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Articles by S Kim
Total Records ( 22 ) for S Kim
  S Kim , G Toncheva , C Anderson Evans , B. K Huh , L Gray and T. Yoshizumi

OBJECTIVE. The purpose of this study was to derive from the kerma area product the dose conversion coefficient for estimating the effective dose for lumbar epidural steroid injection procedures.

MATERIALS AND METHODS. A mobile fluoroscopy system was used for fluoroscopic imaging guidance of lumbar epidural steroid injection procedures. For acquisition of organ dose measurements, 20 diagnostic metal oxide semiconductor field effect transistor detectors were placed at each organ in an anthropomorphic phantom of a man, and these detectors were attached to four mobile metal oxide semiconductor field effect transistor wireless bias supplies to obtain the organ dose readings. The kerma area product was recorded from the system console and independently validated with an ion chamber and therapeutic x-ray film. Fluoroscopy was performed on the phantom for 10 minutes for acquisition of the dose rate for each organ, and the average clinical procedure time was multiplied by each organ dose rate for acquisition of individual organ doses. The effective dose was computed by summing the product of each organ dose and the corresponding tissue weighting factor from International Commission on Radiologic Protection publication 60.

RESULTS. The effective dose was computed as 0.93 mSv for an average lumbar epidural steroid injection procedure (fluoroscopic time, 40.7 seconds). The corresponding kerma area product was 2.80 Gy·cm2. The dose conversion coefficient was derived as 0.33 mSv/(Gy·cm2).

CONCLUSION. The effective dose for lumbar epidural steroid injection can be easily estimated by multiplying the derived dose conversion coefficient by the console-displayed kerma area product.

  G. D Schiff , O Hasan , S Kim , R Abrams , K Cosby , B. L Lambert , A. S Elstein , S Hasler , M. L Kabongo , N Krosnjar , R Odwazny , M. F Wisniewski and R. A. McNutt

Background  Missed or delayed diagnoses are a common but understudied area in patient safety research. To better understand the types, causes, and prevention of such errors, we surveyed clinicians to solicit perceived cases of missed and delayed diagnoses.

Methods  A 6-item written survey was administered at 20 grand rounds presentations across the United States and by mail at 2 collaborating institutions. Respondents were asked to report 3 cases of diagnostic errors and to describe their perceived causes, seriousness, and frequency.

Results  A total of 669 cases were reported by 310 clinicians from 22 institutions. After cases without diagnostic errors or lacking sufficient details were excluded, 583 remained. Of these, 162 errors (28%) were rated as major, 241 (41%) as moderate, and 180 (31%) as minor or insignificant. The most common missed or delayed diagnoses were pulmonary embolism (26 cases [4.5% of total]), drug reactions or overdose (26 cases [4.5%]), lung cancer (23 cases [3.9%]), colorectal cancer (19 cases [3.3%]), acute coronary syndrome (18 cases [3.1%]), breast cancer (18 cases [3.1%]), and stroke (15 cases [2.6%]). Errors occurred most frequently in the testing phase (failure to order, report, and follow-up laboratory results) (44%), followed by clinician assessment errors (failure to consider and overweighing competing diagnosis) (32%), history taking (10%), physical examination (10%), and referral or consultation errors and delays (3%).

Conclusions  Physicians readily recalled multiple cases of diagnostic errors and were willing to share their experiences. Using a new taxonomy tool and aggregating cases by diagnosis and error type revealed patterns of diagnostic failures that suggested areas for improvement. Systematic solicitation and analysis of such errors can identify potential preventive strategies.

  S Kim , K. A Sohn and E. P. Xing

Motivation: Many complex disease syndromes such as asthma consist of a large number of highly related, rather than independent, clinical phenotypes, raising a new technical challenge in identifying genetic variations associated simultaneously with correlated traits. Although a causal genetic variation may influence a group of highly correlated traits jointly, most of the previous association analyses considered each phenotype separately, or combined results from a set of single-phenotype analyses.

Results: We propose a new statistical framework called graph-guided fused lasso to address this issue in a principled way. Our approach represents the dependency structure among the quantitative traits explicitly as a network, and leverages this trait network to encode structured regularizations in a multivariate regression model over the genotypes and traits, so that the genetic markers that jointly influence subgroups of highly correlated traits can be detected with high sensitivity and specificity. While most of the traditional methods examined each phenotype independently, our approach analyzes all of the traits jointly in a single statistical method to discover the genetic markers that perturb a subset of correlated triats jointly rather than a single trait. Using simulated datasets based on the HapMap consortium data and an asthma dataset, we compare the performance of our method with the single-marker analysis, and other sparse regression methods that do not use any structural information in the traits. Our results show that there is a significant advantage in detecting the true causal single nucleotide polymorphisms when we incorporate the correlation pattern in traits using our proposed methods.

Availability: Software for GFlasso is available at


  S. A Lee , Y. M Kim , T. K Kwak , H. J Kim , S Kim , W Ko , S. H Kim , K. H Park , M Cho and J. W. Lee

Four-transmembrane L6 family member 5 (TM4SF5) and its homolog L6, a tumor antigen, form a four-transmembrane L6 family. TM4SF5 expression causes uncontrolled cell proliferation and angiogenesis. Although other genuine transmembrane 4 superfamily (TM4SF) members co-operate with integrins for cell migration, roles of TM4SF5 in the cellular spreading and migration are unknown. Using hepatocarcinoma cell clones that ectopically express TM4SF5, we found that cross talks via an extracellular interaction between TM4SF5 and integrin 2 in collagen type I environment inhibited integrin 2 functions such as spreading on and migration toward collagen I, which were recovered by suppression of TM4SF5 or structural disturbance of its second extracellular loop using a peptide or mutagenesis. Altogether, the observations suggest that TM4SF5 in hepatocytes negatively regulates integrin 2 function via an interaction between the extracellular loop 2 of TM4SF5 and integrin 2 during cell spreading on and migration through collagen I environment.

  S Kim , H. Y Kang , E. H Nam , M. S Choi , X. F Zhao , C. S Hong , J. W Lee , J. H Lee and Y. K. Park

TMPRSS4 is a novel type II transmembrane serine protease that is highly expressed on the cell surface in pancreatic, thyroid and other cancer tissues, although its oncogenic significance and molecular mechanisms are unknown. Previously, we have shown that TMPRSS4 promotes invasion, migration and metastasis of human tumor cells by facilitating an epithelial–mesenchymal transition (EMT). In this study, we explored the molecular basis underlying TMPRSS4-mediated effects. We show that multiple downstream signaling pathways, including focal adhesion kinase (FAK), extracellular signal-regulated kinase (ERK), Akt, Src and Rac1, are activated by TMPRSS4 expression and that FAK signaling and ERK activation are required for TMPRSS4-induced invasiveness and EMT, including cadherin switch. Inhibition of PI3K or Src reduced invasiveness and actin rearrangement mediated by TMPRSS4 without restoring E-cadherin expression. Downregulation of E-cadherin was required for TMPRSS4-mediated effects but was not sufficient to induce EMT and invasion. TMPRSS4 induced integrin 5 expression and its signal transduction, leading to invasiveness and EMT accompanied by downregulation of E-cadherin. Functional blocking confirmed that integrin 5β1 is a critical signaling molecule that is sufficient to induce TMPRSS4-mediated effects. Immunohistochemical analysis showed that TMPRSS4 expression was significantly higher in human colorectal cancer tissues from advanced stages than in that of early stage. Furthermore, upregulation of TMPRSS4 was correlated with enhanced integrin 5 expression. These observations implicate integrin 5 upregulation as a molecular mechanism by which TMPRSS4 induces invasion and contributes to cancer progression.

  P. S Son , S. A Park , H. K Na , D. M Jue , S Kim and Y. J. Surh

There are multiple lines of evidence supporting that chronic inflammation is linked to carcinogenesis. Nuclear factor-B (NF-B), a major redox-sensitive transcription factor responsible for the induction of a wide array of pro-inflammatory genes, is frequently overactivated in many tumors. Moreover, constitutive activation of IB kinase (IKK), a key regulator of NF-B signaling, has been implicated in inflammation-associated tumorigenesis. Piceatannol (trans-3,4,3',5'-tetrahydroxystilbene; PIC) derived from grapes, rhubarb and sugarcane exhibits immunosuppressive and antitumorigenic activities in several cell lines, but the underlying mechanisms are poorly understood. In the present study, we found that PIC inhibited migration and anchorage-independent growth of human mammary epithelial cells (MCF-10A) treated with the prototypic tumor promoter, 12-O-tetradecanoylphorbol-13-aceate (TPA). PIC treatment suppressed the TPA-induced activation of NF-B and expression of cyclooxygenase-2 (COX-2) in MCF-10A cells. We speculate that an electrophilic quinone formed as a consequence of oxidation of PIC bearing the catechol moiety may directly interact with critical cysteine thiols of IKKβ, thereby inhibiting its catalytic activity. In support of this speculation, the reducing agent dithiothreitol abrogated the inhibitory effects of PIC on TPA-induced activation of NF-B signaling and expression of COX-2. In addition, the inhibitory effects of PIC on NF-B activation and COX-2 induction were blunted in cells expressing mutant IKKβ (C179A) in which cysteine 179 was replaced by alanine. In conclusion, our results show that direct modification of IKKβ by PIC, presumably at the cysteine 179 residue, blocks NF-B activation signaling and COX-2 induction in TPA-treated MCF-10A cells and also migration and transformation of these cells.

  H Tomita , S Zhilicheva , S Kim and N. Maeda

Rationale: Apolipoprotein E-null mice with a 129S6/SvEvTac strain background (129-apoE) develop atherosclerotic plaques faster in the aortic arch but slower in the aortic root than those with a C57BL/6J background (B6-apoE). The shape of the aortic arch also differs in the 2 strains.

Objective: Because circulating plasma factors are the same at both locations, we tested the hypothesis that genetic factors affecting vascular geometry also affect the location and extent of atherosclerotic plaque development.

Methods and Results: Tests on the F2 progeny from a cross between 129-apoE-null and B6-apoE-null mice showed that the extent of atherosclerosis in the aortic arch is significantly correlated in males, but not in females, with the shape of arch curvature (r=0.34, P<0.0001) and weakly with the arch diameter (r=0.20, P=0.02). Quantitative trait locus (QTL) analysis identified 2 significant peaks for aortic arch lesion size on chromosome 1 (105 Mb, LOD=5.0, and 163 Mb, LOD=6.8), and a suggestive QTL on chromosome 15 (96 Mb, LOD=4.7). A significant QTL for aortic root lesion size was on chromosome 9 (61 Mb, LOD=6.9), but it was distinct from the QTLs for arch lesion size. Remarkably, the QTLs for susceptibility to atherosclerosis in the arch overlapped with a significant QTL that affects curvature of the arch on chromosome 1 (121 Mb, LOD=5.6) and a suggestive QTL on chromosome 15 (76 Mb, LOD=3.5).

Conclusions: The overlapping QTLs for curvature of the aortic arch and atherosclerosis support that the ontogeny of the aortic arch formation is a potential risk factor for atherosclerosis.

  T. N Kim , S Kim , S. J Yang , H. J Yoo , J. A Seo , N. H Kim , S. H Baik , D. S Choi and K. M. Choi

Background— Type 2 diabetes mellitus (T2DM) is associated with an increased risk of atherosclerotic cardiovascular disease. Vascular inflammation is a key factor in both the pathogenesis and outcome of atherosclerosis. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is a promising tool for indentifying and quantifying vascular inflammation within atherosclerotic plaques. This study was designed to examine the vascular inflammation measured using FDG-PET in patients with impaired glucose tolerance and T2DM, in comparison with age- and sex-matched control subjects with normal glucose tolerance.

Methods and Results— We investigated vascular inflammation using FDG-PET in 90 age- and sex-matched subjects with different glucose tolerance (30 normal glucose tolerance subjects, 30 impaired glucose tolerance subjects, and 30 T2DM subjects). Vascular 18F-FDG uptake was measured as both the mean and maximum blood-normalized standardized uptake value, known as the target-to-background ratio (TBR). Both mean and maximum TBR measurements were significantly different, based on glucose tolerance, although the carotid intima-media thickness measurements were not significantly different. The maximum TBR values in patients with impaired glucose tolerance and T2DM were significantly increased compared with the normal subjects. In addition, subjects with metabolic syndrome had increased maximum TBR values compared with those without metabolic syndrome. Age-, sex-, and body mass index–adjusted maximum TBR levels were positively correlated with triglyceride, hemoglobin A1c, insulin resistance, high-sensitivity C-reactive protein, and Framingham risk score and were negatively correlated with high-density lipoprotein cholesterol and adiponectin levels.

Conclusions— The results of the present study suggest that impaired glucose tolerance and T2DM are associated with vascular inflammation in carotid atherosclerosis detected by FDG-PET.

  J. A Govindan , S Nadarajan , S Kim , T. A Starich and D. Greenstein
  J. Amaranath Govindan, Saravanapriah Nadarajan, Seongseop Kim, Todd A. Starich, and David Greenstein

Soma-germline interactions control fertility at many levels, including stem cell proliferation, meiosis and gametogenesis, yet the nature of these fundamental signaling mechanisms and their potential evolutionary conservation are incompletely understood. In C. elegans, a sperm-sensing mechanism regulates oocyte meiotic maturation and ovulation, tightly coordinating sperm availability and fertilization. Sperm release the major sperm protein (MSP) signal to trigger meiotic resumption (meiotic maturation) and to promote contraction of the follicle-like gonadal sheath cells that surround oocytes. Using genetic mosaic analysis, we show that all known MSP-dependent meiotic maturation events in the germline require Gs-adenylate cyclase signaling in the gonadal sheath cells. We show that the MSP hormone promotes the sustained actomyosin-dependent cytoplasmic streaming that drives oocyte growth. Furthermore, we demonstrate that efficient oocyte production and cytoplasmic streaming require Gs-adenylate cyclase signaling in the gonadal sheath cells, thereby providing a somatic mechanism that coordinates oocyte growth and meiotic maturation with sperm availability. We present genetic evidence that MSP and Gs-adenylate cyclase signaling regulate oocyte growth and meiotic maturation in...

  S. W Han , H. J Kim , S Kim and K. H. Ryu

Comprehensive aortic root and valve repair (CARVAR) surgery using specially designed aortic rings was introduced as a new surgical technique for aortic valve disease. We present five consecutive cases of iatrogenic coronary ostial stenosis after CARVAR surgery in patients with aortic stenosis. The preoperative coronary angiography confirmed that all the patients had normal coronary arteries. They underwent aortic valvuloplasty by aortic leaflet extension and insertion of specially designed inner and outer rings at the level of the sinotubular junction. Within 6 months after surgery, all the patients complained of resting chest pain and dyspnea with changes of electrocardiography. Repeated coronary angiography demonstrated right coronary artery (RCA) ostial stenosis in one patient and left main (LM) ostial stenosis in the other four patients. Intravascular ultrasonography demonstrated severe ostial stenosis and extensive echogenic tissue in the extravascular area. Four patients with LM ostial disease successfully underwent coronary bypass graft surgery, and percutaneous coronary intervention with stenting was performed in one case of RCA ostial stenosis. Because the mechanism of this complication is not fully confirmed, more clinical study is required to confirm the safety issues of CARVAR surgery.

  S. M Ahn , T. H Kim , S Lee , D Kim , H Ghang , D. S Kim , B. C Kim , S. Y Kim , W. Y Kim , C Kim , D Park , Y. S Lee , S Kim , R Reja , S Jho , C. G Kim , J. Y Cha , K. H Kim , B Lee , J Bhak and S. J. Kim

We present the first Korean individual genome sequence (SJK) and analysis results. The diploid genome of a Korean male was sequenced to 28.95-fold redundancy using the Illumina paired-end sequencing method. SJK covered 99.9% of the NCBI human reference genome. We identified 420,083 novel single nucleotide polymorphisms (SNPs) that are not in the dbSNP database. Despite a close similarity, significant differences were observed between the Chinese genome (YH), the only other Asian genome available, and SJK: (1) 39.87% (1,371,239 out of 3,439,107) SNPs were SJK-specific (49.51% against Venter's, 46.94% against Watson's, and 44.17% against the Yoruba genomes); (2) 99.5% (22,495 out of 22,605) of short indels (< 4 bp) discovered on the same loci had the same size and type as YH; and (3) 11.3% (331 out of 2920) deletion structural variants were SJK-specific. Even after attempting to map unmapped reads of SJK to unanchored NCBI scaffolds, HGSV, and available personal genomes, there were still 5.77% SJK reads that could not be mapped. All these findings indicate that the overall genetic differences among individuals from closely related ethnic groups may be significant. Hence, constructing reference genomes for minor socio-ethnic groups will be useful for massive individual genome sequencing.

  S Kim , K. K Hammerstom , K. E Conlan and A. R. Thurber

Community structure and diversity are influenced by patterns of disturbance and input of food. In Antarctica, the marine ecosystem undergoes highly seasonal changes in availability of light and in primary production. Near research stations, organic input from human activities can disturb the regular productivity regime with a consistent input of sewage. McMurdo Sound has both high-productivity and low-productivity habitats, thereby providing an ideal test bed for community recovery dynamics under polar conditions. We used experimental manipulations of the subtidal communities to test the hypotheses that (1) benthic communities respond differently to disturbance from organic enrichment versus burial and (2) community response also varies in areas with different natural patterns of food supply. Both in low- and high-food habitats, the strongest community response was to organic enrichment and resulted in dominance of typical organic-enrichment specialists. In habitats with highly seasonal productivity, community response was predictable and recovery was rapid. In habitats with low productivity, community variability was high and caging treatments suggested that inconsistencies were due to patchy impacts by scavengers. In areas normally subject to regular organic enrichment, either from primary production or from further up the food web (defecation by marine mammals), recovery of benthic communities takes only years even in a polar system. However, a low-productivity regime is as common in near shore habitats around the continent; under these conditions, recovery of benthic communities from disturbance is likely to be much slower and follow a variable ecological trajectory.

  S Kim , J. Y Yang , K Lee , K. H Oh , M Gi , J. M Kim , D. J Paik , S Hong and J. Youn

Peripheral naive CD4+ T cells selectively differentiate to type 1 Th, type 2 Th and IL-17-producing Th (Th17) cells, depending on the priming conditions. Since these subsets develop antagonistically to each other to elicit subset-specific adaptive immune responses, balance between these subsets can regulate the susceptibility to diverse immune diseases. The present study was undertaken to determine whether poly--glutamic acid (-PGA), an edible and safe exopolymer that is generated by microorganisms such as Bacillus subtilis, could modulate the development pathways of Th subsets. The presence of -PGA during priming promoted the development of Th1 and Th17 cells but inhibited development of Th2 cells. -PGA up-regulated the expression of T-bet and ROR-t, the master genes of Th1 and Th17 cells, respectively, whereas down-regulating the level of GATA-3, the master gene of Th2 cells. -PGA induced the expression of IL-12p40, CD80 and CD86 in dendritic cells (DC) and macrophages in a Toll-like receptor-4-dependent manner, and the effect of -PGA on Th1/Th2 development was dependent on the presence of antigen-presenting cells (APC). Furthermore, -PGA-stimulated DC favored the polarization of naive CD4+ T cells toward Th1 cells rather than Th2 cells. In contrast, -PGA affected Th17 cell development, regardless of the presence or absence of APC. Thus, these data demonstrate that -PGA has the potential to regulate the development pathways of naive CD4+ T cells through APC-dependent and -independent mechanisms and to be applicable to treating Th2-dominated diseases.

  I. C Song , J. S Lim , H. J Yun , S Kim , D. Y Kang and H. J. Lee

Sunitinib is a small molecular inhibitor of tyrosine kinases and is used to treat advanced renal cell carcinoma and gastrointestinal stromal tumour after disease progression or intolerance to imatinib therapy. Here, we describe biochemical and pathological response of prostate cancer in a patient with metastatic renal cell carcinoma during sunitinib treatment. A 62-year-old man was referred to our hospital because of a mass in the scalp. He was diagnosed with left renal cell carcinoma with right renal and scalp metastases. In addition, synchronous prostate cancer involving less than one-half of the right lobe was found with a prostate-specific antigen (PSA) value of 23.4 ng/ml. Treatment was begun with sunitinib (50 mg daily, 4 weeks on and 2 weeks off). Regarding the prostate cancer, active monitoring was planned considering the far advanced renal cell carcinoma. Surprisingly, the PSA level was 3.4 ng/ml at week 6 and 0.2 ng/ml at week 12, and it subsequently remained normal. At the time of writing (cycle 6 of sunitinib therapy), the prostate nodule significantly decreased in size. Furthermore, a 12-core re-biopsy revealed pathological evidence of regression with sunitinib treatment, with control of his renal cell carcinoma.

  S Kim , T. T Yoshizumi , G Toncheva , D. P Frush and F. F. Yin

The purpose of this study was to establish a dose estimation tool with Monte Carlo (MC) simulations. A 5-y-old paediatric anthropomorphic phantom was computed tomography (CT) scanned to create a voxelised phantom and used as an input for the abdominal cone-beam CT in a BEAMnrc/EGSnrc MC system. An X-ray tube model of the Varian On-Board Imager® was built in the MC system. To validate the model, the absorbed doses at each organ location for standard-dose and low-dose modes were measured in the physical phantom with MOSFET detectors; effective doses were also calculated. In the results, the MC simulations were comparable to the MOSFET measurements. This voxelised phantom approach could produce a more accurate dose estimation than the stylised phantom method. This model can be easily applied to multi-detector CT dosimetry.

  M Endale , S. D Kim , W. M Lee , S Kim , K Suk , J. Y Cho , H. J Park , Y Wagley , J. W Oh and M. H. Rhee

Regulator of G protein signaling (RGS) family members, such as RGS2, interact with G subunits of heterotrimeric G proteins, accelerating the rate of GTP hydrolysis and attenuating the intracellular signaling triggered by the G protein-coupled receptor-ligand interaction. They are also reported to regulate G protein-effector interactions and form multiprotein signaling complexes. Ischemic stress-induced changes in RGS2 expression have been described in astrocytes, and these changes are associated with intracellular signaling cascades, suggesting that RGS2 upregulation may be an important mechanism by which astrocytes may regulate RGS2 function in response to physiological stress. However, information on the functional roles of stress-induced modulation of RGS2 protein expression in astrocyte function is limited. We report the role of ischemic stress in RGS2 protein expression in rat C6 astrocytoma cells and primary mouse astrocytes. A marked increase in RGS2 occurred after ischemic stress induced by chemicals (sodium azide and 2-deoxyglucose) or oxygen-glucose deprivation (OGD, real ischemia). RGS2 mRNA expression was markedly enhanced by 1 h of exposure to chemical ischemia or 6 h of OGD followed by 2 or 6 h of recovery, respectively. This enhanced expression in primary astrocytes and C6 cells was restored to baseline levels after 12 h of recovery from chemically induced ischemic stress or 4–6 h of recovery from OGD. RGS2 protein was also significantly expressed at 12–24 h of recovery from ischemic insult. Ischemia-induced RGS2 upregulation was associated with enhanced apoptosis. It significantly increased annexin V-positive cells, cleaved caspase-3, and enhanced DNA ladder formation and cell cycle arrest. However, a small interfering RNA (siRNA)-mediated RGS2 knockdown reversed the apoptotic cell death associated with ischemia-induced RGS2 upregulation. Upregulated RGS2 was significantly inhibited by SB-203580, a p38 MAPK inhibitor. Rottlerin, a potent inhibitor of PKC, completely abrogated the increased RGS2 expression. We also examine whether ischemia-induced RGS2-mediated apoptosis is affected by siRNA-targeted endogenous PKC downregulation or its phosphorylation. Although RGS2 upregulation was not affected, siRNA transfection significantly suppressed endogenous PKC mRNA and protein expressions. Ischemia-induced PKC phosphorylation and caspase-3 cleavage were dose dependently inhibited by PKC knockdown, and this endogenous PKC suppression reversed ischemia-induced annexin V-positive cells. This study suggests that ischemic stress increases RGS2 expression and that this condition contributes to enhanced apoptosis in C6 cells and primary astrocytes. The signaling it follows may involve PKC and p38 MAPK pathways.

  J Ahn , H Lee , S Kim and T. Ha

Curcumin, a polyphenol found in the rhizomes of Curcuma longa, improves obesity-associated inflammation and diabetes in obese mice. Curcumin also suppresses adipocyte differentiation, although the underlying mechanism remains unclear. Here, we used 3T3-L1 cells to investigate the details of the mechanism underlying the anti-adipogenic effects of curcumin. Curcumin inhibited mitogen-activated protein kinase (MAPK) (ERK, JNK, and p38) phosphorylation that was associated with differentiation of 3T3-L1 cells into adipocytes. During differentiation, curcumin also restored nuclear translocation of the integral Wnt signaling component β-catenin in a dose-dependent manner. In parallel, curcumin reduced differentiation-stimulated expression of CK1, GSK-3β, and Axin, components of the destruction complex targeting β-catenin. Accordingly, quantitative PCR analysis revealed that curcumin inhibited the mRNA expression of AP2 (mature adipocyte marker) and increased the mRNA expression of Wnt10b, Fz2 (Wnt direct receptor), and LRP5 (Wnt coreceptor). Curcumin also increased mRNA levels of c-Myc and cyclin D1, well-known Wnt targets. These results suggest that the Wnt signaling pathway participates in curcumin-induced suppression of adipogenesis in 3T3-L1 cells.

  S Kim , D. B Oh , O Kwon and H. A. Kang

Corynebacterium diphtheriae, a pathogenic Gram-positive bacterium, contains sialic acids on its cell surface, but no genes related to sialic acid decoration or metabolism have been reported in C. diphtheriae. In the present study, we have identified a putative sialidase gene, nanH, from C. diphtheriae KCTC3075 and characterized its product for enzyme activity. Interestingly, the recombinant NanH protein was secreted as a catalytically active sialidase into the periplasmic space in Escherichia coli, while the short region at its C-terminus was truncated by proteolysis. We reconstructed a truncated NanH protein (His6-NanHN) devoid of its signal sequence as a mature enzyme fused with the 6xHis tag at the N-terminal region. The purified His6-NanHN can cleave -2,3- and -2,6-linked sialic acid from sialic acid-containing substrates. In addition, even though the efficiency was low, the recombinant His6-NanHN was able to catalyse the transfer of sialic acid using several sialoconjugates as donor, suggesting that the reversible nature of C. diphtheriae NanH can be used for the synthesis of sialyl oligosaccharides via transglycosylation reaction.

  S Kim , Y. P Wairkar , R. W Daniels and A. DiAntonio

Defective attenuation of BMP signaling causes synapses to overgrow in Drosophila Ema mutants due to impaired endosomal maturation.

  J. V Busik , M Tikhonenko , A Bhatwadekar , M Opreanu , N Yakubova , S Caballero , D Player , T Nakagawa , A Afzal , J Kielczewski , A Sochacki , S Hasty , S. L Calzi , S Kim , S. K Duclas , M. S Segal , D. L Guberski , W. J Esselman , M. E Boulton and M. B. Grant

The present epidemic of diabetes is resulting in a worldwide increase in cardiovascular and microvascular complications including retinopathy. Current thinking has focused on local influences in the retina as being responsible for development of this diabetic complication. However, the contribution of circulating cells in maintenance, repair, and dysfunction of the vasculature is now becoming appreciated. Diabetic individuals have fewer endothelial progenitor cells (EPCs) in their circulation and these cells have diminished migratory potential, which contributes to their decreased reparative capacity. Using a rat model of type 2 diabetes, we show that the decrease in EPC release from diabetic bone marrow is caused by bone marrow neuropathy and that these changes precede the development of diabetic retinopathy. In rats that had diabetes for 4 mo, we observed a dramatic reduction in the number of nerve terminal endings in the bone marrow. Denervation was accompanied by increased numbers of EPCs within the bone marrow but decreased numbers in circulation. Furthermore, denervation was accompanied by a loss of circadian release of EPCs and a marked reduction in clock gene expression in the retina and in EPCs themselves. This reduction in the circadian peak of EPC release led to diminished reparative capacity, resulting in the development of the hallmark feature of diabetic retinopathy, acellular retinal capillaries. Thus, for the first time, diabetic retinopathy is related to neuropathy of the bone marrow. This novel finding shows that bone marrow denervation represents a new therapeutic target for treatment of diabetic vascular complications.

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