6681430
Haplotypes and mutation analysis of 22 Y-chromosomal STRs in Korean father–son pairs
We analyzed 369 Korean father/son haplotype transfers in 355 families at 22 Y-STRs (DYS19, DYS389I/II, DYS390, DYS391, DYS392, DYS393, DYS385, DYS388, DYS437, DYS438, DYS439, DYS446, DYS447, DYS448, DYS449, DYS456, DYS458, DYS464, DYS635, and GATA H4.1). A total of 350 haplotypes were observed with an overall haplotype diversity of 0.9999. Among these, 345 were unique and five were found twice. Furthermore, 36 mutations were identified, giving locus-specific mutation rate estimates between 0.0 and 19.0 × 10−3 per generation and an average mutation rate estimate of 3.9 × 10−3 (95% CI 2.7–5.4 × 10−3). The compilation of Y-STR mutation events for the present study and previous studies demonstrates that DYS449, DYS458, DYS635, DYS456 and DYS439 are the most prone to mutations and that their overall average mutation rate estimate is 2.36 × 10–3 (95% CI 2.03–2.73 × 10–33).
23057742
Rapid direct PCR for ABO blood typing.
Many different molecular typing methods have been reported to complement routine serological ABO blood typing in forensics. However, these ABO genotyping methods are often time-consuming and call for an initial DNA isolation step that requires the use of expensive kits or reagents. We report here a rapid direct ABO genotyping method that eliminates the need for DNA extraction from fresh blood, hair, and body fluid stains before PCR. Using a fast PCR instrument and an optimized polymerase, the genotyping method-which employs a multiplex allele-specific primer set for the simultaneous detection of three single-nucleotide polymorphism (SNP) sites (nucleotides 261, 526, and 803)-identifies A, B, O01/O02, O03, and cis-AB01 alleles in around 70 min from sample collection to electropherogram. Not only will this ABO genotyping method be efficiently used in forensic practice for rapid screening of samples before full-blown multilocus short tandem repeat profiling, but it will also demonstrate an example of rapid direct genotyping of SNPs that offers the advantages of time- and cost-efficiency, convenience, and reduced contamination during DNA analysis.
22611234
Genetic characteristics and population study of 4 X-chromosomal STRs in Koreans: evidence for a null allele at DXS9898
The four X-chromosomal short tandem repeats (STRs), DXS9898, DXS6809, DXS7424 and DXS10011 were analyzed by single multiplex PCR in 150 male and 150 female Koreans. The loss of an allele at DXS9898 was observed in 13 out of 450 chromosomes (2.9%) and the PCR analysis showed that the X-chromosome with a null allele at DXS9898 has more than 1 kb deletion at the DXS9898 locus. Statistical analyses for these four X-STRs showed that they are highly informative for forensic application in Koreans. No linkage disequilibrium was observed among these four STRs and the previously reported five polymorphic STRs, HumARA, DXS101, GATA172D05, HPRTB and DXS8377 in Koreans. The test of homogeneity between allele frequencies revealed that there are some discrepancies in allele distributions between Koreans and Germans.
32233621
A modified mini-primer set for analyzing mitochondrial DNA control region sequences from highly degraded forensic samples.
To facilitate the analysis of mitochondrial DNA (mtDNA) control region sequences from highly degraded skeletal remains, a modified mini-primer set was designed to overcome the limitations of the Armed Forces DNA Identification Laboratory (AFDIL) mini-primer set. This modified mini-primer set is less affected by nucleotide variability and PCR amplification conditions than the AFDIL mini-primer set, and was able to amplify the mtDNA sequences of 55-year-old skeletal remains with high efficiency, indicating that it is a useful tool for analyzing mtDNA control region sequences from highly degraded forensic samples.
42434218
Differential distribution of human mitochondrial DNA in somatic tissues and hairs.
To investigate mitochondrial DNA (mtDNA) distribution within tissues during life, we observed length heteroplasmy in a polycytosine tract of the mitochondrial HV2 region by size-based separation of PCR products, using a mutagenic primer which was designed to avoid stutter production. Blood, brain, heart, liver, skeletal muscle and hair shaft samples were collected during autopsies of 25 individuals. Here, we demonstrate differences in the level of mtDNA length heteroplasmy both within and between individuals and tissues. We also show that mtDNA is distributed randomly in varying proportions in various somatic tissues during growth, resulting in an imbalance in the composition of mtDNA pools among tissues. This mtDNA distribution appears not to be strictly random, and can be explained by the random somatic segregation of nucleoids. On the other hand, significant qualitative/quantitative mtDNA peak pattern variations in hair shafts are thought to be a result of the different developmental origins of hairs. Each hair shaft may have a restricted or clonal set of mtDNA molecules derived from a discrete group of stem cells.
21885090
Quantitative and qualitative profiling of mitochondrial DNA length heteroplasmy.
Quantitative and qualitative analysis of mitochondrial DNA length heteroplasmy for the first hypervariable segment (HV1) and second hypervariable segment (HV2) regions were performed using size-based separation of fluorescently-labeled polymerase chain reaction (PCR) products by capillary electrophoresis. In this report, the relative proportions of length heteroplasmies in individuals were determined, and each length variant in the heteroplasmic mtDNA mixture was identified. The study demonstrated that 36% and 69% of Koreans show length heteroplasmy in the HV1 and HV2 regions, respectively. Electropherograms revealed that length heteroplasmy in the HV1 region resulted in over 5 length variants in an individual. The peak patterns of length heteroplasmy in the HV1 region were classified into five major types. In the HV2 region, length heteroplasmy resulted in 3-6 length variants in an individual, and showed seven variant peak patterns. The increased knowledge concerning mtDNA length heteroplasmy is believed to not only offer a useful means of determining genetic identity due to increased mitochondrial DNA haplotype diversity by allowing mtDNAs to be classified into several peak patterns, but also represent a promising tool for the diagnosis of several common diseases which are etiologically or prognostically associated with mtDNA polymorphisms.
29310135
Ground-glass opacity nodules: histopathology, imaging evaluation, and clinical implications.
Ground-glass opacity (GGO) nodules noted at thin-section computed tomography (CT) scan have been shown to have a histopathologic relationship with atypical adenomatous hyperplasia, bronchioloalveolar carcinoma (BAC, or adenocarcinoma in situ), and adenocarcinoma with a predominant BAC component (minimally invasive adenocarcinoma). Patients harboring GGO nodules of BAC or adenocarcinoma with a predominant BAC component demonstrate negative results for malignancy at positron emission tomography. In peripheral adenocarcinoma of a part-solid (mixed GGO and solid attenuation) nodular nature, both the degree of disappearance of GGO area, when the lung window is changed to a mediastinal window image at CT scanning, and the maximum standardized uptake value at positron emission tomography correlate well with histopathologic BAC and non-BAC ratios. However, a high non-BAC ratio appears to be the only independent prognosis-determining factor. Epidermal growth factor receptor mutations are positively correlated with the GGO ratio at a thin-section CT scan in lung adenocarcinomas. As patients with a GGO nodule of BAC or adenocarcinoma with a predominant BAC component have a good prognosis, a wedge resection is recommended as a treatment option, in preference to lobectomy. Even for multiple malignant pure GGO nodules, minimally invasive surgery (including multiple resections) with the preservation of lung volume and adequate imaging follow-up studies are the recommended diagnostic and therapeutic measures.
8896689
Secretory Low Molecular Weight Phospholipase A2 Plays Important Roles in Cell Elongation and Shoot Gravitropism in Arabidopsis Article, publication date, and citation information can be found at www.plantcell.org/cgi/doi/10.1105/tpc.014423.
To elucidate the cellular functions of phospholipase A2 in plants, an Arabidopsis cDNA encoding a secretory low molecular weight phospholipase A2 (AtsPLA2β) was isolated. Phenotype analyses of transgenic plants showed that overexpression of AtsPLA2β promotes cell elongation, resulting in prolonged leaf petioles and inflorescence stems, whereas RNA interference–mediated silencing of AtsPLA2β expression retards cell elongation, resulting in shortened leaf petioles and stems. AtsPLA2β is expressed in the cortical, vascular, and endodermal cells of the actively growing tissues of inflorescence stems and hypocotyls. AtsPLA2β then is secreted into the extracellular spaces, where signaling for cell wall acidification is thought to occur. AtsPLA2β-overexpressing or -silenced transgenic plants showed altered gravitropism in inflorescence stems and hypocotyls. AtsPLA2β expression is induced rapidly by auxin treatment and in the curving regions of inflorescence stems undergoing the gravitropic response. These results suggest that AtsPLA2β regulates the process of cell elongation and plays important roles in shoot gravitropism by mediating auxin-induced cell elongation.
8724947
Controlling hematopoiesis through sumoylation-dependent regulation of a GATA factor.
GATA factors establish transcriptional networks that control fundamental developmental processes. Whereas the regulator of hematopoiesis GATA-1 is subject to multiple posttranslational modifications, how these modifications influence GATA-1 function at endogenous loci is unknown. We demonstrate that sumoylation of GATA-1 K137 promotes transcriptional activation only at target genes requiring the coregulator Friend of GATA-1 (FOG-1). A mutation of GATA-1 V205G that disrupts FOG-1 binding and K137 mutations yielded similar phenotypes, although sumoylation was FOG-1 independent, and FOG-1 binding did not require sumoylation. Both mutations dysregulated GATA-1 chromatin occupancy at select sites, FOG-1-dependent gene expression, and were rescued by tethering SUMO-1. While FOG-1- and SUMO-1-dependent genes migrated away from the nuclear periphery upon erythroid maturation, FOG-1- and SUMO-1-independent genes persisted at the periphery. These results illustrate a mechanism that controls trans-acting factor function in a locus-specific manner, and differentially regulated members of the target gene ensemble reside in distinct subnuclear compartments.
15275452
Chemopreventive effects of deguelin, a novel Akt inhibitor, on tobacco-induced lung tumorigenesis.
Tobacco carcinogens induce Akt activation and lung carcinogenesis. We previously demonstrated that deguelin, a natural plant product, specifically inhibits the proliferation of premalignant and malignant human bronchial epithelial cells by blocking Akt activation. To evaluate the ability of deguelin to block tobacco carcinogen-induced lung tumorigenesis, we evaluated the in vivo effects of deguelin on Akt activation and lung tumorigenesis in transgenic mice in which Akt expression was induced by tamoxifen and in 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK)/benzo(a)pyrene (BaP)-treated A/J mice. Deguelin suppressed Akt activation in vivo, as measured by immunohistochemistry and immunoblotting, and statistically significantly reduced NNK/BaP-induced lung tumor multiplicity, volume, and load in A/J mice, as monitored by microcomputed tomography image analysis, with no detectable toxicity. These results indicate that deguelin warrants consideration as a chemopreventive agent for early-stage lung carcinogenesis in a clinical lung cancer chemoprevention trial.
44613407
Job satisfaction and trust in Health Insurance Review Agency among Korean physicians.
OBJECTIVES
To measure Korean physicians' job satisfaction and to examine the relationship between trust in Health Insurance Review Agency (HIRA) and job satisfaction.


METHODS
Stratified sampling was used. The sample was representative of Korean office-based physicians; 1593 office-based physicians in Korea were surveyed by mail over a 4-week period using a self-administered questionnaire. Multivariate analysis using logistic regression was performed to investigate predictors of physicians' job satisfaction and to examine whether trust in HIRA was related to job satisfaction.


RESULTS
Overall, the job satisfaction of physicians was very low. The payment denial rate was not related to job satisfaction. Physicians who trusted HIRA were more likely to be satisfied with their job.


CONCLUSIONS
Physicians who trusted in the HIRA were more likely to report satisfaction. These results emphasize that trust in the HIRA is key to physicians' job satisfaction.