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1.
Curr Top Dev Biol ; 120: 103-24, 2016.
Article in English | MEDLINE | ID: mdl-27475850

ABSTRACT

Zygotic genome activation (ZGA, a.k.a. zygotic gene activation) is a critical event in development, when the paternally derived genome and maternally derived genome begin to be activated and transcribed after fertilization. Major ZGA occurs at the two-cell stage in mice and the four- to eight-cell stage in human preimplantation embryos. It has been thought that ZGA exists to provide RNAs and proteins supporting embryonic development after supplies stored in oocytes are used up; however, this paradigm does not seem to explain recent findings. For example, many ZGA genes-once activated-are quickly turned off, and thus ZGA forms a transient wave of transcriptional activation. In addition, ZGA genes are not evolutionarily conserved. In this review, we address these issues by focusing on Zscan4 (zinc finger and SCAN domain-containing 4), which was identified for its specific expression in preimplantation embryos during ZGA. Detailed molecular analyses of Zscan4 expression and function have revealed common features of Zscan4-associated events (Z4 events) in mouse embryonic stem cells and ZGA in preimplantation embryos. One feature is a rapid derepression and rerepression of constitutive heterochromatin, which includes pericentromeric major satellites and telomeres, and facultative heterochromatin, which includes retrotransposons and Z4 event-associated genes. We propose that the Z4 event superimposed on ZGA plays a critical role in the maintenance of genome and chromosome integrity in preimplantation embryos by promoting correction of DNA damage and chromosome abnormalities.


Subject(s)
Gene Expression Regulation, Developmental , Genome , Transcription Factors/metabolism , Zygote/metabolism , Animals , DNA Damage , Evolution, Molecular , Humans
2.
AJNR Am J Neuroradiol ; 36(6): 1188-93, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25678480

ABSTRACT

BACKGROUND AND PURPOSE: Diagnostic test accuracy studies for ultrasonography-guided fine-needle aspiration and ultrasonography-guided core needle biopsy have shown inconclusive results due to their heterogenous study designs. Our aim was to compare the diagnostic accuracy of ultrasonography-guided fine-needle aspiration versus ultrasonography-guided core needle biopsy for detecting malignant tumors of the salivary gland and for the tissue-specific diagnosis of salivary gland tumors in a single tertiary hospital. MATERIALS AND METHODS: This retrospective study was approved by our institutional review board and informed consent was waived. Four hundred twelve patients who underwent ultrasonography-guided fine-needle aspiration (n = 155) or ultrasonography-guided core needle biopsy (n = 257) with subsequent surgical confirmation or clinical follow-up were enrolled. We compared the diagnostic accuracy of ultrasonography-guided fine-needle aspiration and ultrasonography-guided core needle biopsy regarding malignant salivary gland tumors and the correct tissue-specific diagnosis of benign and malignant tumors. We also tested the difference between these procedures according to the operator's experience and lesion characteristics. RESULTS: The inconclusive rates of ultrasonography-guided fine-needle aspiration and ultrasonography-guided core needle biopsy were 19% and 4%, respectively (P < .001). The overall accuracy of ultrasonography-guided core needle biopsy for diagnosing malignant tumors was significantly higher than that of ultrasonography-guided fine-needle aspiration (P = .024). The correct tissue-specific diagnosis rates of ultrasonography-guided fine-needle aspiration and ultrasonography-guided core needle biopsy were 95% versus 97% for benign tumors (P = .648) and 67% versus 80% for malignant tumors (P = .310). Trainees showed significantly lower accuracy with ultrasonography-guided fine-needle aspiration than with ultrasonography-guided core needle biopsy for diagnosing malignant tumors (P = .021). There was no difference between the diagnostic accuracy of ultrasonography-guided fine-needle aspiration and ultrasonography-guided core needle biopsy according to the internal composition of the lesions. There were no complications requiring intervention or hospitalization in our patients. CONCLUSIONS: Ultrasonography-guided core needle biopsy is superior to ultrasonography-guided fine-needle aspiration in detecting and characterizing malignant tumors of the salivary gland and could emerge as the diagnostic method of choice for patients presenting with a salivary gland mass.


Subject(s)
Biopsy, Fine-Needle , Biopsy, Large-Core Needle/methods , Salivary Glands/pathology , Ultrasonography, Interventional/methods , Adult , Aged , Aged, 80 and over , Biopsy, Fine-Needle/methods , Child , Female , Humans , Informed Consent , Male , Middle Aged , Retrospective Studies , Salivary Gland Neoplasms/pathology , Sensitivity and Specificity , Young Adult
3.
Anim Genet ; 45(4): 589-92, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24797173

ABSTRACT

Growth traits, such as body weight and carcass body length, directly affect productivity and economic efficiency in the livestock industry. We performed a genome-wide linkage analysis to detect the quantitative trait loci (QTL) that affect body weight, growth curve parameters and carcass body length in an F2 intercross between Landrace and Korean native pigs. Eight phenotypes related to growth were measured in approximately 1000 F2 progeny. All experimental animals were subjected to genotypic analysis using 173 microsatellite markers located throughout the pig genome. The least squares regression approach was used to conduct the QTL analysis. For body weight traits, we mapped 16 genome-wide significant QTL on SSC1, 3, 5, 6, 8, 9 and 12 as well as 22 suggestive QTL on SSC2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 17. On SSC12, we identified a major QTL affecting body weight at 140 days of age that accounted for 4.3% of the phenotypic variance, which was the highest test statistic (F-ratio = 45.6 under the additive model, nominal P = 2.4 × 10(-11) ) observed in this study. We also showed that there were significant QTL on SSC2, 5, 7, 8, 9 and 12 affecting carcass body length and growth curve parameters. Interestingly, the QTL on SSC2, 3, 5, 6, 8, 9, 10, 12 and 17 influencing the growth-related traits showed an obvious trend for co-localization. In conclusion, the identified QTL may play an important role in investigating the genetic structure underlying the phenotypic variation of growth in pigs.


Subject(s)
Genetic Linkage , Quantitative Trait Loci , Sus scrofa/physiology , Animals , Body Size , Body Weight , Crosses, Genetic , Microsatellite Repeats , Polymerase Chain Reaction/veterinary , Sus scrofa/genetics , Sus scrofa/growth & development
4.
Klin Khir ; (7): 5-8, 2012 Jul.
Article in Ukrainian | MEDLINE | ID: mdl-23033768

ABSTRACT

Results of surgical treatment of 93 primary patients with medullary thyroid carcinoma within 1995-2009 years, including 26 (28%) - with hereditary disease (MEN2 syndrome) were analyzed. The best long-term results were observed in group of noninvasive tumor without metastases at the time of operation (39% - clinical and biochemical recovery, 32% - clinical remission). No one patient with extrathyroid tumor invasion and regional/distant metastases has completely recovered. Hereditary forms of disease are more aggressiveness in comparison with sporadic carcinomas with higher rate of distant metastases (31 and 21%) and worse survival. In sporadic group 3 (6%) patients and in hereditary group - 4 (12%) died from progression of distant metastases within 8-15 years after primary operation. Complete recovery was seen only after radical primary operations. Repeated surgery was palliative. Implementation of calcitonine screening and genetic testing for Ret-protooncogene mutation is an important task for Ukraine medicine to improve results of medullary carcinoma treatment.


Subject(s)
Carcinoma, Medullary/secondary , Carcinoma, Medullary/surgery , Thyroid Neoplasms/mortality , Thyroid Neoplasms/surgery , Adult , Age of Onset , Aged , Carcinoma, Medullary/genetics , Carcinoma, Medullary/mortality , Comorbidity , Female , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Multiple Endocrine Neoplasia Type 2a/genetics , Multiple Endocrine Neoplasia Type 2a/mortality , Survival Rate , Thyroid Neoplasms/genetics , Treatment Outcome
5.
AJNR Am J Neuroradiol ; 33(1): 124-7, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22158923

ABSTRACT

BACKGROUND AND PURPOSE: The US features of benign and malignant nodules overlap, and benign thyroid lesions can mimic thyroid malignancy on US. Benign cystic nodules after spontaneous collapse or needle aspiration, can mimic malignant thyroid nodules. Our aim was to evaluate the US features of CBCNs of the thyroid that distinguish such nodules from malignant thyroid nodules. MATERIALS AND METHODS: US and clinical findings in 13 patients, each with a single CBCN, were evaluated to determine if they showed >50% cystic content on initial US or CT and >30% decrease in maximum diameter on follow-up US. We compared these findings with those of 26 patients, each with a single surgically confirmed PTMC. US scans were analyzed for internal content, shape, margin, echogenicity, presence of echogenic dots suggesting micro- and macrocalcification, inner isoechoic rim, and low-echoic halo. RESULTS: Six of the 13 (46%) CBCNs were classified as malignant on US due to their marked hypoechogenicity, microcalcification, or spiculated margins. US features that differed between CBCNs and PTMCs were shape (ovoid-to-round versus taller-than-wide, P = .016); margins (ill-defined versus spiculated, P < .000); low-echoic halo (P < .000); inner isoechoic rim (P < .000) with high negative predictive values (100%, 91%, 91%, and 89%, respectively); and clinically acceptable diagnostic accuracy (59%, 80%, 82%, and 85%, respectively). CONCLUSIONS: US features helpful for differential diagnosis of CBCNs from PTMCs include shape, margin, and the presence of an inner isoechoic rim and a low-echoic halo. Familiarity with US features suggesting CBCNs may be helpful in reducing unnecessary repeated FNABs.


Subject(s)
Carcinoma, Papillary/diagnostic imaging , Cysts/diagnostic imaging , Thyroid Gland/diagnostic imaging , Thyroid Neoplasms/diagnostic imaging , Ultrasonography/methods , Adult , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity
6.
Anim Genet ; 42(6): 621-6, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22035003

ABSTRACT

Haematological traits play important roles in disease resistance and defence functions. The objective of this study was to locate quantitative trait loci (QTL) and the associated positional candidate genes influencing haematological traits in an F(2) intercross between Landrace and Korean native pigs. Eight blood-related traits (six erythrocyte traits, one leucocyte trait and one platelet trait) were measured in 816 F(2) progeny. All experimental animals were genotyped with 173 informative microsatellite markers located throughout the pig genome. We report that nine chromosomes harboured QTL for the baseline blood parameters: genomic regions on SSC 1, 4, 5, 6, 8, 9, 11, 13 and 17. Eight of twenty identified QTL reached genome-wide significance. In addition, we evaluated the KIT locus, an obvious candidate gene locus affecting variation in blood-related traits. Using dense single nucleotide polymorphism marker data on SSC 8 and the marker-assisted association test, the strong association of the KIT locus with blood phenotypes was confirmed. In conclusion, our study identified both previously reported and novel QTL affecting baseline haematological parameters in pigs. Additionally, the positional candidate genes identified here could play an important role in elucidating the genetic architecture of haematological phenotype variation in swine and in humans.


Subject(s)
Blood Platelets/cytology , Erythrocytes/cytology , Leukocytes/cytology , Quantitative Trait Loci , Sus scrofa/genetics , Animals , Crosses, Genetic , Genome-Wide Association Study , Hematopoiesis , Species Specificity , Sus scrofa/metabolism
7.
Anim Genet ; 42(4): 451-5, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21749430

ABSTRACT

The KIT locus has been suggested to be a strong candidate region linked with whole-body roan in the F(2) population produced by intercrosses between Landrace and Korean Native pigs. In this manuscript, we report the finding of a novel alternative splicing event in the porcine KIT gene that results in the skipping of exon 5 in the I(Rn) allele. KIT mRNAs that lack exon 5 were identified in the large intestine and skin, suggesting that the mechanism responsible for the skipping of exon 5 may be tissue specific. A U(26) repeat in intron 5 showed complete linkage (LOD = 11.8) with the roan phenotype and absolute association with the black phenotype of the Korean Native pig (KNP) population samples, inferring that the repeat pattern may alter the complementary base-pairing-mediated looping-out of introns 4 and 5, which may mediate the exon 5-skipping event. Although the sample size in our study was relatively small, we speculate that the R3 allele containing the U(26) repeat is a causative element for the roan phenotype via alternative control of the exon skipping in our roan pedigree.


Subject(s)
Alternative Splicing/genetics , Exons/genetics , Hair/physiology , Pigmentation/genetics , Proto-Oncogene Proteins c-kit/genetics , RNA, Messenger/genetics , Sus scrofa/genetics , Animals , Base Sequence , Crosses, Genetic , DNA Primers/genetics , Genetic Linkage , Genetics, Population , Molecular Sequence Data , Pedigree , Pigmentation/physiology , Republic of Korea , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis, DNA , Sus scrofa/physiology
8.
AJNR Am J Neuroradiol ; 28(10): 1895-901, 2007.
Article in English | MEDLINE | ID: mdl-17921235

ABSTRACT

BACKGROUND AND PURPOSE: The outcome for simultaneous revascularization of more than 1 supra-aortic arterial stenosis has not been evaluated because of concerns regarding the increased risk of additional procedures. We evaluated the feasibility and safety of concomitant multiple supra-aortic arterial revascularizations (CMSAR). MATERIALS AND METHODS: We retrospectively evaluated 50 consecutive patients who underwent CMSARs with angioplasty and stent placement. The study included a separate lesion group (LG) (n = 28), ipsilateral LG (n = 17) including adjacent (n = 6) and remote (n = 11) tandem lesions, and triple LG (n = 5). We assessed the procedural success (defined as residual stenosis <30%) and periprocedural event rate (ER) (minor or major stroke, and death). We compared the ERs in the lesion (ipsilateral vs separate) and symptom (unstable vs stable) pattern groups with the Fisher exact test. RESULTS: Procedural success was achieved in all patients (50/50). Periprocedural events within 30 days were noted in 5 (10%). ER within 2 days after the procedure was higher in the ipsilateral LG (4/17) than in the separate LG (0/28) (P = .016). Major events consisting of a major stroke and a death occurred in 2 patients in the unstable group (4%) and was more common in the unstable (2 of 7) than in the stable group (0/38) (P = .029). During the mean 11-month follow-up period, there was 1 symptomatic recurrence. CONCLUSION: CMSARs are feasible with a high procedural success rate resulting in a favorable short-term outcome. However, they must be carefully performed in ipsilateral LG, especially in patients in the unstable group.


Subject(s)
Angioplasty, Balloon , Carotid Artery Diseases/therapy , Intracranial Arteriosclerosis/therapy , Stents , Subclavian Steal Syndrome/therapy , Aged , Aged, 80 and over , Angioplasty, Balloon/adverse effects , Carotid Artery Diseases/diagnostic imaging , Cerebral Angiography , Female , Humans , Intracranial Arteriosclerosis/diagnostic imaging , Ischemic Attack, Transient/etiology , Male , Middle Aged , Recurrence , Stents/adverse effects , Stroke/etiology , Subclavian Steal Syndrome/diagnostic imaging , Vertebrobasilar Insufficiency/therapy
10.
Reproduction ; 132(1): 45-57, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16816332

ABSTRACT

A series of Ca(2+) oscillations during mammalian fertilization is necessary and sufficient to stimulate meiotic resumption and pronuclear formation. It is not known how effectively development continues in the absence of the initial Ca(2+) signal. We have triggered parthenogenetic egg activation with cycloheximide that causes no Ca(2+) increase, with ethanol that causes a single large Ca(2+) increase, or with Sr(2+) that causes Ca(2+) oscillations. Eggs were co-treated with cytochalasin D to make them diploid and they formed pronuclei and two-cell embryos at high rates with each activation treatment. However, far fewer of the embryos that were activated by cycloheximide reached the blastocyst stagecompared tothose activated by Sr(2+) orethanol. Any cycloheximide-activated embryos that reached the blastocyst stage had a smaller inner cell mass number and a greater rate of apoptosis than Sr(2+)-activated embryos. The poor development of cycloheximide-activated embryos was due to the lack of Ca(2+) increase because they developed to blastocyst stages at high rates when co-treated with Sr(2+) or ethanol. Embryos activated by either Sr(2+) or cycloheximide showed similar signs of initial embryonic genome activation (EGA) when measured using a reporter gene. However, microarray analysis of gene expression at the eight-cell stage showed that activation by Sr(2+) leads to a distinct pattern of gene expression from that seen with embryos activated by cycloheximide. These data suggest that activation of mouse eggs in the absence of a Ca(2+) signal does not affect initial parthenogenetic events, but can influence later gene expression and development.


Subject(s)
Blastocyst/metabolism , Calcium Signaling , Embryonic Development , Gene Expression Regulation, Developmental , Parthenogenesis , Animals , Apoptosis , Cell Proliferation , Cleavage Stage, Ovum , Cycloheximide/pharmacology , Embryo Culture Techniques , Ethanol/pharmacology , Female , Gene Expression Profiling/methods , In Situ Nick-End Labeling , Mice , Mice, Inbred Strains , Oligonucleotide Array Sequence Analysis , Protein Synthesis Inhibitors/pharmacology
11.
Genome Res ; 11(11): 1833-41, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11691847

ABSTRACT

Mammals achieve gene dosage control by (1) random X-chromosome inactivation in females, (2) parental origin-specific imprinting of selected autosomal genes, and (3) random autosomal inactivation. Genes belonging to the third category of epigenetic phenomenon are just now emerging, with only six identified so far. Here we report three additional genes, Nubp2, Igfals, and Jsap1, that show 50%-methylated CpG sites by Southern blot analyses and primarily monoallelic expression in single-cell allele-specific RT-PCR analysis of bone marrow stromal cells and hepatocytes. Furthermore, we show that, in contrast to X inactivation, alleles can switch between active and inactive states during the formation of daughter cells. These three genes are the first in their category to exist as a tight cluster, in the proximal region of mouse chromosome 17, providing a thus far unique example of a region of autosomal random monoallelic expression.


Subject(s)
Adaptor Proteins, Signal Transducing , Alleles , Gene Expression Regulation/genetics , Genome , Intracellular Signaling Peptides and Proteins , Microtubule-Associated Proteins , Multigene Family/genetics , Nerve Tissue Proteins , Nuclear Proteins/genetics , Animals , Carrier Proteins/genetics , Clone Cells , Female , GTP-Binding Proteins/genetics , Gene Dosage , Gene Silencing , Glycoproteins/genetics , Male , Mice , Mice, Inbred C57BL , Molecular Weight , Sequence Analysis, DNA , Ubiquitin-Protein Ligases , t-Complex Genome Region
12.
Trends Biotechnol ; 19(12): 511-8, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11711195

ABSTRACT

Fundamental questions in developmental biology are: what genes are expressed, where and when they are expressed, what is the level of expression and how are these programs changed by the functional and structural alteration of genes? These questions have been addressed by studying one gene at a time, but a new research field that handles many genes in parallel is emerging. The methodology is at the interface of large-scale genomics approaches and developmental biology. Genomics needs developmental biology because one of the goals of genomics--collection and analysis of all genes in an organism--cannot be completed without working on embryonic tissues in which many genes are uniquely expressed. However, developmental biology needs genomics--the high-throughput approaches of genomics generate information about genes and pathways that can give an integrated view of complex processes. This article discusses these new approaches and their applications to mammalian developmental biology.


Subject(s)
Developmental Biology/trends , Gene Expression Profiling/methods , Genomics/trends , Oligonucleotide Array Sequence Analysis/methods , Animals , Embryonic Structures/cytology , Embryonic Structures/embryology , Expressed Sequence Tags , Gene Library , Humans , In Situ Hybridization , Mice , Proteome
13.
Neurobiol Dis ; 8(5): 822-33, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11592851

ABSTRACT

Due to brain tissue heterogeneity, the molecular genetic profile of any neurotransmitter-specific neuronal subtype is unknown. The purpose of this study was to purify a population of dopamine neurons, construct a cDNA library, and generate an initial gene expression profile and a microarray representative of dopamine neuron transcripts. Ventral mesencephalic dopamine neurons were purified by fluorescent-activated cell sorting from embryonic day 13.5 transgenic mice harboring a 4.5-kb rat tyrosine hydroxylase promoter-lacZ fusion. Nine-hundred sixty dopamine neuron cDNA clones were sequenced and arrayed for use in studies of gene expression changes during methamphetamine neurotoxicity. A neurotoxic dose of methamphetamine produced a greater than twofold up-regulation of the mitochondrial cytochrome c oxidase polypeptide I transcript from adult mouse substantia nigra at 12 h posttreatment. This is the first work to describe a gene expression profile for a neuronal subtype and to identify gene expression changes during methamphetamine neurotoxicity.


Subject(s)
Dopamine Uptake Inhibitors/toxicity , Dopamine/analysis , Electron Transport Complex IV/biosynthesis , Gene Expression Profiling , Gene Library , Methamphetamine/toxicity , Nerve Tissue Proteins/biosynthesis , Neurons/metabolism , Oligonucleotide Array Sequence Analysis , 3,4-Dihydroxyphenylacetic Acid/analysis , Animals , DNA, Complementary/genetics , Electron Transport Complex IV/genetics , Enzyme Induction , Female , Genes, Synthetic , Lac Operon , Male , Mesencephalon/cytology , Mesencephalon/embryology , Mice , Mice, Transgenic , Molecular Sequence Data , Nerve Tissue Proteins/genetics , Promoter Regions, Genetic , Rats , Transcription, Genetic , Tyrosine 3-Monooxygenase/genetics
14.
Nat Genet ; 29(2): 201-5, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11586302

ABSTRACT

A comprehensive gene-based map of a genome is a powerful tool for genetic studies and is especially useful for the positional cloning and positional candidate approaches. The availability of gene maps for multiple organisms provides the foundation for detailed conserved-orthology maps showing the correspondence between conserved genomic segments. These maps make it possible to use cross-species information in gene hunts and shed light on the evolutionary forces that shape the genome. Here we report a radiation hybrid map of mouse genes, a combined project of the Whitehead Institute/Massachusetts Institute of Technology Center for Genome Research, the Medical Research Council UK Mouse Genome Centre, and the National Center for Biotechnology Information. The map contains 11,109 genes, screened against the T31 RH panel and positioned relative to a reference map containing 2,280 mouse genetic markers. It includes 3,658 genes homologous to the human genome sequence and provides a framework for overlaying the human genome sequence to the mouse and for sequencing the mouse genome.


Subject(s)
Chromosome Mapping , Genome , Hybrid Cells/radiation effects , Animals , Expressed Sequence Tags , Mice
15.
Genome Res ; 11(9): 1553-8, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11544199

ABSTRACT

Here we report a novel design of linker primer that allows one to differentially amplify long tracts (average 3.0 kb with size ranges of 1-7 kb) or short DNAs (average 1.5 kb with size ranges of 0.5-3 kb) from a complex mixture. The method allows one to generate cDNA libraries enriched for long transcripts without size selection of insert DNAs. One representative library from newborn kidney includes 70% of clones bearing ATG start codons. A comparable library has been generated from 20 mouse blastocysts, containing only approximately 40 ng of total RNA. This universal PCR amplification scheme can provide a route to isolate very large cDNAs, even if they are expressed at very low levels.


Subject(s)
DNA, Complementary/genetics , Gene Library , Polymerase Chain Reaction/methods , RNA/analysis , RNA/genetics , Animals , Gene Amplification , Mice , Mice, Inbred C57BL , Molecular Sequence Data
16.
Int J Exp Diabetes Res ; 1(4): 249-63, 2001.
Article in English | MEDLINE | ID: mdl-11467416

ABSTRACT

Fetuin/alpha2-HS glycoprotein (alpha2-HSG) homologs have been identified in several species including rat, sheep, pig, rabbit, guinea pig, cattle, mouse and human. Multiple physiological roles for these homologs have been suggested, including ability to bind to hydroxyapatite crystals and to specifically inhibit the tyrosine kinase (TK) activity of the insulin receptor (IR). In this study we report the identification, cloning, and characterization of the mouse Ahsg gene and its function as an IR-TK inhibitor. Genomic clones derived from a mouse Svj 129 genomic library were sequenced in order to characterize the intron-exon organization of the mouse Ahsg gene, including an 875 bp subclone containing 154 bp upstream from the transcription start site, the first exon, and part of the first intron. A second genomic subclone harboring a 3.45 kb Bgl II fragment contained exons 2, 3 and 4 in addition to two adjacent elements within the first intron-a repetitive element of the B1 family (92 bp) and a 271 bp tract of (T,C)n*(A,G)n. We have mapped mouse Ahsg at 16 cM adjacent to the Diacylglycerol kinase 3 (Dagk3) gene on chromosome 16 by genotyping interspecific backcross panels between C57BL/6J and Mus spretus. The position is syntenic with human chromosome 3q27, where the human AHSG gene resides. Using recombinant mouse alpha2-HSG expressed from a recombinant baculovirus, we demonstrate that mouse alpha2-HSG inhibits insulin-stimulated IR autophosphorylation and IR-TKA in vitro. In addition, mouse alpha2-HSG (25 microg/ml) completely abolishes insulin-induced DNA synthesis in H-35 rat hepatoma cells. Based on the sequence data and functional analysis, we conclude that the mouse Ahsg gene is the true ortholog of the human AHSG gene.


Subject(s)
Blood Proteins , Chromosome Mapping , Cystatins/genetics , Enzyme Inhibitors , Protein-Tyrosine Kinases/antagonists & inhibitors , alpha-Fetoproteins/genetics , Amino Acid Sequence , Animals , Base Sequence , Cloning, Molecular , Cystatins/chemistry , Cystatins/pharmacology , DNA/biosynthesis , Gene Expression , Humans , Insulin/pharmacology , Mice , Molecular Sequence Data , Phosphorylation , Receptor, Insulin/metabolism , Recombinant Proteins , Sequence Alignment , alpha-2-HS-Glycoprotein , alpha-Fetoproteins/chemistry , alpha-Fetoproteins/pharmacology
18.
J Nanosci Nanotechnol ; 1(2): 185-90, 2001 Jun.
Article in English | MEDLINE | ID: mdl-12914050

ABSTRACT

Three ternary and four quaternary hafnium-based alloys have been rapidly solidified, and the devitrification of the resultant metallic glasses has been studied to evaluate the influence of composition on the products. The formation of metastable and stable Fd3m (Pearson symbol cF96) Ti2Ni was evident whenever the alloy composition in the stable equilibrium diagrams showed this phase. The replacement of nickel by iron led to the appearance of this phase in preference to the icosahedral quasicrystal. Several common features of the amorphous alloys that form either nanoscale icosahedral or cF96 Ti2Ni-type phases on devitrification are discussed and summarized.


Subject(s)
Alloys/chemistry , Crystallization/methods , Hafnium/chemistry , Nanotechnology/methods , Nickel/chemistry , Titanium/chemistry , Calorimetry, Differential Scanning , Glass/chemistry , Metals/chemistry , Microscopy, Electron , Molecular Conformation , Particle Size , Temperature , X-Ray Diffraction
20.
Genomics ; 68(3): 305-12, 2000 Sep 15.
Article in English | MEDLINE | ID: mdl-10995572

ABSTRACT

A novel human X-linked gene shows placenta-specific expression and has been named PLAC1. The gene maps 65 kb telomeric to HPRT at Xq26 and has been completely sequenced at the cDNA and genomic levels. The mouse orthologue Plac1 maps to the syntenically equivalent region of the mouse X chromosome. In situ hybridization studies with the antisense mRNA during mouse embryogenesis detect Plac1 expression from 7.5 dpc (days postcoitum) to 14.5 dpc in ectoplacental cone, giant cells, and labyrinthine trophoblasts. The putative human and murine PLAC1 proteins are 60% identical and 77% homologous. Both include a signal peptide and a peptide sequence also found in an interaction domain of the ZP3 (zona pellucida 3) protein. These results make PLAC1 a marker for placental development, with a possible role in the establishment of the mother-fetus interface.


Subject(s)
Gene Expression Regulation, Developmental , Placenta/metabolism , Pregnancy Proteins/genetics , X Chromosome , Amino Acid Sequence , Animals , Base Sequence , Chromosome Mapping , Embryonic and Fetal Development , Expressed Sequence Tags , Giant Cells/metabolism , Humans , Mice , Molecular Sequence Data , Open Reading Frames , Pregnancy Proteins/chemistry , RNA, Antisense , RNA, Messenger/genetics , Sequence Alignment , Sequence Homology, Amino Acid , Transcription, Genetic , Trophoblasts/metabolism
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