Mingoo Kim

Mesenchymal stem cells transfer mitochondria to the cells with virtually no mitochondrial function but not with pathogenic mtDNA mutations.

It has been reported that human mesenchymal stem cells (MSCs) can transfer mitochondria to the cells with severely compromised mitochondrial function. We tested whether the reported intercellular mitochondrial transfer could be replicated in different types of cells or under different experimental conditions, and tried to elucidate possible mechanism. Using biochemical selection methods, we found exponentially growing cells in restrictive media (uridine− and bromodeoxyuridine [BrdU]+) during the coculture of MSCs (uridine-independent and BrdU-sensitive) and 143B-derived cells with severe mitochondrial dysfunction induced by either long-term ethidium bromide treatment or short-term rhodamine 6G (R6G) treatment (uridine-dependent but BrdU-resistant). The exponentially growing cells had nuclear DNA fingerprint patterns identical to 143B, and a sequence of mitochondrial DNA (mtDNA) identical to the MSCs. Since R6G causes rapid and irreversible damage to mitochondria without the removal of mtDNA, the mitochondrial function appears to be restored through a direct transfer of mitochondria rather than mtDNA alone. Conditioned media, which were prepared by treating mtDNA-less 143B ρ0 cells under uridine-free condition, induced increased chemotaxis in MSC, which was also supported by transcriptome analysis. Cytochalasin B, an inhibitor of chemotaxis and cytoskeletal assembly, blocked mitochondrial transfer phenomenon in the above condition. However, we could not find any evidence of mitochondrial transfer to the cells harboring human pathogenic mtDNA mutations (A3243G mutation or 4,977 bp deletion). Thus, the mitochondrial transfer is limited to the condition of a near total absence of mitochondrial function. Elucidation of the mechanism of mitochondrial transfer will help us create a potential cell therapy-based mitochondrial restoration or mitochondrial gene therapy for human diseases caused by mitochondrial dysfunction.

Analysis of Lysophosphatidic Acid (LPA) Receptor and LPA-Induced Endometrial Prostaglandin-Endoperoxide Synthase 2 Expression in the Porcine Uterus

Lysophosphatidic acid (LPA), a simple phospholipid-derived mediator with diverse biological actions, acts through the specific G protein-coupled receptors endothelial differentiation gene (EDG) 2, EDG4, EDG7, and GPR23. Recent studies indicate a critical role for LPA receptor signaling in embryo implantation. To understand how LPA acts in the uterus during pregnancy in pigs, we evaluated: 1) spatial and temporal expression of LPA receptors in the uterine endometrium during the estrous cycle and pregnancy and in early-stage concepti, 2) LPA levels in uterine luminal fluids from d 12 of the estrous cycle and pregnancy, 3) effects of steroid hormones on EDG7 mRNA levels, and 4) effects of LPA on prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA levels in the uterine endometrium using explant cultures. Of the four receptors, EDG7 was dominant, and its expression was regulated by pregnancy stage and status. EDG7 expression was highest on d 12 pregnancy, and localized to the luminal and glandular epithelium, and EDG7 mRNA levels were elevated by estrogen in the endometrium. EDG7 expression was also detected in concepti of d 12 and 15. LPA with various fatty acyl groups was present in the uterine lumen on d 12 of both the estrous cycle and pregnancy. LPA increased PTGS2 mRNA abundance in the uterine endometrium. These results indicate that LPA produced in the uterine endometrium may play a critical role in uterine endometrial function and conceptus development through EDG7-mediated PTGS2 expression during implantation and establishment of pregnancy in pigs.

On systematic punctured convolutional codes

This paper investigates high rate systematic punctured convolutional codes based on Forneys (1970) results. High rate systematic punctured convolutional codes of rate-2/3 with constraint length 3/spl les/K/spl les/7 and rate-3/4 through 15/16 with K=7 are derived using the rate-1/2 best known nonsystematic convolutional codes. Weight spectra of newly discovered systematic punctured convolutional codes are provided and compared with the best known nonsystematic punctured codes. Simulation results on bit-error probabilities (BEPs) are also given.

Dynamic expression of calcium-regulatory molecules, TRPV6 and S100G, in the uterine endometrium during pregnancy in pigs.

Calcium ions have been implicated in the establishment and maintenance of pregnancy, but the regulatory mechanisms of calcium ions in the uterine endometrium and conceptus are not well understood in pigs. Recently, we showed that TRPV6, a calcium ion channel protein associated with cellular entry of calcium ions, is highly expressed in the uterine endometrium during the implantation period in pigs. In the present study, we investigated spatial and temporal expression and regulation of TRPV6 and S100G, an intracellular calcium-regulatory molecule, in the uterine endometrium during the estrous cycle and pregnancy in pigs. TRPV6 expression was maintained at significantly higher levels in the uterine endometrium during pregnancy compared with levels during the estrous cycle. TRPV6 transcripts and proteins were localized mainly to luminal epithelial cells (LE) and weakly to glandular epithelial cells (GE) and chorionic membrane (CM) during pregnancy. TRPV6 expression was also detected in conceptuses on Day (D) 12 and D15. TRPV6 mRNA levels in the endometrium were increased by estrogen treatment. S100G expression showed a biphasic pattern of increases on D12 of pregnancy and from D60 to term pregnancy, and it localized primarily to LE during early pregnancy and to LE, GE, and CM from D30 to term pregnancy. These results indicate that spatial and temporal expression of TRPV6 and S100G is dynamically regulated in the uterine endometrium during pregnancy and that endometrial regulation of calcium ion concentration by TRPV6 and S100G may be critical for the establishment and maintenance of pregnancy in pigs.

Undetected error probabilities of binary primitive BCH codes for both error correction and detection

We investigate the undetected error probabilities for bounded-distance decoding of binary primitive BCH codes when they are used for both error correction and detection on a binary symmetric channel. We show that the undetected error probability of binary linear codes can be simplified and quantified if the weight distribution of the code is binomial-like. We obtain bounds on the undetected error probability of binary primitive BCH codes by applying the result to the code and show that the bounds are quantified by the deviation factor of the true weight distribution from the binomial-like weight distribution.

Analysis of hepatic gene expression during fatty liver change due to chronic ethanol administration in mice.

Chronic consumption of ethanol can cause cumulative liver damage that can ultimately lead to cirrhosis. To explore the mechanisms of alcoholic steatosis, we investigated the global intrahepatic gene expression profiles of livers from mice administered alcohol. Ethanol was administered by feeding the standard Lieber-DeCarli diet, of which 36% (high dose) and 3.6% (low dose) of the total calories were supplied from ethanol for 1, 2, or 4 weeks. Histopathological evaluation of the liver samples revealed fatty changes and punctate necrosis in the high-dose group and ballooning degeneration in the low-dose group. In total, 292 genes were identified as ethanol responsive, and several of these differed significantly in expression compared to those of control mice (two-way ANOVA; p<0.05). Specifically, the expression levels of genes involved in hepatic lipid transport and metabolism were examined. An overall net increase in gene expression was observed for genes involved in (i) glucose transport and glycolysis, (ii) fatty acid influx and de novo synthesis, (iii) fatty acid esterification to triglycerides, and (iv) cholesterol transport, de novo cholesterol synthesis, and bile acid synthesis. Collectively, these data provide useful information concerning the global gene expression changes that occur due to alcohol intake and provide important insights into the comprehensive mechanisms of chronic alcoholic steatosis.

Psychosocial Stress in Nurses With Shift Work Schedule Is Associated With Functional Gastrointestinal Disorders

Background/Aims The aim of this study was to investigate the role of psychosocial problems and their associations with rotating shift work in the development of functional gastrointestinal disorders. Methods In this cross-sectional observation study, survey was administered to nurses and nurse assistants in a referral hospital. In addition to demographic questions, subjects were asked to complete the Rome III Questionnaire, Pittsburgh Sleep Quality Index and Rome III Psychosocial Alarm Questionnaire. Results Responses from 301 subjects were assessed. The overall prevalence of irritable bowel syndrome (IBS) and functional dyspepsia (FD) were 15.0% and 19.6%, respectively. Psychosocial alarms were prevalent in the nursing personnel (74.8% with alarm presence and 23.3% with serious condition) and were more frequent among rotating shift workers (84.7% vs. 74.5% for alarm presence and 28.1% vs. 13.3% for serious condition). The prevalence of both IBS and FD significantly increased with psychosocial risk. An independent risk factor for IBS was serious psychosocial alarm (adjusted odds ratio [aOR], 10.75; 95% confidence interval (CI), 1.30–88.99; P = 0.028). Serious psychosocial alarm was an independent risk factor for FD (aOR, 7.84; 95% CI, 1.98–31.02; P = 0.003). Marriage (aOR 0.30; 95% CI, 0.09–0.93; P = 0.037) was associated with the decreased risk of FD. Conclusions The high prevalence of psychosocial stress among nurses who work rotating shifts is associated with the development of functional gastrointestinal disorders.

Identification of differentially expressed genes in the uterine endometrium on day 12 of the estrous cycle and pregnancy in pigs.

Maternal recognition of pregnancy in pigs occurs approximately on Day (D) 12 of pregnancy and is critical for embryo implantation. The presence of the conceptus in the uterine lumen during this period changes uterine endometrial function to prepare for attachment of the conceptus to the endometrial epithelial cells and maintain luteal function in the ovary. Although much is known about endometrial gene expression, the genes expressed in the uterine endometria and the cellular and molecular mechanisms of those gene products during the period of implantation and maternal recognition of pregnancy in pigs are still not completely defined. To better understand the interactions between the maternal uterus and conceptus during the implantation process, we searched genes differentially expressed in the endometria on D12 of pregnancy compared to those on D12 of the estrous cycle. A new reverse transcription‐polymerase chain reaction (RT‐PCR)‐based method that involves annealing control primers (ACPs) was employed. Using 120 ACPs, we sequenced 12 differentially expressed genes (DEGs) and identified those genes using the Basic Local Alignment Search Tool (BLAST). Northern blot hybridization analysis confirmed the differential expression of those DEGs in the uterine endometrium. In situ hybridization analysis determined the cell‐type specific expression of the DEGs in the uterine endometrium. Further analysis of the DEGs found in this study will provide insights into the cellular and molecular basis of maternal and fetal interactions during the period of maternal recognition of pregnancy in the pig. Mol. Reprod. Dev. 76: 75–84, 2009.

Gene expression profiles of murine fatty liver induced by the administration of methotrexate

Methotrexate (MTX) is used to treat a variety of chronic inflammatory and neoplastic diseases. However, it can induce hepatotoxicity such as microvesicular steatosis and necrosis. To explore the mechanisms of MTX-induced hepatic steatosis, we used microarray analysis to profile the gene expression patterns of mouse liver after MTX treatment. MTX was administered orally as a single dose of 10mg/kg (low dose) or 100 mg/kg (high dose) to ICR mice, and the livers were obtained 6 h, 24 h, and 72 h after treatment. Serum alanine aminotransferase, aspartate aminotransferase and triacylglycerol levels were not significantly altered in the experimental animals. Signs of steatosis were observed at 24 h after administration of high dose of MTX. From microarray data analysis, 908 genes were selected as MTX-responsive genes (P<0.05, two-way ANOVA; cutoff > or =1.5-fold). Database for Annotation, Visualization and Integrated Discovery (DAVID) analysis revealed that the predominant biological processes associated with these genes are response to unfolded proteins, phosphate metabolism, and cellular lipid metabolism. Functional categorization of these genes identified 28 genes involved in lipid metabolism that was interconnected with the biological pathways of biosynthesis, catabolism, and transport of lipids and fatty acids. Taken together, these data provide a better understanding of the molecular mechanisms of MTX-induced steatogenic hepatotoxicity, and useful information for predicting hepatotoxicity through pattern recognition.

Aberrant expression of retinol-binding protein, osteopontin and fibroblast growth factor 7 in the porcine uterine endometrium of pregnant recipients carrying embryos produced by somatic cell nuclear transfer

The technique of somatic cell nuclear transfer (NT) is a useful tool to produce cloned animals for various purposes, but the efficiency to generate cloned animals using this technique is still very low. To improve the low efficiency in production of cloned pigs it is critical to understand the reprogramming process during development of cloned embryos, but it is also essential to understand the uterine function interacting with the transferred cloned embryos during implantation and placentation. Thus, to understand the uterine responsiveness to NT cloned embryos during pregnancy, we investigated expression of retinol-binding protein (RBP), osteopontin (OPN) and fibroblast growth factor 7 (FGF7), which play important roles in implantation and/or maintenance of pregnancy as a transport protein, an extracellular matrix protein and a growth factor, respectively, in the uterine endometrium in pigs. The uterine tissue samples were obtained by C-section from pigs with NT cloned normal (NT-normal) embryos and NT cloned abnormal (NT-abnormal) embryos and pigs with non-NT (Non-NT) embryos at term. Immunoblot analysis showed that expression of RBP and FGF7 decreased in the uterine endometrium of recipient gilts carrying NT embryos than in the endometrium of gilts carrying Non-NT embryos. Levels of OPN protein of 70 and 45kDa were not different in between the uterine endometrium of gilts carrying Non-NT and NT-normal embryos, but in the uterine endometrium of gilts carrying NT-abnormal embryos 70 and 45kDa OPN proteins increased compared to those in the endometrium of gilts carrying Non-NT embryos. Immunohistochemistry results showed that RBP expression was lower in the endometrial glandular epithelial cells, while OPN expression was higher in the endometrial luminal epithelial cells of the uterus of gilts carrying NT embryos than in the uterus of gilts carrying Non-NT embryos. Results of this study showed that maternal uterine genes were aberrantly expressed in the uterine endometrium of gilts carrying NT cloned embryos in varying degrees depending on the normality of the developing embryos. These results indicate that abnormal maternal-fetal interactions of the uterus carrying the developing NT cloned embryos may cause problems in development of cloned embryos.