ABSTRACT
Thirteen new alkaloids (1-13) as well as ten known compounds were isolated from the solid-state fermented rice medium of the fungus Chaetomium nigricolor YT-2. Their structures were elucidated on the basis of spectroscopic data, quantum calculations, and single crystal X-ray crystallographic analysis. Chaetonigrisin A (1) represents an unprecedented carbon skeleton featuring a polycyclic 1H-pyrano[3,2:3,4-]âfuro[2,â3-âb]âindole. Chaetonigrisin B (2) displays a unique carbon skeleton with a 1,3dioxolane bridged-ring. Chaetonigrisin C (3) is a spirocyclic indole alkaloid. Chaetonigrisins D-H (4-8) are a group of asymmetric dimers, formed with two 3-indol-3yl-1,2-propanediol (4-6) or with a 3-indol-3yl-1,2-propanediol and a 3-indol-2yl-1,2-propanediol (7-8) by a pyran ring. Chaetonigrisins I-L (9-12) each contains a 3-indol-3yl-1,2-propanediol or 3-indol-2yl-1,2-propanediol substructure. Chaetonigrisin M (13) is a new quinoline alkaloid. The neuroprotective activity assay showed that at the concentration of 40 µM, compounds (4-7, 11, and 12) improved the cell viability of PC12 cells were 49.26 %, 74.69 %, 74.76 %, 86.63 %, 66.89 %, and 69.92 %, respectively induced by 6-OHDA, compound 7 showed significant neuroprotective activity via upregulation of SOD1 mRNA and Bcl-2 mRNA.
Subject(s)
Alkaloids , Chaetomium , Chaetomium/chemistry , Propylene Glycol , Indole Alkaloids/chemistry , Alkaloids/chemistry , Carbon , RNA, Messenger , Molecular StructureABSTRACT
Five hydroxamate siderophores, chaetomadramines A-E (1-5), along with seven known compounds were isolated from the fermented rice culture of the fungus Chaetomium madrasense cib-1. Compounds 1-5 were structurally elucidated on the basis of spectroscopic data, which were a group of unusual hydroxamate siderophores, bearing a long fatty acyl on the α-NH2 of the Nδ-hydroxylated ornithine. Compounds 2-5 were new. The structural elucidation and spectroscopic data of 1 were reported for the first time. Compounds 2-4 significantly improved the survival rates of PC12 cells in the neuroprotective activity assay at the concentration of 40 µM.
Subject(s)
Chaetomium , Siderophores , Siderophores/chemistry , Molecular Structure , Chaetomium/chemistry , Hydroxamic AcidsABSTRACT
OBJECTIVE: To evaluate the efficacy of the digital cytopathological lung cancer diagnosing system (DCLCDS) utilizing the latest computer technologies (including reinforcement learning, image segmentation and classifier) and the cytopathological knowledge on lung cancer cells. METHODS: Separate the overlapped lung cancer cells in a slice image applying the improved deBoor-Cox B-Spline algorithm; Segment cell regions in a slice image using an image segmentation algorithm based on reinforcement learning; Ensemble different classifiers, including Decision Tree classifier, Support Vector Machine (SVM) classifier and Bayesian classifier, to achieve an accurate result of cytopathological lung cancer diagnosis. RESULTS: The accurate diagnosis rate for lung cancer identification of 224 images of small lung lesions aspiration biopsy from 120 cases randomly selected was 92.3%. The accurate diagnosis rate for type classification of lung cancer was 82.5%. The identification rate for abnormal nuclear cells was 71.6%. CONCLUSIONS: The DCLCDS achieves a high accuracy on cytopathological lung cancer diagnosis by solving some major problems on the cytology smears, including cell overlapping, uneven coloration and impurity. It provides a relatively objective, standard tool on cytopathological lung cancer diagnosis. It has good efficacy on early diagnosis of lung cancer.
Subject(s)
Diagnosis, Computer-Assisted/methods , Lung Neoplasms/diagnosis , Software Design , Algorithms , Artificial Intelligence , Cytodiagnosis/methods , Decision Trees , Humans , Image Processing, Computer-Assisted , Lung Neoplasms/pathology , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
It is known that in the pathogenesis of mental retardation (MR), both genetic and environmental factors (particularly iodine deficiency) appear to play a critical role. Transthyretin (TTR) transports between 20% and 30% of serum thyroxine in normal individuals and it is the main T(4)-binding protein in CSF. Variability in the TTR gene may influence risk for iodine-deficiency-based MR. The SNPs we selected from dbSNP were detected and identified using ARMS-PCR and sequencing methods, and we identified five novel sequence variants. Singular-locus association analysis indicated no association between the TTR gene and MR. In haplotype analysis, however, we found a haplotype CGTG+ (rs723744/G+6649C/T+6690C/rs2276382/del9) showed a weak positive association with MR (chi(2) = 6.699, p = 0.035). Finally, we concluded that the weak positive result is more likely to be due to sampling error and the small size of this haplotype resulting from its relative low frequency. Our negative results provide no evidence that variants of TTR gene influence susceptibility to MR in the iodine-deficient areas of China and suggest that there may be a compensatory mechanism(s) in humans and mice, which work(s) to compensate the effect of mutation in the TTR gene on MR.
Subject(s)
Genetic Predisposition to Disease , Intellectual Disability/genetics , Polymorphism, Single Nucleotide/genetics , Prealbumin/genetics , Child , China/epidemiology , Genotype , Haplotypes , Humans , Polymerase Chain ReactionABSTRACT
Osteogenesis imperfecta (OI) is heritable bone fragility,which is inherited as an autosomal dominant trait clinical presentation. Clinical symptom, in general, is dominantly inherited OI with blue sclerae, hearing loss and mild-moderate skeletal deformity. Genetic loci of OI have been mapped to17q21.31-q22 and 7q22.1, in which COL1A1 and COL1A2 are known to be the causal genes. In this work,we performed linkage analysis in a kindred with autosomal dominant hereditary OI. A tight linkage to the markers on chromosome 17q21.31-q22 (maximum two-point lod score: 9.31 at theta = .00) was observed. Sequence analysis of COL1A1 revealed a single-base mutation that converted the consensus sequence at the 5' end of intron 26 from GT to AT to form an abnormal splicing site leading to OI.
Subject(s)
Chromosomes, Human, Pair 17 , Collagen Type I/genetics , Osteogenesis Imperfecta/genetics , Point Mutation , Adolescent , Base Sequence , Collagen Type I, alpha 1 Chain , DNA Mutational Analysis , Female , Genetic Linkage , Humans , Introns , Lod Score , Male , PedigreeABSTRACT
OBJECTIVE: To investigate the relationship between two polymorphisms (Intronic VNTR and 5-HTTLPR) of the serotonin transporter gene and schizophrenia. METHODS: A set of 314 schizophrenic trio samples collected from Shanghai, Xi'an and Jilin regions of China independently was subjected to analysis of the polymorphisms by transmission/disequilibrium test(TDT). RESULTS: No significantly preferential transmission of any allele was detected from both polymorphisms investigated. CONCLUSION: The results suggest that the serotonin transporter gene is unlikely to have a major contribution to susceptibility to schizophrenia in Han Chinese population.
Subject(s)
Polymorphism, Genetic , Schizophrenia/genetics , Serotonin Plasma Membrane Transport Proteins/genetics , Adult , Female , Genetic Predisposition to Disease/genetics , Humans , Male , Minisatellite Repeats/genetics , Nuclear Family , Polymerase Chain ReactionABSTRACT
Dyschromatosis symmetrica hereditaria (DSH) is a hereditary skin disease characterized by the presence of hyperpigmented and hypopigmented macules on extremities and face. The gene, or even its chromosomal location, for DSH has not yet been identified. In this study, two Chinese families with DSH were identified and subjected to a genomewide screen for linkage analysis. Two-point linkage analysis for pedigree A (maximum LOD score [Z(max)] = 7.28 at recombination fraction [theta] = 0.00) and pedigree B (Z(max) = 2.41 at theta = 0.00) mapped the locus for DSH in the two families to chromosome 6q. Subsequent multipoint analysis of the two families also provided additional support for the DSH gene being located within the region 6q24.2-q25.2, with Z(max) = 10.64. Haplotype analysis confined the locus within an interval of 10.2 Mbp, flanked by markers D6S1703 and D6S1708. The two families had no identical haplotype within the defined region, which suggests that the two families were different in origin. Further work on identification of the gene for DSH will open new avenues to exploration of the genetics of pigmentation.