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G X Yu

Publications and source records attributed to G X Yu.

11 recordsLinked to original sources
PubMed2005

Knowledge-based voting algorithm for automated protein functional annotation.

Automated annotation of high-throughput genome sequences is one of the earliest steps toward a comprehensive understanding of the dynamic behavior of living organisms. However, the step is often error-prone because of its underlying algorithms, which rely mainly on a simple similarity analysis, and lack of guidance from biological rules. We present herein a knowledge-based protein annotation algorithm. Our objectives are to reduce errors and to improve annotation confidences. This algorithm consists of two major components: a knowledge system, called "RuleMiner," and a voting procedure. The knowledge system, which includes biological rules and functional profiles for each function, provides a platform for seamless integration of multiple sequence analysis tools and guidance for function annotation. The voting procedure, which relies on the knowledge system, is designed to make (possibly) unbiased judgments in functional assignments among complicated, sometimes conflicting, information. We have applied this algorithm to 10 prokaryotic bacterial genomes and observed a significant improvement in annotation confidences. We also discuss the current limitations of the algorithm and the potential for future improvement.

Algorithms↗
PubMed2004

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in a Chinese family: clinical, radiological and skin biopsy features.

We describe the clinical, radiological, genetic and skin biopsy findings of the first Chinese family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Of the 43-member family tree extending over three generations, eight had typical clinical features of CADASIL with recurrent ischemic stroke. In the three surviving affected family members, brain MRI showed extensive leukoaraiosis. Genotyping revealed heterozygous C to T mutation at nucleotide 406 in exon 3. Unusual clinical features were cerebellar infarction as a presenting complaint and a late age of onset with mild symptoms at age 69. A novel finding is the suggestion of a direct correlation between clinical disease severity and the quantity of ultrastructural pathognomonic granular osmophilic material (GOM) seen on skin biopsy.

Aged↗
PubMed2002

Sentra, a database of signal transduction proteins.

Sentra (http://www-wit.mcs.anl.gov/sentra) is a database of signal transduction proteins with the emphasis on microbial signal transduction. The database was updated to include classes of signal transduction systems modulated by either phosphorylation or methylation reactions such as PAS proteins and serine/threonine kinases, as well as the classical two-component histidine kinases and methyl-accepting chemotaxis proteins. Currently, Sentra contains signal transduction proteins from 43 completely sequenced prokaryotic genomes as well as sequences from SWISS-PROT and TrEMBL. Signal transduction proteins are annotated with information describing conserved domains, paralogous and orthologous sequences, and conserved chromosomal gene clusters. The newly developed user interface supports flexible search capabilities and extensive visualization of the data.

Chemotaxis↗
PubMed2001

Thermal and photochemical epimerization/equilibration of carbohydrate cobaloximes.

Epimeric carbohydrate alkyl cobaloximes 4:5, 9:10, and 12:13 can be equilibrated thermally or photochemically. In each case, one isomer is strongly favored: exo-3-deoxy-3-pyridyldimethylglyoximatocobalt-1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose 4 for the 4:5 epimer pair, exo-3-deoxy-3-pyridyldimethylglyoximatocobalt-5-O-carboxymethyl-1,2-O-isopropylidene-alpha-D-xylofuranose 9 for the 9:10 epimer pair, and equatorial 1-deoxy-1-pyridyldimethylglyoximatocobalt-2,3,4,6-tetra-O-benzyl-beta-D-glucopyranose 12 for the 12:13 epimer pair. These data indicate that there is a strong facial preference for the coupling of py(dmgH)(2)Co(*) radicals with alkyl R(*) free radicals, with the preferred kinetic path leading to the more stable product.

Cobamides↗
PubMed2001

Rds and Rih mediate hypersensitive cell death independent of gene-for-gene resistance to the oat crown rust pathogen Puccinia coronata f. sp. avenae.

The Pca crown rust resistance cluster in the diploid Avena genus confers gene-for-gene specificity to numerous isolates of Puccinia coronata f. sp. avenae. Recombination breakpoint analysis indicates that specificities conferred by the Pca cluster are controlled by at least five distinct genes, designated Pc81, Pc82, Pc83, Pc84, and Pc85. Avena plants with the appropriate genotype frequently respond to P. coronata by undergoing hypersensitive cell death at the sites of fungal infection. Autofluorescence of host cells in response to P. coronata occurs in plants that develop visible necrotic lesions but not in plants that lack this phenotype. Two newly described, non-Pc loci were shown to control hypersensitive cell death. Rds (resistance-dependent suppressor of cell death) suppresses the hypersensitive response (HR), but not the resistance, mediated by the Pc82 resistance gene. In contrast, Rih (resistance-independent hypersensitive cell death) confers HR in both resistant and susceptible plants. Linkage analysis indicates that Rds is unlinked to the Pca cluster, whereas Rih is tightly linked to it. These results indicate that multiple synchronous pathways affect the development of hypersensitive cell death and that HR is not essential for resistance to crown rust. Further characterization of these genes will clarify the relationship between plant disease resistance and localized hypersensitive cell death.

Avena↗
PubMed2001

[Patient-controlled analgesia with lornoxicam in patients undergoing gynecological surgery].

OBJECTIVE: To assess the analgesic effect and side effects of PCA with lornoxicam compared with morphine and tramadol. METHODS: 89 patients, scheduled for elective hysterectomy or hysteromyomectomy, were randomly divided into Group L, Group M and Group T. Three drugs administered i.v. via a patient-controlled analgesia for up to 24 h postoperatively. RESULTS: Efficacy was assessed by comparing total pain relief (TOTPAR) and sum of pain intensity difference (SPID) over 24 h. Statistically significant equivalence of lornoxicam, morphine and tramadol was shown by TOTPAR values 15.2 +/- 3.9, 16.4 +/- 3.5 and 15.9 +/- 4.4, by SPID values 10.3 +/- 3.1, 9.0 +/- 2.0 and 9.2 +/- 4.7, respectively (P > 0.05). Lornoxicam caused fewer adverse events than morphine and tramadol (10.0%, 26.7% and 17.2% of patients, respectively). CONCLUSION: The study suggests that lornoxicam provides an alternative to morphine or tramadaol for the treatment of postoperative pain.

Adult↗
PubMed2000

An anchored AFLP- and retrotransposon-based map of diploid Avena.

A saturated genetic map of diploid oat was constructed based on a recombinant inbred (RI) population developed from a cross between Avena strigosa (Cereal Introduction, C.I. 3815) and A. wiestii (C.I. 1994). This 513-locus map includes 372 AFLP (amplified fragment length polymorphism) and 78 S-SAP (sequence-specific-amplification polymorphism) markers, 6 crown-rust resistance loci, 8 resistance-gene analogs (RGAs), one morphological marker, one RAPD (random amplified polymorphic DNA) marker, and is anchored by 45 grass-genome RFLP (restriction fragment length polymorphism) markers. This new A. strigosa x A. wiestii RI map is colinear with a diploid Avena map from an A. atlantica x A. hirtula F2 population. However, some linkage blocks were rearranged as compared to the RFLP map derived from the progenitor A. strigosa x A. wiestii F2 population. Mapping of Bare-1-like sequences via sequence-specific AFLP indicated that related retrotransposons had considerable heterogeneity and widespread distribution in the diploid Avena genome. Novel amplified fragments detected in the RI population suggested that some of these retrotransposon-like sequences are active in diploid Avena. Three markers closely linked to the Pca crown-rust resistance cluster were identified via AFLP-based bulk-segregant analysis. The derived STS (sequence-tagged-site) marker, Agx4, cosegregates with Pc85, the gene that provides resistance specificity to crown-rust isolate 202 at the end of the cluster. This framework map will be useful in gene cloning, genetic mapping of qualitative genes, and positioning QTL (quantitative trait loci) of agricultural importance.

Avena↗
PubMed1992

A model for the role of multiple cysteine residues involved in ribonucleotide reduction: amazing and still confusing.

Ribonucleotide reductase from Escherichia coli catalyzes the conversion of nucleotides to deoxynucleotides. Multiple cysteins have been postulated to play a key role in this process. To test the role of various cysteines in nucleotide reduction, a variety of single and double mutants of the R1 subunit were prepared: C754S, C759S, C754-759S, C462S, C462A, C230S, and C292S. Due to the expression system, each mutant contains small amounts of contaminating wt-R1 (estimated to be 1.5-3% based on activity). An epitope tagging method in conjunction with anion exchange chromatography was used to partially resolve the mutant R1 from the wt-R1. The interaction of these mutants with the normal substrate was studied, which allowed a model to be proposed in which five cysteines of the R1 subunit of RDPR play a role in catalysis. C754S and C759S R1s catalyze CDP formation at rates similar to wt-R1 when DTT is used as a reductant. However, when thioredoxin (TR)/thioredoxin reductase (TRR)/NADPH is used as reductant, the rates of dNDP production are similar to those expected for contaminating wt-R1 present as a heterodimer with the mutant. The impaired nature of these mutants with respect to reduction by TR suggests that their function is to transfer reducing equivalents from TR to the active site disulfide of R1 produced during NDP reduction. Single-turnover experiments, designed to avoid the problem of contaminating wt-R1, also support this role for C754 and C759. The double serine mutant of 754 and 759 has catalytic activity with DTT that is one-third the rate of wt-R1 with thioredoxin. C225 and C462 are thought to be the active site cysteines oxidized concomitantly with NDP reduction. Conversion of these cysteines to serines results in R1 mutants which convert the normal substrate into a mechanism-based inhibitor. C462SR1 upon incubation with R2 and [3'-3H,U-14C]UDP results in uracil release, 3H2O production, 3H,14C-labeled protein which has an absorbance change at 320 nm, and slow loss of the tyrosyl radical on R2. The isotope effect (kH/k3H) on 3' carbon-hydrogen bond cleavage is 1.7. This sequence of events is independent of the reductant, consistent with the postulate that C462 is an active site thiol. The C462AR1 has properties similar to C462SR1. Several additional mutant R1s, C230SR1, and C292SR1 were shown to have activities similar to wt-R1 with both TR/TRR/NADPH and DTT.

Base Sequence↗
PubMed1992

Interaction of C225SR1 mutant subunit of ribonucleotide reductase with R2 and nucleoside diphosphates: tales of a suicidal enzyme.

Ribonucleotide reductase (RDPR) from Escherichia coli is composed of two subunits, R1 and R2, both of which are required to catalyze the conversion of nucleotides to deoxynucleotides. This reduction process is accompanied by oxidation of two cysteines within the active site to a disulfide. One of these putative active site cysteines, C225, has been mutated to a serine, and the properties of this mutant (C225SR1) have been investigated in detail. Incubation of C225SR1 and R2 with [3'-3H,U-14C]UDP results in time-dependent inactivation of the enzyme! This inactivation is accompanied by production of 2.4 uracils, 3H2O, and 3H,14C-labeled protein with an absorbance change at 320 nm. There is an isotope effect (kH/k3H) on uracil production of 3.2. In addition, the tyrosyl radical on R2 is reduced. The observation of 3H2O, indicative of 3' carbon-hydrogen bond cleavage and loss of the tyrosyl radical, provides a direct test of our mechanistic hypothesis that cleavage of this bond occurs concomitantly with tyrosyl radical reduction. Incubation of [3'-2H]UDP with C225SR1 and R2 resulted in a V and V/K isotope effect on loss of the radical of 2.0 and 2.0, respectively. These studies provide the first direct evidence for protein radical involvement in catalysis. Reduction of the tyrosyl radical on R2 is accompanied by a stoichiometric cleavage of the R1 polypeptide into two new polypeptides of 26 and 61 kDa. The 26-kDa polypeptide is the N-terminus of R1, and hence cleavage of the polypeptide is occurring in the region of the mutation. The N-terminus of the 61-kDa polypeptide is blocked.(ABSTRACT TRUNCATED AT 250 WORDS)

Catalysis↗
PubMed1992

Characterization of C439SR1, a mutant of Escherichia coli ribonucleotide diphosphate reductase: evidence that C439 is a residue essential for nucleotide reduction and C439SR1 is a protein possessing novel thioredoxin-like activity.

Ribonucleotide reductase from Escherichia coli catalyzes the conversion of nucleotides to deoxynucleotides. Cysteine 439 is proposed to be the protein radical on R1 which initiates the reduction reaction by cleavage of the 3' carbon-hydrogen bond of the nucleotide (Mao et al., 1992a,b). C439 is thus proposed to be essential for catalysis. The C439S mutant of R1 (C439SR1) was prepared. The structure of this mutant was determined to be similar to wt-R1, based on identical CD spectra, isolation via an affinity column specific for the allosteric binding domain, binding of the substrate GDP, and competition with R1 for binding to R2. Preparations of C439SR1 are contaminated with low levels of wt-R1 due to the expression system. The wt-R1 in these preparations can be specifically inactivated by the stoichiometric mechanism-based inhibitor, 2'-azido-2'-deoxyuridine 5'-diphosphate. The activity of the resulting C439SR1 was shown to be less than 0.03% that of the corresponding wt-R1. This is the lower limit of detection with the present assay method. Thus C439 appears to be essential for catalysis. During these studies an unexpected activity of the C439SR1 was uncovered. Its additional cysteines, presumably C754 and C759, appear to function as a thioredoxin with the wt-R1, even though it is incapacitated with respect to nucleotide reduction.

Base Sequence↗