Time Dependent Gene Expression Changes in the Liver of Mice Treated with Benzene

Benzene is used as a general purpose solvent. Benzene metabolism starts from phenol and ends with p-benzoquinone and o-benzoquinone. Liver injury inducted by benzene still remains a toxicologic problem. Tumor related genes and immune responsive genes have been studied in patients suffering from benzene exposure. However, gene expression profiles and pathways related to its hepatotoxicity are not known. This study reports the results obtained in the liver of BALB/C mice (SLC, Inc., Japan) administered 0.05 ml/100 g body weight of 2% benzene for six days. Serum, ALT, AST and ALP were determined using automated analyzer (Fuji., Japan). Histopathological observations were made to support gene expression data. c-DNA microarray analyses were performed using Affymetrix Gene-chip system. After six days of benzene exposure, twenty five genes were down regulated whereas nineteen genes were up-regulated. These gene expression changes were found to be related to pathways of biotransformation, detoxification, apoptosis, oxidative stress and cell cycle. It has been shown for the first time that genes corresponding to circadian rhythms are affected by benzene. Results suggest that gene expression profile might serve as potential biomarkers of hepatotoxicity during benzene exposure

Bone marrow-derived, alternatively activated macrophages enhance solid tumor growth and lung metastasis of mammary carcinoma cells in a Balb/C mouse orthotopic model

INTRODUCTION: Tumor-associated macrophages, which are derived from the infiltration of circulating bone marrow-derived monocytes, consist primarily of a polarized M2 macrophage (M2-Mϕ) population and are associated with poor prognosis in various cancers. In the present study, we attempted to assess whether M2-Mϕs derived from bone marrow stimulate the promotion and progression of mammary tumors. METHODS: 4T1 murine mammary carcinoma cells were injected either alone or coupled with M2-Mϕs into the mammary fat pads of syngeneic female Balb/C mice. M2-Mϕs were prepared by treating monocytes isolated from female Balb/C mouse bone marrow with IL-4. Tumor cell growth was determined using an in vivo imaging system and the expression of cell proliferation-related, angiogenesis-related, and lymphangiogenesis-related proteins in tumor tissues was immunohistochemically analyzed. To evaluate the effects of the crosstalk between 4T1 cells and M2-Mϕs on the secretion and mRNA expression of cytokines and the migration of monocytes, 4T1 cells and M2-Mϕs were co-cultured and cytokine antibody array, real-time RT-PCR, and trans-well migration assays were conducted. RESULTS: The co-injection of M2-Mϕs into the mammary fat pads of mice increased solid tumor growth and lung metastasis of 4T1 cells as well as the infiltration of CD45(+ )leukocytes into tumor tissues. The proportions of Ki-67(+ )proliferating cells and the expression of hypoxia inducible factor-1α, vascular endothelial cell growth factor A, CD31, vascular endothelial cell growth factor C, and lymphatic vessel endothelial receptor-1 were increased significantly in the tumor tissues of mice co-injected with 4T1 cells and M2-Mϕs. The in vitro results revealed that the proliferation of 4T1 cells, the migration of monocytes, and the secretion of granulocyte colony-stimulating factor, IFNγ, IL-1α, IL-2, IL-16, IFNγ-induced protein-10, keratinocyte-derived chemokine, macrophage colony-stimulating factor, monocyte chemotactic protein-1, macrophage inflammatory protein-1α, and RANTES were increased when 4T1 cells were co-cultured with M2-Mϕs, as compared with when the 4T1 cells were cultured alone. CONCLUSION: The crosstalk between 4T1 cells and M2-Mϕs increased the production of cytokines, which may have induced immune cell infiltration into tumor tissues, tumor cell proliferation, angiogenesis, and lymph angiogenesis, thereby increasing solid tumor growth and lung metastasis

Facile Method to Prepare for the Ni2P Nanostructures with Controlled Crystallinity and Morphology as Anode Materials of Lithium-Ion Batteries

Conversion reaction materials (transition metal oxides, sulfides, phosphides, etc.) are attractive in the field of lithium-ion batteries because of their high theoretical capacity and low cost. However, the realization of these materials in lithium-ion batteries is impeded by large voltage hysteresis, high polarization, inferior cycle stability, rate capability, irreversible capacity loss in first cycling, and dramatic volume change during redox reactions. One method to overcome these problems is the introduction of amorphous materials. This work introduces a facile method to synthesize amorphous and crystalline dinickel phosphide (Ni2P) nanoparticle clusters with identical morphology and presents a direct comparison of the two materials as anode materials for rechargeable lithium-ion batteries. To assess the effect of crystallinity and hierarchical structure of nanomaterials, it is crucial to conserve other factors including size, morphology, and ligand of nanoparticles. Although it is rarely studied about synthetic methods of well-controlled Ni2P nanomaterials to meet the above criteria, we synthesized amorphous, crystalline Ni2P, and self-assembled Ni2P nanoparticle clusters via thermal decomposition of nickel-surfactant complex. Interestingly, simple modulation of the quantity of nickel acetylacetonate produced amorphous, crystalline, and self-assembled Ni2P nanoparticles. A 0.357 M nickel-trioctylphosphine (TOP) solution leads to a reaction temperature limitation (similar to 315 degrees C) by the nickel precursor, and crystalline Ni2P (c-Ni2P) nanoparticles clusters are generated. On the contrary, a lower concentration (0.1 M) does not accompany a temperature limitation and hence high reaction temperature (330 degrees C) can be exploited for the self-assembly of Ni2P (s-Ni2P) nanoparticle clusters. Amorphous Ni2P (a-Ni2P) nanoparticle clusters are generated with a high concentration (0.714 M) of nickel-TOP solution and a temperature limitation (similar to 290 degrees C). The a-Ni2P nanoparticle cluster electrode exhibits higher capacities and Coulombic efficiency than the electrode based on c-Ni2P nanoparticle clusters. In addition, the amorphous structure of Ni2P can reduce irreversible capacity and voltage hysteresis upon cycling. The amorphous morphology of Ni2P also improves the rate capability, resulting in superior performance to those of c-Ni2P nanoparticle clusters in terms of electrode performance

Chiral orbital-angular-momentum in the surface states of Bi2Se3

Locking of the spin of a quasi-particle to its momentum in split bands of on the surfaces of metals and topological insulators (TIs) is understood in terms of Rashba effect where a free electron in the surface states feels an effective magnetic field. On the other hand, the orbital part of the angular momentum (OAM) is usually neglected. We performed angle resolved photoemission experiments with circularly polarized lights and first principles density functional calculation with spin-orbit coupling on a TI, Bi2Se3, to study the local OAM of the surface states. We show from the results that OAM in the surface states of Bi2Se3 is significant and locked to the electron momentum in opposite direction to the spin, forming chiral OAM states. Our finding opens a new possibility to have strong light-induced spin-polarized current in the surface states.Comment: 5 pages, 4 figures, 1 tabl

Isolated vestibular nuclear infarction: report of two cases and review of the literature

Cerebral infarction presenting with isolated vertigo remains a diagnostic challenge. To define the clinical characteristics of unilateral infarctions restricted to the vestibular nuclei, two patients with isolated unilateral vestibular nuclear infarction had bedside and laboratory evaluation of the ocular motor and vestibular function, including video-oculography, bithermal caloric irrigation, the head impulse test (HIT) using magnetic scleral coils, and cervical and ocular vestibular-evoked myogenic potentials (VEMPs). We also reviewed the literature on isolated vertigo from lesions restricted to the vestibular nuclei, and analyzed the clinical features of seven additional patients. Both patients showed spontaneous torsional-horizontal nystagmus that beat away from the lesion side, and direction-changing gaze-evoked nystagmus. Recording of HIT using a magnetic search coil system documented decreased gains of the vestibular-ocular reflex for the horizontal and posterior semicircular canals on both sides, but more for the ipsilesional canals. Bithermal caloric tests showed ipsilesional canal paresis in both patients. Cervical and ocular VEMPs showed decreased or absent responses during stimulation of the ipsilesional ear. Initial MRIs including diffusion-weighted images were normal or equivocal, but follow-up imaging disclosed a circumscribed acute infarction in the area of the vestibular nuclei. Infarctions restricted to the vestibular nuclei may present with isolated vertigo with features of both peripheral and central vestibulopathies. Central signs should be sought even in patients with spontaneous horizontal-torsional nystagmus and positive HIT. In patients with combined peripheral and central vestibulopathy, a vestibular nuclear lesion should be considered especially when hearing is preserved.OAIID:oai:osos.snu.ac.kr:snu2014-01/102/0000004487/4SEQ:4PERF_CD:SNU2014-01EVAL_ITEM_CD:102USER_ID:0000004487ADJUST_YN:YEMP_ID:A075641DEPT_CD:801CITE_RATE:3.841FILENAME:kimhj-isolated vn inf-j neurol-2014-261(1)121.pdfDEPT_NM:의학과SCOPUS_YN:YCONFIRM:

Endoplasmic reticulum stress and apoptosis induced by manganese trigger α-synuclein accumulation

Purpose: To explore whether α-synuclein aggregation is linked to endoplasmic reticulum (ER) stress and apoptosis induced by manganese (Mn) on CATH.a dopaminergic cell lines.Methods: Western blot analysis for the expression of 78 kDa glucose-regulated protein (GRP78), phosphorylated eukaryotic initiation factor 2α (p-eIF-2α), eIF2α, inositol requiring enzyme 1(IRE-1α), cleaved caspase-3, and C/EBP homologous protein (CHOP) was performed, including overexpression of recombinant adenovirus-mediated α-synuclein on CATH.a dopaminergic cell line.Results: It was observed that cell viability (p < 0.05) was significantly reduced by 250 μM exposed for 3h and 1,000 μM of MnCl2 exposed for 24 h. The expression of p-elF-2α, IRE-1α, and GRP78 was especially induced by 1,000 μM of MnCl2 exposed at 3, 6, and 12 h, respectively (p < 0.05). Twenty four-hour exposure of 250 uM of MnCl2 and the 3 h exposure of 1,000 uM of MnCl2 significantly induced CHOP, active caspase 3 and α-synuclein expression (p < 0.05). α-Synuclein combined with recombinant adenoviral transduction increased GRP78, IRE-1α and eIF2a, CHOP and caspase 3 expression at longer times and at higher concentrations of manganese exposure on CATH.a dopaminergic cells.Conclusion: Based on these findings, Mn is a risk factor for diseases associated with α-synuclein accumulation. Furthermore, α-synuclein accumulation is associated with apoptosis via ER stress induced by Mn.Keywords: Manganese (Mn), α- Synuclein, Endoplasmic reticulum (ER) stress, Apoptosi

A copula method for modeling directional dependence of genes

<p>Abstract</p> <p>Background</p> <p>Genes interact with each other as basic building blocks of life, forming a complicated network. The relationship between groups of genes with different functions can be represented as gene networks. With the deposition of huge microarray data sets in public domains, study on gene networking is now possible. In recent years, there has been an increasing interest in the reconstruction of gene networks from gene expression data. Recent work includes linear models, Boolean network models, and Bayesian networks. Among them, Bayesian networks seem to be the most effective in constructing gene networks. A major problem with the Bayesian network approach is the excessive computational time. This problem is due to the interactive feature of the method that requires large search space. Since fitting a model by using the copulas does not require iterations, elicitation of the priors, and complicated calculations of posterior distributions, the need for reference to extensive search spaces can be eliminated leading to manageable computational affords. Bayesian network approach produces a discretely expression of conditional probabilities. Discreteness of the characteristics is not required in the copula approach which involves use of uniform representation of the continuous random variables. Our method is able to overcome the limitation of Bayesian network method for gene-gene interaction, i.e. information loss due to binary transformation.</p> <p>Results</p> <p>We analyzed the gene interactions for two gene data sets (one group is eight histone genes and the other group is 19 genes which include DNA polymerases, DNA helicase, type B cyclin genes, DNA primases, radiation sensitive genes, repaire related genes, replication protein A encoding gene, DNA replication initiation factor, securin gene, nucleosome assembly factor, and a subunit of the cohesin complex) by adopting a measure of directional dependence based on a copula function. We have compared our results with those from other methods in the literature. Although microarray results show a transcriptional co-regulation pattern and do not imply that the gene products are physically interactive, this tight genetic connection may suggest that each gene product has either direct or indirect connections between the other gene products. Indeed, recent comprehensive analysis of a protein interaction map revealed that those histone genes are physically connected with each other, supporting the results obtained by our method.</p> <p>Conclusion</p> <p>The results illustrate that our method can be an alternative to Bayesian networks in modeling gene interactions. One advantage of our approach is that dependence between genes is not assumed to be linear. Another advantage is that our approach can detect directional dependence. We expect that our study may help to design artificial drug candidates, which can block or activate biologically meaningful pathways. Moreover, our copula approach can be extended to investigate the effects of local environments on protein-protein interactions. The copula mutual information approach will help to propose the new variant of ARACNE (Algorithm for the Reconstruction of Accurate Cellular Networks): an algorithm for the reconstruction of gene regulatory networks.</p

Small non-coding RNA profiling and the role of piRNA pathway genes in the protection of chicken primordial germ cells

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Background Genes, RNAs, and proteins play important roles during germline development. However, the functions of non-coding RNAs (ncRNAs) on germline development remain unclear in avian species. Recent high-throughput techniques have identified several classes of ncRNAs, including micro RNAs (miRNAs), small-interfering RNAs (siRNAs), and PIWI-interacting RNAs (piRNAs). These ncRNAs are functionally important in the genome, however, the identification and annotation of ncRNAs in a genome is challenging. The aim of this study was to identify different types of small ncRNAs particularly piRNAs, and the role of piRNA pathway genes in the protection of chicken primordial germ cells (PGCs). Results At first, we performed next-generation sequencing to identify ncRNAs in chicken PGCs, and we performed ab initio predictive analysis to identify putative piRNAs in PGCs. Then, we examined the expression of three repetitive sequence-linked piRNAs and 14 genic-transcript-linked piRNAs along with their linked genes using real-time PCR. All piRNAs and their linked genes were highly expressed in PGCs. Subsequently, we knocked down two known piRNA pathway genes of chicken, PIWI-like protein 1 (CIWI) and 2 (CILI), in PGCs using siRNAs. After knockdown of CIWI and CILI, we examined their effects on the expression of six putative piRNA-linked genes and DNA double-strand breakage in PGCs. The knockdown of CIWI and CILI upregulated chicken repetitive 1 (CR1) element and RAP2B, a member of RAS oncogene family, and increased DNA double-strand breakage in PGCs. Conclusions Our results increase the understanding of PGC-expressed piRNAs and the role of piRNA pathway genes in the protection of germ cells

Allelic and Haplotypic Diversity of HLA-A, -B, -C, and-DRB1 Genes in Koreans Defined by High-resolution DNA Typing

배경 : HLA 형별은 혈청학적 수준(generic level)에서도 다형성이 심하지만 대립유전자 수준에서는 더욱 심한 다형성을 보이고 인종 간에 큰 차이를 나타내는 것으로 알려졌다. 본 연구에서는 고해상도 DNA 검사법을 이용하여 한국인에서 HLA대립유전자 형별과 일배체형의 종류 및 빈도를 알아보고자 하였다. 방법 : 건강한 한국인 474명을 대상으로 HLA-A, -B, -C, -DRB1 유전자에 대해 두 단계의 검사로 대립유전자(4자리수) 형별 분석을 실시하였다. 1단계로 혈청학적 수준의 형별검사를 혈청학적 검사법이나 sequence-specific oligonucleotide(PCR-SSO) 방법으로 시행하였고, 그 다음 단계로 대립유전자 형별검사를 class I은 exon 2와 exon3, DRB1은 exon 2에 대해 single-strand conformation polymorphism (PCR-SSCP) 또는 직접염기서열분석법을 이용하여 실시하였다. HLA 대립 유전자의 유전자 빈도, 일배체형 빈도, 연쇄불평형 값은 maximum likelihood 원리에 근거한 제11차 국제조직적합성워크숍 컴퓨터 프로그램을 이용하여 산출하였다. 결과 : 한국인에서 검출된 HLA-A, -B, -C, DRB1 대립유전자 형별은 각각 21, 40, 22, 29종이었다. 이 중에 유전자 빈도 10% 이상을 보인 대립유전자 형별(빈도순 나열)은 A*02:01, A*24:02, A*33:03; B*51:01; C*01:02, C*03:03; RB1*09:01등이었다. HLA 일배체형의 분석 결과 0.5% 이상의 빈도를 나타내는 2-유전자좌 일배체형은 A-C 44종, B-C 42종, A-B 51종, B-DRB1 52종이었고, 3-유전자좌 일배체형은 A-C-B 42종, A-B-DRB1 34종이었다. 한국인에서 빈도 1% 이상의 A-B-DR 일배체형은 13종으로, 전체 일배체형의 26.0%를 차지하였고, 2% 이상으로 가장 흔한 A-B-DR 일배체형은 A*33:03-B*44:03-DRB1*13:02 (3.7%), A*33:03-B*44:03-DRB1*07:01 (3.0%), A*33:03-B*58:01-DRB1*13:02 (3.0%), A*24:02-B*07:02-DRB1*01:01 (2.8%), A*30:01-B*13:02-DRB1* 07:01 (2.3%), A*11:01-B*15:01-DRB1*04:06 (2.2%) 등 6종이었다. 결론 : 본 연구를 통해 한국인의 대립유전자 수준의 HLA 형별과 HLA 일배체형 빈도에 대한 자료를 제시하였으며, 본 연구의 결과는 한국인에서 장기이식, 질환연관성 연구, 인류유전학적 연구 등에서 중요한 기초자료로 이용될 수 있을 것으로 기대된다. Background : In this study, we used high-resolution DNA typing to investigate the distribution of HLA alleles and haplotypes in Koreans. Methods : HLA-A, -B, -C, and -DRB1 alleles were genotyped at the allelic (4-digit) level in 474 healthy Koreans. HLA genotyping was performed in two steps. Initially, serologic typing or generic-level DNA typing was performed using the FOR-sequence-specific oligonucleotide method, and then allelic DNA typing (exons 2 and 3 for class I, and exon 2 for DRB1) was carried out using the FOR-single-strand conformation polymorphism method or sequence-based typing. HLA allele and haplotype frequencies and linkage disequilibrium values were calculated by the maximum likelihood method using a computer program developed for the 11th International Histocompatibility Workshop. Results : A total of 21 HLA-A, 40 HLA-B, 22 HLA-C, and 29 HLA-DRB1 alleles were found in Koreans. The most frequent alleles in each locus with frequencies of >= 10% were, in decreasing order of frequency, as follows: A star 24:02, A star 02:01, A(star)33:03; B(star)51:01; C(star)01:02, C(star)03:03; and DRB1(star)09:01. The numbers of two- and three-locus haplotypes with frequencies of >0.5% were as follows: 44 A-C, 42 B-C, 51 A-B, 52 B-DRB1, 42 A-C-B, and 34 A-B-DRB1. Thirteen A-B-DRB1 haplotypes with frequencies of >= 1.0% comprised 26.0% of the total haplotypes. The six most common haplotypes were as follows: A(star)33:03-B(star)44:03-DRB1(star)3:02 (3.7%), A(star)33:03-B(star)44:03-DRB1(star)07:01 (3.0%), A(star)33:03-B(star)58: 01-DRB1(star)13:02 (3.0%), A(star)24:02-B(star)07:02-DRB1(star)01:01 (2.8%), A(star)30:01-B(star)13:02-DRB1(star)07:01 (2.3%), and A(star)11:01-B(star)15:01-DR81(star)04:06 (2.2%). Conclusions : The information obtained in this study can be used as basic data for Koreans in the fields of organ transplantation, disease association, and anthropologic studies. 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