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At least 631 records · Page 35Linked to original sources
PubMed2006

QTL mapping for plant architecture traits in upland cotton using RILs and SSR markers.

Xiangzamian 2 (XZM2) is the most widely cultivated cotton hybrid in China. By crossing two parents Zhongmiansuo12 and 8891 and upon subsequent selfings, we got F8 and F9 populations having 180 recombinant inbred lines. Ten plant architecture traits were investigated in two years with this population. A genetic map was constructed mainly with SSR markers. Quantitative trait loci (QTL) conditioning plant architecture traits were determined at the single-locus and double-locus levels. The results showed that epistastic effects as well as additive effects of QTL played an important role as the genetic basis of cotton plant architecture. The QTL detected in our research might provide new information on improving plant architecture traits. The polymorphism of molecular markers between ZMS12 and 8891 were quite limited, while significant differences between their phenotypes were found and the hybrid XZM2 expressed high heterosis in yield. All these could be partly explained by the effect of epistatic QTL.

Breeding↗
PubMed2001

Integration of genome data and protein structures: prediction of protein folds, protein interactions and "molecular phenotypes" of single nucleotide polymorphisms.

With the massive amount of sequence and structural data being produced, new avenues emerge for exploiting the information therein for applications in several fields. Fold distributions can be mapped onto entire genomes to learn about the nature of the protein universe and many of the interactions between proteins can now be predicted solely on the basis of the genomic context of their genes. Furthermore, by utilising the new incoming data on single nucleotide polymorphisms by mapping them onto three-dimensional structures of proteins, problems concerning population, medical and evolutionary genetics can be addressed.

Apolipoproteins E↗
PubMed2000

The leader of the HIV-1 RNA genome forms a compactly folded tertiary structure.

The untranslated leader of the RNA genome of the human immunodeficiency virus type 1 (HIV-1) encodes multiple signals that regulate distinct steps of the viral replication cycle. The RNA secondary structure of several replicative signals in the HIV-1 leader is critical for function. Well-known examples include the TAR hairpin that forms the binding site for the viral Tat trans-activator protein and the DIS hairpin that is important for dimerization and subsequent packaging of the viral RNA into virion particles. In this study, we present evidence for the formation of a tertiary structure by the complete HIV-1 leader RNA. This conformer was recognized as a fast-migrating band on nondenaturing polyacrylamide gels, and such a migration effect is generally attributed to differences in compactness. Both the 5' and 3' domains of the 335-nt HIV-1 leader RNA are required for the formation of the compact RNA structure, and the presence of several putative interaction domains was revealed by an extensive analysis of the denaturing effect of antisense DNA oligonucleotides. The buffer conditions and sequence requirements for conformer formation are strikingly different from that of the RNA-dimerization reaction. In particular, the conformer was destabilized in the presence of Mg2+ ions and by the viral nucleocapsid (NC) protein. The presence of a stable RNA structure in the HIV-1 leader was also apparent when this RNA was used as template for reverse transcription, which yielded massive stops ahead of the structured leader domain. Formation of the conformer is a reversible event, suggesting that the HIV-1 leader is a dynamic molecule. The putative biological function of this conformational polymorphism as molecular RNA switch in the HIV-1 replication cycle is discussed.

5' Untranslated Regions↗
PubMed1980

Model for antenatal diagnosis of beta-thalassaemia and other monogenic disorders by molecular analysis of linked DNA polymorphisms.

Polymorphisms of DNA restriction sites within the human fetal globin genes have been used to identify chromosomes that carry beta-thalassaemia genes in individuals heterozygous for this disease. This has allowed an antenatal diagnosis for beta-thalassaemia to be carried out by observation of the pattern of the inherited polymorphism of a linked DNA sequence not involved in the genetic pathogenesis of the disease. In the populations we have investigated there is no constant pattern of polymorphism that segregates with the beta-thalassaemia gene. The use of linked polymorphisms should, therefore, be applicable to antenatal diagnosis both of beta-thalassaemia and of any other single-gene defect for which there is a DNA probe specific for a sequence linked to the affected locus.

DNA↗
PubMed1989

Monoclonal antibodies reactive with mucin expressed in breast cancer.

Three murine monoclonal antibodies (BC1, BC2 and BC3) were developed against human milk fat globule membrane (HMFGM). By immunoperoxidase staining, it was found that the antigenic determinants had a predominant distribution in breast cancer tissue. In addition, the antibodies reacted preferentially with mucin derived from human milk rather than that derived from the breast cancer cell line ZR75; they also recognized polymorphic high molecular weight components (MW greater than or equal to 230,000) in serum and in human milk fat globule membrane. Thus the antibodies appear to react with a component of the family of mucins found in breast cancer and human milk and it appears likely that at least part of each epitope is protein in nature. Antibodies BC1, BC2 and BC3 recognized related but not identical epitopes, and they appear to be co-expressed on the same molecules as 3E1.2-defined antigen (mammary serum antigen, MSA) which is also a member of the family of breast cancer-related mucin. However, the 3E1.2 epitope is distinct and non-cross-reactive with those described for BC1, BC2 and BC3. The BC2 and BC3 defined epitopes were examined for their value in serum assays. Immunoassay was developed with a combination of two antibodies, using antibody BC3 for antigen capture and antibody BC2 or 3E1.2 for antigen detection and gave reasonable sensitivity (approximately 85%) and specificity (approximately 95%) in such serum tests for breast cancer. In a limited study, these tests appeared to complement the MSA test in the detection of breast cancer.

Antibodies, Monoclonal↗
PubMed2000

Association study on the DUSP6 gene, an affective disorder candidate gene on 12q23, performed by using fluorescence resonance energy transfer-based melting curve analysis on the LightCycler.

We introduced a new genotyping method, fluorescence resonance energy transfer-based melting curve analysis on the LightCycler, for the analysis of the gene, DUSP6 (dual specificity MAP kinase phosphatase 6), in affective disorder patients. The DUSP6 gene is located on chromosome 12q22-23, which overlaps one of the reported bipolar disorder susceptibility loci. Because of its role in intracellular signalling pathways, the gene may be involved in the pathogenesis of affective disorders not only on the basis of its position but also of its function. We performed association analysis using a T>G polymorphism that gives rise to a missense mutation (Leu114Val). No evidence for a significant disease-causing effect was found in Japanese unipolars (n = 132) and bipolars (n = 122), when compared with controls (n = 299). More importantly, this study demonstrates that melting curve analysis on the LightCycler is an accurate, rapid and robust method for discriminating genotypes from biallelic markers. This strategy has the potential for use in high throughput scanning for and genotyping of single nucleotide polymorphisms (SNPs). Molecular Psychiatry (2000) 5, 489-494.

Journal Article↗
PubMed2004

Glutamate carboxypeptidase II gene expression in the human frontal and temporal lobe in schizophrenia.

There is decreased activity of glutamate carboxypeptidase II (GCP II) in the dorsolateral prefrontal cortex (DLPFC) and hippocampus of patients with schizophrenia. GCP II hydrolzses N-acetyl-alpha L-aspartyl-L-glutamate (NAAG), a peptide in the mammalian brain that binds to the N-methyl D-aspartate (NMDA) receptor and a group II metabotropic glutamate receptor, both of which have been implicated in the pathophysiology of schizophrenia. We examined the expression of GCP II mRNA in the DLPFC, entorhinal cortex (ERC), and hippocampus in postmortem samples from patients with schizophrenia and normal controls using in situ hybridization followed by silver grain detection. GCP II mRNA was detected in glial cells. Glial-rich regions, specifically the DLPFC and ERC white matter and the molecular and polymorphic layers in the hippocampus, express high levels of GCP II mRNA. Given the earlier finding of decreased GCP II activity in brains of subjects with schizophrenia, we expected to find lower GCP II mRNA levels in schizophrenia. Contrary to this expectation, we found a significantly higher expression of GCP II mRNA in one of the brain areas examined, the hippocampal CA3 polymorphic region. This may reflect a compensatory increase to correct for the decreased activity of GCP II activity. Our findings support the notion that the hydrolysis of NAAG is disrupted in schizophrenia and that specific anatomical regions may show discrete abnormalities in GCP II synthesis.

Adolescent↗
PubMed2001

Structure, function and evolution of glutathione transferases: implications for classification of non-mammalian members of an ancient enzyme superfamily.

The glutathione transferases (GSTs; also known as glutathione S-transferases) are major phase II detoxification enzymes found mainly in the cytosol. In addition to their role in catalysing the conjugation of electrophilic substrates to glutathione (GSH), these enzymes also carry out a range of other functions. They have peroxidase and isomerase activities, they can inhibit the Jun N-terminal kinase (thus protecting cells against H(2)O(2)-induced cell death), and they are able to bind non-catalytically a wide range of endogenous and exogenous ligands. Cytosolic GSTs of mammals have been particularly well characterized, and were originally classified into Alpha, Mu, Pi and Theta classes on the basis of a combination of criteria such as substrate/inhibitor specificity, primary and tertiary structure similarities and immunological identity. Non-mammalian GSTs have been much less well characterized, but have provided a disproportionately large number of three-dimensional structures, thus extending our structure-function knowledge of the superfamily as a whole. Moreover, several novel classes identified in non-mammalian species have been subsequently identified in mammals, sometimes carrying out functions not previously associated with GSTs. These studies have revealed that the GSTs comprise a widespread and highly versatile superfamily which show similarities to non-GST stress-related proteins. Independent classification systems have arisen for groups of organisms such as plants and insects. This review surveys the classification of GSTs in non-mammalian sources, such as bacteria, fungi, plants, insects and helminths, and attempts to relate them to the more mainstream classification system for mammalian enzymes. The implications of this classification with regard to the evolution of GSTs are discussed.

Animals↗
PubMed2003

Glyoxalase I--structure, function and a critical role in the enzymatic defence against glycation.

Glyoxalase I is part of the glyoxalase system present in the cytosol of cells. The glyoxalase system catalyses the conversion of reactive, acyclic alpha-oxoaldehydes into the corresponding alpha-hydroxyacids. Glyoxalase I catalyses the isomerization of the hemithioacetal, formed spontaneously from alpha-oxoaldehyde and GSH, to S -2-hydroxyacylglutathione derivatives [RCOCH(OH)-SG-->RCH(OH)CO-SG], and in so doing decreases the steady-state concentrations of physiological alpha-oxoaldehydes and associated glycation reactions. Physiological substrates of glyoxalase I are methylglyoxal, glyoxal and other acyclic alpha-oxoaldehydes. Human glyoxalase I is a dimeric Zn(2+) metalloenzyme of molecular mass 42 kDa. Glyoxalase I from Escherichia coli is a Ni(2+) metalloenzyme. The crystal structures of human and E. coli glyoxalase I have been determined to 1.7 and 1.5 A resolution. The Zn(2+) site comprises two structurally equivalent residues from each domain--Gln-33A, Glu-99A, His-126B, Glu-172B and two water molecules. The Ni(2+) binding site comprises His-5A, Glu-56A, His-74B, Glu-122B and two water molecules. The catalytic reaction involves base-catalysed shielded-proton transfer from C-1 to C-2 of the hemithioacetal to form an ene-diol intermediate and rapid ketonization to the thioester product. R - and S-enantiomers of the hemithioacetal are bound in the active site, displacing the water molecules in the metal ion primary co-ordination shell. It has been proposed that Glu-172 is the catalytic base for the S-substrate enantiomer and Glu-99 the catalytic base for the R-substrate enantiomer; Glu-172 then reprotonates the ene-diol stereospecifically to form the R-2-hydroxyacylglutathione product. By analogy with the human enzyme, Glu-56 and Glu-122 may be the bases involved in the catalytic mechanism of E. coli glyoxalase I. The suppression of alpha-oxoaldehyde-mediated glycation by glyoxalase I is particularly important in diabetes and uraemia, where alpha-oxoaldehyde concentrations are increased. Decreased glyoxalase I activity in situ due to the aging process and oxidative stress results in increased glycation and tissue damage. Inhibition of glyoxalase I pharmacologically with specific inhibitors leads to the accumulation of alpha-oxoaldehydes to cytotoxic levels; cell-permeable glyoxalase I inhibitors are antitumour and antimalarial agents. Glyoxalase I has a critical role in the prevention of glycation reactions mediated by methylglyoxal, glyoxal and other alpha-oxoaldehydes in vivo.

Catalysis↗
PubMed2001

Molecular characterization of ribosomal DNA polymorphisms discriminating among chromosomal forms of Anopheles gambiae s.s.

The sequence of a 2.3 kb long DNA segment derived from the 5'-most end of the ribosomal intergenic spacer was determined in three chromosomal forms of Anopheles gambiae s.s. The analysis revealed that the sequence of the Mopti form differed from that of the Bamako and Savanna forms by a total of ten nucleotide substitutions. Using these sequence variations we set up a diagnostic polymerase chain reaction (PCR) assay to distinguish mosquitoes belonging to the three chromosomal forms, facilitating studies on the distribution and the ecology of these incipient taxa. The assay also allows to distinguish whether a given specimen could represent a heterozygote between Mopti and Savanna or Bamako.

Animals↗
PubMed2001

Neuropathological findings in a patient with epilepsy and the Parry-Romberg syndrome.

PURPOSE: The Parry-Romberg syndrome is an unusual disorder frequently associated with epilepsy. The origin of this disease, and the cause of epilepsy, are unknown. This study is the first reported case of the Parry-Romberg syndrome, with intractable temporal lobe epilepsy, in which detailed microanatomic analyses have been performed on resected brain tissue obtained after surgical intervention. METHODS: Standard histopathologic methods and correlative light and electron microscopy, combined with immunocytochemical techniques, were used to study in detail the synaptic microorganization of the resected hippocampal formation. RESULTS: After surgery, the patient was seizure free (follow-up period of 4 years and 7 months). The resected temporal lobe showed a variety of dramatic microanatomic alterations (small groups of ectopic cells, neuronal loss, gliosis, and activated microglial cells) in mesial structures, including the entorhinal cortex, subiculum, and dentate gyrus. At the electron-microscopic level, we found that in the dentate gyrus, the number of synapses in the cell-sparse region adjacent to the ectopic mass of neurons was almost twice that found in the molecular and polymorph cell layers, indicating the intrusion of neuritic processes and synapse formation. In addition, the symmetrical axosomatic synapses characteristically found on granule cells, which are likely derived from gamma-aminobutyric acid (GABA)ergic inhibitory basket cells, were not observed. CONCLUSION: The complete seizure relief after surgery suggests that the pacemaker region(s) of seizure activity were within the resected tissue. However, we do not know which of the multiple neuropathologic findings reported here were the primary cause of seizure activity. Nevertheless, the changes found in the dentate gyrus circuitry appear to be among the most important alterations that would lead to epilepsy.

Adult↗
PubMed1997

Molecular keys to speciation: DNA polymorphism and the control of genetic exchange in enterobacteria.

Speciation involves the establishment of genetic barriers between closely related organisms. The extent of genetic recombination is a key determinant and a measure of genetic isolation. The results reported here reveal that genetic barriers can be established, eliminated, or modified by manipulating two systems which control genetic recombination, SOS and mismatch repair. The extent of genetic isolation between enterobacteria is a simple mathematical function of DNA sequence divergence. The function does not depend on hybrid DNA stability, but rather on the number of blocks of sequences identical in the two mating partners and sufficiently large to allow the initiation of recombination. Further, there is no obvious discontinuity in the function that could be used to define a level of divergence for distinguishing species.

Biological Evolution↗
PubMed2006

Computational studies of ligand-receptor interactions in bitter taste receptors.

Phenylthiocarbamide tastes intensely bitter to some individuals, but others find it completely tasteless. Recently, it was suggested that phenylthiocarbamide elicits bitter taste by interacting with a human G protein-coupled receptor (hTAS2R38) encoded by the PTC gene. The phenylthiocarbamide nontaster trait was linked to three single nucleotide polymorphisms occurring in the PTC gene. Using the crystal structure of bovine rhodopsin as template, we generated the 3D structure of hTAS2R38 bitter taste receptor. We were able to map on the receptor structure the amino acids affected by the genetic polymorphisms and to propose molecular functions for two of them that explained the emergence of the nontaster trait. We used molecular docking simulations to find that phenylthiocarbamide exhibited a higher affinity for the target receptor than the structurally similar molecule 6-n-propylthiouracil, in line with recent experimental studies. A 3D model was constructed for the hTAS2R16 bitter taste receptor as well, by applying the same protocol. We found that the recently published experimental ligand binding affinity data for this receptor correlated well with the binding scores obtained from our molecular docking calculations.

Animals↗
PubMedDate not supplied

Low-affinity nerve growth factor receptor (p75NGFR)- and choline acetyltransferase (ChAT)-immunoreactive axons in the cerebral cortex and hippocampus of adult macaque monkeys and humans.

Low-affinity nerve growth factor receptor (p75NGFR) was analyzed in the adult monkey and human cerebral cortex and hippocampus by light and electron microscopic immunohistochemistry using a mouse monoclonal antibody raised against human p75NGFR. In the monkey only, the morphology and laminar and areal distribution of the p75NGFR-immunoreactive fibers were further compared with distribution of the ACh-synthesizing enzyme ChAT. We found that the p75NGFR fiber distribution is remarkably dense throughout the cerebral neocortex and highly similar in homologous cortical areas of monkey and human. In both species, p75NGFR-immunoreactive fibers are contracted in layers I, II, and the superficial portions of layer III in all frontal, parietal, temporal, and occipital areas examined. In the primary visual and somatosensory cortices, dense p75NGFR fiber plexuses are additionally found in layer IV. In the hippocampal formation, this fiber system is most dense in the CA2 and CA3 subfields as well as in the molecular and polymorphic layers of the dentate gyrus. The distribution and characteristics of the p75NGFR-positive fibers in the primates correspond almost exactly to those of the cholinergic fiber system as revealed by ChAT immunohistochemistry in the present study as well as in the literature (Lewis, 1991; Mesulam et al., 1992; Voytko et al., 1992). Electron microscopy revealed that p75NGFR is associated mainly with axonal membranes and portions of the axoplasm in labeled fibers. Although the function of p75NGFR is still a matter of debate, its widespread distribution opens up new questions regarding its physiological role in the large and functionally differentiated cerebral cortex and hippocampus of monkey and human.

Adult↗
PubMed2006

MODBASE: a database of annotated comparative protein structure models and associated resources.

MODBASE (http://salilab.org/modbase) is a database of annotated comparative protein structure models for all available protein sequences that can be matched to at least one known protein structure. The models are calculated by MODPIPE, an automated modeling pipeline that relies on MODELLER for fold assignment, sequence-structure alignment, model building and model assessment (http:/salilab.org/modeller). MODBASE is updated regularly to reflect the growth in protein sequence and structure databases, and improvements in the software for calculating the models. MODBASE currently contains 3 094 524 reliable models for domains in 1 094 750 out of 1 817 889 unique protein sequences in the UniProt database (July 5, 2005); only models based on statistically significant alignments and models assessed to have the correct fold despite insignificant alignments are included. MODBASE also allows users to generate comparative models for proteins of interest with the automated modeling server MODWEB (http://salilab.org/modweb). Our other resources integrated with MODBASE include comprehensive databases of multiple protein structure alignments (DBAli, http://salilab.org/dbali), structurally defined ligand binding sites and structurally defined binary domain interfaces (PIBASE, http://salilab.org/pibase) as well as predictions of ligand binding sites, interactions between yeast proteins, and functional consequences of human nsSNPs (LS-SNP, http://salilab.org/LS-SNP).

Binding Sites↗