCs during aging. To examine the role of increased Notch activity, we deleted Nicastrin, an essential Notch pathway component, in SSPCs in vivo. Middle-aged conditional knockout mice displayed elevated SSPC osteo-lineage gene expression, increased trabecular bone mass, reduced bone marrow adiposity, and enhanced bone repair. Thus, Notch regulates SSPC cell fate decisions, and moderating Notch signaling ameliorates the skeletal aging phenotype, increasing bone mass even beyond that of young mice. Finally, we identified the transcription factor Ebf3 as a downstream mediator of Notch signaling in SSPCs that is dysregulated with aging, highlighting it as a promising therapeutic target to rejuvenate the aged skeleton.
文摘Background The clinical significance of complete revascularization for ST segment elevation myocardial infarction （STEMI） pa- tients during admission is still debatable. Methods A total of 1406 STEMI patients from the Korean Myocardial Infarction Registry with multivessel diseases without cardiogenic shock who underwent primary percutaneous coronary intervention （PPCI） were analyzed. We used propensity score matching （PSM） to control differences of baseline characteristics between culprit only intervention （CP） and multivessel percutaneous coronary interventions （MP）, and between double vessel disease （DVD） and triple vessel disease （TVD）. The major adverse cardiac event （MACE） was analyzed for one year after discharge. Results TVD patients showed higher incidence of MACE （14.2% vs. 8.6%, P = 0.01）, any cause of revascularization （10.6% vs. 5.9%, P - 0.01）, and repeated PCI （9.5% vs. 5.7%, P = 0.02）, as compared to DVD patients during one year after discharge. MP reduced MACE effectively （7.3% vs. 13.8%, P = 0.03）, as compared to CP for one year, but all cause of death （1.6% vs. 3.2%, P= 0.38）, Ml （0.4% vs. 0.8%, P = 1.00）, and any cause ofrevascularization （5.3% vs. 9.7%, P = 0.09） were comparable in the two treatment groups. Conclusions STEMI patients with TVD showed higher rate of MACE, as compared to DVD MP performed during PPCI or ad hoc during admission for STEMI patients without cardiogenic shock showed lower rate of MACE in this large scaled database. Therefore, MP could be considered as an effective treatment option for STEMI patients without cardiogenic shock.
文摘The present study is concerned with the isolation and screening of different strains of Aspergillus oryzae for the production of alpha amylase. Ninety strains were isolated from soil and tested for the production of alpha amylase in shake flasks. Of all the strains tested, Aspergillus oryzae GCB-32 and Aspergillus oryzae GCB-35 gave maximum production of alpha amylase. Different culture media were screened for the production of alpha amylase by these two strains. M1 medium containing starch, yeast extract, NH4Cl, MgSO4·7H2O and CaCl2 gave the maximum production of alpha amylase by both the strains Aspergillus oryzae GCB-32 and Aspergillus oryzae GCB-35.Kinetic analysis revealed that the values of product yield coefficient（Y p/x ） and specific product yield coefficient（qp） were found highly significant（p≤0.05） when medium M1 was used for the enzyme production.
文摘Objective:To explore natural compounds as potential inhibitors against main protease(Mpro)of SARS-CoV-2.Methods:In the current study,systematic molecular docking analysis was conducted using AutoDock 4.2 to determine the binding affinities and interactions between natural compounds and Mpro.Selected natural compounds were further validated using a combination of molecular dynamic(MD)simulations and molecular mechanic Poisson-Boltzmann surface area(MM/PBSA)free energy c alculation s.Results:Out of twenty natural compounds,four natural metabolites namely,amentoflavone,guggulsterone,puerarin,and piperine were found to have strong interaction with Mpro of SARS-CoV-2 based on docking analysis.During MD simulations,all four natural compounds bound to Mpro at 50 ns and MM/G/P/BSA free energy calculations showed that all four shortlisted ligands had stable and favorable energies with strong binding to Mpro protein.Conclusions:Guggulsterone is a potential inhibitor of COVID-19 main protease Mpro.Further in vitro and pre-clinical studies are needed.
基金National Natural Science Foundation of China under Grant Nos.10335010 and 70431002the Nonlinear Science 973 Project under Grant No.10675020
文摘Gene transcriptional regulation （TR） processes are often described by coupled nonlinear ordinary differential equations （ODEs）. When the dimension of TR circuits is high （e.g. n≥3） the motions of the corresponding ODEs may, very probably, show self-sustained oscillations and chaos. On the other hand, chaoticity may be harmful for the normal biological functions of TR processes. In this letter we numerically study the dynamics of 3-gene TR ODEs in great detail, and investigate many 4-, 5-, and lO-gene TR systems by randomly choosing figures and parameters in the conventionally accepted ranges. And we find that oscillations are very seldom and no chaotic motion is observed, even if the dimension of systems is sufficiently high （n≥3）. It is argued that the observation of nonchaoticity of these ODEs agrees with normal functions of actual TR processes.
基金supported by funding from the National Natural Science Foundation of China,China(grants 31621005 and 31600093 to F.G.L.)the Young Elite Scientists Sponsorship Program by CAST(2019zx08010033-002-012 to Z.E.Y.)Central Public-interest Scientific Institution Basal Research Fund(Y2020PT13)。
文摘Chromatin interactions functionally affect genome architecture and gene regulation,but to date,only fresh samples must be used in High-through chromosome conformation capture(Hi-C)to keep natural chromatin conformation intact.This requirement has impeded the advancement of 3 D genome research by limiting sample collection and storage options for researchers and severely limiting the number of samples that can be processed in a short time.Here,we develop a freeze substitution Hi-C(FS-Hi-C)technique that overcomes the need for fresh samples.FS-Hi-C can be used with samples stored in liquid nitrogen(LN2):the water in a vitreous form in the sample cells is replaced with ethanol via automated freeze substitution.After confirming that the FS step preserves the natural chromosome conformation during sample thawing,we tested the performance of FS-Hi-C with Drosophila melanogaster and Gossypium hirsutum.Beyond allowing the use of frozen samples and confirming that FS-Hi-C delivers robust data for generating contact heat maps and delineating A/B compartments and topologically associating domains,we found that FS-HiC outperforms the in situ Hi-C in terms of library quality,reproducibility,and valid interactions.Thus,FS-HiC will probably extend the application of 3D genome structure analysis to the vast number of experimental contexts in biological and medical research for which Hi-C methods have been unfeasible to date.
基金supported by the National Natural Science Foundation of China(81630060 to P.W.,31771402 to G.L.,81830074 and 81772786 to H.W.,81572569 to G.C.,and 81772775 to J.W.)National Science and Technology Major Project(2019YFC1005202 and 2019YFC1005201 to K.L.,and 2018ZX10301402-002 to Q.G.)the research-oriented clinician funding program of Tongji Medical College,Huazhong University of Science and Technology for P.W
文摘Integration of human papillomavirus(HPV)DNA into the human genome is a reputed key driver of cervical cancer.However,the effects of HPV integration on chromatin structural organization and gene expression are largely unknown.We studied a cohort of 61 samples and identified an integration hot spot in the CCDC106 gene on chromosome 19.We then selected fresh cancer tissue that contained the unique integration loci at CCDC106 with no HPV episomal DNA and performed whole-genome,RNA,chromatin immunoprecipitation and high-throughput chromosome conformation capture(Hi-C)sequencing to identify the mechanisms of HPV integration in cervical carcinogenesis.Molecular analyses indicated that chromosome 19 exhibited significant genomic variation and differential expression densities,with correlation found between three-dimensional(3D)structural change and gene expression.Importantly,HPV integration divided one topologically associated domain(TAD)into two smaller TADs and hijacked an enhancer from PEG3 to CCDC106,with a decrease in PEG3 expression and an increase in CCDC106 expression.This expression dysregulation was further confirmed using 10 samples from our cohort,which exhibited the same HPV-CCDC106 integration.In summary,we found that HPV-CCDC106 integration altered local chromosome architecture and hijacked an enhancer via 3D genome structure remodeling.Thus,this study provides insight into the 3D structural mechanism underlying HPV integration in cervical carcinogenesis.
基金supported by the Joe,Pentti,and Tor Borg Memorial Fund.
文摘Objective:To investigate the renoprotective effects of luteolin on diabetes in rats.Methods:One week after administration of streptozotocin 55 mg/kg intraperitoneally,rats were given 25,50,and 75 mg/kg/day of luteolin orally for another eight weeks.At the end of the experiment,body weight,blood glucose level,biochemical parameters for renal function(serum creatinine,blood urea nitrogen,uric acid,serum albumin,and total protein),kidney histology,matrix metalloproteinase(MMP)-2,MMP-9,and histone deacetylase 2(HDAC-2)expression,and malondialdehyde,myeloperoxidase,and hydroxyproline content in renal tissue were evaluated.High glucose-induced damage using NRK-52E cell line was studied to evaluate cell viability and metalloenzyme expression.Additionally,in silico studies including docking and molecular dynamics simulations were conducted.Results:MMP-2,MMP-9,and HDAC-2 expressions were significantly increased in high glucose-induced NRK-52E cells and the renal tissue of diabetic rats.However,these changes were reversed by luteolin at the administered doses.Additionally,luteolin significantly reduced oxidative stress,inflammation,and fibrosis,as well as improved biochemical parameters in diabetic rats.Furthermore,luteolin at the examined doses markedly alleviated diabetes-induced histopathological changes in renal tissues.Conclusions:Luteolin effectively attenuates streptozotocin-induced diabetic nephropathy in rats by inhibiting MMP-2,MMP-9,and HDAC-2 expression,and reducing oxidative stress and inflammation.
文摘Understanding the genetic architecture of indi-vidual taxa of medical importance is the first step for designing disease preventive strategies. To understand the genetic details and evolu-tionary perspective of the model malaria vector, Anopheles gambiae and to use the information in other species of local importance, we scanned the published X-chromosome se-quence for detail characterization and obtain evolutionary status of different genes. The te-locentric X-chromosome contains 106 genes of known functions and 982 novel genes. Majori-ties of both the known and novel genes are with introns. The known genes are strictly biased towards less number of introns;about half of the total known genes have only one or two in-trons. The extreme sized (either long or short) genes were found to be most prevalent (58% short and 23% large). Statistically significant positive correlations between gene length and intron length as well as with intron number and intron length were obtained signifying the role of introns in contributing to the overall size of the known genes of X-chromosome in An. gam-biae. We compared each individual gene of An. gambiae with 33 other taxa having whole ge-nome sequence information. In general, the mosquito Aedes aegypti was found to be ge-netically closest and the yeast Saccharomyces cerevisiae as most distant taxa to An. gambiae. Further, only about a quarter of the known genes of X-chromosome were unique to An. gambiae and majorities have orthologs in dif-ferent taxa. A phylogenetic tree was constructed based on a single gene found to be highly orthologous across all the 34 taxa. Evolutionary relationships among 13 different taxa were in-ferred which corroborate the previous and pre-sent findings on genetic relationships across various taxa.
基金supported by the grants from the National Key Research and Development Plan (2016YFA0100702,2016YFC0902502)the National Key Basic Research Program (973 Program) (Nos.2013CB531304 and 2011CBA01104)+1 种基金the National Sciences Foundation of China (Nos. 31301152,31670789,31671316,31370789 and 30825023)CAMS Innovation Fund for Medical Sciences (CIFMS,2016-I2M-2-001,2016-I2M-1-001,2016-I2M-1-004)
文摘Although only about 2%of the human genome has proved to be protein-coding genes,recent advances in genome wide analysis have revealed that the majority of the genome is transcribed,mainly from noncoding segments that were once considered＂junk sequences＂or＂dark matters＂（Liu et al.,2011a;Zhang et al.,2014b）. In addition to the well-characterized housekeeping non- coding RNAs （ncRNAs） （tRNA, rRNA, small nuclear RNA and small nucleolar RNAs） and some small regulatory ncRNAs （microRNAs and small interfering RNAs）, the transcriptome of mammals could also pervasively have been transcribed long noncoding RNAs （lncRNAs, at least 200 nt） （Rinn and Chang, 2012; Xie et al., 2012）.
文摘Cancer is a leading cause of death globally, claiming about 9.6 million lives and approximately 420 million new cases of cancer will be diagnosed in the world by the year 2025. The aim of this study was to synthesize and computationally evaluate pharmacological potential of some derivatives of 9-amino-3-phenylacridone, as topoisomerase II (Topo II) inhibitors. In this study, 10 derivatives of 3-phenyl-9-aminoacridone were chemically synthesized and characterized, and the potential pharmacological indications of these compounds were computationally predicted by methods such as ADMET prediction, molecular target prediction and molecular docking. The results showed that two derivatives (58e and 58j) were non-permeant of blood-brain barrier, and this property was found similar to that of amsacrine and etoposide. The results of molecular docking of the ten derivatives of 3-phenyl-9-aminoacridone that were synthesized in this work showed that the synthetic compounds (58a-j) and the standard drugs have overall best binding affinities for human acetylcholine esterase than butyrylcholinesterase, and overall best binding affinities for human topo IIα than human topo IIβ. Overall, the results of this study suggest that the synthetic compounds 58a, 58c, 58f, 58g, and 58i could probably inhibit topo IIα by catalytic inhibition as seen with amsacrine, but only 58b and 58e possessed DNA non-intercalation properties as seen with etoposide, serving as topo II poison. In conclusion, this study showed that 3-phenyl-9-aminoacridone derivatives are potential inhibitor of topo IIα/β both by catalytic inhibition and poison as non-intercalator of DNA.
基金supported by the National Natural Science Foundation of China(31900432 to D.L.,31771402 to G.L.)the National Postdoctoral Program for Innovative Talents(BX20180113 to D.L.)+1 种基金China Postdoctoral Science Foundation(2018M640710 to D.L.)the Fundamental Research Funds for the Central Universities(2662018PY025 to G.C.)
文摘The human genome contains around 20,000 protein-coding genes and a vast of transcriptional regulatory elements(ENCODE Project Consortium,2012;Roadmap Epigenomics Consortium et al.,2015;Stunnenberg and Hirst,2016).It still remains elusive how these regulatory elements regulate their target genes across genomic distances of millions of bases.
文摘Dear Editor,Oryza sativa subsp, indica and japonica are two subspecies of Asian cultivated rice, among which indica rice is much more widely grown and genetically diverse. Over the past years, the Rice Annotation Project Database （RAP-DB） （Ohyanagi et al., 2006） and Michigan State University Rice Genome Annotation Project （MSU-RGAP） （Ouyang et al., 2007） are two popular databases that have been developed to manage rice genomic and transcriptomic data based on the unified reference genome of japonica cultivar Nipponbare （International Rice Genome Sequencing Project, 2005）. Beijing Genomics Institute Rice Information System （BGI-RIS） （Zhao et ai., 2004） is an available resource for indica rice cultivar 93-11;
