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Biomedical subjects

W K Sung

Publications and source records attributed to W K Sung.

18 recordsLinked to original sources
PubMed2005

The mutated subsequence problem and locating conserved genes.

MOTIVATION: For the purpose of locating conserved genes in a whole genome scale, this paper proposes a new structural optimization problem called the Mutated Subsequence Problem, which gives consideration to possible mutations between two species (in the form of reversals and transpositions) when comparing the genomes. RESULTS: A practical algorithm called mutated subsequence algorithm (MSS) is devised to solve this optimization problem, and it has been evaluated using different pairs of human and mouse chromosomes, and different pairs of virus genomes of Baculoviridae. MSS is found to be effective and efficient; in particular, MSS can reveal >90% of the conserved genes of human and mouse that have been reported in the literature. When compared with existing softwares MUMmer and MaxMinCluster, MSS uncovers 14 and 7% more genes on average, respectively. Furthermore, this paper shows a hybrid approach to integrate MUMmer or MaxMinCluster with MSS, which has better performance and reliability.

Algorithms↗
PubMed2004

Protein structure and fold prediction using tree-augmented naive Bayesian classifier.

For determining the structure class and fold class of Protein Structure, computer-based techniques have became essential considering the large volume of the data. Several techniques based on sequence similarity. Neural Networks, SVMs, etc have been applied. This paper presents a framework using the Tree-Augmented Networks (TAN) based on the theory of learning Bayesian networks but with less restrictive assumptions than the naive Bayesian networks. In order to enhance TAN's performance, pre-processing of data is done by feature discretization and post-processing is done by using Mean Probability Voting (MPV) scheme. The advantage of using Bayesian approach over other learning methods is that the network structure is intuitive. In addition, one can read off the TAN structure probabilities to determine the significance of each feature (say, Hydrophobicity) for each class, which help to further understand the mystery of protein structure. Experimental results and comparison with other works over two databases show the effectiveness of our TAN based framework. The idea is implemented as the BAYESPROT web server and it is available at http://www-appn.comp.nus.edu.sg/-bioinfo/bayesprot/Default.htm.

Artificial Intelligence↗
PubMed1998

Cyclin A1 is required for meiosis in the male mouse.

The mammalian A-type cyclin family consists of two members, cyclin A1 (encoded by Ccna1) and cyclin A2 (encoded by Ccna2). Cyclin A2 promotes both G1/S and G2/M transitions, and targeted deletion of Ccna2 in mouse is embryonic lethal3. Cyclin A1 is expressed in mice exclusively in the germ cell lineage and is expressed in humans at highest levels in the testis and certain myeloid leukaemia cells. To investigate the role of cyclin A1 and possible redundancy among the cyclins in vivo, we generated mice bearing a null mutation of Ccna1. Ccna1-/- males were sterile due to a block of spermatogenesis before the first meiotic division, whereas females were normal. Meiosis arrest in Ccna1-/- males was associated with increased germ cell apoptosis, desynapsis abnormalities and reduction of Cdc2 kinase activation at the end of meiotic prophase. Cyclin A1 is therefore essential for spermatocyte passage into the first meiotic division in male mice, a function that cannot be complemented by the concurrently expressed B-type cyclins.

Animals↗
PubMed1994

Phospholipase C-gamma 1 can induce DNA synthesis by a mechanism independent of its lipase activity.

Inositol phospholipid-specific phospholipase C (PLC) is involved in several signaling pathways leading to cellular growth and differentiation. Our previous studies reported the induction of DNA synthesis in quiescent NIH 3T3 cells after microinjection of PLC and the inhibition of serum- or Ras-stimulated DNA synthesis by a mixture of monoclonal antibodies to PLC-gamma 1. In the course of our investigation of anti-PLC-gamma 1 monoclonal antibodies, we found that each antibody exerts different inhibitory effects on the phosphatidylinositol-hydrolyzing activity of PLC-gamma 1 and that the inhibition of enzymatic activity does not correlate with the inhibition of DNA synthesis observed in the microinjection assay. PLC-gamma 1 with defective enzymatic activity was synthesized by substituting phenylalanine for histidine within the PLC-gamma 1 catalytic domain at amino acids 335 and 380, and mutant enzymes were expressed using a vaccinia expression system. The mutant enzymes were purified and microinjected into quiescent NIH 3T3 cells to evaluate their mitogenic activity. A moderate induction of DNA synthesis occurred after injection of mutant PLC-gamma 1. This mitogenic activity was inhibited by an antibody (alpha E 8-4) that does not significantly inhibit PLC-gamma 1 enzyme activity, which indicates that something else has to be inhibited. Furthermore, the partial induction of DNA synthesis observed with mutant PLC-gamma 1 was increased to levels seen with wild-type PLC-gamma 1 by coinjection of mutant PLC-gamma 1 with two second messengers, diacylglycerol and inositol trisphosphate. These results suggest that the mitogenic activity of PLC-gamma 1 does not exclusively result from the enzymatic activity of the lipase and that another activity inherent to the PLC-gamma 1 molecule can also induce DNA synthesis in quiescent cells.

3T3 Cells↗
PubMed1990

Localization of cellular retinol-binding protein mRNA in rat testis and epididymis and its stage-dependent expression during the cycle of the seminiferous epithelium.

Anatomical localization of cellular retinol-binding protein (CRBP) mRNA was examined in normal rat testis and epididymis and also in retinoid-deficient rat testis. In situ hybridization was performed with 35S-labeled rat CRBP cRNA probes on frozen tissue sections. In normal testis, CRBP mRNA was mainly localized in the Sertoli cells and to some extent in peritubular cells. A distinct cyclic variation of the relative levels of hybridizable CRBP mRNA was observed during the spermatogenic cycle. The peak of CRBP mRNA content was seen in the stages of the cycle that preceded those in which peak CRBP protein content had been observed previously in our laboratory by immunohistochemistry. No appreciable amount of CRBP mRNA was observed in the interstitial space or in the lumen of the tubules. CRBP mRNA displayed the same anatomical localization in the retinoid-deficient testis, but the level of hybridizable CRBP mRNA was substantially reduced. A strong hybridization signal for CRBP mRNA was seen in proximal epididymis and was strikingly localized in the ductular epithelium. CRBP mRNA was not detectable in the distal portion of the epididymis. These studies provide information about the cell-specific expression of CRBP synthesis within the testis and epididymis and about its cyclic variation and regulation.

Animals↗
PubMed1989

Colcemid effects on homologue pairing and crossing over during fetal mouse oogenesis.

Colcemid was administered to gestational day 13 female mice to test effects on homologue pairing, synapsis and recombination of fetal oogenesis. Pairing abnormalities were detected in pachytene oocytes by light and electron microscopy examination of bivalents and synaptonemal complexes. Reduction of total chiasmata per treated diplotene oocyte (22.74) compared to controls (31.07) was found.

Animals↗
PubMed1988

A quantitative analysis of mitochondria during fetal mouse oogenesis.

A quantitative analysis of mitochondrial populations during the meiotic prophase of mouse oogenesis was carried out. The mean absolute area occupied by mitochondria and the mean number of mitochondria per cell increases in a linear fashion from pachytene through dictyate. The mean area occupied by mitochondria increases at pachytene and thereafter. Both small and large aggregations of mitochondria are seen, particularly during the later stages of prophase. Vacuolated mitochondria are present from preleptotene through pachytene. Mitochondria show major dynamic changes throughout fetal mouse oogenesis, which may suggest significant functional activities yet to be elucidated.

Animals↗
PubMed1987

Chromosome 21 behavior during fetal oogenesis in Down's syndrome.

Oogenesis of four cases of 47,XX,+21 at gestational ages of 19 and 20 weeks was studied using pachytene cytogenetic methods. We found a variable pattern of pairing behavior of the 21 chromosomes among the cases, which included partially synapsed trivalents, a bivalent plus a univalent, and three univalents. The bivalent/univalent conformation of 21 chromosomes predominated. Pachytene chromomere maps were normal for all autosomal bivalents in 84 oocytes analyzed, except for minor variations in some 21 chromosomes. This complex system of pairing behavior of the 21 chromosomes theoretically affects subsequent disjunctional behavior and therefore may account for the observations of normal and trisomic progeny observed for Down's syndrome mothers. Further study of meiotic behavior during all stages of oogenesis in such patients would provide essential data for predicting chromosomal outcome of pregnancy in this population.

Adult↗
PubMed1986

DNA synthesis studies in pre-meiotic mouse oogenesis.

DNA fiber autoradiography was used in mouse oogenesis to test Callan's hypothesis that a longer S phase results from a reduction in the number of active initiation sites. The data indicated that the premeiotic increase in the duration of S phase in mouse oogenesis was characterized by a rapid initial rate of chain growth and a larger replicon size when compared with replicating DNA of somatic mouse cells. These findings were at variance with those in mouse spermatogenesis and also did not support the Callan hypothesis of activation site repression.

Animals↗
PubMed1986

The hibernating male golden hamster as a model for studying homologue pairing, chiasma formation and disjunction during spermatogenesis.

Although many studies have been made in an attempt to understand the mechanisms of chromosome pairing and genetic recombination, data on mammalian oogenesis and spermatogenesis are sparse. In the experiments reported here, spermatogenesis of the hibernating male golden hamster was used to test the effect of hibernation in the cold on some essential aspects of meiosis in this species. It was demonstrated that this physiologic state can result in increased duration of preleptotene synthesis of deoxyribonucleic acid (DNA), abnormalities in bivalent pairing, reduced crossing-over, and increased chromosomal nondisjunction. These data provide evidence of the usefulness of this model for further studies of these genetic phenomena in a male mammal.

Animals↗
PubMed1985

Immunohistochemical studies on the localization of cellular retinol-binding protein in rat testis and epididymis.

The immunohistochemical localization of cellular retinol-binding protein (CRBP) was studied in rat testis and epididymis. Parallel studies were also carried out on the localization of plasma retinol-binding protein (RBP) and transthyretin (TTR) in testis. The studies employed antibodies purified by immunosorbent affinity chromatography, permitting the specific staining and localization of each antigen by the unlabeled peroxidase-antiperoxidase method. For RBP and TTR, specific immune staining was found in the interstitial spaces between the seminiferous tubules, and not in the tubules themselves. In contrast, strong specific immune staining for CRBP was found in the seminiferous tubules, with a striking localization within Sertoli cells. Moreover, a distinct cyclic variation of specific staining for CRBP within Sertoli cells was observed during the spermatogenic cycle. This cyclic variation was seen with regard to both the intensity of staining and to the anatomic distribution of CRBP within the Sertoli cells. Within the epididymis CRBP was selectively localized to the proximal portion of the caput epididymidis, with variations in intensity of the staining of the epithelium of the ducts in different histological zones. Specific immune staining for CRBP was very weak or absent in the other portions of the epididymis. These results were confirmed by radioimmunoassay. Vitamin A-deficient rats showed markedly reduced specific immune staining for CRBP in both testes and epididymides, and greatly reduced levels of CRBP in these tissues on radioimmunoassay. These studies on the localization of CRBP provide information concerning the specific cells and anatomic loci within the testis and epididymis where retinol may be playing an important role in sperm formation and maturation.

Animals↗
PubMed1983

Fiber DNA studies of premeiotic mouse spermatogenesis.

The technique of fiber DNA measurement was used to study the possibility that the lengthening of the DNA "S" phase previously reported for mouse premeiotic spermatogonia was due to a reduced number of initiation sites. The mean replicon size of neonatal mouse preleptotene cells was similar to sizes reported for adult mouse somatic cells. A slow rate of DNA chain growth was observed in all cells from day 1 through days 10-12 of age. It was felt that the meiotic entry in male mouse germ cells may involve a slower replication fork rate and other factors which increased the time between activation and replication of replicon families.

Animals↗
PubMed1977

[Discriminant analysis applied to blood components in dairy cows before and after delivery].

Ten blood properties--total protein, cholesterol, zinc turbidity test, leucine amino peptidase, alkaline phosphatase, lactate dehydrogenase, hemoglobin, hematocrit, and red and white blood cell counts--were measured in primiparous cows at three different stages near parturition, 260 days of pregnancy, 5 days and 35 days after parturition. Experiments were performed in two seasons, winter (January to April) and summer (June to September), using eleven cows in each seasonal group. The degree of inclusive variation of the ten blood properties by discriminant analysis was low in winter and very high in summer between 260 days of pregnancy and 5 days after parturition. It was high in both seasons between 5 days and 35 days after parturition. In addition, in comparison between the corresponding stages in the two seasonal groups, the degree was higher in summer than in winter. The discrepancy in the seasonal patterns seemed to occur by the differences in environmental factors, such as temperature and feeding conditions, in addition to stresses due to pregnancy, parturition and lactation. It was verified that discriminant analysis, one of the multivariate analyses was useful for an inclusive, objective judgment on data of multiple clinical examinations in dairy cows.

Alkaline Phosphatase↗