Biomedical subjects

Wook Kim

Publications and source records attributed to Wook Kim.

At least 19 recordsLinked to original sources

PubMed2006

Formation of a new solo-LTR of the human endogenous retrovirus H family in human chromosome 21.

Human endogenous retroviruses (HERVs) contribute to various kinds of genomic instability via rearrangement and retrotransposition events. In the present study the formation of a new human-specific solo-LTR belonging to the HERV-H family (AP001667; chromosome 21q21) was detected by a comparative analysis of human chromosome 21 and chimpanzee chromosome 22. The solo-LTR was formed as a result of an equal homologous recombination excision event. Several evolutionary processes have occurred at this locus during primate evolution, indicating that mammalian-wide interspersed repeat (MIR) and full-length HERV-H elements integrated into hominoid genomes after the divergence of Old World monkeys and hominoids, and that the solo-LTR element was created by recombination excision of the HERV-H only in the human genome.

Animals↗

PubMed2006

Haplotypes for 12 Y-chromosomal STR loci in a Korean population (the central region).

Haplotypes and allele frequencies of 12 STR loci included in the PowerPlex Y system (DYS391, DYS389I, DYS439, DYS389II, DYS438, DYS437, DYS19, DYS392, DYS393, DYS390, and DYS385a/b) were obtained from a sample of 569 unrelated individuals living in the central region of Korea. A total of 473 haplotypes were observed in the 569 individuals studied, of which 426 (90.06%) were unique. The overall haplotype diversity for the 12 Y-STR loci was 0.9985, and the discrimination capacity was 0.8313. In DYS439, we found a new intermediate-sized allele that added an A at base 3 upstream from the repeat region's first GATA motif. The allele was named 11 (U3Ains) according to its sequence structure.

Chromosomes, Human, Y↗

PubMed2006

Coordinated regulation of two independent cell-cell signaling systems and swarmer differentiation in Salmonella enterica serovar Typhimurium.

Almost all members of the genus Salmonella differentiate and migrate on semisolid surfaces in a coordinated population behavior known as swarming. Important virulence determinants are coupled to swarmer differentiation in several other pathogenic organisms, collectively suggesting that conditions that trigger swarming in the laboratory may fortuitously promote the cells to enter a robust physiological state relevant to the host environment. Here, we present evidence that expression of two independent cell-cell signaling systems are also coupled to swarmer differentiation in S. enterica serovar Typhimurium. Expression of both pfs and sdiA genes was up-regulated in the actively migrating swarmers compared to their vegetative counterparts propagated in broth or spread plated on the surface of swim, swarm, and solid media. Accordingly, swarmers produced elevated levels of a universally recognized signaling molecule, autoinducer-2, and exhibited increased sensitivity to N-acyl homoserine lactones (AHLs), signaling molecules that Salmonella does not produce. Expression of the rck operon was concomitantly up-regulated in the swarmers in an SdiA-dependent manner only in the presence of exogenous AHLs. In addition to the previously reported adaptive antibiotic resistance phenotype and global shift in metabolism, this work presents another component of the physiological changes that are specifically associated with swarmer differentiation in serovar Typhimurium and not simply due to growth on a surface.

4-Butyrolactone↗

PubMed2005

Y-chromosome STR haplotype profiling in the Mongolian population.

Eleven Y-chromosome STR loci (DYS19, DYS388, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, two DYS385 loci and DXYS156Y) were analyzed in 92 randomly chosen males from Mongolia. Allelic frequencies and gene diversity for each Y-STR locus and haplotype diversity were determined to evaluate their usefulness in forensic casework. A total of 84 different haplotypes were identified, among which 77 (83.7%) were individual-specific. The most frequent haplotype surveyed here was found in three individuals (3.6%), of which the 'minimal haplotype' (excluding DYS388 and DXYS156Y) was not found in the worldwide Y-STR haplotype reference database (YHRD) available at .

Chromosomes, Human, Y↗

PubMed2005

Forensic genetic analysis of mitochondrial DNA hypervariable region I/II sequences: an expanded Korean population database.

We have analyzed variation of the mitochondrial DNA (mtDNA) hypervariable segments I and II (HVS-I and HVS-II) in 185 randomly chosen individuals from Korea to provide an expanded and reliable Korean database. Combined sequence comparison of HVS-I and HVS-II led to the identification of 167 different haplotypes characterized by 154 variable sites. One hundred and fifty-one of the haplotypes were individual-specific, 14 were found in two individuals and 2 were found in three individuals. A pairwise comparison of the 185 HVS-I/II sequences found an average of 10.11 +/- 4.63 differences between individuals. The random match probability and gene diversity for the combined hypervariable regions were estimated at 0.66% and 0.9988, respectively. Analyzing the expanded database including three previously reported data sets and the present data using haplogroup-based comparisons and comparison with closely related sequences allowed errors to be detected and eliminated, thus considerably improving data quality. Sample division comparisons based on PhiST genetic distance measures revealed no significant population differentiation in the distribution of mtDNA sequence variations between the present data set and a database in The Scientific Working Group on DNA Analysis Methods (SWGDAM), but did indicate differences from other sets of data. Based on the results of mtDNA profiles, almost all of the mtDNA types studied here could be classified into subsets of haplogroups common in east Asia, and show that the Koreans possess lineages from both the southern and the northern haplogroup complexes of east Asian populations. The new data, combined with other mtDNA sequences, demonstrate how useful comparison with closely related mtDNA sequences can be for improving database quality, as well as providing haplotype information for forensic and population genetic analyses in the Korean population.

Asian People↗

PubMed2005

Y-chromosomal STR haplotypes and their applications to forensic and population studies in east Asia.

We have analyzed 11 Y-STR loci (DYS19, the two DYS385 loci, DYS388, DYS389I/II, DYS390, DYS391, DYS392, DYS393, DXYS156Y) in 700 males from ten ethnic groups in east Asia in order to evaluate their usefulness for forensic and population genetic studies. A total of 644 different haplotypes were identified, among which 603 (86.14%) were individual-specific. The haplotype diversity averaged over all populations was 0.9997; using only the nine Y-STRs comprising the "minimal haplotype" (excluding DYS388 and DXYS156Y) it was 0.9996, a value similar to that found in 1924 samples from other Asian populations (0.9996; Lessig et al. Legal Medicine 5(2003) 160-163), and slightly higher than in European populations (0.9976; n=11,610; Roewer et al. For Sci International (2001) 118:103-111). All of the individual east Asian populations examined here had high haplotype diversity (> or =0.997), except for the Mongolians (0.992) and Manchurians (0.960). The most frequent haplotype identified by the nine markers was present at only 1% (7/700). Population comparisons based on Phi(ST) or rho genetic distance measures revealed clustering according to the traditional northeast-southeast distinction, but with exceptions. For example, the Yunnan population from southern China lay among the northern populations, possibly reflecting recent migration, while the Korean population, traditionally considered northern, lay at the boundary between northern and southern populations. An admixture estimate suggested 55(51-59)% northern, 45(41-49)% southern contribution to the Koreans, illustrating the complexity of the genetic history of this region.

Asia, Southeastern↗

PubMed2005

Prevalence of surface swarming behavior in Salmonella.

Swarming behavior among 167 Salmonella sp. isolates, representing all eight groups, was assessed. Only eight strains failed to swarm under standard conditions. Four of the defective strains swarmed on alternate carbon sources, and four harbored general defects in motility or lipopolysaccharide. Thus, swarming may represent an evolutionarily conserved behavior in Salmonella spp.

Agar↗

PubMed2005

Analysis of newly identified low copy AluYj subfamily.

Human specific AluY elements were investigated by comparative analysis between human chromosome 21 and chimpanzee chromosome 22. Human specific AluY element was identified on human chromosome 21q22 (accession no. AL163282), and then that was a new member of AluYj subfamily. From the bioinformatic analysis, AluYj subfamily was investigated in human whole genome using AluYj4 consensus sequence (accession no. AL163282). Thirteen members of the AluYj4 elements (4 diagnostic mutations) and eight members of the AluYj3 elements (3 diagnostic mutations) were identified with distinct diagnostic mutation from AluY consensus sequence. The results of the molecular clock calculation of non-CpG region substitution indicated that, AluYj4 elements (2.1 million years old) may be proliferated more recent time than AluYj3 elements (14.1 million years old). For the verification of recent insertion time, four of AluYj4 elements (ch2-AC017101, ch10-AC044786, ch12-AC007656 and ch21-AL163282) from human chromosomes 2, 10, 12, 21 were analyzed by PCR amplification using various human and primate DNA samples. Though, no polymorphism was detected in human population, we identified the new AluYj4 subfamily as the human specific elements.

Alu Elements↗

PubMed2004

Metabolic differentiation in actively swarming Salmonella.

Most current paradigms of microbial metabolism have been derived from studying cells grown under a variety of nutrient compositions in aqueous environments. With recent advances in genomics and experimental techniques, alternative forms of bacterial growth are increasingly being explored. When propagated on nutrient-rich semi-solid media, several species of bacteria undergo a morphological differentiation into swarmers that are capable of migrating on surfaces. Recent studies indicate that swarmer differentiation represents much more than a motility phenotype, as several clinically important attributes are also co-regulated. We demonstrate that migrating swarmer cells of Salmonella are metabolically differentiated compared to the vegetative swimmer cells grown in the same nutrient environment. Furthermore, once the cells have differentiated, the swarmers remain in this physiological state under conditions that do not promote the initial differentiation. The bacterium's capacity to override some of the classic paradigms of metabolic regulation established in aqueous environments represents a unique physiological response by the pathogen that may be advantageous in polymicrobial environments such as the host.

Bacterial Proteins↗

PubMed2004

Ileal malignant melanoma presenting as a mass with aneurysmal dilatation: a case report.

Malignant melanoma is the most common metastatic tumor of the gastrointestinal tract and can present with fairly common constitutional symptoms. A 36-yr-old woman was found to have a secondary malignant melanoma in the terminal ileum with profuse aneurysmal dilatation, which is not the typical presentation of the malignant melanoma in the small intestine. Radiologic studies revealed a large tumor involving the distal ileum with aneurysmal dilatations having afferent and efferent loops, which needed to be differentiated from malignant lymphoma and other gastrointestinal tumors. Exploratory laparotomy was done, and we found a huge mass with plentiful aneurysmal dilatations; much the same of the findings from the previous studies. Segmental resection with the surrounding omentum was done followed by end-to-end anastomosis between both ends of the remaining ileum. She had been free from any evidence of the local or systemic recurrence for one year after the completion of eighteen months of the subcutaneous interferon treatment; postoperatively however, the occurrence of metastatic mass at the right axilla rendered us from complete resection due to severe penetration into the vital nerves and vessels in the axilla.

Adult↗

PubMed2003

The 31-kDa caspase-generated cleavage product of p130cas functions as a transcriptional repressor of E2A in apoptotic cells.

In response to integrin receptor binding to the extracellular matrix, the multidomain docking protein p130(cas) (Crk-associated substrate) activates various signaling cascades modulating such cellular processes as proliferation, migration, and apoptosis. During apoptosis, caspase-mediated cleavage of p130(cas) generated a C-terminal 31-kDa fragment (31-kDa) and promoted morphological changes characteristic of apoptosis, including loss of focal adhesions, cell rounding, and nuclear condensation and fragmentation. By contrast, a p130(cas) D748E mutant, which was unable to produce 31-kDa, attenuated the disassembly of focal adhesions at the bottom of the cell. 31-kDa contains a helix-loop-helix (HLH) domain that shows greater sequence homology with Id proteins than with basic HLH proteins, which enabled heterodimerization with E2A. Once coupled to E2A, 31-kDa was translocated to the cell nucleus, where it inhibited E2A-mediated p21(Waf1/Cip1) transcription. Moreover, overexpression of 31-kDa led to cell death that could be inhibited by treatment with the caspase inhibitor ZVAD-fluoromethyl ketone or by ectopic expression of E2A or p21(Waf1/Cip1). These data suggest that during etoposide-induced apoptosis, 31-kDa promotes caspase-mediated cell death by inhibiting E2A-mediated activation of p21(Waf1/Cip1) transcription.

Adaptor Proteins, Vesicular Transport↗

PubMed2003

Swarming populations of Salmonella represent a unique physiological state coupled to multiple mechanisms of antibiotic resistance.

Salmonella enterica serovar Typhimurium is capable of swarming over semi-solid surfaces. Although its swarming behavior shares many readily observable similarities with other swarming bacteria, the phenomenon remains somewhat of an enigma in this bacterium since some attributes skew away from the better characterized systems. Swarming is quite distinct from the classic swimming motility, as there is a prerequisite for cells to first undergo a morphological transformation into swarmer cells. In some organisms, swarming is controlled by quorum sensing, and in others, swarming has been shown to be coupled to increased expression of important virulence factors. Swarming in serovar Typhimurium is coupled to elevated resistance to a wide variety of structurally and functionally distinct classes of antimicrobial compounds. As serovar Typhimurium differentiates into swarm cells, the pmrHFIJKLM operon is up-regulated, resulting in a more positively charged LPS core. Furthermore, as swarm cells begin to de-differentiate, the pmr operon expression is down-regulated, rapidly reaching the levels observed in swim cells. This is one potential mechanism which confers swarm cells increased resistance to antibiotics such as the cationic antimicrobial peptides. However, additional mechanisms are likely associated with the cells in the swarm state that confer elevated resistance to such a broad spectrum of antimicrobial agents.

Journal Article↗

PubMed2003

Y-chromosomal DNA haplogroups and their implications for the dual origins of the Koreans.

We have analyzed eight Y-chromosomal binary markers (YAP, RPS4Y(711), M9, M175, LINE1, SRY(+465), 47z, and M95) and three Y-STR markers (DYS390, DYS391, and DYS393) in 738 males from 11 ethnic groups in east Asia in order to study the male lineage history of Korea. Haplogroup DE-YAP was found at a high frequency only in Japan but was also present at low frequencies in northeast Asia, including 2.5% in Korea, suggesting a northern origin for these chromosomes. Haplogroup C-RPS4Y(711) was present in Korea and Manchuria at moderate frequencies: higher than in populations from southeast Asia, but lower than those in the northeast, which may imply a northern Asian expansion of these lineages, perhaps from Mongolia or Siberia. The major Y-chromosomal expansions in east Asia were those of haplogroup O-M175 (and its sublineages). This haplogroup is likely to have originated in southern east Asia and subsequently expanded to all of east Asia. The moderate frequency of one sublineage in the Koreans, haplogroup O-LINE1 (12.5%), could be a result of interaction with Chinese populations. The age of another sublineage, haplogroup O-SRY(+465), and Y-STR haplotype diversity provide evidence for relatively recent male migration, originally from China, through Korea into Japan. In conclusion, the distribution pattern of Y-chromosomal haplogroups reveals the complex origin of the Koreans, resulting from genetic contributions involving the northern Asian settlement and range expansions mostly from southern-to-northern China.

Asian People↗

PubMed2003

Caspase-dependent cleavage of tensin induces disruption of actin cytoskeleton during apoptosis.

Members of both calpain and caspase protease families can degrade several components of focal adhesions, leading to disassembly of these complexes. In this report, we investigated the disappearance of tensin from cell adhesion sites of chicken embryonic fibroblast cells (CEFs) exposed to etoposide and demonstrated that loss of tensin from cell adhesions during etoposide-induced apoptosis may be due to degradation of tensin by caspase-3. Tensin cleavage by caspase-3 at the sequence DYPD(1226)G separates the amino-terminal region containing the actin binding domain and the carboxyl-terminal region containing the SH2 domain. The resultant carboxyl-terminal fragment of tensin is unable to bind phosphoinositide 3-kinase (PI3-kinase) transducing cell survival signaling. We also demonstrated that overexpression of the amino-terminal tensin fragment induced disruption of actin cytoskeleton in chicken embryonic fibroblasts. Therefore, caspase-mediated cleavage of tensin contributes to the disruption of actin organization and interrupts ECM-mediated survival signals through phosphatidylinositol 3-kinase.

Actins↗

PubMed2003

Trait-to-gene: a computational method for predicting the function of uncharacterized genes.

The function of unknown genes is often inferred from comparisons to well-characterized homologs. In this paper, we show that, even if all of the homologs of a gene are unannotated, its function may be deduced through phylogenetic profiling. We have designed a series of algorithms that make functional predictions of genes based on orthology and set theory, but our approach to predicting gene function requires no previous knowledge of homolog function. With this technique, we successfully identified 94% of the clusters of orthologous groups that are known to be involved in flagella development or function. As a test, we removed the function of three putative flagellar genes that had been previously uncharacterized in Bacillus subtilis. We observed a motility phenotype for two of these three genes. Thus, these algorithms allow for high-throughput functional prediction of genes beyond that provided by simple orthology-based annotation endeavors.

Algorithms↗

PubMed2003

Phosphorylation-dependent cleavage of p130cas in apoptotic rat-1 cells.

We previously demonstrated caspase-mediated cleavage of p130cas during apoptosis and identified two caspase-3 cleavage sites [1]. In this study, we investigated the phosphorylation-dependent cleavage of p130cas in apoptotic Rat-1 fibroblast cells. Lysophosphatidic acid and fibronectin induced p130cas phosphorylation, which in turn resulted in resistance to caspase-mediated cleavage. Alternatively, dephosphorylation by calf intestinal alkaline phosphatase, PP1, and LAR stimulated cleavage of p130cas by caspase-3, generating a 31-kDa fragment. During apoptosis, p130cas dephosphorylation seems to precede its cleavage. The phosphorylation of tyrosine and serine residues immediately adjacent to the two cleavage sites (DVPD(416) and DSPD(748)) strongly affected p130cas cleavage by caspase-3, both in vitro and in vivo. Furthermore, the generation of the 31-kDa cleavage fragment was strongly regulated by phosphorylation of a tyrosine residue at position 751 (DSPD(748) and GQY(751)). Our results collectively suggest that degradation of p130cas during apoptosis is modulated in a phosphorylation-dependent manner.

Animals↗

PubMed2003

Asian online Y-STR Haplotype Reference Database.

For several years Y-chromosomal microsatellites (short tandem repeats, STRs) have been well established in forensic practice. In this context, the genetic characteristics of the Y chromosome (i.e. its paternal inheritance and lack of recombination) render STRs particularly powerful. However, genetic differences between male populations appear to be larger for Y-STRs than for autosomal STRs, a fact that is most likely due to the higher sensitivity of Y-chromosomal lineages to genetic drift (Forensic Sci Int 118 (2001) 153). The assessment of probabilities for matches between haplotyped male persons or traces/persons requires the typing of a large number of haplotypes in the appropriate reference populations. The haplotype data of a large number of European as well as South and North American populations have been collected and are continuously published online (Y-STR Haplotype Reference Database--YHRD; http://www.ystr.org). The most recent multicentric effort has led to the establishment of an Asian YHRD (http://www.ystr.org/asia) which has been available since January 2002. All databases are maintained and curated at the Institute of Legal Medicine, Humboldt-University, Berlin and will soon be fused to a global repository including populations from all continents.

Asia↗

PubMed2003

Swarm-cell differentiation in Salmonella enterica serovar typhimurium results in elevated resistance to multiple antibiotics.

Although a wealth of knowledge exists about the molecular and biochemical mechanisms governing the swimming motility of Salmonella enterica serovar Typhimurium, its surface swarming behavior has not been extensively characterized. When inoculated onto a semisolid agar medium supplemented with appropriate nutrients, serovar Typhimurium undergoes a morphological differentiation whereby single cells hyperflagellate and elongate into nonseptate, multinucleate swarm cells. Swarm migration is a collective behavior of groups of cells. We have isolated a MudJ insertion mutant of serovar Typhimurium 14028 that failed to swarm under any conditions. The site of the MudJ insertion was determined to be in the pmrK locus within the pmrHFIJKLM operon, which was previously demonstrated to confer resistance to cationic antimicrobial peptides. beta-Galactosidase assays, using the pmrK::lacZ transcriptional fusion, showed increased expression of the pmr operon in swarm cells compared to that in vegetative cells. In concurrence with the expression data, swarm cells exhibited greater tolerance to polymyxin. To compare the profiles of vegetative and swarm-cell resistance to other antibiotics, E-test strips representing a wide range of antibiotic classes were used. Swarm cells exhibited elevated resistance to a variety of antibiotics, including those that target the cell envelope, protein translation, DNA replication, and transcription. These observations, in addition to the dramatic morphological changes associated with the swarming phenotype, provide an intriguing model for examining global differences between the physiological states of vegetative and swarm cells of serovar Typhimurium.

Adaptation, Biological↗