Biomedical subjects

Yufeng Wang

Publications and source records attributed to Yufeng Wang.

34 records · Page 2Linked to original sources

PubMed2004

Synthesis and structure-activity relationship of 3-arylbenzoxazines as selective estrogen receptor beta agonists.

A series of 3-aryl-7-hydroxybenzoxazine analogues have been prepared and evaluated as ligands for the two estrogen receptor subtypes (ERalpha and ERbeta). From the radioligand binding assay, compounds with more than a 10-fold binding selectivity toward the ERbeta subtype have been identified. These compounds have also been shown to be potent full agonists in the functional assay by activation of ERE promoted transcription, with the best compound being 20-fold more potent than genistein.

Benzoxazines↗

PubMed2004

Proteomics approach reveals novel proteins on the surface of malaria-infected erythrocytes.

Proteins on the surface of parasite-infected erythrocytes (PIESPs) have been one of the major focuses of malaria research due to their role in pathogenesis and their potential as targets for immunity and drug intervention. Despite intense scrutiny, only a few surface proteins have been identified and characterized. We report the identification of two novel surface proteins from Plasmodium falciparum-infected erythrocytes. Surface proteins were fractionated through biotin-streptavidin interaction and analyzed by shotgun proteomics. From a list of 36 candidates, two were selected for further characterization. The surface location of both proteins was confirmed by confocal microscopy using specific antibodies. PIESP1 and PIESP2 are unlikely to be associated with knobs, the protrusions on the parasite-infected erythrocyte (PIE) surface. In contrast to other known PIESPs, such as PfEMP1 and Rifin, these novel proteins are encoded by single copy genes, highly conserved across Plasmodium ssp., making them good targets for interventions with a broad specificity to various P. falciparum isolates.

Amino Acid Sequence↗

PubMed2004

Computer assisted searches for drug targets with emphasis on malarial proteases and their inhibitors.

The creation of databases that make enormous and diverse amounts of information available, the coding of algorithms that allow the collection and investigation of these data and the wide availability of desktop computers capable of handling the data and running the algorithms have set the stage for innovative approaches to drug target identification. Here we review the main currents in this new field, providing an overview of some of the databases and software used to generate and shorten the lists of potential drug targets using in silico methods. As a case study, we look at the identification and investigation of malarial proteases as therapeutic targets in the Plasmodium spp. parasites.

Algorithms↗

PubMed2003

Efficient synthesis of 2-aryl-6-chloronicotinamides via PXPd2-catalyzed regioselective Suzuki coupling.

[reaction: see text] A short and convergent synthesis of 2-aryl-6-chloronicotinamides via regioselective Suzuki coupling of 2,6-dichloronicotinamide with aryl boronic acids is described. Regioselectivity was achieved by chelation of the palladium(0) species to an ester/amide group. The air-stable palladium catalyst PXPd2, when used in reagent-grade methanol with K(2)CO(3) as the base, afforded the best regioselectivity and shortest reaction times among the catalysts screened.

Boronic Acids↗

PubMed2003

[A case-control study on balance function of attention deficit hyperactivity disorder (ADHD) children].

OBJECTIVE: To explore the character of the balance function of ADHD and difference with control. METHODS: Subjects were 80 ADHD children and 80 non-ADHD children classified according to the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders (IV) and matched by age and sex. We used the Balance Master to evaluate their stability in different conditions. The CART was used to find the relationship between the balance function and the clinical symptoms. RESULTS: Under the conditions of firm surface with eyes closed(FS/EC), foam surface with eyes opened (FoS/EO) and eyes closed(FoS/EC), unilateral stance with eyes open(VS/EO) and closed(VS/EC), the sway velocity of ADHD children was higher significantly than that of the control. There was correlationship between the result of sway velocity under the condition of FoS/EC and the vestibular dysfunction, somasensory dysfunction in the sensory integration check scale, the performance IQ, verbal comprehension facter and freedom from distractibility facter in C-WISC and the hyperactivity index in conner scale. CONCLUSION: ADHD children have poor stability, abnormal sensory integration and visual, somatosensory, vestibular function deficits. There is correlation between the balance dysfunction and the clinical symptoms and the deficits in behaviour and cognition.

Adolescent↗

PubMed2003

[Exploratory eye movement in children with ADHD].

OBJECTIVE: To explore the character of the exploratory eye movement in ADHD children. METHODS: The eye mark recorder (model IV) was used to record the eye movements in 33 ADHD children and 33 normal controls matched by age and sex, using t-test to compare the differences of the numbers of eye fixations, total eye scanning lengths, mean eye scanning lengths, cognitive search scores, responsive search scores and D values between the two groups. RESULTS: ADHD children showed significantly fewer frequent numbers of eye fixations and longer mean eye scanning lengths than the normal controls. The responsive search score of ADHD children was significantly lower than that of the control group. ADHD children had a positive D value and the normal controls had a negative D value. CONCLUSION: ADHD children had fewer frequent numbers of eye fixation, longer mean eye scanning length and lower responsive search score than the normal controls, which may be the evidence of executive dysfunctions.

Adolescent↗

PubMed2003

Single-nucleotide polymorphisms and genome diversity in Plasmodium vivax.

The study of genetic variation in malaria parasites has practical significance for developing strategies to control the disease. Vaccines based on highly polymorphic antigens may be confounded by allelic restriction of the host immune response. In response to drug pressure, a highly plastic genome may generate resistant mutants more easily than a monomorphic one. Additionally, the study of the distribution of genomic polymorphisms may provide information leading to the identification of genes associated with traits such as parasite development and drug resistance. Indeed, the age and diversity of the human malaria parasite Plasmodium falciparum has been the subject of recent debate, because an ancient parasite with a complex genome is expected to present greater challenges for drug and vaccine development. The genome diversity of the important human pathogen Plasmodium vivax, however, remains essentially unknown. Here we analyze an approximately 100-kb contiguous chromosome segment from five isolates, revealing 191 single-nucleotide polymorphisms (SNPs) and 44 size polymorphisms. The SNPs are not evenly distributed across the segment with blocks of high and low diversity. Whereas the majority (approximately 63%) of the SNPs are in intergenic regions, introns contain significantly less SNPs than intergenic sequences. Polymorphic tandem repeats are abundant and are more uniformly distributed at a frequency of about one polymorphic tandem repeat per 3 kb. These data show that P. vivax has a highly diverse genome, and provide useful information for further understanding the genome diversity of the parasite.

Animals↗

PubMed2003

Family-based and case-control association studies of catechol-O-methyltransferase in attention deficit hyperactivity disorder suggest genetic sexual dimorphism.

Attention deficit hyperactivity disorder (ADHD) is the most common childhood-onset behavioral disorder. Boys are more often affected than girls. Family, twin, and adoption studies have supported a strong genetic basis. Some studies show that a catechol-O-methyltransferase (COMT) polymorphism affecting enzyme activity was associated with personality characteristics and diseases, such as novelty-seeking personality, substance abuse, and heroin addiction, whose features are similar to ADHD or are associated with ADHD. These findings suggest that the COMT gene may be a candidate gene for ADHD. TDT, HHRR, and case-control association studies were conducted within a sample of 202 nuclear ADHD families, 340 ADHD cases, and 226 controls in the Han Chinese population. Diagnoses and ADHD subtypes were ascertained according to DSM-IV criteria using American Clinical Diagnostic Interviewing Scales. The HHRR analysis suggested that the low enzyme-activity COMT Met allele was preferentially transmitted to ADHD boys (160 trios, chi(2) = 3.858, P = 0.05, df = 1) but not girls. This association is particularly pronounced among male ADHD probands without any comorbidity (50 trios, HHRR: chi(2) = 5.128, P = 0.024, df = 1; TDT: chi(2) = 4.558, P = 0.033, df = 1), especially the ADHD-I subtype (32 trios, HHRR: chi(2) = 5.792, P = 0.016, df = 1; TDT: chi(2) = 5.333, P = 0.021, df = 1). The case-control study revealed that the Val allele was more frequent in females meeting ICD-10 or DSM-IV criteria for ADHD than in female controls (86 and 79.5%, respectively, chi(2) = 4.059, P = 0.044, df = 1). Although these results suggest the COMT gene exerts some influence on the risk for ADHD in the Han Chinese population, given the potential for Type I error, these findings require replication before drawing definitive conclusions.

Adolescent↗

PubMed2003

Functional organization of the primary motor cortex characterized by event-related fMRI during movement preparation and execution.

Neuronal recording and neuroimaging studies have shown that the primary motor area (M1) not only participates in motor execution, but is also engaged during movement preparation. The purpose of the present study was to map the distribution of the preparation- and execution-related activity within the contralateral M1 using functional magnetic resonance imaging. Eleven subjects performed a delayed sequential finger movement task, in which a CUE signal indicated a movement sequence in advance of an imperative GO signal. The hemodynamic response related to the CUE and GO signals decreased in a linear fashion across the central sulcus, with activity greater along the lateral extent compared to the medial extent. This decrease was especially evident in the epoch following the CUE. Our data reveal a pattern of functional organization within M1 related to the preparation and execution of movement sequences.

Adult↗

PubMed2003

Data-mining approaches reveal hidden families of proteases in the genome of malaria parasite.

The search for novel antimalarial drug targets is urgent due to the growing resistance of Plasmodium falciparum parasites to available drugs. Proteases are attractive antimalarial targets because of their indispensable roles in parasite infection and development, especially in the processes of host erythrocyte rupture/invasion and hemoglobin degradation. However, to date, only a small number of proteases have been identified and characterized in Plasmodium species. Using an extensive sequence similarity search, we have identified 92 putative proteases in the P. falciparum genome. A set of putative proteases including calpain, metacaspase, and signal peptidase I have been implicated to be central mediators for essential parasitic activity and distantly related to the vertebrate host. Moreover, of the 92, at least 88 have been demonstrated to code for gene products at the transcriptional levels, based upon the microarray and RT-PCR results, and the publicly available microarray and proteomics data. The present study represents an initial effort to identify a set of expressed, active, and essential proteases as targets for inhibitor-based drug design.

Amino Acid Sequence↗

PubMed2003

[Association studies of dopamine D4 receptor gene and dopamine transporter gene polymorphisms in Han Chinese patients with attention deficit hyperactivity disorder].

OBJECTIVE: To investigate association of the 48 bp variable number of tandem repeat (VNTR) polymorphism in the D4 receptor gene (DRD4) exon 3 and 40 bp VNTR polymorphism in the dopamine transporter gene (DAT1) 3' untranslated region with attention deficit hyperactivity disorder (ADHD) in Han Chinese children. METHODS: The study samples were comprised of 340 ADHD children, 226 unrelated controls and 202 integrated ADHD trios (included proband and biological parents). The polymorphisms consisted of 48 bp VNTR in exon 3 of DRD4, and 40 bp VNTR in the 3' untranslated region of DAT1. Associations of polymorphisms with ADHD and its subtypes were examined by: (i) comparing cases and controls; and (ii) using family-based association study in an extension of exact transmission-disequilibrium test (ETDT) and haplotype-based haplotype relative risk (HHRR). RESULTS: The repeat numbers at the DRD4 48 bp locus ranged from 2-6 repeats in the Han Chinese controls, with the most common being the 4-repeat (77%) and 2-repeat (19.4%) alleles. Neither the 7-repeat allele nor longer repeats were found. For the DAT1, the repeat numbers at the 40 bp locus ranged from 6-7 repeats and 9-11 repeats. The 10-repeat allele was the most frequent (90.7%). The long-repeat alleles of DRD4 (ranging from 4-6 repeats) and DAT1 (ranging from 11-12 repeats), were present more frequently in ADHD probands than in controls. Our primary analyses failed to replicate the associations between ADHD and 7-repeat allele of DRD4 and the 10-repeat allele of DAT1. CONCLUSION: The long-repeat alleles of DRD4 (after a stratification by gender) and DAT1 may increase the risk for ADHD in Han Chinese children.

Alleles↗

PubMed2002

[Association of 5-HT(2A) receptor polymorphism and attention deficit hyperactivity disorder in children].

OBJECTIVE: To stude the association of 5-HT(2A) receptor polymorphism and attention deficit hyperactivity disorder (ADHD) in children. METHODS: Blood samples were taken from 323 6 approximately 17.5-year-old children with ADHD disgnosed based on the DSM-IV criteria, 182 healthy 18 approximately 49-year-old controls, and 195 pairs of parents of affected children, all of Han nationality. DNA was extracted. PCR was performed to examine the 5-hydroxytryptamine (5-HT)(2A) receptor T102C polymorphism. Transmission disequilibrium test (TDT) was used to test the association of alleles of 5-HT(2A) T102C polymorphic sites and AFDHD. RESULTS: The frequency of T102T in patients with ADHD combined subtype was lower than that in the controls (22.35 vs 33.5%, OR = 0.569, P = 0.028, 95% CI 0.344 - 0.943), and the frequency of T102C in patients with ADHD combined subtype was higher than that in the controls (64.0% vs 47.3%, OR = 1.987, P = 0.003, 95% CI 1.264 approximately 3.124). TDT showed biased transmission of the alleles of T102C polymorphism among families of girl patients with ADHD combined subtype (P = 0.031). CONCLUSION: For the ADHD combined subtype, the T102T genotype is a protective factor and the T102C genotype is a risk factor. For the girl with ADHD combined subtype, the allele C102 is a disease-predisposing gene.

Adolescent↗

PubMed2002

Age distribution of human gene families shows significant roles of both large- and small-scale duplications in vertebrate evolution.

The classical (two-round) hypothesis of vertebrate genome duplication proposes two successive whole-genome duplication(s) (polyploidizations) predating the origin of fishes, a view now being seriously challenged. As the debate largely concerns the relative merits of the 'big-bang mode' theory (large-scale duplication) and the 'continuous mode' theory (constant creation by small-scale duplications), we tested whether a significant proportion of paralogous genes in the contemporary human genome was indeed generated in the early stage of vertebrate evolution. After an extensive search of major databases, we dated 1,739 gene duplication events from the phylogenetic analysis of 749 vertebrate gene families. We found a pattern characterized by two waves (I, II) and an ancient component. Wave I represents a recent gene family expansion by tandem or segmental duplications, whereas wave II, a rapid paralogous gene increase in the early stage of vertebrate evolution, supports the idea of genome duplication(s) (the big-bang mode). Further analysis indicated that large- and small-scale gene duplications both make a significant contribution during the early stage of vertebrate evolution to build the current hierarchy of the human proteome.

Animals↗

PubMed2002

[Cognitive functions of children with attention deficit/hyperactivity disorder].

OBJECTIVE: To investigate the features of cognitive function in children with attention deficit/hyperactivity disorder (ADHD). METHODS: Wechsler Intelligence Scale for Children-RC, Wechsler Memory Scale (WMS), Number Cancellation Test, Ravin's Standard Progressive Matrices, and Stroop test were conducted among 60 7 approximately 12-year-old children diagnosed with ADHD and 60 children matched by age, sex, and maternal education level. RESULTS: The verbal intelligence quotient, performance IQ, full scale IQ, verbal comprehension IQ, perceptual organization IQ, and freedom from distractibility IQ of the ADHD CHILDREN were 104 +/- 13, 98 +/- 14, 102 +/- 13, 100 +/- 15, and 102 +/- 15, all less than those of the controls (112 +/- 11, 108 +/- 13, 112 +/- 12, 111 +/- 12, 107 +/- 13, and 116 +/- 13, all P < 0.01). The scores of long-term memory, short-term memory, immediate memory, memory quotient, and reverse digit span in the children with ADHD were 40 +/- 7, 58 +/- 12, 7 +/- 3, 95 +/- 15, and 4.2 +/- 1.7 respectively, all less than those in the controls (49 +/- 5, 63 +/- 10, 8.4 +/- 3.0, 109 +/- 12.5, and 5.0 +/- 1.4 respectively, all P < 0.05). Number cancellation test showed significantly lower total score and higher error rate in ADHD children than in the controls (51.5 and 76.4 VS 77.3 and 38.0, both P = 0.000). In Stroop test, the ADHD children spent more time for all the four parts, had to make more effort to eliminate the interference of word meaning, and made more errors in the C and D parts. The average standard score of Raven's Standard Progressive Matrices was 4.0 +/- 1.5, significantly higher than that in the controls (2.7 +/- 1.2, P = 0.000). CONCLUSION: The levels of intelligence, memory, and attention in ADHD children are lower that those in normal children. ADHD children have deficiency in executive functions, such as selective inhibition, working memory and plan implementation.

Attention Deficit Disorder with Hyperactivity↗

PubMed2002

Evolutionary analysis for functional divergence of Jak protein kinase domains and tissue-specific genes.

Jak (Janus kinase) is a nonreceptor tyrosine kinase, which plays important roles in signal transduction pathways. The unique feature of Jak is that, in addition to a fully functional tyrosine kinase domain (JH1), Jak possesses a pseudokinase domain (JH2). Although JH2 lost its catalytic function, experimental evidence has shown that this domain may have acquired some new but unknown functions. This apparent functional divergence after the (internal) domain duplication may result in dramatic changes of selective constraints at some sites. We conducted a data analysis to test this hypothesis. Our result shows that shifted selective constraints (or shifted evolutionary rates) between the JH1 and the JH2 domains are statistically significant. Predicted amino acid sites by posterior analysis can be classified into two groups: very conserved in JH1 but highly variable in JH2, and vice versa. Moreover, we have studied the evolutionary pattern of four tissue-specific genes, Jak1, Jak2, Jak3, and Tyk2, which were generated in the early stages of vertebrates. We found that after the (first) gene duplication, site-specific rate shifts between Jak2/Jak3 and Jak1/Tyk are significant, presumably as a consequence of functional divergence among these genes. The implication of our study for functional genomics is discussed.

Amino Acids↗

PubMedDate not supplied

The effective number of a population that varies cyclically in size. II. Overlapping generations.

We consider haploid and dioecious age-structured populations that vary over time in cycles of length k. Results are obtained for both autosomal and sex-linked loci if the population is dioecious. It is assumed that k is small in comparison with numbers of haploid individuals (or of numbers of males and females) in any generation of a cycle. The inbreeding effective population size N(e) is then approximately given by the expression [T summation operator (k-1)(j=0)1/[N(e)(j)T(j)]](-1), where N(e)(j) and T(j) are, respectively, the effective population size and generation interval that would hold if the population was at all times generated in the same way as at time j. The constant T, which is the effective overall generation interval, is defined to be k times the harmonic mean of the quantities T(j). Our expressions for T and N(e), in terms of N(e)(j) and T(j), are general, but the N(e)(j)s are derived under the assumption that offspring are produced according to Poisson distributions.

Alleles↗