WorldWideScience

Sample records for mouse full metallothionein-1

  1. Efficient Expression of the Mouse Balb/C Metallothionein-1 Gene in Escherichi a Coli%Balb/C小鼠金属硫蛋白-1基因在大肠杆菌中的高效表达

    Institute of Scientific and Technical Information of China (English)

    林琳; 任凤; 赵宝昌; 金晓艳

    2001-01-01

    将Balb/C小鼠金属硫蛋白-1基因克隆于质粒表达载体pET-21a 上,克隆采用限制性内切酶BamH1与EcoR1酶切pET21a及金属硫蛋白-1基因PCR产物,连接成 pET21a-MT重组质粒,并将其转化进入大肠杆菌表达受体菌BL21(DE3)中,经异丙基-β-D -硫代半乳糖苷(IPTG)诱导,SDS-聚丙烯酰胺凝胶电泳(PAGE)证实产生高效表达金属硫蛋白-1 基因的金属硫蛋白融合蛋白。表达蛋白在胞内主要以不溶性包涵体存在。%Mouse Balb/C metallothionein cDNA was cloned into pET21 a with the rest riction endonuclease BamH1 and EcoR1 to form the recombinant plasmid pET21a-MT . pET21a-MT was then transformed into the BL21(DE3).After the induction of IPTG , the protein produced from the BL21(pET21a-MT) was proved to be the metallothion e in fusion protein (99 amino acids/per protein molecule).SDS-PAGE showed that the induced protein was present mainly as the inclusion body in E.coli.

  2. Metallothionein-1+2 protect the CNS after a focal brain injury

    DEFF Research Database (Denmark)

    Giralt, Mercedes; Penkowa, Milena; Lago, Natalia;

    2002-01-01

    We have evaluated the physiological relevance of metallothionein-1+2 (MT-1+2) in the CNS following damage caused by a focal cryolesion onto the cortex. In comparison to normal mice, transgenic mice overexpressing the MT-1 isoform (TgMTI* mice) showed a significant decrease of the number of activa...

  3. Metallothionein 1+2 protect the CNS during neuroglial degeneration induced by 6-aminonicotinamide

    DEFF Research Database (Denmark)

    Penkowa, Milena; Giralt, Mercedes; Camats, Jordi

    2002-01-01

    6-Aminonicotinamide (6-AN) is a niacin antagonist, which leads to degeneration of gray matter astrocytes. Metallothionein 1+2 (MT-1+2) are neuroprotective factors in the central nervous system (CNS), and to determine the roles for MT after 6-AN, we have examined transgenic mice overexpressing MT-1...

  4. Functional annotation of a full-length mouse cDNA collection

    Energy Technology Data Exchange (ETDEWEB)

    Kawai, J.; Shinagawa, A.; Shibata, K.; Yoshino, M.; Itoh, M.; Ishii, Y.; Arakawa, T.; Hara, A.; Fukunishi, Y.; Konno, H.; Adachi, J.; Fukuda, S.; Aizawa, K.; Izawa, M.; Nishi, K.; Kiyosawa, H.; Kondo, S.; Yamanaka, I.; Saito, T.; Okazaki, Y.; Gojobori, T.; Bono, H.; Kasukawa, T.; Saito, R.; Kadota, K.; Matsuda, H.; Ashburner, M.; Batalov, S.; Casavant, T.; Fleischmann, W.; Gaasterland, T.; Gissi, C.; King, B.; Kochiwa, H.; Kuehl, P.; Lewis, S.; Matsuo, Y.; Nikaido, I.; Pesole, G.; Quackenbush, J.; Schriml, L.M.; Staubli, F.; Suzuki, R.; Tomita, M.; Wagner, L.; Washio, T.; Sakai, K.; Okido, T.; Furuno, M.; Aono, H.; Baldarelli, R.; Barsh, G.; Blake, J.; Boffelli, D.; Bojunga, N.; Carninci, P.; de Bonaldo, M.F.; Brownstein, M.J.; Bult, C.; Fletcher, C.; Fujita, M.; Gariboldi, M.; Gustincich, S.; Hill, D.; Hofmann, M.; Hume, D.A.; Kamiya, M.; Lee, N.H.; Lyons, P.; Marchionni, L.; Mashima, J.; Mazzarelli, J.; Mombaerts, P.; Nordone, P.; Ring, B.; Ringwald, M.; Rodriguez, I.; Sakamoto, N.; Sasaki, H.; Sato, K.; Schonbach, C.; Seya, T.; Shibata, Y.; Storch, K.-F.; Suzuki, H.; Toyo-oka, K.; Wang, K.H.; Weitz, C.; Whittaker, C.; Wilming, L.; Wynshaw-Boris, A.; Yoshida, K.; Hasegawa, Y.; Kawaji, H.; Kohtsuki, S.; Hayashizaki, Y.; RIKEN Genome Exploration Research Group Phase II T; FANTOM Consortium

    2001-01-01

    The RIKEN Mouse Gene Encyclopedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analyzed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones.

  5. Metallothionein 1 Isoform Gene Expression Induced by Cadmium in Human Peripheral Blood Lymphocytes

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    To study the gene expression of metallothionein 1 (MT-1) isoforms in human peripheral blood lymphocytes (HPBLs). Methods The expression of mRNA representing the seven active MT-1 genes was determined in HPBLs by quantitative RT-PCR before and after exposure to cadmium. Results Basal expressions of MT-1X, and MT-1A in HPBLs were similar to expression of housekeeping gene. In contrast, the basal gene expressions of MT-1H, 1F, 1E, and 1G were a little transcripts in human HPBLs. No signal was detected for MT-1B. There was a sex difference (P<0.05). in basal gene expression of MT-1E. The levels of gene expression of MT-1A, 1E, 1F, 1G, 1H, and 1X increased, but the level of MT-1B did not increase after exposure to cadmium. Conclusions Gene expressions of MT-1G, MT-1H, MT-1F, and MT-1X in HPBLs can be used as a potential biomarker of cadmium exposure.

  6. A microfluidic system supports single mouse embryo culture leading to full-term development

    NARCIS (Netherlands)

    Esteves, Telma Cristina; Rossem, van Fleur; Nordhoff, Verena; Schlatt, Stefan; Boiani, Michele; Le Gac, Séverine

    2013-01-01

    The present study demonstrates the feasibility of application of a microfluidic system for in vitro culture of pre-implantation mouse embryos, with subsequent development to full-term upon embryo transfer. Specifically, embryos cultured in groups in nL volume chambers achieve pre-implantation develo

  7. Use of adenovirus vector expressing the mouse full estrogen receptor alpha gene to infect mouse primary neurons

    Institute of Scientific and Technical Information of China (English)

    Xiao HU; Lei Lou; Jun Yuan; Xing Wan; Jianyi Wang; Xinyue Qin

    2010-01-01

    Estrogen plays important regulatory and protective roles in the central nervous system through estrogen receptor a mediation.Previous studies applied eukaryotic expression and lentiviral vectors carrying estrogen receptor a to clarify the undedying mechanisms,in the present study,an adenovirus vector expressing the mouse full estrogen receptor a gene was constructed to identify biological characteristics of estrogen receptor a recombinant adenovirus infecting nerve cells.Primary cultured mouse nerve cells were first infected with estrogen receptor a recombinant adenovirus at various multiplicities of infection,followed by 100 multiplicity of infection.Results showed overexpression of estrogen receptor a mRNA and protein in the infected nerve cells.Estrogen receptor a recombinant adenovirus at 100 multiplicity of infection successfully infected neurons and upregulated estrogen receptor a mRNA and protein expression.

  8. Electrotransfer of the full-length dog dystrophin into mouse and dystrophic dog muscles.

    Science.gov (United States)

    Pichavant, Christophe; Chapdelaine, Pierre; Cerri, Daniel G; Bizario, Joao C S; Tremblay, Jacques P

    2010-11-01

    Duchenne muscular dystrophy (DMD) is an X-linked genetic disease characterized by the absence of dystrophin (427 kDa). An approach to eventually restore this protein in patients with DMD is to introduce into their muscles a plasmid encoding dystrophin cDNA. Because the phenotype of the dystrophic dog is closer to the human phenotype than is the mdx mouse phenotype, we have studied the electrotransfer of a plasmid carrying the full-length dog dystrophin (FLDYS(dog)) in dystrophic dog muscle. To achieve this nonviral delivery, the FLDYS(dog) cDNA was cloned in two plasmids containing either a cytomegalovirus or a muscle creatine kinase promoter. In both cases, our results showed that the electrotransfer of these large plasmids (∼17 kb) into mouse muscle allowed FLDYS(dog) expression in the treated muscle. The electrotransfer of pCMV.FLDYS(dog) in a dystrophic dog muscle also led to the expression of dystrophin. In conclusion, introduction of the full-length dog dystrophin cDNA by electrotransfer into dystrophic dog muscle is a potential approach to restore dystrophin in patients with DMD. However, the electrotransfer procedure should be improved before applying it to humans.

  9. Generation of a Mouse Full-length Balancer with Versatile Cassette-shuttling Selection Strategy.

    Science.gov (United States)

    Ye, Zhisheng; Sun, Lei; Li, Rongbo; Han, Min; Zhuang, Yuan; Wu, Xiaohui; Xu, Tian

    2016-01-01

    Balancer chromosomes are important tools for a variety of genetic manipulations in lower model organisms, owing to their ability to suppress recombination. In mouse, however, such effort has not been accomplished, mostly due to the size of the chromosomes and the complexity of multiple step chromosomal engineering. We developed an effective and versatile cassette-shuttling selection (CASS) strategy involving only two selection markers to achieve the sequential production of multiple large inversions along the chromosome. Using this strategy, we successfully generated the first full-length balancer in mice and showed that Balancer 17M-GFP can efficiently suppress recombination. Our study has not only generated a useful genetic resource, but also provided a strategy for constructing mammalian balancer chromosomes.

  10. Targeting a complex transcriptome: the construction of the mouse full-length cDNA encyclopedia.

    Science.gov (United States)

    Carninci, Piero; Waki, Kazunori; Shiraki, Toshiyuki; Konno, Hideaki; Shibata, Kazuhiro; Itoh, Masayoshi; Aizawa, Katsunori; Arakawa, Takahiro; Ishii, Yoshiyuki; Sasaki, Daisuke; Bono, Hidemasa; Kondo, Shinji; Sugahara, Yuichi; Saito, Rintaro; Osato, Naoki; Fukuda, Shiro; Sato, Kenjiro; Watahiki, Akira; Hirozane-Kishikawa, Tomoko; Nakamura, Mari; Shibata, Yuko; Yasunishi, Ayako; Kikuchi, Noriko; Yoshiki, Atsushi; Kusakabe, Moriaki; Gustincich, Stefano; Beisel, Kirk; Pavan, William; Aidinis, Vassilis; Nakagawara, Akira; Held, William A; Iwata, Hiroo; Kono, Tomohiro; Nakauchi, Hiromitsu; Lyons, Paul; Wells, Christine; Hume, David A; Fagiolini, Michela; Hensch, Takao K; Brinkmeier, Michelle; Camper, Sally; Hirota, Junji; Mombaerts, Peter; Muramatsu, Masami; Okazaki, Yasushi; Kawai, Jun; Hayashizaki, Yoshihide

    2003-06-01

    We report the construction of the mouse full-length cDNA encyclopedia,the most extensive view of a complex transcriptome,on the basis of preparing and sequencing 246 libraries. Before cloning,cDNAs were enriched in full-length by Cap-Trapper,and in most cases,aggressively subtracted/normalized. We have produced 1,442,236 successful 3'-end sequences clustered into 171,144 groups, from which 60,770 clones were fully sequenced cDNAs annotated in the FANTOM-2 annotation. We have also produced 547,149 5' end reads,which clustered into 124,258 groups. Altogether, these cDNAs were further grouped in 70,000 transcriptional units (TU),which represent the best coverage of a transcriptome so far. By monitoring the extent of normalization/subtraction, we define the tentative equivalent coverage (TEC),which was estimated to be equivalent to >12,000,000 ESTs derived from standard libraries. High coverage explains discrepancies between the very large numbers of clusters (and TUs) of this project,which also include non-protein-coding RNAs,and the lower gene number estimation of genome annotations. Altogether,5'-end clusters identify regions that are potential promoters for 8637 known genes and 5'-end clusters suggest the presence of almost 63,000 transcriptional starting points. An estimate of the frequency of polyadenylation signals suggests that at least half of the singletons in the EST set represent real mRNAs. Clones accounting for about half of the predicted TUs await further sequencing. The continued high-discovery rate suggests that the task of transcriptome discovery is not yet complete.

  11. Uroporphyrinogen-III synthase: Molecular cloning, nucleotide sequence, expression of a mouse full-length cDNA, and its localization on mouse chromosome 7

    Energy Technology Data Exchange (ETDEWEB)

    Xu, W.; Desnick, R.J. [Mount Sinai School of Medicine, New York, NY (United States); Kozak, C.A. [National Institute of Health, Bethesda, MD (United States)

    1995-04-10

    Uroporphyrinogen-III synthase, the fourth enzyme in the heme biosynthetic pathway, is responsible for the conversion of hydroxymethylbilane to the cyclic tetrapyrrole, uroporphyrinogen III. The deficient activity of URO-S is the enzymatic defect in congenital erythropoietic porphyria (CEP), an autosomal recessive disorder. For the generation of a mouse model of CEP, the human URO-S cDNA was used to screen 2 X 10{sup 6} recombinants from a mouse adult liver cDNA library. Ten positive clones were isolated, and dideoxy sequencing of the entire 1.6-kb insert of clone pmUROS-1 revealed 5{prime} and 3{prime} untranslated sequences of 144 and 623 bp, respectively, and an open reading frame of 798 bp encoding a 265-amino-acid polypeptide with a predicted molecular mass of 28,501 Da. The mouse and human coding sequences had 80.5 and 77.8% nucleotide and amino acid identity, respectively. The authenticity of the mouse cDNA was established by expression of the active monomeric enzyme in Escherichia coli. In addition, the analysis of two multilocus genetic crosses localized the mouse gene on chromosome 7, consistent with the mapping of the human gene to a position of conserved synteny on chromosome 10. The isolation, expression, and chromosomal mapping of this full-length cDNA should facilitate studies of the structure and organization of the mouse genomic sequence and the development of a mouse model of CEP for characterization of the disease pathogenesis and evaluation of gene therapy. 38 refs., 1 tab.

  12. FULL-GENOME ANALYSIS OF ALTERNATIVE SPLICING IN MOUSE LIVER AFTER HEPATOTOXICANT EXPOSURE

    Science.gov (United States)

    Alternative splicing plays a role in determining gene function and protein diversity. We have employed whole genome exon profiling using Affymetrix Mouse Exon 1.0 ST arrays to understand the significance of alternative splicing on a genome-wide scale in response to multiple toxic...

  13. Metallothionein-1 and nitric oxide expression are inversely correlated in a murine model of Chagas disease

    Directory of Open Access Journals (Sweden)

    Martha Elba Gonzalez-Mejia

    2014-04-01

    Full Text Available Chagas disease, caused by Trypanosoma cruzi, represents an endemic among Latin America countries. The participation of free radicals, especially nitric oxide (NO, has been demonstrated in the pathophysiology of seropositive individuals with T. cruzi. In Chagas disease, increased NO contributes to the development of cardiomyopathy and megacolon. Metallothioneins (MTs are efficient free radicals scavengers of NO in vitro and in vivo. Here, we developed a murine model of the chronic phase of Chagas disease using endemic T. cruzi RyCH1 in BALB/c mice, which were divided into four groups: infected non-treated (Inf, infected N-monomethyl-L-arginine treated (Inf L-NAME, non-infected L-NAME treated and non-infected vehicle-treated. We determined blood parasitaemia and NO levels, the extent of parasite nests in tissues and liver MT-I expression levels. It was observed that NO levels were increasing in Inf mice in a time-dependent manner. Inf L-NAME mice had fewer T. cruzi nests in cardiac and skeletal muscle with decreased blood NO levels at day 135 post infection. This affect was negatively correlated with an increase of MT-I expression (r = -0.8462, p < 0.0001. In conclusion, we determined that in Chagas disease, an unknown inhibitory mechanism reduces MT-I expression, allowing augmented NO levels.

  14. Live, full-term mouse pups from oocytes grown and matured in vitro with serum substitutes.

    Science.gov (United States)

    Motohashi, Hideyuki H; Taniguchi, Ryoma; Sakamoto, Junpei; Sankai, Tadashi; Kada, Hidemi

    2017-06-01

    For in vitro growth and maturation of mouse oocytes (IVG-IVM), serum is added to media up to and including the stage of oocyte maturation; this subsequently supports oocytes through fertilization and early embryo development. However, problems may occur with sera, such as batch differences and issues of biosafety. The purpose of the present study was to determine the capacity for fertilization and pre- and post-implantation development of oocytes that underwent IVG-IVM with a serum substitute. Oocyte-granulosa cell complexes from preantral follicles were cultured in medium with either fetal bovine serum (FBS), Serum Substitute Supplement™ (SSS), or Knockout™ Serum Replacement (KSR) for 10days, and were then allowed to mature for 17 h. Subsequently, more than 90% of oocytes underwent germinal vesicle breakdown (GVBD) and more than 70% reached metaphase II, with no significant difference between the groups. A lower fertilization rate, presumably due to zona hardening, was found in the serum substitute groups. Nevertheless, more than 50% of the inseminated oocytes were fertilized and 35%-45% of them underwent first cleavage and developed to the blastocyst stage. Following embryo transfer, one and four live offspring were produced from the SSS and KSR groups, respectively. The present study demonstrated that murine IVG-IVM oocytes cultured in media with a serum substitute, achieved fertilization in vitro, pre- and post-implantation development, and the delivery of live pups, although the efficiency of the process is reduced compared to FBS supplementation. Copyright © 2017 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  15. Construction of human and mouse brain cDNA libraries and isolation of full-length cDNAs

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    cDNA libraries from aborted human 3-month fetal brain,adult rat and mouse brain were constructed by using a yZAP express cDNA library construction kin.Low molecular weight fragments of the second strand cDNASA were removed by flowing through the Sepharose CL-4B column and the frractionated long,Middle,Short fragments and the combined fragments weire respectively inserted into clone vectors to construct the cDNA libraries of the brain of human 3-month fetus.The 5'ends of 1200 clones from each of human fetal brain cDNA libraries were sequenced.A total of 894 ESTs were obtained and some full-length clones were squenced.By andalyaing the se-quences,12 novel full-length cDNAs were obtained.

  16. Milligram quantities of homogeneous recombinant full-length mouse Munc18c from Escherichia coli cultures.

    Directory of Open Access Journals (Sweden)

    Asma Rehman

    Full Text Available Vesicle fusion is an indispensable cellular process required for eukaryotic cargo delivery. The Sec/Munc18 protein Munc18c is essential for insulin-regulated trafficking of glucose transporter4 (GLUT4 vesicles to the cell surface in muscle and adipose tissue. Previously, our biophysical and structural studies have used Munc18c expressed in SF9 insect cells. However to maximize efficiency, minimize cost and negate any possible effects of post-translational modifications of Munc18c, we investigated the use of Escherichia coli as an expression host for Munc18c. We were encouraged by previous reports describing Munc18c production in E. coli cultures for use in in vitro fusion assay, pulldown assays and immunoprecipitations. Our approach differs from the previously reported method in that it uses a codon-optimized gene, lower temperature expression and autoinduction media. Three N-terminal His-tagged constructs were engineered, two with a tobacco etch virus (TEV or thrombin protease cleavage site to enable removal of the fusion tag. The optimized protocol generated 1-2 mg of purified Munc18c per L of culture at much reduced cost compared to Munc18c generated using insect cell culture. The purified recombinant Munc18c protein expressed in bacteria was monodisperse, monomeric, and functional. In summary, we developed methods that decrease the cost and time required to generate functional Munc18c compared with previous insect cell protocols, and which generates sufficient purified protein for structural and biophysical studies.

  17. Putting the pieces into place: Properties of intact zinc metallothionein 1A determined from interaction of its isolated domains with carbonic anhydrase.

    Science.gov (United States)

    Pinter, Tyler B J; Stillman, Martin J

    2015-11-01

    Mammalian metallothioneins (MTs) bind up to seven Zn(2+) using a large number of cysteine residues relative to their small size and can act as zinc-chaperones. In metal-saturated Zn7-MTs, the seven zinc ions are co-ordinated tetrahedrally into two distinct clusters separated by a linker; the N-terminal β-domain [(Zn3Cys9)(3-)] and C-terminal α-domain [(Zn4Cys11)(3-)]. We report on the competitive zinc metalation of apo-carbonic anhydrase [CA; metal-free CA (apo-CA)] in the presence of apo-metallothionein 1A domain fragments to identify domain specific determinants of zinc binding and zinc donation in the intact two-domain Znn-βαMT1A (human metallothionein 1A isoform; n=0-7). The apo-CA is shown to compete effectively only with Zn2-3-βMT and Zn4-αMT. Detailed modelling of the ESI mass spectral data have revealed the zinc-binding affinities of each of the zinc-binding sites in the two isolated fragments. The three calculated equilibrium zinc affinities [log(KF)] of the isolated β-domain were: 12.2, 11.7 and 11.4 and the four isolated α-domain affinities were: 13.5, 13.2, 12.7 and 12.6. These data provide guidance in identification of the location of the strongest-bound and weakest-bound zinc in the intact two-domain Zn7βαMT. The β-domain has the weakest zinc-binding site and this is where zinc ions are donated from in the Zn7-βαMT. The α-domain with the highest affinity binds the first zinc, which we propose leads to an unscrambling of the cysteine ligands from the apo-peptide bundle. We propose that stabilization of the intact Zn6-MT and Zn7-MT, relative to that of the sum of the separated fragments, is due to the availability of additional cysteine ligand orientations (through interdomain interactions) to support the clustered structures.

  18. A PU.1 suppressive target gene, metallothionein 1G, inhibits retinoic acid-induced NB4 cell differentiation.

    Directory of Open Access Journals (Sweden)

    Naomi Hirako

    Full Text Available We recently revealed that myeloid master regulator SPI1/PU.1 directly represses metallothionein (MT 1G through its epigenetic activity of PU.1, but the functions of MT1G in myeloid differentiation remain unknown. To clarify this, we established MT1G-overexpressing acute promyelocytic leukemia NB4 (NB4MTOE cells, and investigated whether MT1G functionally contributes to all-trans retinoic acid (ATRA-induced NB4 cell differentiation. Real-time PCR analyses demonstrated that the inductions of CD11b and CD11c and reductions in myeloperoxidase and c-myc by ATRA were significantly attenuated in NB4MTOE cells. Morphological examination revealed that the percentages of differentiated cells induced by ATRA were reduced in NB4MTOE cells. Since G1 arrest is a hallmark of ATRA-induced NB4 cell differentiation, we observed a decrease in G1 accumulation, as well as decreases in p21WAF1/CIP1 and cyclin D1 inductions, by ATRA in NB4MTOE cells. Nitroblue tetrazolium (NBT reduction assays revealed that the proportions of NBT-positive cells were decreased in NB4MTOE cells in the presence of ATRA. Microarray analyses showed that the changes in expression of several myeloid differentiation-related genes (GATA2, azurocidin 1, pyrroline-5-carboxylate reductase 1, matrix metallopeptidase -8, S100 calcium-binding protein A12, neutrophil cytosolic factor 2 and oncostatin M induced by ATRA were disturbed in NB4MTOE cells. Collectively, overexpression of MT1G inhibits the proper differentiation of myeloid cells.

  19. Expression and purification of full length mouse metal response element binding transcription factor-1 using Pichia pastoris.

    Science.gov (United States)

    Huyck, Ryan W; Keightley, Andrew; Laity, John H

    2012-09-01

    The metal response element binding transcription factor-1 (MTF-1) is an important stress response, heavy metal detoxification, and zinc homeostasis factor in eukaryotic organisms from Drosophila to humans. MTF-1 transcriptional regulation is primarily mediated by elevated levels of labile zinc, which direct MTF-1 to bind the metal response element (MRE). This process involves direct zinc binding to the MTF-1 zinc fingers, and zinc dependent interaction of the MTF-1 acidic region with the p300 coactivator protein. Here, the first recombinant expression system for mutant and wild type (WT) mouse MTF-1 (mMTF-1) suitable for biochemical and biophysical studies in vitro is reported. Using the methyltropic yeast Pichia pastoris, nearly half-milligram recombinant WT and mutant mMTF-1 were produced per liter of P. pastoris cell culture, and purified by a FLAG-tag epitope. Using a first pass ammonium sulfate purification, followed by anti-FLAG affinity resin, mMTF-1 was purified to >95% purity. This recombinant mMTF-1 was then assayed for direct protein-protein interactions with p300 by co-immunoprecipitation. Surface plasmon resonance studies on mMTF-1 provided the first quantitative DNA binding affinity measurements to the MRE promotor element (K(d)=5±3 nM). Both assays demonstrated the functional activity of the recombinant mMTF-1, while elucidating the molecular basis for mMTF-1-p300 functional synergy, and provided new insights into the mMTF-1 domain specific roles in DNA binding. Overall, this production system provides accessibility for the first time to a multitude of in vitro studies using recombinant mutant and WT mMTF-1, which greatly facilitates new approaches to understanding the complex and varied functions of this protein.

  20. A polymorphism in metallothionein 1A (MT1A) is associated with cadmium-related excretion of urinary beta 2‐microglobulin

    Energy Technology Data Exchange (ETDEWEB)

    Lei, Lijian [Department of Occupational Health, School of Public Health, Fudan University, Shanghai (China); Department of Epidemiology, School of Public Health, Shanxi Medical University, Shanxi (China); Chang, Xiuli [Department of Occupational Health, School of Public Health, Fudan University, Shanghai (China); Rentschler, Gerda [Department of Occupational and Environmental Medicine, Lund University, SE-22185, Lund (Sweden); Tian, Liting [Department of Occupational Health, School of Public Health, Fudan University, Shanghai (China); Zhu, Guoying; Chen, Xiao [Department of Bone Metabolism, Institute of Radiation Medicine, Fudan University, Shanghai (China); Jin, Taiyi, E-mail: tyjinster@gmail.com [Department of Occupational Health, School of Public Health, Fudan University, Shanghai (China); Broberg, Karin, E-mail: karin.broberg_palmgren@med.lu.se [Department of Occupational and Environmental Medicine, Lund University, SE-22185, Lund (Sweden)

    2012-12-15

    metallothionein 1A was genotyped in 512 cadmium exposed humans. ► Variant carriers of this polymorphism showed more kidney damage from cadmium. ► The frequency of these variants needs to be taken into account in risk assessment.

  1. Full-length PGC-1α salvages the phenotype of a mouse model of human neuropathy through mitochondrial proliferation.

    Science.gov (United States)

    Rona-Voros, Krisztina; Eschbach, Judith; Vernay, Aurélia; Wiesner, Diana; Schwalenstocker, Birgit; Geniquet, Pauline; Mousson De Camaret, Bénédicte; Echaniz-Laguna, Andoni; Loeffler, Jean-Philippe; Ludolph, Albert C; Weydt, Patrick; Dupuis, Luc

    2013-12-20

    Increased mitochondrial mass, commonly termed mitochondrial proliferation, is frequently observed in many human diseases directly or indirectly involving mitochondrial dysfunction. Mitochondrial proliferation is thought to counterbalance a compromised energy metabolism, yet it might also be detrimental through alterations of mitochondrial regulatory functions such as apoptosis, calcium metabolism or oxidative stress. Here, we show that prominent mitochondrial proliferation occurs in Cramping mice, a model of hereditary neuropathy caused by a mutation in the dynein heavy chain gene Dync1h1. The mitochondrial proliferation correlates with post-prandial induction of full-length (FL) and N-terminal truncated (NT) isoforms of the transcriptional co-activator PGC-1α. The selective knock-out of FL-PGC-1α isoform, preserving expression and function of NT-PGC-1α, led to a complete reversal of mitochondrial proliferation. Moreover, FL-PGC-1α ablation potently exacerbated the mitochondrial dysfunction and led to severe weight loss. Finally, FL-PGC-1α ablation triggered pronounced locomotor dysfunction, tremors and inability to rear in Cramping mice. In summary, endogenous FL-PGC-1α activates mitochondrial proliferation and salvages neurological and metabolic health upon disease. NT-PGC-1α cannot fulfil this protective action. Activation of this endogenous salvage pathway might thus be a valuable therapeutic target for diseases involving mitochondrial dysfunction.

  2. Hair Follicle Morphogenesis in the Treatment of Mouse Full-Thickness Skin Defects Using Composite Human Acellular Amniotic Membrane and Adipose Derived Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Wu Minjuan

    2016-01-01

    Full Text Available Early repair of skin injury and maximal restoration of the function and appearance have become important targets of clinical treatment. In the present study, we observed the healing process of skin defects in nude mice and structural characteristics of the new skin after transplantation of isolated and cultured adipose derived mesenchymal stem cells (ADMSCs onto the human acellular amniotic membrane (AAM. The result showed that ADMSCs were closely attached to the surface of AAM and grew well 24 h after seeding. Comparison of the wound healing rate at days 7, 14, and 28 after transplantation showed that ADMSCs seeded on AAM facilitated the healing of full-thickness skin wounds more effectively as compared with either hAM or AAM alone, indicating that ADMSCs participated in skin regeneration. More importantly, we noticed a phenomenon of hair follicle development during the process of skin repair. Composite ADMSCs and AAM not only promoted the healing of the mouse full-thickness defects but also facilitated generation of the appendages of the affected skin, thus promoting restoration of the skin function. Our results provide a new possible therapy idea for the treatment of skin wounds with respect to both anatomical regeneration and functional restoration.

  3. Biological effects and use of PrPSc- and PrP-specific antibodies generated by immunization with purified full-length native mouse prions.

    Science.gov (United States)

    Petsch, Benjamin; Müller-Schiffmann, Andreas; Lehle, Anna; Zirdum, Elizabeta; Prikulis, Ingrid; Kuhn, Franziska; Raeber, Alex J; Ironside, James W; Korth, Carsten; Stitz, Lothar

    2011-05-01

    The prion agent is the infectious particle causing spongiform encephalopathies in animals and humans and is thought to consist of an altered conformation (PrP(Sc)) of the normal and ubiquitous prion protein PrP(C). The interaction of the prion agent with the immune system, particularly the humoral immune response, has remained unresolved. Here we investigated the immunogenicity of full-length native and infectious prions, as well as the specific biological effects of the resulting monoclonal antibodies (MAbs) on the binding and clearance of prions in cell culture and in in vivo therapy. Immunization of prion knockout (Prnp(0/0)) mice with phosphotungstic acid-purified mouse prions resulted in PrP-specific monoclonal antibodies with binding specificities selective for PrP(Sc) or for both PrP(C) and PrP(Sc). PrP(Sc)-specific MAb W261, of the IgG1 isotype, reacted with prions from mice, sheep with scrapie, deer with chronic wasting disease (CWD), and humans with sporadic and variant Creutzfeldt-Jakob disease (CJD) in assays including a capture enzyme-linked immunosorbent assay (ELISA) system. This PrP(Sc)-specific antibody was unable to clear prions from mouse neuroblastoma cells (ScN2a) permanently infected with scrapie, whereas the high-affinity MAb W226, recognizing both isoforms, PrP(Sc) and PrP(C), did clear prions from ScN2a cells, as determined by a bioassay. However, an attempt to treat intraperitoneally prion infected mice with full-length W226 or with a recombinant variable-chain fragment (scFv) from W226 could only slightly delay the incubation time. We conclude that (i) native, full-length PrP(Sc) elicits a prion-specific antibody response in PrP knockout mice, (ii) a PrP(Sc)-specific antibody had no prion-clearing effect, and (iii) even a high-affinity MAb that clears prions in vitro (W226) may not necessarily protect against prion infection, contrary to previous reports using different antibodies.

  4. Hair Follicle Morphogenesis in the Treatment of Mouse Full-Thickness Skin Defects Using Composite Human Acellular Amniotic Membrane and Adipose Derived Mesenchymal Stem Cells

    Science.gov (United States)

    Minjuan, Wu; Jun, Xiong; Shiyun, Shao; Sha, Xu; Haitao, Ni

    2016-01-01

    Early repair of skin injury and maximal restoration of the function and appearance have become important targets of clinical treatment. In the present study, we observed the healing process of skin defects in nude mice and structural characteristics of the new skin after transplantation of isolated and cultured adipose derived mesenchymal stem cells (ADMSCs) onto the human acellular amniotic membrane (AAM). The result showed that ADMSCs were closely attached to the surface of AAM and grew well 24 h after seeding. Comparison of the wound healing rate at days 7, 14, and 28 after transplantation showed that ADMSCs seeded on AAM facilitated the healing of full-thickness skin wounds more effectively as compared with either hAM or AAM alone, indicating that ADMSCs participated in skin regeneration. More importantly, we noticed a phenomenon of hair follicle development during the process of skin repair. Composite ADMSCs and AAM not only promoted the healing of the mouse full-thickness defects but also facilitated generation of the appendages of the affected skin, thus promoting restoration of the skin function. Our results provide a new possible therapy idea for the treatment of skin wounds with respect to both anatomical regeneration and functional restoration. PMID:27597871

  5. Understanding three-dimensional spatial relationship between the mouse second polar body and first cleavage plane with full-field optical coherence tomography.

    Science.gov (United States)

    Zheng, Jing-gao; Huo, Tiancheng; Chen, Tianyuan; Wang, Chengming; Zhang, Ning; Tian, Ning; Zhao, Fengying; Lu, Danyu; Chen, Dieyan; Ma, Wanyun; Sun, Jia-lin; Xue, Ping

    2013-01-01

    The morphogenetic relationship between early patterning and polarity formation is of fundamental interest and remains a controversial issue in preimplantation embryonic development. We use a label-free three-dimensional (3-D) imaging technique of full-field optical coherence tomography (FF-OCT) successfully for the first time to study the dynamics of developmental processes in mouse preimplantation lives. Label-free 3-D subcellular time-lapse images are demonstrated to investigate 3-D spatial relationship between the second polar body (2PB) and the first cleavage plane. By using FF-OCT together with quantitative study, we show that only 25% of the predicted first cleavage planes, defined by the apposing plane of two pronuclei, pass through the 2PB. Also only 27% of the real cleavage planes pass through the 2PB. These results suggest that the 2PB is not a convincing spatial cue for the event of the first cleavage. Our studies demonstrate the feasibility of FF-OCT in providing new insights and potential breakthroughs to the controversial issues of early patterning and polarity in mammalian developmental biology.

  6. In vivo Dopamine Efflux is Decreased in Striatum of both Fragment (R6/2) and Full-Length (YAC128) Transgenic Mouse Models of Huntington's Disease.

    Science.gov (United States)

    Callahan, Joshua W; Abercrombie, Elizabeth D

    2011-01-01

    Huntington's disease (HD) is characterized by numerous alterations within the corticostriatal circuitry. The striatum is innervated by a dense array of dopaminergic (DA) terminals and these DA synapses are critical to the proper execution of motor functions. As motor disturbances are prevalent in HD we examined DA neurotransmission in the striatum in transgenic (tg) murine models of HD. We used in vivo microdialysis to compare extracellular concentrations of striatal DA in both a fragment (R6/2) model, which displays a rapid and severe phenotype, and a full-length (YAC128) model that expresses a more progressive phenotype. Extracellular striatal DA concentrations were significantly reduced in R6/2 mice and decreased concomitantly with age-dependent increasing motor impairments on the rotarod task (7, 9, and 11 weeks). In a sample of 11-week-old R6/2 mice, we also measured tissue concentrations of striatal DA and found that total levels of DA were significantly depleted. However, the loss of total DA content (<50%) was insufficient to account for the full extent of DA depletion in the extracellular fluid (ECF; ∼75%). We also observed a significant reduction in extracellular DA concentrations in the striatum of 7-month-old YAC128 mice. In a separate set of experiments, we applied d-amphetamine (AMPH; 10 μm) locally into the striatum to stimulate the release of intracellular DA into the ECF. The AMPH-induced increase in extracellular DA levels was significantly blunted in 9-week-old R6/2 mice. There also was a decrease in AMPH-stimulated DA efflux in 7-month-old YAC128 mice in comparison to WT controls, although the effect was milder. In the same cohort of 7-month-old YAC128 mice we observed a significant reduction in the total locomotor activity in response to systemic AMPH (2 mg/kg). Our data demonstrate that extracellular DA release is attenuated in both a fragment and full-length tg mouse model of HD and support the concept of DA involvement in aspects of

  7. The Mycobacterium avium ssp. paratuberculosis specific mptD gene is required for maintenance of the metabolic homeostasis necessary for full virulence in mouse infections.

    Science.gov (United States)

    Meißner, Thorsten; Eckelt, Elke; Basler, Tina; Meens, Jochen; Heinzmann, Julia; Suwandi, Abdulhadi; Oelemann, Walter M R; Trenkamp, Sandra; Holst, Otto; Weiss, Siegfried; Bunk, Boyke; Spröer, Cathrin; Gerlach, Gerald-F; Goethe, Ralph

    2014-01-01

    Mycobacterium avium subspecies paratuberculosis (MAP) causes Johne's disease, a chronic granulomatous enteritis in ruminants. Furthermore, infections of humans with MAP have been reported and a possible association with Crohn's disease and diabetes type I is currently discussed. MAP owns large sequence polymorphisms (LSPs) that were exclusively found in this mycobacteria species. The relevance of these LSPs in the pathobiology of MAP is still unclear. The mptD gene (MAP3733c) of MAP belongs to a small group of functionally uncharacterized genes, which are not present in any other sequenced mycobacteria species. mptD is part of a predicted operon (mptABCDEF), encoding a putative ATP binding cassette-transporter, located on the MAP-specific LSP14. In the present study, we generated an mptD knockout strain (MAPΔmptD) by specialized transduction. In order to investigate the potential role of mptD in the host, we performed infection experiments with macrophages. By this, we observed a significantly reduced cell number of MAPΔmptD early after infection, indicating that the mutant was hampered with respect to adaptation to the early macrophage environment. This important role of mptD was supported in mouse infection experiments where MAPΔmptD was significantly attenuated after peritoneal challenge. Metabolic profiling was performed to determine the cause for the reduced virulence and identified profound metabolic disorders especially in the lipid metabolism of MAPΔmptD. Overall our data revealed the mptD gene to be an important factor for the metabolic adaptation of MAP required for persistence in the host.

  8. Delivery of full-length factor VIII using a piggyBac transposon vector to correct a mouse model of hemophilia A.

    Directory of Open Access Journals (Sweden)

    Hideto Matsui

    Full Text Available Viral vectors have been used for hemophilia A gene therapy. However, due to its large size, full-length Factor VIII (FVIII cDNA has not been successfully delivered using conventional viral vectors. Moreover, viral vectors may pose safety risks, e.g., adverse immunological reactions or virus-mediated cytotoxicity. Here, we took advantages of the non-viral vector gene delivery system based on piggyBac DNA transposon to transfer the full-length FVIII cDNA, for the purpose of treating hemophilia A. We tested the efficiency of this new vector system in human 293T cells and iPS cells, and confirmed the expression of the full-length FVIII in culture media using activity-sensitive coagulation assays. Hydrodynamic injection of the piggyBac vectors into hemophilia A mice temporally treated with an immunosuppressant resulted in stable production of circulating FVIII for over 300 days without development of anti-FVIII antibodies. Furthermore, tail-clip assay revealed significant improvement of blood coagulation time in the treated mice. piggyBac transposon vectors can facilitate the long-term expression of therapeutic transgenes in vitro and in vivo. This novel gene transfer strategy should provide safe and efficient delivery of FVIII.

  9. Delivery of full-length factor VIII using a piggyBac transposon vector to correct a mouse model of hemophilia A.

    Science.gov (United States)

    Matsui, Hideto; Fujimoto, Naoko; Sasakawa, Noriko; Ohinata, Yasuhide; Shima, Midori; Yamanaka, Shinya; Sugimoto, Mitsuhiko; Hotta, Akitsu

    2014-01-01

    Viral vectors have been used for hemophilia A gene therapy. However, due to its large size, full-length Factor VIII (FVIII) cDNA has not been successfully delivered using conventional viral vectors. Moreover, viral vectors may pose safety risks, e.g., adverse immunological reactions or virus-mediated cytotoxicity. Here, we took advantages of the non-viral vector gene delivery system based on piggyBac DNA transposon to transfer the full-length FVIII cDNA, for the purpose of treating hemophilia A. We tested the efficiency of this new vector system in human 293T cells and iPS cells, and confirmed the expression of the full-length FVIII in culture media using activity-sensitive coagulation assays. Hydrodynamic injection of the piggyBac vectors into hemophilia A mice temporally treated with an immunosuppressant resulted in stable production of circulating FVIII for over 300 days without development of anti-FVIII antibodies. Furthermore, tail-clip assay revealed significant improvement of blood coagulation time in the treated mice. piggyBac transposon vectors can facilitate the long-term expression of therapeutic transgenes in vitro and in vivo. This novel gene transfer strategy should provide safe and efficient delivery of FVIII.

  10. DRPLA transgenic mouse substrains carrying single copy of full-length mutant human DRPLA gene with variable sizes of expanded CAG repeats exhibit CAG repeat length- and age-dependent changes in behavioral abnormalities and gene expression profiles.

    Science.gov (United States)

    Suzuki, Kazushi; Zhou, Jiayi; Sato, Toshiya; Takao, Keizo; Miyagawa, Tsuyoshi; Oyake, Mutsuo; Yamada, Mitunori; Takahashi, Hitoshi; Takahashi, Yuji; Goto, Jun; Tsuji, Shoji

    2012-05-01

    Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant progressive neurodegenerative disorder with intellectual deterioration and various motor deficits including ataxia, choreoathetosis, and myoclonus, caused by an abnormal expansion of CAG repeats in the DRPLA gene. Longer expanded CAG repeats contribute to an earlier age of onset, faster progression, and more severe neurological symptoms in DRPLA patients. In this study, we have established DRPLA transgenic mouse lines (sublines) harboring a single copy of the full-length mutant human DRPLA gene carrying various lengths of expanded CAG repeats (Q76, Q96, Q113, and Q129), which have clearly shown motor deficits and memory disturbance whose severity increases with the length of expanded CAG repeats and age, and successfully replicated the CAG repeat length- and age-dependent features of DRPLA patients. Neuronal intranuclear accumulation of the mutant DRPLA protein has been suggested to cause transcriptional dysregulation, leading to alteration in gene expression and neuronal dysfunction. In this study, we have conducted a comprehensive analysis of gene expression profiles in the cerebrum and cerebellum of transgenic mouse lines at 4, 8, and 12 weeks using multiple microarray platforms, and demonstrated that both the number and expression levels of the altered genes are highly dependent on CAG repeat length and age in both brain regions. Specific groups of genes and their function categories were identified by further agglomerative cluster analysis and gene functional annotation analysis. Calcium signaling and neuropeptide signaling, among others, were implicated in the pathophysiology of DRPLA. Our study provides unprecedented CAG-repeat-length-dependent mouse models of DRPLA, which are highly valuable not only for elucidating the CAG-repeat-length-dependent pathophysiology of DRPLA but also for developing therapeutic strategies for DRPLA.

  11. The effect of multifunctional polymer-based gels on wound healing in full thickness bacteria-contaminated mouse skin wound models.

    Science.gov (United States)

    Yates, Cecelia C; Whaley, Diana; Babu, Ranjith; Zhang, Jianying; Krishna, Priya; Beckman, Eric; Pasculle, A William; Wells, Alan

    2007-09-01

    We determined whether a two-part space-conforming polyethylene glycol/dopa polymer-based gel promoted healing of contaminated wounds in mice. This silver-catalysed gel was previously developed to be broadly microbiocidal in vitro while being biocompatible with human wound cell functioning. Full-thickness wounds were created on the backs of mice. The wounds were inoculated with 10(4) CFU of each of four common skin wound contaminants, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumanii and Clostridium perfringens. The wounds were then treated with our multifunctional polymer-based gel, the commercially available NewSkin product, or left to heal untreated. The untreated wounds were overtly infected, and presented detectable bacterial loads over the entire 21-day healing period, while the gel and NewSkin groups presented significantly smaller rises in bacterial levels and were cleared of detectable colonies by the third week, with the gel group clearing the bacteria earlier. While all three groups healed their wounds, the polymer-based gel-treated group demonstrated significantly earlier re-epithelialization and dermal maturation (Phealing wound. These preclinical studies show that the anti-microbial polymer gel not only supports but also accelerates healing of bacterially contaminated wounds.

  12. Alfabetización digital: el pleno dominio del lápiz y el ratón Digital literacy: full control of pen drive and mouse

    Directory of Open Access Journals (Sweden)

    María Dolores Moreno Rodríguez

    2008-03-01

    Full Text Available La alfabetización digital (AD es una segunda alfabetización que nos lleva a reorganizar competencias ya adquiridas y que se hace necesaria a raíz de la creciente presencia de la tecnología en todos los ámbitos sociales. De ahí que la AD promueva el aprendizaje de los lenguajes propios de las nuevas tecnologías, un proceso que ha de alcanzar a todos los estamentos y colectivos sociales para evitar la discriminación de cuantos nacieron antes que las TIC (tecnologías de la información y la comunicación cuyo uso ahora se impone y que carecen de destrezas sobre su utilización y potencialidades. Tampoco podemos olvidar las necesidades orientativas de las nuevas generaciones digitales que utilizan las tecnologías de manera acrítica y poco reflexiva porque carecen de un aprendizaje previo. Digital literacy (DA is a second literacy which makes us reorganize competences already acquired. It is necessary because of the increasing presence of technology at every social sphere. That is why AD promotes learning in all the new technology languages. A process which has to reach all the strata and social groups to avoid the discrimination of people who were born before the spread of CIT (communication and information technologies which are now used and who lack the skills for their use and possibilities. Nevertherless, we can´t forget the guiding needs of the new digital generations which use technologies without any criteria and in a little reflexive way because they lack a previous learning process.

  13. In Vivo Dopamine Efflux is Decreased in Striatum of both Fragment (R6/2 and Full-length (YAC128 Transgenic Mouse Models of Huntington’s Disease

    Directory of Open Access Journals (Sweden)

    Joshua W Callahan

    2011-07-01

    Full Text Available Huntington’s disease (HD is characterized by alterations within the corticostriatal circuitry. The striatum is innervated by a dense array of dopaminergic (DA terminals and these DA synapses are critical to the proper execution of motor functions. As motor disturbances are prevalent in HD we examined DA neurotransmission in the striatum in transgenic (tg murine models of HD. We used in vivo microdialysis to compare extracellular concentrations of striatal DA in both a fragment (R6/2 model, which displays a rapid and severe phenotype, and a full-length (YAC128 model that expresses a more progressive phenotype. Extracellular striatal DA concentrations were significantly reduced in R6/2 mice and decreased concomitantly with age-dependent increasing motor impairments on the rotarod task (7, 9, and 11 weeks. In a sample of 11-week-old R6/2 mice, we also measured tissue concentrations of striatal DA and found that total levels of DA were significantly depleted. However, the loss of total DA content (<50% was insufficient to account for the full extent of DA depletion in the extracellular fluid (ECF (~75%. We also observed a significant reduction in extracellular DA concentrations in the striatum of 7-month-old YAC128 mice. In a separate set of experiments, we applied d-amphetamine (AMPH (10 μm locally into the striatum to stimulate the release of intracellular DA into the ECF. The AMPH-induced increase in extracellular DA levels was significantly blunted in 9-week-old R6/2 mice. There also was a decrease in AMPH-stimulated DA efflux in 7-month-old YAC128 mice in comparison to WT controls, although the effect was milder. In the same cohort of 7-month-old YAC128 mice we observed a significant reduction in the total locomotor activity in response to systemic AMPH (2 mg/kg. Our data demonstrate that extracellular DA release is attenuated in both a fragment and full-length tg mouse model of HD and support the concept of DA involvement in aspects of the

  14. Mouse genetics: Catalogue and scissors

    Directory of Open Access Journals (Sweden)

    Han-Woong Lee

    2012-12-01

    Full Text Available Phenotypic analysis of gene-specific knockout (KO mice hasrevolutionized our understanding of in vivo gene functions. Asthe use of mouse embryonic stem (ES cells is inevitable forconventional gene targeting, the generation of knockout miceremains a very time-consuming and expensive process. Toaccelerate the large-scale production and phenotype analyses ofKO mice, international efforts have organized global consortiasuch as the International Knockout Mouse Consortium (IKMCand International Mouse Phenotype Consortium (IMPC, andthey are persistently expanding the KO mouse catalogue that ispublicly available for the researches studying specific genes ofinterests in vivo. However, new technologies, adoptingzinc-finger nucleases (ZFNs or Transcription Activator-LikeEffector (TALE Nucleases (TALENs to edit the mouse genome,are now emerging as valuable and effective shortcuts alternativefor the conventional gene targeting using ES cells. Here, weintroduce the recent achievement of IKMC, and evaluate thesignificance of ZFN/TALEN technology in mouse genetics.

  15. Colonization, mouse-style

    Directory of Open Access Journals (Sweden)

    Searle Jeremy B

    2010-10-01

    Full Text Available Abstract Several recent papers, including one in BMC Evolutionary Biology, examine the colonization history of house mice. As well as background for the analysis of mouse adaptation, such studies offer a perspective on the history of movements of the humans that accidentally transported the mice. See research article: http://www.biomedcentral.com/1471-2148/10/325

  16. Mouse bladder wall injection.

    Science.gov (United States)

    Fu, Chi-Ling; Apelo, Charity A; Torres, Baldemar; Thai, Kim H; Hsieh, Michael H

    2011-07-12

    Mouse bladder wall injection is a useful technique to orthotopically study bladder phenomena, including stem cell, smooth muscle, and cancer biology. Before starting injections, the surgical area must be cleaned with soap and water and antiseptic solution. Surgical equipment must be sterilized before use and between each animal. Each mouse is placed under inhaled isoflurane anesthesia (2-5% for induction, 1-3% for maintenance) and its bladder exposed by making a midline abdominal incision with scissors. If the bladder is full, it is partially decompressed by gentle squeezing between two fingers. The cell suspension of interest is intramurally injected into the wall of the bladder dome using a 29 or 30 gauge needle and 1 cc or smaller syringe. The wound is then closed using wound clips and the mouse allowed to recover on a warming pad. Bladder wall injection is a delicate microsurgical technique that can be mastered with practice.

  17. Mouse phenotyping.

    Science.gov (United States)

    Fuchs, Helmut; Gailus-Durner, Valérie; Adler, Thure; Aguilar-Pimentel, Juan Antonio; Becker, Lore; Calzada-Wack, Julia; Da Silva-Buttkus, Patricia; Neff, Frauke; Götz, Alexander; Hans, Wolfgang; Hölter, Sabine M; Horsch, Marion; Kastenmüller, Gabi; Kemter, Elisabeth; Lengger, Christoph; Maier, Holger; Matloka, Mikolaj; Möller, Gabriele; Naton, Beatrix; Prehn, Cornelia; Puk, Oliver; Rácz, Ildikó; Rathkolb, Birgit; Römisch-Margl, Werner; Rozman, Jan; Wang-Sattler, Rui; Schrewe, Anja; Stöger, Claudia; Tost, Monica; Adamski, Jerzy; Aigner, Bernhard; Beckers, Johannes; Behrendt, Heidrun; Busch, Dirk H; Esposito, Irene; Graw, Jochen; Illig, Thomas; Ivandic, Boris; Klingenspor, Martin; Klopstock, Thomas; Kremmer, Elisabeth; Mempel, Martin; Neschen, Susanne; Ollert, Markus; Schulz, Holger; Suhre, Karsten; Wolf, Eckhard; Wurst, Wolfgang; Zimmer, Andreas; Hrabě de Angelis, Martin

    2011-02-01

    Model organisms like the mouse are important tools to learn more about gene function in man. Within the last 20 years many mutant mouse lines have been generated by different methods such as ENU mutagenesis, constitutive and conditional knock-out approaches, knock-down, introduction of human genes, and knock-in techniques, thus creating models which mimic human conditions. Due to pleiotropic effects, one gene may have different functions in different organ systems or time points during development. Therefore mutant mouse lines have to be phenotyped comprehensively in a highly standardized manner to enable the detection of phenotypes which might otherwise remain hidden. The German Mouse Clinic (GMC) has been established at the Helmholtz Zentrum München as a phenotyping platform with open access to the scientific community (www.mousclinic.de; [1]). The GMC is a member of the EUMODIC consortium which created the European standard workflow EMPReSSslim for the systemic phenotyping of mouse models (http://www.eumodic.org/[2]). Copyright © 2010 Elsevier Inc. All rights reserved.

  18. Mouse Leydig Tumor Cells

    Directory of Open Access Journals (Sweden)

    Bo-Syong Pan

    2011-01-01

    Full Text Available Cordycepin is a natural pure compound extracted from Cordyceps sinensis (CS. We have demonstrated that CS stimulates steroidogenesis in primary mouse Leydig cell and activates apoptosis in MA-10 mouse Leydig tumor cells. It is highly possible that cordycepin is the main component in CS modulating Leydig cell functions. Thus, our aim was to investigate the steroidogenic and apoptotic effects with potential mechanism of cordycepin on MA-10 mouse Leydig tumor cells. Results showed that cordycepin significantly stimulated progesterone production in dose- and time-dependent manners. Adenosine receptor (AR subtype agonists were further used to treat MA-10 cells, showing that A1, A 2A , A 2B , and A3, AR agonists could stimulate progesterone production. However, StAR promoter activity and protein expression remained of no difference among all cordycepin treatments, suggesting that cordycepin might activate AR, but not stimulated StAR protein to regulate MA-10 cell steroidogenesis. Meanwhile, cordycepin could also induce apoptotic cell death in MA-10 cells. Moreover, four AR subtype agonists induced cell death in a dose-dependent manner, and four AR subtype antagonists could all rescue cell death under cordycepin treatment in MA-10 cells. In conclusion, cordycepin could activate adenosine subtype receptors and simultaneously induce steroidogenesis and apoptosis in MA-10 mouse Leydig tumor cells.

  19. Hand gestures mouse cursor control

    Directory of Open Access Journals (Sweden)

    Marian-Avram Vincze

    2014-05-01

    Full Text Available The paper describes the implementation of a human-computer interface for controlling the mouse cursor. The test reveal the fact: a low-cost web camera some processing algorithms are quite enough to control the mouse cursor on computers. Even if the system is influenced by the illuminance level on the plane of the hand, the current study may represent a start point for some studies on the hand tracking and gesture recognition field.

  20. Optimization of the virtual mouse HeadMouse to foster its classroom use by children with physical disabilities

    Directory of Open Access Journals (Sweden)

    Merce TEIXIDO

    2014-03-01

    Full Text Available This paper presents the optimization of a virtual mouse called HeadMouse in order to foster its classroom use by children with physical disabilities. HeadMouse is an absolute virtual mouse that converts head movements in cursor displacement and facial gestures in click actions. The virtual mouse combines different image processing algorithms: face detection, pattern matching and optical flow in order to emulate the behaviour of a conventional computer mouse. The original implementation of HeadMouse requires large computational power and this paper proposes specific optimizations in order to enable its use by children with disabilities in standard low cost classroom computers.

  1. RIKEN mouse genome encyclopedia.

    Science.gov (United States)

    Hayashizaki, Yoshihide

    2003-01-01

    We have been working to establish the comprehensive mouse full-length cDNA collection and sequence database to cover as many genes as we can, named Riken mouse genome encyclopedia. Recently we are constructing higher-level annotation (Functional ANnoTation Of Mouse cDNA; FANTOM) not only with homology search based annotation but also with expression data profile, mapping information and protein-protein database. More than 1,000,000 clones prepared from 163 tissues were end-sequenced to classify into 159,789 clusters and 60,770 representative clones were fully sequenced. As a conclusion, the 60,770 sequences contained 33,409 unique. The next generation of life science is clearly based on all of the genome information and resources. Based on our cDNA clones we developed the additional system to explore gene function. We developed cDNA microarray system to print all of these cDNA clones, protein-protein interaction screening system, protein-DNA interaction screening system and so on. The integrated database of all the information is very useful not only for analysis of gene transcriptional network and for the connection of gene to phenotype to facilitate positional candidate approach. In this talk, the prospect of the application of these genome resourced should be discussed. More information is available at the web page: http://genome.gsc.riken.go.jp/.

  2. Full page insight

    DEFF Research Database (Denmark)

    Cortsen, Rikke Platz

    2014-01-01

    Alan Moore and his collaborating artists often manipulate time and space by drawing upon the formal elements of comics and making alternative constellations. This article looks at an element that is used frequently in comics of all kinds – the full page – and discusses how it helps shape spatio......, something that it shares with the full page in comics. Through an analysis of several full pages from Moore titles like Swamp Thing, From Hell, Watchmen and Promethea, it is made clear why the full page provides an apt vehicle for an apocalypse in comics....

  3. Full page insight

    DEFF Research Database (Denmark)

    Cortsen, Rikke Platz

    2014-01-01

    Alan Moore and his collaborating artists often manipulate time and space by drawing upon the formal elements of comics and making alternative constellations. This article looks at an element that is used frequently in comics of all kinds – the full page – and discusses how it helps shape spatio-t......, something that it shares with the full page in comics. Through an analysis of several full pages from Moore titles like Swamp Thing, From Hell, Watchmen and Promethea, it is made clear why the full page provides an apt vehicle for an apocalypse in comics....

  4. Gesture Recognition Based Mouse Events

    Directory of Open Access Journals (Sweden)

    Rachit Puri

    2013-12-01

    Full Text Available This paper presents the maneuver of mouse pointer a nd performs various mouse operations such as left click, right click, double click, drag etc using ge stures recognition technique. Recognizing gestures is a complex task which involves many aspects such as mo tion modeling, motion analysis, pattern recognition and machine learning. Keeping all the essential factors in mind a system has been created which recognizes the movement of fingers and various patterns formed by them. Color caps have been used for fingers to distinguish it f rom the background color such as skin color. Thus recog nizing the gestures various mouse events have been performed. The application has been created on MATL AB environment with operating system as windows 7.

  5. About CABI Full Text

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    <正>Centre for Agriculture and Bioscience International( CABI) is a not-for-profit international Agricultural Information Institute with headquarters in Britain. It aims to improve people’s lives by providing information and applying scientific expertise to solve problems in agriculture and the environment. CABI Full-text is one of the publishing products of CABI.CABI’s full text repository is growing rapidly and has now been integrated into all our databases including CAB Abstracts,Global Health,our Internet Resources and Abstract Journals. There are currently over 60,000 full text articles available to access. These documents,made possible by agreement with third

  6. About CABI Full Text

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

    <正>Centre for Agriculture and Bioscience International(CABI)is a not-for-profit international Agricultural Information Institute with headquarters in Britain.It aims to improve people’s lives by providing information and applying scientific expertise to solve problems in agriculture and the environment.CABI Full-text is one of the publishing products of CABI.CABI’s full text repository is growing rapidly

  7. full on riot

    Directory of Open Access Journals (Sweden)

    Moses Iten

    2005-08-01

    Full Text Available “hey moses full on riot in lawson st the station’s on fire! been going since 4. molotov and more. full on,” reads an SMS message received on the backseat of a Tasmanian bus. What follows is a journey through the landscape of a Gunavidji, whose brothers have all gone to the land of the dead; metallic scraping in the glass cases of the Hobart Museum; a Palestinian woman giving up on her people; land-snails exposing cultural inaccuracies; photographing Australia’s war zone; entering the St Peter’s Basilica of Rome with bulldozers - all in the name of preparing to interview prominent Israeli writer Etgar Keret.

  8. Full moon and crime.

    Science.gov (United States)

    Thakur, C P; Sharma, D

    The incidence of crimes reported to three police stations in different towns (one rural, one urban, one industrial) was studied to see if it varied with the day of the lunar cycle. The period of the study covered 1978-82. The incidence of crimes committed on full moon days was much higher than on all other days, new moon days, and seventh days after the full moon and new moon. A small peak in the incidence of crimes was observed on new moon days, but this was not significant when compared with crimes committed on other days. The incidence of crimes on equinox and solstice days did not differ significantly from those on other days, suggesting that the sun probably does not influence the incidence of crime. The increased incidence of crimes on full moon days may be due to "human tidal waves" caused by the gravitational pull of the moon.

  9. Full tree harvesting update

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, K.; White, K.

    1981-03-01

    An important harvesting alternative in North America is the Full Tree Method, in which trees are felled and transported to roadside, intermediate or primary landings with limbs and branches intact. The acceptance of Full Tree Systems is due to many factors including: labour productivity and increased demands on the forest for ''new products''. These conditions are shaping the future look for forest Harvesting Systems, but must not be the sole determinants. All harvesting implications, such as those affecting Productivity and silviculture, should be thoroughly understood. This paper does not try to discuss every implication, nor any particular one in depth; its purpose is to highlight those areas requiring consideration and to review several current North American Full Tree Systems. (Refs. 5).

  10. About CABI Full Text

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    <正>Centre for Agriculture and Bioscience International(CABI)is a not-for-profit international Agricultural Information Institute with headquarters in Britain.It aims to improve people’s lives by providing information and applying scientific expertise to solve problems in agriculture and the environment.CABI Full-text is one of the publishing products of CABI.CABI’s full text repository is growing rapidly and has now been integrated into all our databases including CAB Abstracts,Global Health

  11. Compressive full waveform lidar

    Science.gov (United States)

    Yang, Weiyi; Ke, Jun

    2017-05-01

    To avoid high bandwidth detector, fast speed A/D converter, and large size memory disk, a compressive full waveform LIDAR system, which uses a temporally modulated laser instead of a pulsed laser, is studied in this paper. Full waveform data from NEON (National Ecological Observatory Network) are used. Random binary patterns are used to modulate the source. To achieve 0.15 m ranging resolution, a 100 MSPS A/D converter is assumed to make measurements. SPIRAL algorithm with canonical basis is employed when Poisson noise is considered in the low illuminated condition.

  12. About CABI Full Text

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    <正>Centre for Agriculture and Bioscience International(CABI)is a not-for-profit international Agricultural Information Institute with headquarters in Britain.It aims to improve people’s lives by providing information and applying scientific expertise to solve problems in agriculture and the environment.CABI Full-text is one of the publishing products of CABI.CABI’s full text repository is growing rapidly and has now been integrated into all our databases including CAB Abstracts,Global Health,our Internet Resources and Jour-

  13. About CABI Full Text

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    <正>Centre for Agriculture and Bioscience International( CABI) is a not-for-profit international Agricultural Information Institute with headquarters in Britain. It aims to improve people’s lives by providing information and applying scientific expertise to solve problems in agriculture and the environment. CABI Full-text is one of the publishing products of CABI.

  14. About CABI Full Text

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    <正>Centre for Agriculture and Bioscience International(CABI) is a not-for-profit international Agricultural Information Institute with headquarters in Britain. It aims to improve people’s lives by providing information and applying scientific expertise to solve problems in agriculture and the environment. CABI Full-text is one of the publishing products of CABI.

  15. About CABI Full Text

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    <正>Centre for Agriculture and Bioscience International(CABI)is a not-for-profit international Agricultural Information Institute with headquarters in Britain. It aims to improve people s lives by providing information and applying scientific expertise to solve problems in agriculture and the environment. CABI Full-text is one of the publishing products of CABI.

  16. Emptiness and Fullness

    DEFF Research Database (Denmark)

    Bregnbæk, Susanne; Bunkenborg, Mikkel

    As critical voices question the quality, authenticity, and value of people, goods, and words in post-Mao China, accusations of emptiness render things open to new investments of meaning, substance, and value. Exploring the production of lack and desire through fine-grained ethnography, this volume......, there is a pervasive concern with states of lack and emptiness and the contributions suggest that this play of emptiness and fullness is crucial to ongoing constructions of quality, value, and subjectivity in China....

  17. Gaze beats mouse

    DEFF Research Database (Denmark)

    Mateo, Julio C.; San Agustin, Javier; Hansen, John Paulin

    2008-01-01

    Facial EMG for selection is fast, easy and, combined with gaze pointing, it can provide completely hands-free interaction. In this pilot study, 5 participants performed a simple point-and-select task using mouse or gaze for pointing and a mouse button or a facial-EMG switch for selection. Gaze...... pointing was faster than mouse pointing, while maintaining a similar error rate. EMG and mouse-button selection had a comparable performance. From analyses of completion time, throughput and error rates, we concluded that the combination of gaze and facial EMG holds potential for outperforming the mouse....

  18. Plate Full of Color

    Centers for Disease Control (CDC) Podcasts

    2008-08-04

    The Eagle Books are a series of four books that are brought to life by wise animal characters - Mr. Eagle, Miss Rabbit, and Coyote - who engage Rain That Dances and his young friends in the joy of physical activity, eating healthy foods, and learning from their elders about health and diabetes prevention. Plate Full of Color teaches the value of eating a variety of colorful and healthy foods.  Created: 8/4/2008 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 8/5/2008.

  19. The Fullness of Space

    Science.gov (United States)

    Wynn-Williams, Gareth

    1992-06-01

    A brief glance at the night sky reveals a remarkable fact about the Universe: it is extremely patchy. The light we see on a moonless night comes from bright specks we call planets and stars. Between the stars we see blackness. Most of astronomy, not to mention geology, biology, and all humanistic studies, is concerned with what happens in and on these bright specks. Yet these lumps and specks, which include the Earth, the Sun, the planets of our solar system, and all the stars together occupy less than one billion billion billionth (10-27) of the total volume of the Universe. It is astonishing to think that the interstellar medium within our Galaxy, the Milky Way, is anything but empty space. But in most of the Galaxy, the density of interstellar matter is thousands of times lower than that of the best vacuum produced on Earth. In fact, there is enough interstellar matter in the Galaxy to make ten billion stars the size of the Sun. In this excellently crafted book, the author gives full treatment to the nature of the stuff between the stars and to the methods that astronomers use to study it. He explains where the matter came from in the first place, how it collects together in clouds and clumps, and the way in which new stars and planets form from material in space. Through his descriptions we see the matter as glorious gas clouds, such as the Orion Nebula, shimmering in rich hues of red and orange. Telescopes reveal inky black clouds, the molecule factories in which new stars and planets are made. Radio, infrared, and ultraviolet telescopes have given astronomers stunning new images of interstellar matter. The Fullness of Space is written for the general reader interested in science. It assumes no scientific or mathematical background, and the only equations in the whole book are found in the appendices. It is beautifully illustrated with many of the finest photographs available of dust clouds and bright nebulae. Readers from high school age to adult will find

  20. Full metal jacket!

    CERN Multimedia

    Laëtitia Pedroso

    2011-01-01

    Ten years ago, standard issue clothing only gave CERN firemen partial protection but today our fire-fighters are equipped with state-of-the-art, full personal protective equipment.   CERN's Fire Brigade team. For many years, the members of CERN's Fire Brigade went on call-outs clad in their work trousers and fire-rescue coats, which only afforded them partial protection. Today, textile manufacturing techniques have moved on a long way and CERN's firemen are now kitted out with state-of-the-art personal protective equipment. The coat and trousers are three-layered, comprising fire-resistant aramide, a protective membrane and a thermal lining. The CERN Fire Brigade' new state-of-the-art personal protection equipment. "This equipment is fully compliant with the standards in force and is therefore resistant to cuts, abrasion, electrical arcs with thermal effects and, of course, fire," explains Patrick Berlinghi, the CERN Fire Brigade's Logistics Officer. You might think that su...

  1. Full Color Holographic Endoscopy

    Science.gov (United States)

    Osanlou, A.; Bjelkhagen, H.; Mirlis, E.; Crosby, P.; Shore, A.; Henderson, P.; Napier, P.

    2013-02-01

    The ability to produce color holograms from the human tissue represents a major medical advance, specifically in the areas of diagnosis and teaching. This has been achieved at Glyndwr University. In corporation with partners at Gooch & Housego, Moor Instruments, Vivid Components and peninsula medical school, Exeter, UK, for the first time, we have produced full color holograms of human cell samples in which the cell boundary and the nuclei inside the cells could be clearly focused at different depths - something impossible with a two-dimensional photographic image. This was the main objective set by the peninsula medical school at Exeter, UK. Achieving this objective means that clinically useful images essentially indistinguishable from the object human cells could be routinely recorded. This could potentially be done at the tip of a holo-endoscopic probe inside the body. Optimised recording exposure and development processes for the holograms were defined for bulk exposures. This included the optimisation of in-house recording emulsions for coating evaluation onto polymer substrates (rather than glass plates), a key step for large volume commercial exploitation. At Glyndwr University, we also developed a new version of our in-house holographic (world-leading resolution) emulsion.

  2. SOHO Resumes Full Operation

    Science.gov (United States)

    2003-07-01

    SOHO orbit hi-res Size hi-res: 324 kb Credits: SOHO (ESA & NASA) SOHO orbit Because of its static position, every three months the high-gain antenna loses sight of Earth. During this time, engineers will rotate the spacecraft by 180 degrees to regain full contact a few days later. Since 19 June 2003, SOHO's high-gain antenna (HGA), which transmits high-speed data to Earth, has been fixed in position following the discovery of a malfunction in its pointing mechanism. This resulted in a loss of signal through SOHO's usual 26-metre ground stations on 27 June 2003. However, 34-metre radio dishes continued to receive high-speed transmissions from the HGA until 1 July 2003. Since then, astronomers have been relying primarily on a slower transmission rate signal, sent through SOHO's backup antenna. It can be picked up whenever a 34-metre dish is available. However, this signal could not transmit all of SOHO's data. Some data was recorded on board, however, and downloaded using high-speed transmissions through the backup antenna when time on the largest, 70-metre dishes could be spared. SOHO itself orbits a point in space, 1.5 million kilometres closer to the Sun than the Earth, once every 6 months. To reorient the HGA for the next half of this orbit, engineers rolled the spacecraft through a half-circle on 8 July 2003. On 10 July, the 34-metre radio dish in Madrid re-established contact with SOHO's HGA. Then on the morning of 14 July 2003, normal operations with the spacecraft resumed through its usual 26-metre ground stations, as predicted. With the HGA now static, the blackouts, lasting between 9 and 16 days, will continue to occur every 3 months. Engineers will rotate SOHO by 180 degrees every time this occurs. This manoeuvre will minimise data losses. Stein Haugan, acting SOHO project scientist, says "It is good to welcome SOHO back to normal operations, as it proves that we have a good understanding of the situation and can confidently work around it."

  3. The Knockout Mouse Project

    OpenAIRE

    Austin, Christopher P.; Battey, James F.; Bradley, Allan; Bucan, Maja; Capecchi, Mario; Collins, Francis S; Dove, William F.; Duyk, Geoffrey; Dymecki, Susan; Eppig, Janan T.; Grieder, Franziska B.; Heintz, Nathaniel; Hicks, Geoff; Insel, Thomas R; Joyner, Alexandra

    2004-01-01

    Mouse knockout technology provides a powerful means of elucidating gene function in vivo, and a publicly available genome-wide collection of mouse knockouts would be significantly enabling for biomedical discovery. To date, published knockouts exist for only about 10% of mouse genes. Furthermore, many of these are limited in utility because they have not been made or phenotyped in standardized ways, and many are not freely available to researchers. It is time to harness new technologies and e...

  4. Replacing the computer mouse

    OpenAIRE

    Dernoncourt, Franck

    2014-01-01

    In a few months the computer mouse will be half-a-century-old. It is known to have many drawbacks, the main ones being: loss of productivity due to constant switching between keyboard and mouse, and health issues such as RSI. Like the keyboard, it is an unnatural human-computer interface. However the vast majority of computer users still use computer mice nowadays. In this article, we explore computer mouse alternatives. Our research shows that moving the mouse cursor can be done efficiently ...

  5. An encyclopedia of mouse DNA elements (Mouse ENCODE).

    Science.gov (United States)

    Stamatoyannopoulos, John A; Snyder, Michael; Hardison, Ross; Ren, Bing; Gingeras, Thomas; Gilbert, David M; Groudine, Mark; Bender, Michael; Kaul, Rajinder; Canfield, Theresa; Giste, Erica; Johnson, Audra; Zhang, Mia; Balasundaram, Gayathri; Byron, Rachel; Roach, Vaughan; Sabo, Peter J; Sandstrom, Richard; Stehling, A Sandra; Thurman, Robert E; Weissman, Sherman M; Cayting, Philip; Hariharan, Manoj; Lian, Jin; Cheng, Yong; Landt, Stephen G; Ma, Zhihai; Wold, Barbara J; Dekker, Job; Crawford, Gregory E; Keller, Cheryl A; Wu, Weisheng; Morrissey, Christopher; Kumar, Swathi A; Mishra, Tejaswini; Jain, Deepti; Byrska-Bishop, Marta; Blankenberg, Daniel; Lajoie, Bryan R; Jain, Gaurav; Sanyal, Amartya; Chen, Kaun-Bei; Denas, Olgert; Taylor, James; Blobel, Gerd A; Weiss, Mitchell J; Pimkin, Max; Deng, Wulan; Marinov, Georgi K; Williams, Brian A; Fisher-Aylor, Katherine I; Desalvo, Gilberto; Kiralusha, Anthony; Trout, Diane; Amrhein, Henry; Mortazavi, Ali; Edsall, Lee; McCleary, David; Kuan, Samantha; Shen, Yin; Yue, Feng; Ye, Zhen; Davis, Carrie A; Zaleski, Chris; Jha, Sonali; Xue, Chenghai; Dobin, Alex; Lin, Wei; Fastuca, Meagan; Wang, Huaien; Guigo, Roderic; Djebali, Sarah; Lagarde, Julien; Ryba, Tyrone; Sasaki, Takayo; Malladi, Venkat S; Cline, Melissa S; Kirkup, Vanessa M; Learned, Katrina; Rosenbloom, Kate R; Kent, W James; Feingold, Elise A; Good, Peter J; Pazin, Michael; Lowdon, Rebecca F; Adams, Leslie B

    2012-08-13

    To complement the human Encyclopedia of DNA Elements (ENCODE) project and to enable a broad range of mouse genomics efforts, the Mouse ENCODE Consortium is applying the same experimental pipelines developed for human ENCODE to annotate the mouse genome.

  6. The MOUSE Squad

    Science.gov (United States)

    Borja, Rhea R.

    2004-01-01

    This article presents a New York city after-school program started by MOUSE (Making Opportunities for Upgrading Schools and Education), a national nonprofit group that teaches students how to fix computers, and equips them with the communication and problem-solving skills to help them in the working world. The MOUSE program is part of a trend…

  7. Detecting mRNA Predictors of Acetaminophen-Induced Hepatotoxicity in Mouse Blood Using Quantitative Real-Time PCR.

    Science.gov (United States)

    Kanno, Syu-ichi; Tomizawa, Ayako; Yomogida, Shin

    2016-01-01

    Acetaminophen (APAP) is a widely used analgesic and antipyretic drug. Drug-induced liver injury from agents such as APAP is known to vary between individuals within a species. To avoid liver injury and ensure the proper use of pharmaceutical products, it is important to be able to predict such risks using genetic information. This study evaluated the use of quantitative real-time polymerase chain reaction (RT-qPCR) to identify mRNAs (carried in the blood of male ddY mice) capable of predicting susceptibility to APAP-induced hepatotoxicity. Screening was performed on samples obtained at 18 h after treatment from mice that had been orally treated with 500 mg/kg APAP. APAP-induced hepatotoxicity was seen in 60% of the mice, and the mortality rate was 12%. Blood APAP concentration did not differ significantly between mice with and without APAP-induced hepatotoxicity. We compared blood mRNA expression levels between mice with (positive, serious or lethal injury) and without hepatotoxicity in the APAP-treated group. The transcript levels of interleukin-encoding loci Il1β, Il10, and tumor necrosis factor (Tnf) were increased in the lethal injury group. Transcripts of the loci encoding transthyretin (Ttr) and metallothionein 1 (Mt1) showed increases in the liver injury group, while those of the glutathione peroxidase 3-encoding locus (Gpx3) were decreased. APAP hepatotoxicity was potentiated in fasted animals, although fasting did not appear to affect the level of expression of these genes. These results indicate that mRNA expression of Il1β, Il10, Tnf, Ttr, Mt1, and Gpx3 in mouse blood may provide useful surrogate markers of APAP-induced hepatotoxicity.

  8. Mouse genome database 2016.

    Science.gov (United States)

    Bult, Carol J; Eppig, Janan T; Blake, Judith A; Kadin, James A; Richardson, Joel E

    2016-01-01

    The Mouse Genome Database (MGD; http://www.informatics.jax.org) is the primary community model organism database for the laboratory mouse and serves as the source for key biological reference data related to mouse genes, gene functions, phenotypes and disease models with a strong emphasis on the relationship of these data to human biology and disease. As the cost of genome-scale sequencing continues to decrease and new technologies for genome editing become widely adopted, the laboratory mouse is more important than ever as a model system for understanding the biological significance of human genetic variation and for advancing the basic research needed to support the emergence of genome-guided precision medicine. Recent enhancements to MGD include new graphical summaries of biological annotations for mouse genes, support for mobile access to the database, tools to support the annotation and analysis of sets of genes, and expanded support for comparative biology through the expansion of homology data.

  9. GENE KICKED MOUSE: KNOCK OUT MOUSE AND ITS APPLICATION

    Directory of Open Access Journals (Sweden)

    Rajashekar B

    2013-07-01

    Full Text Available A knockout mouse is a laboratory mouse in which genes are inactivated, or "knocked out," an existing gene by replacing it or disrupting it with an artificial piece of DNA. The 2007 Nobel Prize in physiology or medicine is awarded to Drs Mario R. Capecchi, Martin J. Evans and Oliver Smithies for their discoveries of principles for introducing specific gene modifications in mice by using embryonic stem cells. Progress to gene targeting using embryonic cell was developed by Evans and his co-workers. Ingenious development of gene targeting has been made by introducing recognition sites for the enzyme Cre recombinase, called loxP sites, into existing genes. When mice carrying such "floxed" genes are mated with transgenic mice expressing Cre recombinase, the target gene of the offspring is modified through Cre action. Gene targeting has transformed scientific medicine by permitting experimental testing of hypotheses regarding the function of specific genes. The first area to which experimental geneticists turned their attention after the birth of gene targeting in mammals was monogenic diseases. Gene targeting has been exceptionally useful in cancer research. A large number of protooncogenes, tumor suppressor genes, angiogenetic factors etc have been targeted in different tissues in mice to shed light on the induction and spreading of tumours. Gene-targeted mouse models have also become increasingly important in studies of host defense against pathogens. Gene targeted mice have become indispensable in virtually all aspects of medical research.

  10. 阻滞血管紧张素Ⅱ1型受体对创面愈合的影响%Effect of blocking angiotensin Ⅱ type 1 receptor on wound healing in mouse skin full-thickness injury model

    Institute of Scientific and Technical Information of China (English)

    李升红; 刘宏伟; 程飚; 徐媛; 肖静; 肖丽玲; 邵建立

    2012-01-01

    influenced wound healing.Methods Two full-thickness skin wounds were created on the dorsum of C57/BL6J mice.Animals were treated with or without AT1R blocker,Losartan at a dose of 20 mg/kg daily after wounding.Specimens were taken from the wound of each mouse on the day 3,5,7,9,11,13 and 15 after wounding.Reepitheliazation and granulation tissue formation in wounded skin tissue were evaluated by hematoxylin and eosin (HE) staining.The production of growth factors in wounded tissue during the healing process was detected by using enzyme linked immunosorbent assay (ELISA).Results Treatment with AT1R blocker,Losartan,significantly inhibited the rate of reepithelialization and the thickness of granulation tissue as compared with untreated group at the day 5 and 7 after wounding.Moreover,peritoneal application of Losartan decreased the production of epidermal growth factor (EGF),vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in the wounded tissues at the indicated time after wounding.Conclusion These results indicate that AT1R blocker impaired wound healing at least partially via inhibiting growth factors production.

  11. Mouse models for methylmalonic aciduria.

    Directory of Open Access Journals (Sweden)

    Heidi L Peters

    Full Text Available Methylmalonic aciduria (MMA is a disorder of organic acid metabolism resulting from a functional defect of methylmalonyl-CoA mutase (MCM. MMA is associated with significant morbidity and mortality, thus therapies are necessary to help improve quality of life and prevent renal and neurological complications. Transgenic mice carrying an intact human MCM locus have been produced. Four separate transgenic lines were established and characterised as carrying two, four, five or six copies of the transgene in a single integration site. Transgenic mice from the 2-copy line were crossed with heterozygous knockout MCM mice to generate mice hemizygous for the human transgene on a homozygous knockout background. Partial rescue of the uniform neonatal lethality seen in homozygous knockout mice was observed. These rescued mice were significantly smaller than control littermates (mice with mouse MCM gene. Biochemically, these partial rescue mice exhibited elevated methylmalonic acid levels in urine, plasma, kidney, liver and brain tissue. Acylcarnitine analysis of blood spots revealed elevated propionylcarnitine levels. Analysis of mRNA expression confirms the human transgene is expressed at higher levels than observed for the wild type, with highest expression in the kidney followed closely by brain and liver. Partial rescue mouse fibroblast cultures had only 20% of the wild type MCM enzyme activity. It is anticipated that this humanised partial rescue mouse model of MMA will enable evaluation of long-term pathophysiological effects of elevated methylmalonic acid levels and be a valuable model for the investigation of therapeutic strategies, such as cell transplantation.

  12. Mouse Models of Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Timothy C. Wang

    2013-01-01

    Full Text Available Animal models have greatly enriched our understanding of the molecular mechanisms of numerous types of cancers. Gastric cancer is one of the most common cancers worldwide, with a poor prognosis and high incidence of drug-resistance. However, most inbred strains of mice have proven resistant to gastric carcinogenesis. To establish useful models which mimic human gastric cancer phenotypes, investigators have utilized animals infected with Helicobacter species and treated with carcinogens. In addition, by exploiting genetic engineering, a variety of transgenic and knockout mouse models of gastric cancer have emerged, such as INS-GAS mice and TFF1 knockout mice. Investigators have used the combination of carcinogens and gene alteration to accelerate gastric cancer development, but rarely do mouse models show an aggressive and metastatic gastric cancer phenotype that could be relevant to preclinical studies, which may require more specific targeting of gastric progenitor cells. Here, we review current gastric carcinogenesis mouse models and provide our future perspectives on this field.

  13. Mouse Genome Informatics (MGI)

    Data.gov (United States)

    U.S. Department of Health & Human Services — MGI is the international database resource for the laboratory mouse, providing integrated genetic, genomic, and biological data to facilitate the study of human...

  14. Mouse Phenome Database (MPD)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Mouse Phenome Database (MPD) has characterizations of hundreds of strains of laboratory mice to facilitate translational discoveries and to assist in selection...

  15. An Intelligent Multilingual Mouse Gesture Recognition System

    Directory of Open Access Journals (Sweden)

    Nidal F. Shilbayeh

    2005-01-01

    Full Text Available A comprehensive mouse gesture system is designed and tested successfully. The system is based on UNIPEN algorithm in terms of mouse movements and applies its geometrical principles such as angles and transposition steps. The system incorporates Neural Networks as its learning and recognition engine. The designed algorithm is not only capable of translating discrete gesture moves, but also continuous sentences and complete paragraphs. Hopfield Network is also used for initial learning to add a feature of language independence to the system.

  16. The Riken mouse genome encyclopedia project.

    Science.gov (United States)

    Hayashizaki, Yoshihide

    2003-01-01

    The Riken mouse genome encyclopedia a comprehensive full-length cDNA collection and sequence database. High-level functional annotation is based on sequence homology search, expression profiling, mapping and protein-protein interactions. More than 1000000 clones prepared from 163 tissues were end-sequenced and classified into 128000 clusters, and 60000 representative clones were fully sequenced representing 24000 clear protein-encoding genes. The application of the mouse genome database for positional cloning and gene network regulation analysis is reported.

  17. A Color Based Touchless Finger Mouse

    Directory of Open Access Journals (Sweden)

    Kah-Meng Kwong

    2012-01-01

    Full Text Available People work with computers almost anytime, everywhere  in the current trend. However, continuously controlling a computer with mouse for a long time might cause much strains to people’s wrist. This work proposes a touchless finger mouse using webcam. A marker with different colours representing different actions is used. The webcam will capture the information on the marker and trigger the associated actions. This prototype is proven to be able to perform most of the actions a normal mouser can perform.

  18. In amnio MRI of mouse embryos.

    Directory of Open Access Journals (Sweden)

    Thomas A Roberts

    Full Text Available Mouse embryo imaging is conventionally carried out on ex vivo embryos excised from the amniotic sac, omitting vital structures and abnormalities external to the body. Here, we present an in amnio MR imaging methodology in which the mouse embryo is retained in the amniotic sac and demonstrate how important embryonic structures can be visualised in 3D with high spatial resolution (100 µm/px. To illustrate the utility of in amnio imaging, we subsequently apply the technique to examine abnormal mouse embryos with abdominal wall defects. Mouse embryos at E17.5 were imaged and compared, including three normal phenotype embryos, an abnormal embryo with a clear exomphalos defect, and one with a suspected gastroschisis phenotype. Embryos were excised from the mother ensuring the amnion remained intact and stereo microscopy was performed. Embryos were next embedded in agarose for 3D, high resolution MRI on a 9.4T scanner. Identification of the abnormal embryo phenotypes was not possible using stereo microscopy or conventional ex vivo MRI. Using in amnio MRI, we determined that the abnormal embryos had an exomphalos phenotype with varying severities. In amnio MRI is ideally suited to investigate the complex relationship between embryo and amnion, together with screening for other abnormalities located outside of the mouse embryo, providing a valuable complement to histology and existing imaging methods available to the phenotyping community.

  19. Age-related changes of metallothionein 1/2 and metallothionein 3 expression in rat brain.

    Science.gov (United States)

    Scudiero, Rosaria; Cigliano, Luisa; Verderame, Mariailaria

    2017-01-01

    Neurodegeneration is one of the main physiological consequences of aging on brain. Metallothioneins (MTs), low molecular weight, cysteine-rich proteins that bind heavy-metal ions and oxygen-free radicals, are commonly expressed in various tissues of mammals. MTs are involved in the regulation of cell proliferation and protection, and may be engaged in aging. Expression of the ubiquitous MTs (1 and 2) and the brain specific MT3 have been studied in many neurodegenerative disorders. The research results indicate that MTs may play important, although not yet fully known, roles in brain diseases; in addition, data lack the ability to identify the MT isoforms functionally involved. The aim of this study was to analyse the level of gene expression of selected MT isoforms during brain aging. By using real-time PCR analysis, we determined the MT1/2 and MT3 expression profiles in cerebral cortex and hippocampus of adolescent (2months), adult (4 and 8months), and middle-aged (16months) rats. We show that the relative abundance of all types of MT transcripts changes during aging in both hippocampus and cortex; the first effect is a generalized decrease in the content of MTs transcripts from 2- to 8-months-old rats. After passing middle age, at 16months, we observe a huge increase in MT3 transcripts in both cortical and hippocampal areas, while the MT1/2 mRNA content increases slightly, returning to the levels measured in adolescent rats. These findings demonstrate an age-related expression of the MT3 gene. A possible link between the increasing amount of MT3 in brain aging and its different metal-binding behaviour is discussed.

  20. Metallothionein-1 and nitric oxide expression are inversely correlated in a murine model of Chagas disease

    OpenAIRE

    2014-01-01

    Chagas disease, caused by Trypanosoma cruzi, represents an endemic among Latin America countries. The participation of free radicals, especially nitric oxide (NO), has been demonstrated in the pathophysiology of seropositive individuals with T. cruzi. In Chagas disease, increased NO contributes to the development of cardiomyopathy and megacolon. Metallothioneins (MTs) are efficient free radicals scavengers of NO in vitro and in vivo. Here, we developed a murine model of the chronic phase of C...

  1. Metallothionein-1 and nitric oxide expression are inversely correlated in a murine model of Chagas disease

    Science.gov (United States)

    Gonzalez-Mejia, Martha Elba; Torres-Rasgado, Enrique; Porchia, Leonardo M; Salgado, Hilda Rosas; Totolhua, José-Luis; Ortega, Arturo; Hernández-Kelly, Luisa Clara Regina; Ruiz-Vivanco, Guadalupe; Báez-Duarte, Blanca G; Pérez-Fuentes, Ricardo

    2014-01-01

    Chagas disease, caused by Trypanosoma cruzi, represents an endemic among Latin America countries. The participation of free radicals, especially nitric oxide (NO), has been demonstrated in the pathophysiology of seropositive individuals with T. cruzi. In Chagas disease, increased NO contributes to the development of cardiomyopathy and megacolon. Metallothioneins (MTs) are efficient free radicals scavengers of NO in vitro and in vivo. Here, we developed a murine model of the chronic phase of Chagas disease using endemic T. cruzi RyCH1 in BALB/c mice, which were divided into four groups: infected non-treated (Inf), infected N-monomethyl-L-arginine treated (Inf L-NAME), non-infected L-NAME treated and non-infected vehicle-treated. We determined blood parasitaemia and NO levels, the extent of parasite nests in tissues and liver MT-I expression levels. It was observed that NO levels were increasing in Inf mice in a time-dependent manner. Inf L-NAME mice had fewer T. cruzi nests in cardiac and skeletal muscle with decreased blood NO levels at day 135 post infection. This affect was negatively correlated with an increase of MT-I expression (r = -0.8462, p < 0.0001). In conclusion, we determined that in Chagas disease, an unknown inhibitory mechanism reduces MT-I expression, allowing augmented NO levels. PMID:24676665

  2. Metallothioneins 1 and 2 Modulate Inflammation and Support Remodeling in Ischemic Cardiomyopathy in Mice

    Science.gov (United States)

    Dewald, Daniela; Schmitz, Eva J.; Verfuerth, Luise; Keppel, Katharina; Peigney, Christine; Ghanem, Alexander; Welz, Armin; Dewald, Oliver

    2016-01-01

    Aims. Repetitive brief ischemia and reperfusion (I/R) is associated with left ventricular dysfunction during development of ischemic cardiomyopathy. We investigated the role of zinc-donor proteins metallothionein MT1 and MT2 in a closed-chest murine model of I/R. Methods. Daily 15-minute LAD-occlusion was performed for 1, 3, and 7 days in SV129 (WT)- and MT1/2 knockout (MT−/−)-mice (n = 8–10/group). Hearts were examined with M-mode echocardiography and processed for histological and mRNA studies. Results. Expression of MT1/2 mRNA was transiently induced during repetitive I/R in WT-mice, accompanied by a transient inflammation, leading to interstitial fibrosis with left ventricular dysfunction without infarction. In contrast, MT−/−-hearts presented with enhanced apoptosis and small infarctions leading to impaired global and regional pump function. Molecular analysis revealed maladaptation of myosin heavy chain isoforms and antioxidative enzymes in MT1/2−/−-hearts. Despite their postponed chemokine induction we found a higher total neutrophil density and macrophage infiltration in small infarctions in MT−/−-hearts. Subsequently, higher expression of osteopontin 1 and tenascin C was associated with increased myofibroblast density resulting in predominately nonreversible fibrosis and adverse remodeling in MT1/2−/−-hearts. Conclusion. Cardioprotective effects of MT1/2 seem to be exerted via modulation of contractile elements, antioxidative enzymes, inflammatory response, and myocardial remodeling. PMID:27403038

  3. Role of Metallothionein1H in Cisplatin Resistance of Non-Small Cell Lung Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    Xin-fang Hou; Qing-xia Fan; Liu-xing Wang; Shi-xin Lu

    2009-01-01

    Objective: Despite platinum-based adjuvant chemotherapy has improved greatly patients' outcomes, drug resistance poses a major impediment to the successful use of such an effective agent. Metallothioneins(MTs) are known to play putative roles in cancer cell proliferation, apoptosis, differentiation, drug resistance and prognosis. The present studiy was to investigte the role of metallethioein1H(MT1H) in cisplatin resistance of human non-small cell lung cancer(NSCLC) cell lines in vitro or its possible molecular mechanisms. Methods: MT1H mRNA expression in A549 and A549/DDP cells was detected by RT-PCR. A recombinant eukaryotic expression plasmid pcDNA3.1(-)-MT1H was constructed and transfected into A549 cells which express no MT1H. MT1H siRNA was transfected into A549/DDP cells which express MT1H highly. MT1H expression was detected by RT-PCR and Immunoblot. The chemosensitivity to cisplatin was assessed by MTT assay. Apoptosis rate was determined by Tunel and FCM. Bcl-2 and Bax were determined by immunohistochemistry. Results: MT1H mRNA was expressed in A549/DDP but not in A549. After transfection of MT1H, MT1H expression was enhanced and the chemosensitivity to cisplatin was decreased in A549 cells. Inversely, after transfection of MT1H siRNA, MT1H expression was decreased and the chemosensitivity to cisplatin was increased in A549/DDP. The apoptosis rate induced by cisplatin was increased and Bcl-2 was down-regulated but Bax showed little change in A549/DDP cells interferred with MT1H siRNA. Conclusion: MT1H overexpression can promote drug resistance in A549 cells . Down-regulation of MT1H interfered with siRNA can effectively reverses the drug resistance in A549/DDP cells by down-regulating the expression of Bcl-2 and increasing cisplatin induced apoptosis. SiRNA targeting MT1H combined with chemotherapy may be a very promising strategy for treatment of lung cancer.

  4. Mouse gestation length is genetically determined.

    Directory of Open Access Journals (Sweden)

    Stephen A Murray

    Full Text Available BACKGROUND: Preterm birth is an enormous public health problem, affecting over 12% of live births and costing over $26 billion in the United States alone. The causes are complex, but twin studies support the role of genetics in determining gestation length. Despite widespread use of the mouse in studies of the genetics of preterm birth, there have been few studies that actually address the precise natural gestation length of the mouse, and to what degree the timing of labor and birth is genetically determined. METHODOLOGY/PRINCIPAL FINDINGS: To further develop the mouse as a genetic model of preterm birth, we developed a high-throughput monitoring system and measured the gestation length in 15 inbred strains. Our results show an unexpectedly wide variation in overall gestation length between strains that approaches two full days, while intra-strain variation is quite low. Although litter size shows a strong inverse correlation with gestation length, genetic difference alone accounts for a significant portion of the variation. In addition, ovarian transplant experiments support a primary role of maternal genetics in the determination of gestation length. Preliminary analysis of gestation length in the C57BL/6J-Chr#(A/J/NaJ chromosome substitution strain (B.A CSS panel suggests complex genetic control of gestation length. CONCLUSIONS/SIGNIFICANCE: Together, these data support the role of genetics in regulating gestation length and present the mouse as an important tool for the discovery of genes governing preterm birth.

  5. The Mouse SAGE Site: database of public mouse SAGE libraries.

    Science.gov (United States)

    Divina, Petr; Forejt, Jirí

    2004-01-01

    The Mouse SAGE Site is a web-based database of all available public libraries generated by the Serial Analysis of Gene Expression (SAGE) from various mouse tissues and cell lines. The database contains mouse SAGE libraries organized in a uniform way and provides web-based tools for browsing, comparing and searching SAGE data with reliable tag-to-gene identification. A modified approach based on the SAGEmap database is used for reliable tag identification. The Mouse SAGE Site is maintained on an ongoing basis at the Institute of Molecular Genetics, Academy of Sciences of the Czech Republic and is accessible at the internet address http://mouse.biomed.cas.cz/sage/.

  6. Full Static Output Feedback Equivalence

    Directory of Open Access Journals (Sweden)

    Aristotle G. Yannakoudakis

    2013-01-01

    Full Text Available We present a constructive solution to the problem of full output feedback equivalence, of linear, minimal, time-invariant systems. The equivalence relation on the set of systems is transformed to another on the set of invertible block Bezout/Hankel matrices using the isotropy subgroups of the full state feedback group and the full output injection group. The transformation achieving equivalence is calculated solving linear systems of equations. We give a polynomial version of the results proving that two systems are full output feedback equivalent, if and only if they have the same family of generalized Bezoutians. We present a new set of output feedback invariant polynomials that generalize the breakaway polynomial of scalar systems.

  7. Deconfining transition in Full QCD

    CERN Document Server

    Carmona, J M; Del Debbio, L; Di Giacomo, Adriano; Lucini, B; Paffuti, G; Pica, C

    2002-01-01

    We present evidence that in full QCD with two dynamical quarks confinement is produced by dual superconductivity of the vacuum as in the quenched theory. Preliminary information is obtained on the nature of the deconfining transition.

  8. Principle extremum of full action

    Directory of Open Access Journals (Sweden)

    Solomon I. Khmelnik

    2011-10-01

    Full Text Available A new variational principle extremum of full action is proposed, which extends the Lagrange formalism on dissipative systems. It is shown that this principle is applicable in electrical engineering, electrodynamics, mechanics and hydrodynamics, taking into account the friction forces. The proposed variational principle may be considered as a new formalism used as an universal method of physical equations derivation, and also as a method for solving these equations.

  9. Neuron Loss in Transgenic Mouse Models of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Oliver Wirths

    2010-01-01

    Full Text Available Since their initial generation in the mid 1990s, transgenic mouse models of Alzheimers's disease (AD have been proven to be valuable model systems which are indispensable for modern AD research. Whereas most of these models are characterized by extensive amyloid plaque pathology, inflammatory changes and often behavioral deficits, modeling of neuron loss was much less successful. The present paper discusses the current achievements of modeling neuron loss in transgenic mouse models based on APP/Aβ and Tau overexpression and provides an overview of currently available AD mouse models showing these pathological alterations.

  10. MPHASYS: a mouse phenotype analysis system

    Directory of Open Access Journals (Sweden)

    Mian I

    2007-06-01

    Full Text Available Abstract Background Systematic, high-throughput studies of mouse phenotypes have been hampered by the inability to analyze individual animal data from a multitude of sources in an integrated manner. Studies generally make comparisons at the level of genotype or treatment thereby excluding associations that may be subtle or involve compound phenotypes. Additionally, the lack of integrated, standardized ontologies and methodologies for data exchange has inhibited scientific collaboration and discovery. Results Here we introduce a Mouse Phenotype Analysis System (MPHASYS, a platform for integrating data generated by studies of mouse models of human biology and disease such as aging and cancer. This computational platform is designed to provide a standardized methodology for working with animal data; a framework for data entry, analysis and sharing; and ontologies and methodologies for ensuring accurate data capture. We describe the tools that currently comprise MPHASYS, primarily ones related to mouse pathology, and outline its use in a study of individual animal-specific patterns of multiple pathology in mice harboring a specific germline mutation in the DNA repair and transcription-specific gene Xpd. Conclusion MPHASYS is a system for analyzing multiple data types from individual animals. It provides a framework for developing data analysis applications, and tools for collecting and distributing high-quality data. The software is platform independent and freely available under an open-source license 1.

  11. An update on the mouse liver proteome

    Directory of Open Access Journals (Sweden)

    Borlak Jürgen

    2009-09-01

    Full Text Available Abstract Background Decoding of the liver proteome is subject of intense research, but hampered by methodological constraints. We recently developed an improved protocol for studying rat liver proteins based on 2-DE-MALDI-TOF-MS peptide mass finger printing. This methodology was now applied to develop a mouse liver protein database. Results Liver proteins were extracted by two different lysis buffers in sequence followed by a liquid-phase IEF pre-fractionation and separation of proteins by 2 DE at two different pH ranges, notably 5-8 and 7-10. Based on 9600 in gel digests a total of 643 mouse liver proteins with high sequence coverage (> 20 peptides per protein could be identified by MALDI-TOF-MS peptide mass finger printing. Notably, 255 proteins are novel and have not been reported so far by conventional two-dimensional electrophoresis proteome mapping. Additionally, the results of the present findings for mouse liver were compared to published data of the rat proteome to compile as many proteins as possible in a rodent liver database. Conclusion Based on 2-DE MALDI-TOF-MS a significantly improved proteome map of mouse liver was obtained. We discuss some prominent members of newly identified proteins for a better understanding of liver biology.

  12. Isolation of Mouse Neutrophils.

    Science.gov (United States)

    Swamydas, Muthulekha; Luo, Yi; Dorf, Martin E; Lionakis, Michail S

    2015-08-03

    Neutrophils represent the first line of defense against bacterial and fungal pathogens. Indeed, patients with inherited and acquired qualitative and quantitative neutrophil defects are at high risk for developing bacterial and fungal infections and suffering adverse outcomes from these infections. Therefore, research aiming at defining the molecular factors that modulate neutrophil effector function under homeostatic conditions and during infection is essential for devising strategies to augment neutrophil function and improve the outcome of infected individuals. This unit describes a reproducible density gradient centrifugation-based protocol that can be applied in any laboratory to harvest large numbers of highly enriched and highly viable neutrophils from the bone marrow of mice both at the steady state and following infection with Candida albicans as described in UNIT. In another protocol, we also present a method that combines gentle enzymatic tissue digestion with a positive immunomagnetic selection technique or Fluorescence-activated cell sorting (FACS) to harvest highly pure and highly viable preparations of neutrophils directly from mouse tissues such as the kidney, the liver or the spleen. Finally, methods for isolating neutrophils from mouse peritoneal fluid and peripheral blood are included. Mouse neutrophils isolated by these protocols can be used for examining several aspects of cellular function ex vivo including pathogen binding, phagocytosis and killing, neutrophil chemotaxis, oxidative burst, degranulation and cytokine production, and for performing neutrophil adoptive transfer experiments.

  13. Mouse models in oncoimmunology.

    Science.gov (United States)

    Zitvogel, Laurence; Pitt, Jonathan M; Daillère, Romain; Smyth, Mark J; Kroemer, Guido

    2016-12-01

    Fundamental cancer research and the development of efficacious antineoplastic treatments both rely on experimental systems in which the relationship between malignant cells and immune cells can be studied. Mouse models of transplantable, carcinogen-induced or genetically engineered malignancies - each with their specific advantages and difficulties - have laid the foundations of oncoimmunology. These models have guided the immunosurveillance theory that postulates that evasion from immune control is an essential feature of cancer, the concept that the long-term effects of conventional cancer treatments mostly rely on the reinstatement of anticancer immune responses and the preclinical development of immunotherapies, including currently approved immune checkpoint blockers. Specific aspects of pharmacological development, as well as attempts to personalize cancer treatments using patient-derived xenografts, require the development of mouse models in which murine genes and cells are replaced with their human equivalents. Such 'humanized' mouse models are being progressively refined to characterize the leukocyte subpopulations that belong to the innate and acquired arms of the immune system as they infiltrate human cancers that are subjected to experimental therapies. We surmise that the ever-advancing refinement of murine preclinical models will accelerate the pace of therapeutic optimization in patients.

  14. Goldenhar Syndrome and full inclusion

    OpenAIRE

    Claus Dieter Stobäus; Carla Rejane Crixel Fernandes

    2014-01-01

    We discuss the information included in Fernandes’ Monograph and opinions of his advisor (Stobäus), centered in interfaces with Special Education/Full Inclusion, pointing anatomic-functional elements of this Syndrome, reviewing difficulties encountered in full inclusion, by an interview with his mother and teacher. http://dx.doi.org/10.5902/1984686X4444 Discutimos elementos da Monografia de Conclusão de Curso de Fernandes com opiniões de seu orientador (Stobäus), centrando em interfaces com...

  15. Full autonomy; Autarkie im Komplettpaket

    Energy Technology Data Exchange (ETDEWEB)

    Augsten, Eva

    2011-05-31

    Normally, those who talk of full solar autonomy refer to the annual balance of a house. Now, architect Timo Leukefeld and Helma Eigenheimbau AG presented a really autonomous solar house which is available on a turnkey basis for 363,000 Euros.

  16. Rectilinear Full Steiner Tree Generation

    DEFF Research Database (Denmark)

    Zachariasen, Martin

    1999-01-01

    The fastest exact algorithm (in practice) for the rectilinear Steiner tree problem in the plane uses a two-phase scheme: First, a small but sufficient set of full Steiner trees (FSTs) is generated and then a Steiner minimum tree is constructed from this set by using simple backtrack search, dynamic...

  17. Empty calories and phantom fullness

    NARCIS (Netherlands)

    Camps, Guido; Mars, Monica; Graaf, De Cees; Smeets, Paul A.M.

    2016-01-01

    Background: Stomach fullness is a determinant of satiety. Although both the viscosity and energy content have been shown to delay gastric emptying, their relative importance is not well understood. Objective: We compared the relative effects of and interactions between the viscosity and energy de

  18. Mouse genetics: catalogue and scissors.

    Science.gov (United States)

    Sung, Young Hoon; Baek, In-Jeoung; Seong, Je Kyung; Kim, Jin Soo; Lee, Han-Woong

    2012-12-01

    Phenotypic analysis of gene-specific knockout (KO) mice has revolutionized our understanding of in vivo gene functions. As the use of mouse embryonic stem (ES) cells is inevitable for conventional gene targeting, the generation of knockout mice remains a very time-consuming and expensive process. To accelerate the large-scale production and phenotype analyses of KO mice, international efforts have organized global consortia such as the International Knockout Mouse Consortium (IKMC) and International Mouse Phenotype Consortium (IMPC), and they are persistently expanding the KO mouse catalogue that is publicly available for the researches studying specific genes of interests in vivo. However, new technologies, adopting zinc-finger nucleases (ZFNs) or Transcription Activator-Like Effector (TALE) Nucleases (TALENs) to edit the mouse genome, are now emerging as valuable and effective shortcuts alternative for the conventional gene targeting using ES cells. Here, we introduce the recent achievement of IKMC, and evaluate the significance of ZFN/TALEN technology in mouse genetics.

  19. Full scale lightning test technique

    Science.gov (United States)

    Walko, L. C.; Schneider, J. G.

    1980-01-01

    A test technique was developed for applying a full scale mean value (30 kiloampere peak) simulated lightning return stroke current on a complete flight ready aircraft to assess the threat of lightning to aircraft electrical circuits. A computer-aided generator design was used to establish the parameters of the test system. Data from previous work done on development of low inductance current paths determined the basic system configuration.

  20. Workflows for Full Waveform Inversions

    Science.gov (United States)

    Boehm, Christian; Krischer, Lion; Afanasiev, Michael; van Driel, Martin; May, Dave A.; Rietmann, Max; Fichtner, Andreas

    2017-04-01

    Despite many theoretical advances and the increasing availability of high-performance computing clusters, full seismic waveform inversions still face considerable challenges regarding data and workflow management. While the community has access to solvers which can harness modern heterogeneous computing architectures, the computational bottleneck has fallen to these often manpower-bounded issues that need to be overcome to facilitate further progress. Modern inversions involve huge amounts of data and require a tight integration between numerical PDE solvers, data acquisition and processing systems, nonlinear optimization libraries, and job orchestration frameworks. To this end we created a set of libraries and applications revolving around Salvus (http://salvus.io), a novel software package designed to solve large-scale full waveform inverse problems. This presentation focuses on solving passive source seismic full waveform inversions from local to global scales with Salvus. We discuss (i) design choices for the aforementioned components required for full waveform modeling and inversion, (ii) their implementation in the Salvus framework, and (iii) how it is all tied together by a usable workflow system. We combine state-of-the-art algorithms ranging from high-order finite-element solutions of the wave equation to quasi-Newton optimization algorithms using trust-region methods that can handle inexact derivatives. All is steered by an automated interactive graph-based workflow framework capable of orchestrating all necessary pieces. This naturally facilitates the creation of new Earth models and hopefully sparks new scientific insights. Additionally, and even more importantly, it enhances reproducibility and reliability of the final results.

  1. Full-F gyrofluid model

    DEFF Research Database (Denmark)

    Madsen, Jens

    2013-01-01

    variables. The fluid moment hierarchy is closed by approximating the gyrokinetic distribution function as a finite order Hermite-Laguerre polynomial and by determining closure approximations for terms involving the gyrokinetic gyro-averaging operator. The model exactly conserves the gyrokinetic full......-F energy invariant evaluated using the Hermite-Laguerre decomposition. The model is suited for qualitative studies of the interplay between turbulence, flows, and dynamically evolving profiles in magnetically confined plasmas....

  2. Effect of Duplicate Genes on Mouse Genetic Robustness: An Update

    Directory of Open Access Journals (Sweden)

    Zhixi Su

    2014-01-01

    Full Text Available In contrast to S. cerevisiae and C. elegans, analyses based on the current knockout (KO mouse phenotypes led to the conclusion that duplicate genes had almost no role in mouse genetic robustness. It has been suggested that the bias of mouse KO database toward ancient duplicates may possibly cause this knockout duplicate puzzle, that is, a very similar proportion of essential genes (PE between duplicate genes and singletons. In this paper, we conducted an extensive and careful analysis for the mouse KO phenotype data and corroborated a strong effect of duplicate genes on mouse genetics robustness. Moreover, the effect of duplicate genes on mouse genetic robustness is duplication-age dependent, which holds after ruling out the potential confounding effect from coding-sequence conservation, protein-protein connectivity, functional bias, or the bias of duplicates generated by whole genome duplication (WGD. Our findings suggest that two factors, the sampling bias toward ancient duplicates and very ancient duplicates with a proportion of essential genes higher than that of singletons, have caused the mouse knockout duplicate puzzle; meanwhile, the effect of genetic buffering may be correlated with sequence conservation as well as protein-protein interactivity.

  3. LHCb : Full Experiment System Test

    CERN Multimedia

    Cattaneo, M

    2009-01-01

    LHCb had been planning to commission its High Level Trigger software and Data Quality monitoring procedures using real collisions data from the LHC pilot run. Following the LHC incident on 19th September 2008, it was decided to commission the system using simulated data. This “Full Experiment System Test” consists of: - Injection of simulated minimum bias events into the full HLT farm, after selection by a simulated Level 0 trigger. - Processing in the HLT farm to achieve the output rate expected for nominal LHC luminosity running, sustained over the typical duration of an LHC fill. - Real time Data Quality validation of the HLT output, validation of calibration and alignment parameters for use in the reconstruction. - Transmission of the event data, calibration data and book-keeping information to Tier1 sites and full reconstruction of the event data. - Data Quality validation of the reconstruction output. We will report on the preparations and results of FEST09, and on the status of commissioning for no...

  4. Technology development for gene discovery and full-length sequencing

    Energy Technology Data Exchange (ETDEWEB)

    Marcelo Bento Soares

    2004-07-19

    In previous years, with support from the U.S. Department of Energy, we developed methods for construction of normalized and subtracted cDNA libraries, and constructed hundreds of high-quality libraries for production of Expressed Sequence Tags (ESTs). Our clones were made widely available to the scientific community through the IMAGE Consortium, and millions of ESTs were produced from our libraries either by collaborators or by our own sequencing laboratory at the University of Iowa. During this grant period, we focused on (1) the development of a method for preferential cloning of tissue-specific and/or rare transcripts, (2) its utilization to expedite EST-based gene discovery for the NIH Mouse Brain Molecular Anatomy Project, (3) further development and optimization of a method for construction of full-length-enriched cDNA libraries, and (4) modification of a plasmid vector to maximize efficiency of full-length cDNA sequencing by the transposon-mediated approach. It is noteworthy that the technology developed for preferential cloning of rare mRNAs enabled identification of over 2,000 mouse transcripts differentially expressed in the hippocampus. In addition, the method that we optimized for construction of full-length-enriched cDNA libraries was successfully utilized for the production of approximately fifty libraries from the developing mouse nervous system, from which over 2,500 full-ORF-containing cDNAs have been identified and accurately sequenced in their entirety either by our group or by the NIH-Mammalian Gene Collection Program Sequencing Team.

  5. Human anti-mouse antibodies.

    Science.gov (United States)

    Klee, G G

    2000-06-01

    Human anti-mouse antibodies (HAMA) are human immunoglobulins with specificity for mouse immunoglobulins. This topic currently is of interest because of the increased use of monoclonal mouse antibodies as diagnostic reagents both for in vitro laboratory measurements and for in vivo imaging studies. Monoclonal mouse antibodies also are being used therapeutically. This short article reviews the production of HAMA in patients receiving monoclonal antibodies and illustrates the potential ways that HAMA can interfere with immunoassay measurements. Methods for measuring and neutralizing HAMA also are discussed.

  6. Mouse models of medulloblastoma

    Institute of Scientific and Technical Information of China (English)

    Xiaochong Wu; Paul A. Northcott; Sidney Croul; Michael D. Taylor

    2011-01-01

    Medulloblastoma is the most common malignant pediatric brain tumor. Despite its prevalence and importance in pediatric neuro-oncology, the genes and pathways responsible for its initiation, maintenance,and progression remain poorly understood. Genetically engineered mouse models are an essential tool for uncovering the molecular and cellular basis of human diseases, including cancer, and serve a valuable role as preclinical models for testing targeted therapies. In this review, we summarize how such models have been successfully applied to the study of medulloblastoma over the past decade and what we might expect in the coming years.

  7. Global Prospects for Full Employment

    Directory of Open Access Journals (Sweden)

    Ivo Šlaus

    2011-04-01

    Full Text Available The recent international financial crisis highlights the crucial role of employment in human welfare and social stability. Access to remunerative employment opportunities is essential for economic security in a market-based economic system. As the rise of democracy compelled nations to extend the voting right to all citizens, employment must be recognized as a fundamental human right. In total defiance of conventional wisdom, since 1950 job growth has outpaced the explosive growth of population, the rapid adoption of labor-saving technologies, the manifold expansion of world trade, and the dramatic shift from manual labor to white collar work. In an increasingly globalized labor market, current nation-centric theories and models of employment need to be replaced with a human-centered global perspective complemented by new indicators that recognize the central and essential contribution of employment to human economic welfare. Employment and economy are subsets of society and their growth is driven by the more fundamental process of social development. A vast array of unmet social needs combined with an enormous reservoir of underutilized social resources – technological, scientific, educational, organizational, cultural and psychological – can be harnessed to dramatically expand employment opportunities and achieve full employment on a global basis. This paper examines the theoretical basis, policy issues and strategies required to eradicate unemployment nationally and globally.

  8. Achieving and sustaining full employment.

    Science.gov (United States)

    Rosen, S M

    1995-01-01

    Human rights and public health considerations provide strong support for policies that maximize employment. Ample historical and conceptual evidence supports the feasibility of full employment policies. New factors affecting the labor force, the rate of technological change, and the globalization of economic activity require appropriate policies--international as well as national--but do not invalidate the ability of modern states to apply the measures needed. Among these the most important include: (I) systematic reduction in working time with no loss of income, (2) active labor market policies, (3) use of fiscal and monetary measures to sustain the needed level of aggregate demand, (4) restoration of equal bargaining power between labor and capital, (5) social investment in neglected and outmoded infrastructure, (6) accountability of corporations for decisions to shift or reduce capital investment, (7) major reductions in military spending, to be replaced by socially needed and economically productive expenditures, (8) direct public sector job creation, (9) reform of monetary policy to restore emphasis on minimizing unemployment and promoting full employment. None are without precedent in modern economies. The obstacles are ideological and political. To overcome them will require intellectual clarity and effective advocacy.

  9. A Mouse Model of Chronic West Nile Virus Disease.

    Directory of Open Access Journals (Sweden)

    Jessica B Graham

    2016-11-01

    Full Text Available Infection with West Nile virus (WNV leads to a range of disease outcomes, including chronic infection, though lack of a robust mouse model of chronic WNV infection has precluded identification of the immune events contributing to persistent infection. Using the Collaborative Cross, a population of recombinant inbred mouse strains with high levels of standing genetic variation, we have identified a mouse model of persistent WNV disease, with persistence of viral loads within the brain. Compared to lines exhibiting no disease or marked disease, the F1 cross CC(032x013F1 displays a strong immunoregulatory signature upon infection that correlates with restraint of the WNV-directed cytolytic response. We hypothesize that this regulatory T cell response sufficiently restrains the immune response such that a chronic infection can be maintained in the CNS. Use of this new mouse model of chronic neuroinvasive virus will be critical in developing improved strategies to prevent prolonged disease in humans.

  10. Experimental Characterization of the Twin-Eye Laser Mouse Sensor

    Directory of Open Access Journals (Sweden)

    Javier Moreno

    2016-01-01

    Full Text Available This paper proposes the experimental characterization of a laser mouse sensor used in some optical mouse devices. The sensor characterized is called twin-eye laser mouse sensor and uses the Doppler effect to measure displacement as an alternative to optical flow-based mouse sensors. The experimental characterization showed similar measurement performances to optical flow sensors except in the sensitivity to height changes and when measuring nonlinear displacements, where the twin-eye sensor offered better performance. The measurement principle of this optical sensor can be applied to the development of alternative inexpensive applications that require planar displacement measurement and poor sensitivity to z-axis changes such as mobile robotics.

  11. Mouse cell culture - Methods and protocols

    Directory of Open Access Journals (Sweden)

    CarloAlberto Redi

    2010-12-01

    Full Text Available The mouse is, out of any doubt, the experimental animal par excellence for many many colleagues within the scientific community, notably for those working in mammalian biology (in a broad sense, from basic genetic to modeling human diseases, starting at least from 1664 Robert Hooke experiments on air’s propertyn. Not surprising then that mouse cell cultures is a well established field of research itself and that there are several handbooks devoted to this discipline. Here, Andrew Ward and David Tosh provide a necessary update of the protocols currently needed. In fact, nearly half of the book is devoted to stem cells culture protocols, mainly embryonic, from a list of several organs (kidney, lung, oesophagus and intestine, pancreas and liver to mention some........

  12. Full-Scale Tunnel (FST)

    Science.gov (United States)

    1929-01-01

    Modified propeller and spinner in Full-Scale Tunnel (FST) model. On June 26, 1929, Elton W. Miller wrote to George W. Lewis proposing the construction of a model of the full-scale tunnel. 'The excellent energy ratio obtained in the new wind tunnel of the California Institute of Technology suggests that before proceeding with our full scale tunnel design, we ought to investigate the effect on energy ratio of such factors as: 1. small included angle for the exit cone; 2. carefully designed return passages of circular section as far as possible, without sudden changes in cross sections; 3. tightness of walls. It is believed that much useful information can be obtained by building a model of about 1/16 scale, that is, having a closed throat of 2 ft. by 4 ft. The outside dimensions would be about 12 ft. by 25 ft. in plan and the height 4 ft. Two propellers will be required about 28 in. in diameter, each to be driven by direct current motor at a maximum speed of 4500 R.P.M. Provision can be made for altering the length of certain portions, particularly the exit cone, and possibly for the application of boundary layer control in order to effect satisfactory air flow. This model can be constructed in a comparatively short time, using 2 by 4 framing with matched sheathing inside, and where circular sections are desired they can be obtained by nailing sheet metal to wooden ribs, which can be cut on the band saw. It is estimated that three months will be required for the construction and testing of such a model and that the cost will be approximately three thousand dollars, one thousand dollars of which will be for the motors. No suitable location appears to exist in any of our present buildings, and it may be necessary to build it outside and cover it with a roof.' George Lewis responded immediately (June 27) granting the authority to proceed. He urged Langley to expedite construction and to employ extra carpenters if necessary. Funds for the model came from the FST project

  13. Burn mouse models

    DEFF Research Database (Denmark)

    Calum, Henrik; Høiby, Niels; Moser, Claus

    2014-01-01

    Severe thermal injury induces immunosuppression, involving all parts of the immune system, especially when large fractions of the total body surface area are affected. An animal model was established to characterize the burn-induced immunosuppression. In our novel mouse model a 6 % third-degree b......Severe thermal injury induces immunosuppression, involving all parts of the immune system, especially when large fractions of the total body surface area are affected. An animal model was established to characterize the burn-induced immunosuppression. In our novel mouse model a 6 % third......-degree burn injury was induced with a hot-air blower. The third-degree burn was confirmed histologically. At 48 h, a decline in the concentration of peripheral blood leucocytes was observed in the group of mice with burn wound. The reduction was ascribed to the decline in concentration of polymorphonuclear...... neutrophil leucocytes and monocytes. When infecting the skin with Pseudomonas aeruginosa, a dissemination of bacteria was observed only in the burn wound group. Histological characterization of the skin showed an increased polymorphonuclear neutrophil granulocytes dominated inflammation in the group of mice...

  14. Full-quantum light diode

    CERN Document Server

    Ghobadi, Roohollah

    2015-01-01

    Unidirectional light transport in one-dimensional nanomaterials at the quantum level is a crucial goal to achieve for upcoming computational devices. We here employ a full-quantum mechanical approach based on master equation to describe unidirectional light transport through a pair of two-level systems coupled to a one-dimensional waveguide. By comparing with published semi-classical results, we find that the nonlinearity of the system is reduced, thereby reducing also the unidirectional light transport efficiency. Albeit not fully efficient, we find that the considered quantum system can work as a light diode with an efficiency of approximately 60%. Our results may be used in quantum computation with classical and quantized light.

  15. Pyruvate kinase is necessary for Brucella abortus full virulence in BALB/c mouse

    OpenAIRE

    2016-01-01

    International audience; AbstractBrucellosis, caused by a facultative intracellular pathogen Brucella, is one of the most prevalent zoonosis worldwide. Host infection relies on several uncanonical virulence factors. A recent research hotpot is the links between carbon metabolism and bacterial virulence. In this study, we found that a carbon metabolism-related pyruvate kinase (Pyk) encoded by pyk gene (locus tag BAB_RS24320) was associated with Brucella virulence. Determination of bacterial gro...

  16. Gankyrin expression during mouse embryogenesis

    Institute of Scientific and Technical Information of China (English)

    秦建民; 刘淑琴; 曾锦章; 李慎菁; 付晓勇; 邱秀华; 吴孟超; 王红阳

    2004-01-01

    Objective: To observe the gene expression of Gankyrin during mouse embryogenesis and reveal the gene biological significance during organs and tissues formation. Methods: The expressions of Gankyrin mRNA in various organs and tissues were detected by in situ hybridization at indicated times during embryogenesis. Results: The expression of Gankyrin mRNA in mouse day 12.5 embryo was mainly in midbrain, interbrain and endbrain; in mouse day 14.5 embryo mainly in midbrain, aorta, liver, gonad, cranium and rib; in mouse day 16.5 embryo mainly in cranium, rib and vertebra;and in mouse day 18.5 embryo mainly in cranium, rib and intestinal mucosa. Conclusion: Gankyrin gene probably participates in the development of the neural tissues (such as midbrain, interbrain and endbrain etc. ), aorta, liver and gonad, intestinal mucosa and bone tissues, which may be closely associated with the function of the organs and tissues.

  17. Review Document: Full Software Trigger

    CERN Document Server

    Albrecht, J; Raven, G

    2014-01-01

    This document presents a trigger system for the upgraded LHCb detector, scheduled to begin operation in 2020. This document serves as input for the internal review towards the "DAQ, online and trigger TDR". The proposed trigger system is implemented entirely in software. In this document we show that track reconstruction of a similar quality to that available in the offline algorithms can be performed on the full inelastic $pp$-collision rate, without prior event selections implemented in custom hardware and without relying upon a partial event reconstruction. A track nding eciency of 98.8 % relative to oine can be achieved for tracks with $p_T >$ 500 MeV/$c$. The CPU time required for this reconstruction is about 40 % of the available budget. Proof-of-principle selections are presented which demonstrate that excellent performance is achievable using an inclusive beauty trigger, in addition to exclusive beauty and charm triggers. Finally, it is shown that exclusive beauty and charm selections that do not intr...

  18. A transgenic tri-modality reporter mouse.

    Directory of Open Access Journals (Sweden)

    Xinrui Yan

    Full Text Available Transgenic mouse with a stably integrated reporter gene(s can be a valuable resource for obtaining uniformly labeled stem cells, tissues, and organs for various applications. We have generated a transgenic mouse model that ubiquitously expresses a tri-fusion reporter gene (fluc2-tdTomato-ttk driven by a constitutive chicken β-actin promoter. This "Tri-Modality Reporter Mouse" system allows one to isolate most cells from this donor mouse and image them for bioluminescent (fluc2, fluorescent (tdTomato, and positron emission tomography (PET (ttk modalities. Transgenic colonies with different levels of tri-fusion reporter gene expression showed a linear correlation between all three-reporter proteins (R(2=0.89 for TdTomato vs Fluc, R(2=0.94 for Fluc vs TTK, R(2=0.89 for TdTomato vs TTK in vitro from tissue lysates and in vivo by optical and PET imaging. Mesenchymal stem cells (MSCs isolated from this transgenics showed high level of reporter gene expression, which linearly correlated with the cell numbers (R(2=0.99 for bioluminescence imaging (BLI. Both BLI (R(2=0.93 and micro-PET (R(2=0.94 imaging of the subcutaneous implants of Tri-Modality Reporter Mouse derived MSCs in nude mice showed linear correlation with the cell numbers and across different imaging modalities (R(2=0.97. Serial imaging of MSCs transplanted to mice with acute myocardial infarction (MI by intramyocardial injection exhibited significantly higher signals in MI heart at days 2, 3, 4, and 7 (p<0.01. MSCs transplanted to the ischemic hindlimb of nude mice showed significantly higher BLI and PET signals in the first 2 weeks that dropped by 4(th week due to poor cell survival. However, laser Doppler perfusion imaging revealed that blood circulation in the ischemic limb was significantly improved in the MSCs transplantation group compared with the control group. In summary, this mouse can be used as a source of donor cells and organs in various research areas such as stem cell

  19. Mouse anesthesia and analgesia.

    Science.gov (United States)

    Adams, Sean; Pacharinsak, Cholawat

    2015-03-02

    Providing anesthesia and analgesia for mouse subjects is a common and critical practice in the laboratory setting. These practices are necessary for performing invasive procedures, achieving prolonged immobility for sensitive imaging modalities (magnetic resonance imaging for instance), and providing intra- and post-procedural pain relief. In addition to facilitating the procedures performed by the investigator, the provision of anesthesia and analgesia is crucial for the preservation of animal welfare and for humane treatment of animals used in research. Furthermore, anesthesia and analgesia are important components of animal use protocols reviewed by Institutional Animal Care and Use Committees, requiring careful consideration and planning for the particular animal model. In this article, we provide technical outlines for the investigator covering the provision of anesthesia by two routes (injectable and inhalant), guidelines for monitoring anesthesia, current techniques for recognition of pain, and considerations for administering preventative analgesia. Copyright © 2015 John Wiley & Sons, Inc.

  20. Digenic Inheritance in Cystinuria Mouse Model.

    Directory of Open Access Journals (Sweden)

    Meritxell Espino

    Full Text Available Cystinuria is an aminoaciduria caused by mutations in the genes that encode the two subunits of the amino acid transport system b0,+, responsible for the renal reabsorption of cystine and dibasic amino acids. The clinical symptoms of cystinuria relate to nephrolithiasis, due to the precipitation of cystine in urine. Mutations in SLC3A1, which codes for the heavy subunit rBAT, cause cystinuria type A, whereas mutations in SLC7A9, which encodes the light subunit b0,+AT, cause cystinuria type B. By crossing Slc3a1-/- with Slc7a9-/- mice we generated a type AB cystinuria mouse model to test digenic inheritance of cystinuria. The 9 genotypes obtained have been analyzed at early (2- and 5-months and late stage (8-months of the disease. Monitoring the lithiasic phenotype by X-ray, urine amino acid content analysis and protein expression studies have shown that double heterozygous mice (Slc7a9+/-Slc3a1+/- present lower expression of system b0,+ and higher hyperexcretion of cystine than single heterozygotes (Slc7a9+/-Slc3a1+/+ and Slc7a9+/+Slc3a1+/- and give rise to lithiasis in 4% of the mice, demonstrating that cystinuria has a digenic inheritance in this mouse model. Moreover in this study it has been demonstrated a genotype/phenotype correlation in type AB cystinuria mouse model providing new insights for further molecular and genetic studies of cystinuria patients.

  1. Mouse Models for Filovirus Infections

    Directory of Open Access Journals (Sweden)

    Kelly L. Warfield

    2012-09-01

    Full Text Available The filoviruses marburg- and ebolaviruses can cause severe hemorrhagic fever (HF in humans and nonhuman primates. Because many cases have occurred in geographical areas lacking a medical research infrastructure, most studies of the pathogenesis of filoviral HF, and all efforts to develop drugs and vaccines, have been carried out in biocontainment laboratories in non-endemic countries, using nonhuman primates (NHPs, guinea pigs and mice as animal models. NHPs appear to closely mirror filoviral HF in humans (based on limited clinical data, but only small numbers may be used in carefully regulated experiments; much research is therefore done in rodents. Because of their availability in large numbers and the existence of a wealth of reagents for biochemical and immunological testing, mice have become the preferred small animal model for filovirus research. Since the first experiments following the initial 1967 marburgvirus outbreak, wild-type or mouse-adapted viruses have been tested in immunocompetent or immunodeficient mice. In this paper, we review how these types of studies have been used to investigate the pathogenesis of filoviral disease, identify immune responses to infection and evaluate antiviral drugs and vaccines. We also discuss the strengths and weaknesses of murine models for filovirus research, and identify important questions for further study.

  2. MouseCyc: a curated biochemical pathways database for the laboratory mouse

    OpenAIRE

    Evsikov, Alexei V.; Dolan, Mary E.; Genrich, Michael P; Patek, Emily; Bult, Carol J.

    2009-01-01

    Linking biochemical genetic data to the reference genome for the laboratory mouse is important for comparative physiology and for developing mouse models of human biology and disease. We describe here a new database of curated metabolic pathways for the laboratory mouse called MouseCyc . MouseCyc has been integrated with genetic and genomic data for the laboratory mouse available from the Mouse Genome Informatics database and with pathway data from other organisms, including human.

  3. Gene expression profile analysis of type 2 diabetic mouse liver.

    Directory of Open Access Journals (Sweden)

    Fang Zhang

    Full Text Available Liver plays a key role in glucose metabolism and homeostasis, and impaired hepatic glucose metabolism contributes to the development of type 2 diabetes. However, the precise gene expression profile of diabetic liver and its association with diabetes and related diseases are yet to be further elucidated. In this study, we detected the gene expression profile by high-throughput sequencing in 9-week-old normal and type 2 diabetic db/db mouse liver. Totally 12132 genes were detected, and 2627 genes were significantly changed in diabetic mouse liver. Biological process analysis showed that the upregulated genes in diabetic mouse liver were mainly enriched in metabolic processes. Surprisingly, the downregulated genes in diabetic mouse liver were mainly enriched in immune-related processes, although all the altered genes were still mainly enriched in metabolic processes. Similarly, KEGG pathway analysis showed that metabolic pathways were the major pathways altered in diabetic mouse liver, and downregulated genes were enriched in immune and cancer pathways. Analysis of the key enzyme genes in fatty acid and glucose metabolism showed that some key enzyme genes were significantly increased and none of the detected key enzyme genes were decreased. In addition, FunDo analysis showed that liver cancer and hepatitis were most likely to be associated with diabetes. Taken together, this study provides the digital gene expression profile of diabetic mouse liver, and demonstrates the main diabetes-associated hepatic biological processes, pathways, key enzyme genes in fatty acid and glucose metabolism and potential hepatic diseases.

  4. Mouse models to study dengue virus immunology and pathogenesis

    Directory of Open Access Journals (Sweden)

    Raphaël M. Zellweger

    2014-04-01

    Full Text Available The development of a compelling murine model of dengue virus (DENV infection has been challenging, because dengue virus clinical isolates do not readily replicate or cause pathology in immunocompetent mice. However, research using immunocompromised mice and/or mouse-adapted viruses allows to investigate questions that may be impossible to address in human studies. In this review, we discuss the potential strengths and limitations of existing mouse models of dengue disease. Human studies are descriptive by nature; moreover, the strain, time, and sequence of infection are often unknown. In contrast, in mice, the conditions of infection are well defined and a large number of experimental parameters can be varied at will. Therefore, mouse models offer an opportunity to experimentally test hypotheses that are based on epidemiological observations. In particular, gain-of-function or loss-of-function models can be established to assess how different components of the immune system (either alone or in combination contribute to protection or pathogenesis during secondary infections or after vaccination. In addition, mouse models have been used for pre-clinical testing of antiviral drug or for vaccine development studies. Conclusions based on mouse experiments must be extrapolated to DENV infection in humans with caution due to the inherent limitations of animal models. However, research in mouse models is a useful complement to in vitro and epidemiological data, and may delineate new areas that deserve attention during future human studies.

  5. On Parallel Streams through the Mouse Dorsal Lateral Geniculate Nucleus

    Directory of Open Access Journals (Sweden)

    Daniel eDenman

    2016-03-01

    Full Text Available The mouse visual system is an emerging model for the study of cortical and thalamic circuit function. To maximize the usefulness of this model system, it is important to analyze the similarities and differences between the organization of all levels of the murid visual system with other, better studied systems (e.g., non-human primates and the domestic cat. While the understanding of mouse retina and cortex has expanded rapidly, less is known about mouse dorsal lateral geniculate nucleus (dLGN. Here, we study whether parallel processing streams exist in mouse dLGN. We use a battery of stimuli that have been previously shown to successfully distinguish parallel streams in other species: electrical stimulation of the optic chiasm, contrast-reversing stationary gratings at varying spatial phase, drifting sinusoidal gratings, dense noise for receptive field reconstruction, and frozen contrast-modulating noise. As in the optic nerves of domestic cats and non-human primates, we find evidence for multiple conduction velocity groups after optic chiasm stimulation. As in so-called ‘visual mammals’, we find a subpopulation of mouse dLGN cells showing non-linear spatial summation. However, differences in stimulus selectivity and sensitivity do not provide sufficient basis for identification of clearly distinct classes of relay cells. Nevertheless, consistent with presumptively homologous status of dLGNs of all mammals, there are substantial similarities between response properties of mouse dLGN neurons and those of cats and primates.

  6. Whole mouse cryo-imaging

    Science.gov (United States)

    Wilson, David; Roy, Debashish; Steyer, Grant; Gargesha, Madhusudhana; Stone, Meredith; McKinley, Eliot

    2008-03-01

    The Case cryo-imaging system is a section and image system which allows one to acquire micron-scale, information rich, whole mouse color bright field and molecular fluorescence images of an entire mouse. Cryo-imaging is used in a variety of applications, including mouse and embryo anatomical phenotyping, drug delivery, imaging agents, metastastic cancer, stem cells, and very high resolution vascular imaging, among many. Cryo-imaging fills the gap between whole animal in vivo imaging and histology, allowing one to image a mouse along the continuum from the mouse -> organ -> tissue structure -> cell -> sub-cellular domains. In this overview, we describe the technology and a variety of exciting applications. Enhancements to the system now enable tiled acquisition of high resolution images to cover an entire mouse. High resolution fluorescence imaging, aided by a novel subtraction processing algorithm to remove sub-surface fluorescence, makes it possible to detect fluorescently-labeled single cells. Multi-modality experiments in Magnetic Resonance Imaging and Cryo-imaging of a whole mouse demonstrate superior resolution of cryo-images and efficiency of registration techniques. The 3D results demonstrate the novel true-color volume visualization tools we have developed and the inherent advantage of cryo-imaging in providing unlimited depth of field and spatial resolution. The recent results continue to demonstrate the value cryo-imaging provides in the field of small animal imaging research.

  7. Complex Loci in human and mouse genomes.

    Directory of Open Access Journals (Sweden)

    Pär G Engström

    2006-04-01

    Full Text Available Mammalian genomes harbor a larger than expected number of complex loci, in which multiple genes are coupled by shared transcribed regions in antisense orientation and/or by bidirectional core promoters. To determine the incidence, functional significance, and evolutionary context of mammalian complex loci, we identified and characterized 5,248 cis-antisense pairs, 1,638 bidirectional promoters, and 1,153 chains of multiple cis-antisense and/or bidirectionally promoted pairs from 36,606 mouse transcriptional units (TUs, along with 6,141 cis-antisense pairs, 2,113 bidirectional promoters, and 1,480 chains from 42,887 human TUs. In both human and mouse, 25% of TUs resided in cis-antisense pairs, only 17% of which were conserved between the two organisms, indicating frequent species specificity of antisense gene arrangements. A sampling approach indicated that over 40% of all TUs might actually be in cis-antisense pairs, and that only a minority of these arrangements are likely to be conserved between human and mouse. Bidirectional promoters were characterized by variable transcriptional start sites and an identifiable midpoint at which overall sequence composition changed strand and the direction of transcriptional initiation switched. In microarray data covering a wide range of mouse tissues, genes in cis-antisense and bidirectionally promoted arrangement showed a higher probability of being coordinately expressed than random pairs of genes. In a case study on homeotic loci, we observed extensive transcription of nonconserved sequences on the noncoding strand, implying that the presence rather than the sequence of these transcripts is of functional importance. Complex loci are ubiquitous, host numerous nonconserved gene structures and lineage-specific exonification events, and may have a cis-regulatory impact on the member genes.

  8. The LEGSKO mouse: a mouse model of age-related nuclear cataract based on genetic suppression of lens glutathione synthesis.

    Directory of Open Access Journals (Sweden)

    Xingjun Fan

    Full Text Available Age-related nuclear cataracts are associated with progressive post-synthetic modifications of crystallins from various physical chemical and metabolic insults, of which oxidative stress is a major factor. The latter is normally suppressed by high concentrations of glutathione (GSH, which however are very low in the nucleus of the old lens. Here we generated a mouse model of oxidant stress by knocking out glutathione synthesis in the mouse in the hope of recapitulating some of the changes observed in human age-related nuclear cataract (ARNC. A floxed Gclc mouse was generated and crossed with a transgenic mouse expressing Cre in the lens to generate the LEGSKO mouse in which de novo GSH synthesis was completely abolished in the lens. Lens GSH levels were reduced up to 60% in homozygous LEGSKO mice, and a decreasing GSH gradient was noticed from cortical to nuclear region at 4 months of age. Oxidation of crystallin methionine and sulfhydryls into sulfoxides was dramatically increased, but methylglyoxal hydroimidazolones levels that are GSH/glyoxalase dependent were surprisingly normal. Homozygous LEGSKO mice developed nuclear opacities starting at 4 months that progressed into severe nuclear cataract by 9 months. We conclude that the LEGSKO mouse lens mimics several features of human ARNC and is thus expected to be a useful model for the development of anti-cataract agents.

  9. Taxonomy Icon Data: house mouse [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available house mouse Mus musculus Chordata/Vertebrata/Mammalia/Theria/Eutheria/etc. Mus_musculus_L.png Mus_musculus..._NL.png Mus_musculus_S.png Mus_musculus_NS.png http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Mus+musculus...&t=L http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Mus+musculus&t=NL http://biosci...encedbc.jp/taxonomy_icon/icon.cgi?i=Mus+musculus&t=S http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Mus...+musculus&t=NS http://togodb.biosciencedbc.jp/togodb/view/taxonomy_icon_comment_en?species_id=146 ...

  10. Mouse models for cancer research

    Institute of Scientific and Technical Information of China (English)

    Wei Zhang; Lynette Moore; Ping Ji

    2011-01-01

    Mouse models of cancer enable researchers to leamn about tumor biology in complicated and dynamic physiological systems. Since the development of gene targeting in mice, cancer biologists have been among the most frequent users of transgenic mouse models, which have dramatically increased knowledge about how cancers form and grow. The Chinese Joumnal of Cancer will publish a series of papers reporting the use of mouse models in studying genetic events in cancer cases. This editorial is an overview of the development and applications of mouse models of cancer and directs the reader to upcoming papers describing the use of these models to be published in coming issues, beginning with three articles in the current issue.

  11. Computer Workstation: Pointer/Mouse

    Science.gov (United States)

    ... Safety and Health Program Recommendations It's the Law Poster REGULATIONS Law and Regulations Standard Interpretations Training Requirements ... when evaluating your computer workstation. Pointer Placement Pointer Size, Shape, and Settings Pointer/Mouse Quick Tips Keep ...

  12. Mass spectrometry analysis of hepcidin peptides in experimental mouse models.

    Directory of Open Access Journals (Sweden)

    Harold Tjalsma

    Full Text Available The mouse is a valuable model for unravelling the role of hepcidin in iron homeostasis, however, such studies still report hepcidin mRNA levels as a surrogate marker for bioactive hepcidin in its pivotal function to block ferroportin-mediated iron transport. Here, we aimed to assess bioactive mouse Hepcidin-1 (Hep-1 and its paralogue Hepcidin-2 (Hep-2 at the peptide level. To this purpose, Fourier transform ion cyclotron resonance (FTICR and tandem-MS was used for hepcidin identification, after which a time-of-flight (TOF MS-based methodology was exploited to routinely determine Hep-1 and -2 levels in mouse serum and urine. This method was biologically validated by hepcidin assessment in: i 3 mouse strains (C57Bl/6; DBA/2 and BABL/c upon stimulation with intravenous iron and LPS, ii homozygous Hfe knock out, homozygous transferrin receptor 2 (Y245X mutated mice and double affected mice, and iii mice treated with a sublethal hepatotoxic dose of paracetamol. The results showed that detection of Hep-1 was restricted to serum, whereas Hep-2 and its presumed isoforms were predominantly present in urine. Elevations in serum Hep-1 and urine Hep-2 upon intravenous iron or LPS were only moderate and varied considerably between mouse strains. Serum Hep-1 was decreased in all three hemochromatosis models, being lowest in the double affected mice. Serum Hep-1 levels correlated with liver hepcidin-1 gene expression, while acute liver damage by paracetamol depleted Hep-1 from serum. Furthermore, serum Hep-1 appeared to be an excellent indicator of splenic iron accumulation. In conclusion, Hep-1 and Hep-2 peptide responses in experimental mouse agree with the known biology of hepcidin mRNA regulators, and their measurement can now be implemented in experimental mouse models to provide novel insights in post-transcriptional regulation, hepcidin function, and kinetics.

  13. Gene expression and functional annotation of the human and mouse choroid plexus epithelium.

    Directory of Open Access Journals (Sweden)

    Sarah F Janssen

    Full Text Available BACKGROUND: The choroid plexus epithelium (CPE is a lobed neuro-epithelial structure that forms the outer blood-brain barrier. The CPE protrudes into the brain ventricles and produces the cerebrospinal fluid (CSF, which is crucial for brain homeostasis. Malfunction of the CPE is possibly implicated in disorders like Alzheimer disease, hydrocephalus or glaucoma. To study human genetic diseases and potential new therapies, mouse models are widely used. This requires a detailed knowledge of similarities and differences in gene expression and functional annotation between the species. The aim of this study is to analyze and compare gene expression and functional annotation of healthy human and mouse CPE. METHODS: We performed 44k Agilent microarray hybridizations with RNA derived from laser dissected healthy human and mouse CPE cells. We functionally annotated and compared the gene expression data of human and mouse CPE using the knowledge database Ingenuity. We searched for common and species specific gene expression patterns and function between human and mouse CPE. We also made a comparison with previously published CPE human and mouse gene expression data. RESULTS: Overall, the human and mouse CPE transcriptomes are very similar. Their major functionalities included epithelial junctions, transport, energy production, neuro-endocrine signaling, as well as immunological, neurological and hematological functions and disorders. The mouse CPE presented two additional functions not found in the human CPE: carbohydrate metabolism and a more extensive list of (neural developmental functions. We found three genes specifically expressed in the mouse CPE compared to human CPE, being ACE, PON1 and TRIM3 and no human specifically expressed CPE genes compared to mouse CPE. CONCLUSION: Human and mouse CPE transcriptomes are very similar, and display many common functionalities. Nonetheless, we also identified a few genes and pathways which suggest that the CPE

  14. Immune Responses Following Mouse Peripheral Nerve Xenotransplantation in Rats

    Directory of Open Access Journals (Sweden)

    Lai-Jin Lu

    2009-01-01

    Full Text Available Xenotransplantation offers a potentially unlimited source for tissues and organs for transplantation, but the strong xenoimmune responses pose a major obstacle to its application in the clinic. In this study, we investigate the rejection of mouse peripheral nerve xenografts in rats. Severe intragraft mononuclear cell infiltration, graft distension, and necrosis were detected in the recipients as early as 2 weeks after mouse nerve xenotransplantation. The number of axons in xenografts reduced progressively and became almost undetectable at week 8. However, mouse nerve xenotransplantation only led to a transient and moderate increase in the production of Th1 cytokines, including IL-2, IFN-γ, and TNF-α. The data implicate that cellular immune responses play a critical role in nerve xenograft rejection but that further identification of the major effector cells mediating the rejection is required for developing effective means to prevent peripheral nerve xenograft rejection.

  15. A provisional gene regulatory atlas for mouse heart development.

    Directory of Open Access Journals (Sweden)

    Hailin Chen

    Full Text Available Congenital Heart Disease (CHD is one of the most common birth defects. Elucidating the molecular mechanisms underlying normal cardiac development is an important step towards early identification of abnormalities during the developmental program and towards the creation of early intervention strategies. We developed a novel computational strategy for leveraging high-content data sets, including a large selection of microarray data associated with mouse cardiac development, mouse genome sequence, ChIP-seq data of selected mouse transcription factors and Y2H data of mouse protein-protein interactions, to infer the active transcriptional regulatory network of mouse cardiac development. We identified phase-specific expression activity for 765 overlapping gene co-expression modules that were defined for obtained cardiac lineage microarray data. For each co-expression module, we identified the phase of cardiac development where gene expression for that module was higher than other phases. Co-expression modules were found to be consistent with biological pathway knowledge in Wikipathways, and met expectations for enrichment of pathways involved in heart lineage development. Over 359,000 transcription factor-target relationships were inferred by analyzing the promoter sequences within each gene module for overrepresentation against the JASPAR database of Transcription Factor Binding Site (TFBS motifs. The provisional regulatory network will provide a framework of studying the genetic basis of CHD.

  16. Dipole source localization of mouse electroencephalogram using the Fieldtrip toolbox.

    Directory of Open Access Journals (Sweden)

    Chungki Lee

    Full Text Available The mouse model is an important research tool in neurosciences to examine brain function and diseases with genetic perturbation in different brain regions. However, the limited techniques to map activated brain regions under specific experimental manipulations has been a drawback of the mouse model compared to human functional brain mapping. Here, we present a functional brain mapping method for fast and robust in vivo brain mapping of the mouse brain. The method is based on the acquisition of high density electroencephalography (EEG with a microarray and EEG source estimation to localize the electrophysiological origins. We adapted the Fieldtrip toolbox for the source estimation, taking advantage of its software openness and flexibility in modeling the EEG volume conduction. Three source estimation techniques were compared: Distribution source modeling with minimum-norm estimation (MNE, scanning with multiple signal classification (MUSIC, and single-dipole fitting. Known sources to evaluate the performance of the localization methods were provided using optogenetic tools. The accuracy was quantified based on the receiver operating characteristic (ROC analysis. The mean detection accuracy was high, with a false positive rate less than 1.3% and 7% at the sensitivity of 90% plotted with the MNE and MUSIC algorithms, respectively. The mean center-to-center distance was less than 1.2 mm in single dipole fitting algorithm. Mouse microarray EEG source localization using microarray allows a reliable method for functional brain mapping in awake mouse opening an access to cross-species study with human brain.

  17. Mouse tissues express multiple splice variants of prominin-1.

    Directory of Open Access Journals (Sweden)

    Kristel Kemper

    Full Text Available Prominin-1, a heavily glycosylated pentaspan membrane protein, is mainly known for its function as a marker for (cancer stem cells, although it can also be detected on differentiated cells. Mouse prominin-1 expression is heavily regulated by splicing in eight different variants. The function or the expression pattern of prominin-1 and its splice variants (SVs is thus far unknown. In this study, we analyzed the expression of the prominin-1 splice variants on mRNA level in several mouse tissues and found a broad tissue expression of the majority of SVs, but a specific set of SVs had a much more restricted expression profile. For instance, the testis expressed only SV3 and SV7. Moreover, SV8 was solely detected in the eye. Intriguingly, prominin-1 knockout mice do not suffer from gross abnormalities, but do show signs of blindness, which suggest that SV8 has a specific function in this tissue. In addition, databases searches for putative promoter regions in the mouse prominin-1 gene revealed three potential promoter regions that could be linked to specific SVs. Interestingly, for both SV7 and SV8, a specific potential promoter region could be identified. To conclude, the majority of mouse prominin-1 splice variants are widely expressed in mouse tissues. However, specific expression of a few variants, likely driven by specific promoters, suggests distinct regulation and a potential important function for these variants in certain tissues.

  18. Mouse models of Fanconi anemia

    Energy Technology Data Exchange (ETDEWEB)

    Parmar, Kalindi; D' Andrea, Alan [Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115 (United States); Niedernhofer, Laura J., E-mail: niedernhoferl@upmc.edu [Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine and Cancer Institute, 5117 Centre Avenue, Hillman Cancer Center, Research Pavilion 2.6, Pittsburgh, PA 15213-1863 (United States)

    2009-07-31

    Fanconi anemia is a rare inherited disease characterized by congenital anomalies, growth retardation, aplastic anemia and an increased risk of acute myeloid leukemia and squamous cell carcinomas. The disease is caused by mutation in genes encoding proteins required for the Fanconi anemia pathway, a response mechanism to replicative stress, including that caused by genotoxins that cause DNA interstrand crosslinks. Defects in the Fanconi anemia pathway lead to genomic instability and apoptosis of proliferating cells. To date, 13 complementation groups of Fanconi anemia were identified. Five of these genes have been deleted or mutated in the mouse, as well as a sixth key regulatory gene, to create mouse models of Fanconi anemia. This review summarizes the phenotype of each of the Fanconi anemia mouse models and highlights how genetic and interventional studies using the strains have yielded novel insight into therapeutic strategies for Fanconi anemia and into how the Fanconi anemia pathway protects against genomic instability.

  19. 10. international mouse genome conference

    Energy Technology Data Exchange (ETDEWEB)

    Meisler, M.H.

    1996-12-31

    Ten years after hosting the First International Mammalian Genome Conference in Paris in 1986, Dr. Jean-Louis Guenet presided over the Tenth Conference at the Pasteur Institute, October 7--10, 1996. The 1986 conference was a satellite to the Human Gene Mapping Workshop and had approximately 50 attendees. The 1996 meeting was attended by 300 scientists from around the world. In the interim, the number of mapped loci in the mouse increased from 1,000 to over 20,000. This report contains a listing of the program and its participants, and two articles that review the meeting and the role of the laboratory mouse in the Human Genome project. More than 200 papers were presented at the conference covering the following topics: International mouse chromosome committee meetings; Mutant generation and identification; Physical and genetic maps; New technology and resources; Chromatin structure and gene regulation; Rate and hamster genetic maps; Informatics and databases; and Quantitative trait analysis.

  20. Teratology studies in the mouse.

    Science.gov (United States)

    Marsden, Edward; Leroy, Mariline

    2013-01-01

    The rat is the routine species of choice as the rodent model for regulatory safety testing of xenobiotics such as medicinal products, food additives, and other chemicals. However, the rat is not always suitable for pharmacological, toxicological, immunogenic, pharmacokinetic, or even practical reasons. Under such circumstances, the mouse offers an alternative for finding a suitable rodent model acceptable to the regulatory authorities. Since all essential routes of administration are possible, the short reproductive cycle and large litter size of the mouse make it a species well adapted for use in teratology studies. Given that good quality animals, including virgin mated females, can be acquired relatively easily and inexpensively, the mouse has been used in reproductive toxicity studies for decades and study protocols are well established.

  1. The vasculome of the mouse brain.

    Directory of Open Access Journals (Sweden)

    Shuzhen Guo

    Full Text Available The blood vessel is no longer viewed as passive plumbing for the brain. Increasingly, experimental and clinical findings suggest that cerebral endothelium may possess endocrine and paracrine properties - actively releasing signals into and receiving signals from the neuronal parenchyma. Hence, metabolically perturbed microvessels may contribute to central nervous system (CNS injury and disease. Furthermore, cerebral endothelium can serve as sensors and integrators of CNS dysfunction, releasing measurable biomarkers into the circulating bloodstream. Here, we define and analyze the concept of a brain vasculome, i.e. a database of gene expression patterns in cerebral endothelium that can be linked to other databases and systems of CNS mediators and markers. Endothelial cells were purified from mouse brain, heart and kidney glomeruli. Total RNA were extracted and profiled on Affymetrix mouse 430 2.0 micro-arrays. Gene expression analysis confirmed that these brain, heart and glomerular preparations were not contaminated by brain cells (astrocytes, oligodendrocytes, or neurons, cardiomyocytes or kidney tubular cells respectively. Comparison of the vasculome between brain, heart and kidney glomeruli showed that endothelial gene expression patterns were highly organ-dependent. Analysis of the brain vasculome demonstrated that many functionally active networks were present, including cell adhesion, transporter activity, plasma membrane, leukocyte transmigration, Wnt signaling pathways and angiogenesis. Analysis of representative genome-wide-association-studies showed that genes linked with Alzheimer's disease, Parkinson's disease and stroke were detected in the brain vasculome. Finally, comparison of our mouse brain vasculome with representative plasma protein databases demonstrated significant overlap, suggesting that the vasculome may be an important source of circulating signals in blood. Perturbations in cerebral endothelial function may profoundly

  2. Significant determinants of mouse pain behaviour.

    Directory of Open Access Journals (Sweden)

    Michael S Minett

    Full Text Available Transgenic mouse behavioural analysis has furthered our understanding of the molecular and cellular mechanisms underlying damage sensing and pain. However, it is not unusual for conflicting data on the pain phenotypes of knockout mice to be generated by reputable groups. Here we focus on some technical aspects of measuring mouse pain behaviour that are often overlooked, which may help explain discrepancies in the pain literature. We examined touch perception using von Frey hairs and mechanical pain thresholds using the Randall-Selitto test. Thermal pain thresholds were measured using the Hargreaves apparatus and a thermal place preference test. Sodium channel Nav1.7 knockout mice show a mechanical deficit in the hairy skin, but not the paw, whilst shaving the abdominal hair abolished this phenotype. Nav1.7, Nav1.8 and Nav1.9 knockout mice show deficits in noxious mechanosensation in the tail, but not the paw. TRPA1 knockout mice, however, have a loss of noxious mechanosensation in the paw but not the tail. Studies of heat and cold sensitivity also show variability depending on the intensity of the stimulus. Deleting Nav1.7, Nav1.8 or Nav1.9 in Nav1.8-positive sensory neurons attenuates responses to slow noxious heat ramps, whilst responses to fast noxious heat ramps are only reduced when Nav1.7 is lost in large diameter sensory neurons. Deleting Nav1.7 from all sensory neurons attenuates responses to noxious cooling but not extreme cold. Finally, circadian rhythms dramatically influence behavioural outcome measures such as von Frey responses, which change by 80% over the day. These observations demonstrate that fully characterising the phenotype of a transgenic mouse strain requires a range of behavioural pain models. Failure to conduct behavioural tests at different anatomical locations, stimulus intensities, and at different points in the circadian cycle may lead to a pain behavioural phenotype being misinterpreted, or missed altogether.

  3. mouseTube – a database to collaboratively unravel mouse ultrasonic communication [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Nicolas Torquet

    2016-09-01

    Full Text Available Ultrasonic vocalisation is a broadly used proxy to evaluate social communication in mouse models of neuropsychiatric disorders. The efficacy and robustness of testing these models suffer from limited knowledge of the structure and functions of these vocalisations as well as of the way to analyse the data. We created mouseTube, an open database with a web interface, to facilitate sharing and comparison of ultrasonic vocalisations data and metadata attached to a recording file. Metadata describe 1 the acquisition procedure, e.g., hardware, software, sampling frequency, bit depth; 2 the biological protocol used to elicit ultrasonic vocalisations; 3 the characteristics of the individual emitting ultrasonic vocalisations (e.g., strain, sex, age. To promote open science and enable reproducibility, data are made freely available. The website provides searching functions to facilitate the retrieval of recording files of interest. It is designed to enable comparisons of ultrasonic vocalisation emission between strains, protocols or laboratories, as well as to test different analysis algorithms and to search for protocols established to elicit mouse ultrasonic vocalisations. Over the long term, users will be able to download and compare different analysis results for each data file. Such application will boost the knowledge on mouse ultrasonic communication and stimulate sharing and comparison of automatic analysis methods to refine phenotyping techniques in mouse models of neuropsychiatric disorders.

  4. Index of /data/mouse-b6n-bac-clone-db/20120215 [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available Index of /data/mouse-b6n-bac-clone-db/20120215 Name Last modified Size Description ...Parent Directory - README.html 02-Apr-2014 10:25 8.1K mouse_b6n_bac_clone.zip 15-Feb-2012 13:33 64M Index of /data/mouse-b6n-bac-clone-db/20120215 ...

  5. Using the mouse to model human disease: increasing validity and reproducibility

    Directory of Open Access Journals (Sweden)

    Monica J. Justice

    2016-02-01

    Full Text Available Experiments that use the mouse as a model for disease have recently come under scrutiny because of the repeated failure of data, particularly derived from preclinical studies, to be replicated or translated to humans. The usefulness of mouse models has been questioned because of irreproducibility and poor recapitulation of human conditions. Newer studies, however, point to bias in reporting results and improper data analysis as key factors that limit reproducibility and validity of preclinical mouse research. Inaccurate and incomplete descriptions of experimental conditions also contribute. Here, we provide guidance on best practice in mouse experimentation, focusing on appropriate selection and validation of the model, sources of variation and their influence on phenotypic outcomes, minimum requirements for control sets, and the importance of rigorous statistics. Our goal is to raise the standards in mouse disease modeling to enhance reproducibility, reliability and clinical translation of findings.

  6. Interaction of Mouse Pem Protein and Cell Division Cycle 37 Homolog

    Institute of Scientific and Technical Information of China (English)

    Fen GUO; Yue-Qin LI; Shi-Qian LI; Zhi-Wen LUO; Xin ZHANG; Dong-Sheng TANG; Tian-Hong ZHOU

    2005-01-01

    Mouse Pem, a homeobox gene, encodes a protein consisting of 210 amino acid residues. To study the function of mouse Pem protein, we used the yeast two-hybrid system to screen the library of 7-day mouse embryo with full-length mouse Pem eDNA. Fifty-two colonies were obtained after 1.57×108 colonies were screened by nutrition limitation and β-galactosidase assay. Seven individual insert fragments were obtained from the library, and three of them were identified, one of which was confirmed to be the cell division cycle 37 (Cdc37) homolog gene by sequencing. The interaction between mouse Pem and Cdc37homolog was then confirmed by glutathione S-transferase pull-down assay, and the possible interaction model was suggested.

  7. Camera Mouse Including “Ctrl-Alt-Del” Key Operation Using Gaze, Blink, and Mouth Shape

    Directory of Open Access Journals (Sweden)

    Kohei Arai

    2013-04-01

    Full Text Available This paper presents camera mouse system with additional feature: "CTRL - ALT - DEL" key. The previous gaze-based camera mouse systems are only considering how to obtain gaze and making selection. We proposed gaze-based camera mouse with "CTRL - ALT - DEL" key. Infrared camera is put on top of display while user looking ahead. User gaze is estimated based on eye gaze and head pose. Blinking and mouth detections are used to create "CTR - ALT - DEL" key. Pupil knowledge is used to improve robustness of eye gaze estimation against different users. Also, Gabor filter is used to extract face features. Skin color information and face features are used to estimate head pose. The experiments of each method have done and the results show that all methods work perfectly. By implemented this system, troubleshooting of camera mouse can be done by user itself and makes camera mouse be more sophisticated.

  8. IL-6 and mouse oocyte spindle.

    Directory of Open Access Journals (Sweden)

    Jashoman Banerjee

    Full Text Available Interleukin 6 (IL-6 is considered a major indicator of the acute-phase inflammatory response. Endometriosis and pelvic inflammation, diseases that manifest elevated levels of IL-6, are commonly associated with higher infertility. However, the mechanistic link between elevated levels of IL-6 and poor oocyte quality is still unclear. In this work, we explored the direct role of this cytokine as a possible mediator for impaired oocyte spindle and chromosomal structure, which is a critical hurdle in the management of infertility. Metaphase-II mouse oocytes were exposed to recombinant mouse IL-6 (50, 100 and 200 ng/mL for 30 minutes and subjected to indirect immunofluorescent staining to identify alterations in the microtubule and chromosomal alignment compared to untreated controls. The deterioration in microtubule and chromosomal alignment were evaluated utilizing both fluorescence and confocal microscopy, and were quantitated with a previously reported scoring system. Our results showed that IL-6 caused a dose-dependent deterioration in microtubule and chromosomal alignment in the treated oocytes as compared to the untreated group. Indeed, IL-6 at a concentration as low as 50 ng/mL caused deterioration in the spindle structure in 60% of the oocytes, which increased significantly (P<0.0001 as IL-6 concentration was increased. In conclusion, elevated levels of IL-6 associated with endometriosis and pelvic inflammation may reduce the fertilizing capacity of human oocyte through a mechanism that involves impairment of the microtubule and chromosomal structure.

  9. Genetic Networks in Mouse Retinal Ganglion Cells

    Directory of Open Access Journals (Sweden)

    Felix L Struebing

    2016-09-01

    Full Text Available Retinal ganglion cells (RGCs are the output neuron of the eye, transmitting visual information from the retina through the optic nerve to the brain. The importance of RGCs for vision is demonstrated in blinding diseases where RGCs are lost, such as in glaucoma or after optic nerve injury. In the present study, we hypothesize that normal RGC function is transcriptionally regulated. To test our hypothesis, we examine large retinal expression microarray datasets from recombinant inbred mouse strains in GeneNetwork and define transcriptional networks of RGCs and their subtypes. Two major and functionally distinct transcriptional networks centering around Thy1 and Tubb3 (Class III beta-tubulin were identified. Each network is independently regulated and modulated by unique genomic loci. Meta-analysis of publically available data confirms that RGC subtypes are differentially susceptible to death, with alpha-RGCs and intrinsically photosensitive RGCs (ipRGCs being less sensitive to cell death than other RGC subtypes in a mouse model of glaucoma.

  10. Mouse models of anemia of cancer.

    Directory of Open Access Journals (Sweden)

    Airie Kim

    Full Text Available Anemia of cancer (AC may contribute to cancer-related fatigue and impair quality of life. Improved understanding of the pathogenesis of AC could facilitate better treatment, but animal models to study AC are lacking. We characterized four syngeneic C57BL/6 mouse cancers that cause AC. Mice with two different rapidly-growing metastatic lung cancers developed the characteristic findings of anemia of inflammation (AI, with dramatically different degrees of anemia. Mice with rapidly-growing metastatic melanoma also developed a severe anemia by 14 days, with hematologic and inflammatory parameters similar to AI. Mice with a slow-growing peritoneal ovarian cancer developed an iron-deficiency anemia, likely secondary to chronically impaired nutrition and bleeding into the peritoneal cavity. Of the four models, hepcidin mRNA levels were increased only in the milder lung cancer model. Unlike in our model of systemic inflammation induced by heat-killed Brucella abortus, ablation of hepcidin in the ovarian cancer and the milder lung cancer mouse models did not affect the severity of anemia. Hepcidin-independent mechanisms play an important role in these murine models of AC.

  11. Mouse Models of Rheumatoid Arthritis.

    Science.gov (United States)

    Caplazi, P; Baca, M; Barck, K; Carano, R A D; DeVoss, J; Lee, W P; Bolon, B; Diehl, L

    2015-09-01

    Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disorder characterized by synovitis that leads to cartilage and bone erosion by invading fibrovascular tissue. Mouse models of RA recapitulate many features of the human disease. Despite the availability of medicines that are highly effective in many patient populations, autoimmune diseases (including RA) remain an area of active biomedical research, and consequently mouse models of RA are still extensively used for mechanistic studies and validation of therapeutic targets. This review aims to integrate morphologic features with model biology and cover the key characteristics of the most commonly used induced and spontaneous mouse models of RA. Induced models emphasized in this review include collagen-induced arthritis and antibody-induced arthritis. Collagen-induced arthritis is an example of an active immunization strategy, whereas antibody- induced arthritis models, such as collagen antibody-induced arthritis and K/BxN antibody transfer arthritis, represent examples of passive immunization strategies. The coverage of spontaneous models in this review is focused on the TNFΔ (ARE) mouse, in which arthritis results from overexpression of TNF-α, a master proinflammatory cytokine that drives disease in many patients.

  12. Mouse models of myasthenia gravis.

    Science.gov (United States)

    Ban, Joanne; Phillips, William D

    2015-01-01

    Myasthenia gravis is a muscle weakness disease characterized by autoantibodies that target components of the neuromuscular junction, impairing synaptic transmission. The most common form of myasthenia gravis involves antibodies that bind the nicotinic acetylcholine receptors in the postsynaptic membrane. Many of the remaining cases are due to antibodies against muscle specific tyrosine kinase (MuSK). Recently, autoantibodies against LRP4 (another component of the MuSK signaling complex in the postsynaptic membrane) were identified as the likely cause of myasthenia gravis in some patients. Fatiguing weakness is the common symptom in all forms of myasthenia gravis, but muscles of the body are differentially affected, for reasons that are not fully understood. Much of what we have learnt about the immunological and neurobiological aspects of the pathogenesis derives from mouse models. The most widely used mouse models involve either passive transfer of autoantibodies, or active immunization of the mouse with acetylcholine receptors or MuSK protein. These models can provide a robust replication of many of the features of the human disease. Depending upon the protocol, acute fatiguing weakness develops 2 - 14 days after the start of autoantibody injections (passive transfer) or might require repeated immunizations over several weeks (active models). Here we review mouse models of myasthenia gravis, including what they have contributed to current understanding of the pathogenic mechanisms and their current application to the testing of therapeutics.

  13. Human/mouse homology relationships

    Energy Technology Data Exchange (ETDEWEB)

    DeBry, R.W.; Seldin, M.F. [Duke Univ. Medical Center, Durham, NC (United States)

    1996-05-01

    Conservation of genomic organization in different mammalian species has long been recognized, but only recently has it been possible to examine these relationships systematically on a genome-wide scale in some detail. Mapping of several mammalian species in progressing rapidly, but by far the most detailed information is still to be found in the human and mouse databases. Perhaps the most important aspect of recent progress in genome mapping data. With mapping databases continuing to expand at a greater than linear rate, any attempt at a comprehensive comparative map is doomed to be out of date by the time it is published. However, we feel that it is valuable to provide a summary that is as nearly up to date as possible. We have made a particular effort to include recent human physical mapping data and to identify those mouse genes that have been well-mapped with respect to each other by virtue of having been examined in the same cross. As the human-mouse comparative map becomes more dense, it is not surprising that the observed number of conserved linkage groups continues to increase. Nadeau et al. placed 425 loci on both maps, which delineated over 100 conserved linkage groups. Copeland et al. put a total of 917 markers on both the human and the mouse maps, marking 101 segments of conserved linkage groups. In the present summary, we have placed 1416 loci, and these define at least 181 different conserved linkage groups. 47 refs., 1 fig.

  14. An encyclopedia of mouse genes.

    Science.gov (United States)

    Marra, M; Hillier, L; Kucaba, T; Allen, M; Barstead, R; Beck, C; Blistain, A; Bonaldo, M; Bowers, Y; Bowles, L; Cardenas, M; Chamberlain, A; Chappell, J; Clifton, S; Favello, A; Geisel, S; Gibbons, M; Harvey, N; Hill, F; Jackson, Y; Kohn, S; Lennon, G; Mardis, E; Martin, J; Mila, L; McCann, R; Morales, R; Pape, D; Person, B; Prange, C; Ritter, E; Soares, M; Schurk, R; Shin, T; Steptoe, M; Swaller, T; Theising, B; Underwood, K; Wylie, T; Yount, T; Wilson, R; Waterston, R

    1999-02-01

    The laboratory mouse is the premier model system for studies of mammalian development due to the powerful classical genetic analysis possible (see also the Jackson Laboratory web site, http://www.jax.org/) and the ever-expanding collection of molecular tools. To enhance the utility of the mouse system, we initiated a program to generate a large database of expressed sequence tags (ESTs) that can provide rapid access to genes. Of particular significance was the possibility that cDNA libraries could be prepared from very early stages of development, a situation unrealized in human EST projects. We report here the development of a comprehensive database of ESTs for the mouse. The project, initiated in March 1996, has focused on 5' end sequences from directionally cloned, oligo-dT primed cDNA libraries. As of 23 October 1998, 352,040 sequences had been generated, annotated and deposited in dbEST, where they comprised 93% of the total ESTs available for mouse. EST data are versatile and have been applied to gene identification, comparative sequence analysis, comparative gene mapping and candidate disease gene identification, genome sequence annotation, microarray development and the development of gene-based map resources.

  15. High-throughput mouse phenotyping.

    Science.gov (United States)

    Gates, Hilary; Mallon, Ann-Marie; Brown, Steve D M

    2011-04-01

    Comprehensive phenotyping will be required to reveal the pleiotropic functions of a gene and to uncover the wider role of genetic loci within diverse biological systems. The challenge will be to devise phenotyping approaches to characterise the thousands of mutants that are being generated as part of international efforts to acquire a mutant for every gene in the mouse genome. In order to acquire robust datasets of broad based phenotypes from mouse mutants it is necessary to design and implement pipelines that incorporate standardised phenotyping platforms that are validated across diverse mouse genetics centres or mouse clinics. We describe here the rationale and methodology behind one phenotyping pipeline, EMPReSSslim, that was designed as part of the work of the EUMORPHIA and EUMODIC consortia, and which exemplifies some of the challenges facing large-scale phenotyping. EMPReSSslim captures a broad range of data on diverse biological systems, from biochemical to physiological amongst others. Data capture and dissemination is pivotal to the operation of large-scale phenotyping pipelines, including the definition of parameters integral to each phenotyping test and the associated ontological descriptions. EMPReSSslim data is displayed within the EuroPhenome database, where a variety of tools are available to allow the user to search for interesting biological or clinical phenotypes. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Enhancement of mouse sperm motility by trophinin-binding peptide

    Directory of Open Access Journals (Sweden)

    Park Seong

    2012-11-01

    Full Text Available Abstract Background Trophinin is an intrinsic membrane protein that forms a complex in the cytoplasm with bystin and tastin, linking it microtubule-associated motor dynein (ATPase in some cell types. Previously, we found that human sperm tails contain trophinin, bystin and tastin proteins, and that trophinin-binding GWRQ (glycine, tryptophan, arginine, glutamine peptide enhanced motility of human sperm. Methods Immunohistochemistry was employed to determine trophinin protein in mouse spermatozoa from wild type mouse, by using spermatozoa from trophinin null mutant mice as a negative control. Multivalent 8-branched GWRQ (glycine, tryptophan, arginine, glutamine peptide or GWRQ-MAPS, was chemically synthesized, purified by HPLC and its structure was confirmed by MALDI-TOF mass spectrometry. Effect of GWRQ-MAPS on mouse spermatozoa from wild type and trophinin null mutant was assessed by a computer-assisted semen analyzer (CASA. Results Anti-trophinin antibody stained the principal (central piece of the tail of wild type mouse sperm, whereas the antibody showed no staining on trophinin null sperm. Phage particles displaying GWRQ bound to the principal piece of sperm tail from wild type but not trophinin null mice. GWRQ-MAPS enhanced motility of spermatozoa from wild type but not trophinin null mice. CASA showed that GWRQ-MAPS enhanced both progressive motility and rapid motility in wild type mouse sperm. Conclusions Present study established the expression of trophinin in the mouse sperm tail and trophinin-dependent effect of GWRQ-MAPS on sperm motility. GWRQ causes a significant increase in sperm motility.

  17. Spallanzani's mouse: a model of restoration and regeneration.

    Science.gov (United States)

    Heber-Katz, E; Leferovich, J M; Bedelbaeva, K; Gourevitch, D

    2004-01-01

    The ability to regenerate is thought to be a lost phenotype in mammals, though there are certainly sporadic examples of mammalian regeneration. Our laboratory has identified a strain of mouse, the MRL mouse, which has a unique capacity to heal complex tissue in an epimorphic fashion, i.e., to restore a damaged limb or organ to its normal structure and function. Initial studies using through-and-through ear punches showed rapid full closure of the ear holes with cartilage growth, new hair follicles, and normal tissue architecture reminiscent of regeneration seen in amphibians as opposed to the scarring usually seen in mammals. Since the ear hole closure phenotype is a quantitative trait, this has been used to show-through extensive breeding and backcrossing--that the trait is heritable. Such analysis reveals that there is a complex genetic basis for this trait with multiple loci. One of the major phenotypes of the MRL mouse is a potent remodeling response with the absence or a reduced level of scarring. MRL healing is associated with the upregulation of the metalloproteinases MMP-2 and MMP-9 and the downregulation of their inhibitors TIMP-2 and TIMP-3, both present in inflammatory cells such as neutrophils and macrophages. This model has more recently been extended to the heart. In this case, a cryoinjury to the right ventricle leads to near complete scarless healing in the MRL mouse whereas scarring is seen in the control mouse. In the MRL heart, bromodeoxyuridine uptake by cardiomyocytes filling the wound site can be seen 60 days after injury. This does not occur in the control mouse. Function in the MRL heart, as measured by echocardiography, returns to normal.

  18. Expression of lactoperoxidase in differentiated mouse colon epithelial cells.

    Science.gov (United States)

    Kim, Byung-Wook; Esworthy, R Steven; Hahn, Maria A; Pfeifer, Gerd P; Chu, Fong-Fong

    2012-05-01

    Lactoperoxidase (LPO) is known to be present in secreted fluids, such as milk and saliva. Functionally, LPO teams up with dual oxidases (DUOXs) to generate bactericidal hypothiocyanite in the presence of thiocyanate. DUOX2 is expressed in intestinal epithelium, but there is little information on LPO expression in this tissue. To fill the gap of knowledge, we have analyzed Lpo gene expression and its regulation in mouse intestine. In wild-type (WT) C57BL/6 (B6) mouse intestine, an appreciable level of mouse Lpo gene expression was detected in the colon, but not the ileum. However, in B6 mice deficient in glutathione peroxidase (GPx)-1 and -2, GPx1/2-double-knockout (DKO), which had intestinal pathology, the colon Lpo mRNA levels increased 5- to 12-fold depending on mouse age. The Lpo mRNA levels in WT and DKO 129S1/SvlmJ (129) colon were even higher, 9- and 5-fold, than in B6 DKO colon. Higher levels of Lpo protein and enzymatic activity were also detected in the 129 mouse colon compared to B6 colon. Lpo protein was expressed in the differentiated colon epithelial cells, away from the crypt base, as shown by immunohistochemistry. Similar to human LPO mRNA, mouse Lpo mRNA had multiple spliced forms, although only the full-length variant 1 was translated. Higher methylation was found in the 129 than in the B6 strain, in DKO than in control colon, and in older than in juvenile mice. However, methylation of the Lpo intragenic CpG island was not directly induced by inflammation, because dextran sulfate sodium-induced colitis did not increase DNA methylation in B6 DKO colon. Also, Lpo DNA methylation is not correlated with gene expression.

  19. Cloning the mouse homologue of the human lysosomal acid {alpha}-glucosidase gene

    Energy Technology Data Exchange (ETDEWEB)

    Ding, J.H.; Yang, B.Z.; Liu, H.M. [Duke Univ. Medical Center, Durham, NC (United States)] [and others

    1994-09-01

    Pompe disease (GSD II) is an autosomal recessive disorder caused by a deficiency of lysosomal acid {alpha}-glucosidase (GAA). In an attempt to create a mouse model for Pompe disease, we isolated and characterized the gene encoding the mouse homologue of the human GAA. Twenty clones that extend from exon 2 to the poly(A) tail were isolated from a mouse liver cDNA library, but the remainder of the mRNA proved difficult to obtain by conventional cDNA library screening. Sequences spanning exons 1-2 were cloned by RACE from mouse liver RNA. The full-length liver GAA cDNA contains 3365 nucleotides with a coding region of 2859 nucleotides and a 394 base pair 3{prime}-nontranslated region. The deduced amino acid sequence of the mouse GAA shows 84% identity to the human GAA. Southern blot analysis demonstrated that the mouse GAA was encoded by a single copy gene. Then six bacteriophages containing DNA from the GAA gene were isolated by screening 10{sup 6} phage plaques of a mouse 129 genomic library using a mouse GAA cDNA as a probe. From one of these bacteriophages, an 11-kilobase EcoRI fragment containing exons 3 to 15 was subcloned and sequenced. Work is in progress using this genomic clone to disrupt the GAA gene in murine embryonic stem cells in order to create GSD II mice.

  20. Characterization of Bovine 5′-flanking Region during Differentiation of Mouse Embryonic Stem Cells

    Directory of Open Access Journals (Sweden)

    Hye-Jeong Jang

    2015-12-01

    Full Text Available Embryonic stem cells (ESCs have been used as a powerful tool for research including gene manipulated animal models and the study of developmental gene regulation. Among the critical regulatory factors that maintain the pluripotency and self-renewal of undifferentiated ESCs, NANOG plays a very important role. Nevertheless, because pluripotency maintaining factors and specific markers for livestock ESCs have not yet been probed, few studies of the NANOG gene from domestic animals including bovine have been reported. Therefore, we chose mouse ESCs in order to understand and compare NANOG expression between bovine, human, and mouse during ESCs differentiation. We cloned a 600 bp (−420/+181 bovine NANOG 5′-flanking region, and tagged it with humanized recombinant green fluorescent protein (hrGFP as a tracing reporter. Very high GFP expression for bovine NANOG promoter was observed in the mouse ESC line. GFP expression was monitored upon ESC differentiation and was gradually reduced along with differentiation toward neurons and adipocyte cells. Activity of bovine NANOG (−420/+181 promoter was compared with already known mouse and human NANOG promoters in mouse ESC and they were likely to show a similar pattern of regulation. In conclusion, bovine NANOG 5-flanking region functions in mouse ES cells and has characteristics similar to those of mouse and human. These results suggest that bovine gene function studied in mouse ES cells should be evaluated and extrapolated for application to characterization of bovine ES cells.

  1. The mouse genome database: genotypes, phenotypes, and models of human disease.

    Science.gov (United States)

    Bult, Carol J; Eppig, Janan T; Blake, Judith A; Kadin, James A; Richardson, Joel E

    2013-01-01

    The laboratory mouse is the premier animal model for studying human biology because all life stages can be accessed experimentally, a completely sequenced reference genome is publicly available and there exists a myriad of genomic tools for comparative and experimental research. In the current era of genome scale, data-driven biomedical research, the integration of genetic, genomic and biological data are essential for realizing the full potential of the mouse as an experimental model. The Mouse Genome Database (MGD; http://www.informatics.jax.org), the community model organism database for the laboratory mouse, is designed to facilitate the use of the laboratory mouse as a model system for understanding human biology and disease. To achieve this goal, MGD integrates genetic and genomic data related to the functional and phenotypic characterization of mouse genes and alleles and serves as a comprehensive catalog for mouse models of human disease. Recent enhancements to MGD include the addition of human ortholog details to mouse Gene Detail pages, the inclusion of microRNA knockouts to MGD's catalog of alleles and phenotypes, the addition of video clips to phenotype images, providing access to genotype and phenotype data associated with quantitative trait loci (QTL) and improvements to the layout and display of Gene Ontology annotations.

  2. Transcriptome-scale similarities between mouse and human skeletal muscles with normal and myopathic phenotypes

    Directory of Open Access Journals (Sweden)

    Kang Peter B

    2006-03-01

    Full Text Available Abstract Background Mouse and human skeletal muscle transcriptome profiles vary by muscle type, raising the question of which mouse muscle groups have the greatest molecular similarities to human skeletal muscle. Methods Orthologous (whole, sub- transcriptome profiles were compared among four mouse-human transcriptome datasets: (M six muscle groups obtained from three mouse strains (wildtype, mdx, mdx5cv; (H1 biopsied human quadriceps from controls and Duchenne muscular dystrophy patients; (H2 four different control human muscle types obtained at autopsy; and (H3 12 different control human tissues (ten non-muscle. Results Of the six mouse muscles examined, mouse soleus bore the greatest molecular similarities to human skeletal muscles, independent of the latters' anatomic location/muscle type, disease state, age and sampling method (autopsy versus biopsy. Significant similarity to any one mouse muscle group was not observed for non-muscle human tissues (dataset H3, indicating this finding to be muscle specific. Conclusion This observation may be partly explained by the higher type I fiber content of soleus relative to the other mouse muscles sampled.

  3. Production of Male-Sterility Mouse by Resection of the Tail Epididymis

    Directory of Open Access Journals (Sweden)

    Xianju Huang

    2012-01-01

    Full Text Available Problem statement: Sterile males are bred with females to produce pseudopregnant recipients for oviduct and uterine transfers. Therefore, to make a sterile male mouse maybe the fist and fundamental procedure for embryo transfer. However, when people produce a sterile male mouse always abandon the sperm of the excellent male mouse. Approach: Here, the authrous present an efficient and simple procedure utilizing specific methods that make a sterile male mouse by resection of the caudal epididymis meanwhile collect sperm from the caudal epididymis for in vitro fertilization and then cauterize the vestigial epididymis to produce sterile male mouse. The experimental males and females are all normal mouse. Results: (1 The in vitro fertilization to cater to the demand of the mount of embryo for oviduct and uterine transfers and the sterile mouse are prepare for mate with female to produce pseudopregnant recipients for oviduct and uterine transfers; (2 Accessing the caudal epididymis through the scrotal sac has less invasive with mouse. Conclusion/Recommendations: Ablating the caudal epididymis of male mice has not reduced the achievement rate of copulation and reconversion. In vitro fertilization to harvester embryo can use for embryo and other preparing experiment.

  4. Mouse Models of Neurofibromatosis 1 and 2

    Directory of Open Access Journals (Sweden)

    David H. Gutmann

    2002-01-01

    Full Text Available The neurofibromatoses represent two of the most common inherited tumor predisposition syndromes affecting the nervous system. Individuals with neurofibromatosis 1 (NF1 are prone to the development of astrocytomas and peripheral nerve sheath tumors whereas those affected with neurofibromatosis 2 (NF2 develop schwannomas and meningiomas. The development of traditional homozygous knockout mice has provided insights into the roles of the NF1 and NF2 genes during development and in differentiation, but has been less instructive regarding the contribution of NF1 and NF2 dysfunction to the pathogenesis of specific benign and malignant tumors. Recent progress employing novel mouse targeting strategies has begun to illuminate the roles of the NF1 and NF2 gene products in the molecular pathogenesis of NF-associated tumors.

  5. Metallothionein-1+2 deficiency increases brain pathology in transgenic mice with astrocyte-targeted expression of interleukin 6

    DEFF Research Database (Denmark)

    Giralt, Mercedes; Penkowa, Milena; Hernández, Joaquín

    2002-01-01

    ) mice provided evidence that the increased MT-1+2 expression normally observed in the GFAP-IL6 mice is an important mechanism for coping with brain damage. Thus, the GFAP-IL6xMTKO mice showed a decreased body weight gain and an impaired performance in the rota-rod test, as well as a higher upregulation...... of cytokines such as IL-6, IL-1alpha,beta, and TNFalpha and recruitment and activation of macrophages and T cells throughout the CNS but mainly in the cerebellum. Clear symptoms of increased oxidative stress and apoptotic cell death caused by MT-1+2 deficiency were observed in the GFAP-IL6xMTKO mice...

  6. Effects of gamma-ray-induced free radicals on the metal content and amino acid composition of human metallothionein-1

    Indian Academy of Sciences (India)

    Lieven Goossens

    2011-06-01

    Metallothioneins (MTs), a low-mass class of metalloproteins, are characterized by a high thiolate sulphur and metal content. MTs are involved in metal homeostasis and heavy metal detoxification, and are efficient scavengers of free radicals. This article describes zinc release from human MT-1 and modification of its amino acid composition when subjected to free radicals generated during gamma ray radiolysis. The effect of gamma ray radiolysis of untreated and metal-depleted human MT-1 was tested under multiple aerobic and anaerobic conditions at increasing irradiation doses. Under all conditions, a rapid increase of serine in the early stages of irradiation was observed. Irradiation for longer times led to cysteic acid formation, except under argon atmosphere. Several other amino acid concentrations gradually decreased. Formation of limited amounts of hydroxyproline, hydroxylysine and ornithine as well as some less common derivatives such as cystathionine occurred as side-effects.

  7. Pleiotrophin gene therapy for peripheral ischemia: evaluation of full-length and truncated gene variants.

    Directory of Open Access Journals (Sweden)

    Qizhi Fang

    Full Text Available Pleiotrophin (PTN is a growth factor with both pro-angiogenic and limited pro-tumorigenic activity. We evaluated the potential for PTN to be used for safe angiogenic gene therapy using the full length gene and a truncated gene variant lacking the domain implicated in tumorigenesis. Mouse myoblasts were transduced to express full length or truncated PTN (PTN or T-PTN, along with a LacZ reporter gene, and injected into mouse limb muscle and myocardium. In cultured myoblasts, PTN was expressed and secreted via the Golgi apparatus, but T-PTN was not properly secreted. Nonetheless, no evidence of uncontrolled growth was observed in cells expressing either form of PTN. PTN gene delivery to myocardium, and non-ischemic skeletal muscle, did not result in a detectable change in vascularity or function. In ischemic hindlimb at 14 days post-implantation, intramuscular injection with PTN-expressing myoblasts led to a significant increase in skin perfusion and muscle arteriole density. We conclude that (1 delivery of the full length PTN gene to muscle can be accomplished without tumorigenesis, (2 the truncated PTN gene may be difficult to use in a gene therapy context due to inefficient secretion, (3 PTN gene delivery leads to functional benefit in the mouse acute ischemic hindlimb model.

  8. Dream recall and the full moon.

    Science.gov (United States)

    Schredl, Michael; Fulda, Stephany; Reinhard, Iris

    2006-02-01

    There is ongoing debate on whether the full moon is associated with sleep and dreaming. The analysis of diaries kept by the participants (N = 196) over 28 to 111 nights showed no association of a full moon and dream recall. Psychological factors might explain why some persons associate a full moon with increased dream recall.

  9. Achieving single channel, full duplex wireless communication

    KAUST Repository

    Choi, Jung Il

    2010-01-01

    This paper discusses the design of a single channel full-duplex wireless transceiver. The design uses a combination of RF and baseband techniques to achieve full-duplexing with minimal effect on link reliability. Experiments on real nodes show the full-duplex prototype achieves median performance that is within 8% of an ideal full-duplexing system. This paper presents Antenna Cancellation, a novel technique for self-interference cancellation. In conjunction with existing RF interference cancellation and digital baseband interference cancellation, antenna cancellation achieves the amount of self-interference cancellation required for full-duplex operation. The paper also discusses potential MAC and network gains with full-duplexing. It suggests ways in which a full-duplex system can solve some important problems with existing wireless systems including hidden terminals, loss of throughput due to congestion, and large end-to-end delays. Copyright 2010 ACM.

  10. A simplified immunohistochemical classification of skeletal muscle fibres in mouse

    Directory of Open Access Journals (Sweden)

    M. Kammoun

    2014-06-01

    Full Text Available The classification of muscle fibres is of particular interest for the study of the skeletal muscle properties in a wide range of scientific fields, especially animal phenotyping. It is therefore important to define a reliable method for classifying fibre types. The aim of this study was to establish a simplified method for the immunohistochemical classification of fibres in mouse. To carry it out, we first tested a combination of several anti myosin heavy chain (MyHC antibodies in order to choose a minimum number of antibodies to implement a semi-automatic classification. Then, we compared the classification of fibres to the MyHC electrophoretic pattern on the same samples. Only two anti MyHC antibodies on serial sections with the fluorescent labeling of the Laminin were necessary to classify properly fibre types in Tibialis Anterior and Soleus mouse muscles in normal physiological conditions. This classification was virtually identical to the classification realized by the electrophoretic separation of MyHC. This immunohistochemical classification can be applied to the total area of Tibialis Anterior and Soleus mouse muscles. Thus, we provide here a useful, simple and time-efficient method for immunohistochemical classification of fibres, applicable for research in mouse

  11. Phenotypic and functional characterization of Bst+/− mouse retina

    Directory of Open Access Journals (Sweden)

    Hamidreza Riazifar

    2015-08-01

    Full Text Available The belly spot and tail (Bst+/− mouse phenotype is caused by mutations of the ribosomal protein L24 (Rpl24. Among various phenotypes in Bst+/− mice, the most interesting are its retinal abnormalities, consisting of delayed closure of choroid fissures, decreased ganglion cells and subretinal vascularization. We further characterized the Bst+/− mouse and investigated the underlying molecular mechanisms to assess the feasibility of using this strain as a model for stem cell therapy of retinal degenerative diseases due to retinal ganglion cell (RGC loss. We found that, although RGCs are significantly reduced in retinal ganglion cell layer in Bst+/− mouse, melanopsin+ RGCs, also called ipRGCs, appear to be unchanged. Pupillary light reflex was completely absent in Bst+/− mice but they had a normal circadian rhythm. In order to examine the pathological abnormalities in Bst+/− mice, we performed electron microscopy in RGC and found that mitochondria morphology was deformed, having irregular borders and lacking cristae. The complex activities of the mitochondrial electron transport chain were significantly decreased. Finally, for subretinal vascularization, we also found that angiogenesis is delayed in Bst+/− associated with delayed hyaloid regression. Characterization of Bst+/− retina suggests that the Bst+/− mouse strain could be a useful murine model. It might be used to explore further the pathogenesis and strategy of treatment of retinal degenerative diseases by employing stem cell technology.

  12. The mouse "xenotropic" gammaretroviruses and their XPR1 receptor

    Directory of Open Access Journals (Sweden)

    Kozak Christine A

    2010-11-01

    Full Text Available Abstract The xenotropic/polytropic subgroup of mouse leukemia viruses (MLVs all rely on the XPR1 receptor for entry, but these viruses vary in tropism, distribution among wild and laboratory mice, pathogenicity, strategies used for transmission, and sensitivity to host restriction factors. Most, but not all, isolates have typical xenotropic or polytropic host range, and these two MLV tropism types have now been detected in humans as viral sequences or as infectious virus, termed XMRV, or xenotropic murine leukemia virus-related virus. The mouse xenotropic MLVs (X-MLVs were originally defined by their inability to infect cells of their natural mouse hosts. It is now clear, however, that X-MLVs actually have the broadest host range of the MLVs. Nearly all nonrodent mammals are susceptible to X-MLVs, and all species of wild mice and several common strains of laboratory mice are X-MLV susceptible. The polytropic MLVs, named for their apparent broad host range, show a more limited host range than the X-MLVs in that they fail to infect cells of many mouse species as well as many nonrodent mammals. The co-evolution of these viruses with their receptor and other host factors that affect their replication has produced a heterogeneous group of viruses capable of inducing various diseases, as well as endogenized viral genomes, some of which have been domesticated by their hosts to serve in antiviral defense.

  13. Modeling fragile X syndrome in the Fmr1 knockout mouse.

    Science.gov (United States)

    Kazdoba, Tatiana M; Leach, Prescott T; Silverman, Jill L; Crawley, Jacqueline N

    2014-11-01

    Fragile X Syndrome (FXS) is a commonly inherited form of intellectual disability and one of the leading genetic causes for autism spectrum disorder. Clinical symptoms of FXS can include impaired cognition, anxiety, hyperactivity, social phobia, and repetitive behaviors. FXS is caused by a CGG repeat mutation which expands a region on the X chromosome containing the FMR1 gene. In FXS, a full mutation (> 200 repeats) leads to hypermethylation of FMR1, an epigenetic mechanism that effectively silences FMR1 gene expression and reduces levels of the FMR1 gene product, fragile X mental retardation protein (FMRP). FMRP is an RNA-binding protein that is important for the regulation of protein expression. In an effort to further understand how loss of FMR1 and FMRP contribute to FXS symptomology, several FXS animal models have been created. The most well characterized rodent model is the Fmr1 knockout (KO) mouse, which lacks FMRP protein due to a disruption in its Fmr1 gene. Here, we review the behavioral phenotyping of the Fmr1 KO mouse to date, and discuss the clinical relevance of this mouse model to the human FXS condition. While much remains to be learned about FXS, the Fmr1 KO mouse is a valuable tool for understanding the repercussions of functional loss of FMRP and assessing the efficacy of pharmacological compounds in ameliorating the molecular and behavioral phenotypes relevant to FXS.

  14. Endogenous Mouse Dicer Is an Exclusively Cytoplasmic Protein.

    Directory of Open Access Journals (Sweden)

    Christian Much

    2016-06-01

    Full Text Available Dicer is a large multi-domain protein responsible for the ultimate step of microRNA and short-interfering RNA biogenesis. In human and mouse cell lines, Dicer has been shown to be important in the nuclear clearance of dsRNA as well as the establishment of chromatin modifications. Here we set out to unambiguously define the cellular localization of Dicer in mice to understand if this is a conserved feature of mammalian Dicer in vivo. To this end, we utilized an endogenously epitope tagged Dicer knock-in mouse allele. From primary mouse cell lines and adult tissues, we determined with certainty by biochemical fractionation and confocal immunofluorescence microscopy that endogenous Dicer is exclusively cytoplasmic. We ruled out the possibility that a fraction of Dicer shuttles to and from the nucleus as well as that FGF or DNA damage signaling induce Dicer nuclear translocation. We also explored Dicer localization during the dynamic and developmental context of embryogenesis, where Dicer is ubiquitously expressed and strictly cytoplasmic in all three germ layers as well as extraembryonic tissues. Our data exclude a direct role for Dicer in the nuclear RNA processing in the mouse.

  15. Absence of pathogenic mitochondrial DNA mutations in mouse brain tumors

    Directory of Open Access Journals (Sweden)

    Seyfried Thomas N

    2005-08-01

    Full Text Available Abstract Background Somatic mutations in the mitochondrial genome occur in numerous tumor types including brain tumors. These mutations are generally found in the hypervariable regions I and II of the displacement loop and unlikely alter mitochondrial function. Two hypervariable regions of mononucleotide repeats occur in the mouse mitochondrial genome, i.e., the origin of replication of the light strand (OL and the Arg tRNA. Methods In this study we examined the entire mitochondrial genome in a series of chemically induced brain tumors in the C57BL/6J strain and spontaneous brain tumors in the VM mouse strain. The tumor mtDNA was compared to that of mtDNA in brain mitochondrial populations from the corresponding syngeneic mouse host strain. Results Direct sequencing revealed a few homoplasmic base pair insertions, deletions, and substitutions in the tumor cells mainly in regions of mononucleotide repeats. A heteroplasmic mutation in the 16srRNA gene was detected in a spontaneous metastatic VM brain tumor. Conclusion None of the mutations were considered pathogenic, indicating that mtDNA somatic mutations do not likely contribute to the initiation or progression of these diverse mouse brain tumors.

  16. A method to quantify mouse coat-color proportions.

    Directory of Open Access Journals (Sweden)

    Songthip Ounpraseuth

    Full Text Available Coat-color proportions and patterns in mice are used as assays for many processes such as transgene expression, chimerism, and epigenetics. In many studies, coat-color readouts are estimated from subjective scoring of individual mice. Here we show a method by which mouse coat color is quantified as the proportion of coat shown in one or more digital images. We use the yellow-agouti mouse model of epigenetic variegation to demonstrate this method. We apply this method to live mice using a conventional digital camera for data collection. We use a raster graphics editing program to convert agouti regions of the coat to a standard, uniform, brown color and the yellow regions of the coat to a standard, uniform, yellow color. We use a second program to quantify the proportions of these standard colors. This method provides quantification that relates directly to the visual appearance of the live animal. It also provides an objective analysis with a traceable record, and it should allow for precise comparisons of mouse coats and mouse cohorts within and between studies.

  17. Cardiac disease and arrhythmogenesis: Mechanistic insights from mouse models

    Directory of Open Access Journals (Sweden)

    Lois Choy

    2016-09-01

    Full Text Available The mouse is the second mammalian species, after the human, in which substantial amount of the genomic information has been analyzed. With advances in transgenic technology, mutagenesis is now much easier to carry out in mice. Consequently, an increasing number of transgenic mouse systems have been generated for the study of cardiac arrhythmias in ion channelopathies and cardiomyopathies. Mouse hearts are also amenable to physical manipulation such as coronary artery ligation and transverse aortic constriction to induce heart failure, radiofrequency ablation of the AV node to model complete AV block and even implantation of a miniature pacemaker to induce cardiac dyssynchrony. Last but not least, pharmacological models, despite being simplistic, have enabled us to understand the physiological mechanisms of arrhythmias and evaluate the anti-arrhythmic properties of experimental agents, such as gap junction modulators, that may be exert therapeutic effects in other cardiac diseases. In this article, we examine these in turn, demonstrating that primary inherited arrhythmic syndromes are now recognized to be more complex than abnormality in a particular ion channel, involving alterations in gene expression and structural remodelling. Conversely, in cardiomyopathies and heart failure, mutations in ion channels and proteins have been identified as underlying causes, and electrophysiological remodelling are recognized pathological features. Transgenic techniques causing mutagenesis in mice are extremely powerful in dissecting the relative contributions of different genes play in producing disease phenotypes. Mouse models can serve as useful systems in which to explore how protein defects contribute to arrhythmias and direct future therapy.

  18. Cell proliferation and neurogenesis in adult mouse brain.

    Directory of Open Access Journals (Sweden)

    Olivia L Bordiuk

    Full Text Available Neurogenesis, the formation of new neurons, can be observed in the adult brain of many mammalian species, including humans. Despite significant progress in our understanding of adult neurogenesis, we are still missing data about the extent and location of production of neural precursors in the adult mammalian brain. We used 5-ethynyl-2'-deoxyuridine (EdU to map the location of proliferating cells throughout the entire adult mouse brain and found that neurogenesis occurs at two locations in the mouse brain. The larger one we define as the main proliferative zone (MPZ, and the smaller one corresponds to the subgranular zone of the hippocampus. The MPZ can be divided into three parts. The caudate migratory stream (CMS occupies the middle part of the MPZ. The cable of proliferating cells emanating from the most anterior part of the CMS toward the olfactory bulbs forms the rostral migratory stream. The thin layer of proliferating cells extending posteriorly from the CMS forms the midlayer. We have not found any additional aggregations of proliferating cells in the adult mouse brain that could suggest the existence of other major neurogenic zones in the adult mouse brain.

  19. Interferon regulatory factor 1 is required for mouse Gbp gene activation by gamma interferon.

    OpenAIRE

    1995-01-01

    Full-scale transcriptional activation of the mouse Gbp genes by gamma interferon (IFN-gamma) requires protein synthesis in embryonic fibroblasts. Although the Gbp-1 and Gbp-2 promoters contain binding sites for transcription factors Stat1 and IFN regulatory factor 1 (IRF-1), deletion analysis revealed that the Stat1 binding site is dispensable for IFN-gamma inducibility of Gbp promoter constructs in transfected fibroblasts. However, activation of the mouse Gbp promoter by IFN-gamma requires t...

  20. Mouse Models for Methylmalonic Aciduria

    Science.gov (United States)

    Peters, Heidi L.; Pitt, James J.; Wood, Leonie R.; Hamilton, Natasha J.; Sarsero, Joseph P.; Buck, Nicole E.

    2012-01-01

    Methylmalonic aciduria (MMA) is a disorder of organic acid metabolism resulting from a functional defect of methylmalonyl-CoA mutase (MCM). MMA is associated with significant morbidity and mortality, thus therapies are necessary to help improve quality of life and prevent renal and neurological complications. Transgenic mice carrying an intact human MCM locus have been produced. Four separate transgenic lines were established and characterised as carrying two, four, five or six copies of the transgene in a single integration site. Transgenic mice from the 2-copy line were crossed with heterozygous knockout MCM mice to generate mice hemizygous for the human transgene on a homozygous knockout background. Partial rescue of the uniform neonatal lethality seen in homozygous knockout mice was observed. These rescued mice were significantly smaller than control littermates (mice with mouse MCM gene). Biochemically, these partial rescue mice exhibited elevated methylmalonic acid levels in urine, plasma, kidney, liver and brain tissue. Acylcarnitine analysis of blood spots revealed elevated propionylcarnitine levels. Analysis of mRNA expression confirms the human transgene is expressed at higher levels than observed for the wild type, with highest expression in the kidney followed closely by brain and liver. Partial rescue mouse fibroblast cultures had only 20% of the wild type MCM enzyme activity. It is anticipated that this humanised partial rescue mouse model of MMA will enable evaluation of long-term pathophysiological effects of elevated methylmalonic acid levels and be a valuable model for the investigation of therapeutic strategies, such as cell transplantation. PMID:22792386

  1. Development of mouse hepatocyte lines permissive for hepatitis C virus (HCV.

    Directory of Open Access Journals (Sweden)

    Hussein Hassan Aly

    Full Text Available The lack of a suitable small animal model for the analysis of hepatitis C virus (HCV infection has hampered elucidation of the HCV life cycle and the development of both protective and therapeutic strategies against HCV infection. Human and mouse harbor a comparable system for antiviral type I interferon (IFN induction and amplification, which regulates viral infection and replication. Using hepatocytes from knockout (ko mice, we determined the critical step of the IFN-inducing/amplification pathways regulating HCV replication in mouse. The results infer that interferon-beta promoter stimulator (IPS-1 or interferon A receptor (IFNAR were a crucial barrier to HCV replication in mouse hepatocytes. Although both IFNARko and IPS-1ko hepatocytes showed a reduced induction of type I interferons in response to viral infection, only IPS-1-/- cells circumvented cell death from HCV cytopathic effect and significantly improved J6JFH1 replication, suggesting IPS-1 to be a key player regulating HCV replication in mouse hepatocytes. We then established mouse hepatocyte lines lacking IPS-1 or IFNAR through immortalization with SV40T antigen. Expression of human (hCD81 on these hepatocyte lines rendered both lines HCVcc-permissive. We also found that the chimeric J6JFH1 construct, having the structure region from J6 isolate enhanced HCV replication in mouse hepatocytes rather than the full length original JFH1 construct, a new finding that suggests the possible role of the HCV structural region in HCV replication. This is the first report on the entry and replication of HCV infectious particles in mouse hepatocytes. These mouse hepatocyte lines will facilitate establishing a mouse HCV infection model with multifarious applications.

  2. Osteopontin is expressed in the mouse uterus during early pregnancy and promotes mouse blastocyst attachment and invasion in vitro.

    Directory of Open Access Journals (Sweden)

    Qian-Rong Qi

    Full Text Available Embryo implantation into the maternal uterus is a decisive step for successful mammalian pregnancy. Osteopontin (OPN is a member of the small integrin-binding ligand N-linked glycoprotein family and participates in cell adhesion and invasion. In this study, we showed that Opn mRNA levels are up-regulated in the mouse uterus on day 4 and at the implantation sites on days 5 and 8 of pregnancy. Immunohistochemistry localized the OPN protein to the glandular epithelium on day 4 and to the decidual zone on day 8 of pregnancy. OPN mRNA and proteins are induced by in vivo and in vitro decidualization. OPN expression in the endometrial stromal cells is regulated by progesterone, a key regulator during decidualization. As a secreted protein, the protein level of OPN in the uterine cavity is enriched on day 4, and in vitro embryo culturing has indicated that OPN can facilitate blastocyst hatching and adhesion. Knockdown of OPN attenuates the adhesion and invasion of blastocysts in mouse endometrial stromal cells by suppressing the expression and enzymatic activity of matrix metalloproteinase-9 in the trophoblast. Our data indicated that OPN expression in the mouse uterus during early pregnancy is essential for blastocyst hatching and adhesion and that the knockdown of OPN in mouse endometrial stroma cells could lead to a restrained in vitro trophoblast invasion.

  3. Rapid genetic algorithm optimization of a mouse computational model: Benefits for anthropomorphization of neonatal mouse cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Corina Teodora Bot

    2012-11-01

    Full Text Available While the mouse presents an invaluable experimental model organism in biology, its usefulness in cardiac arrhythmia research is limited in some aspects due to major electrophysiological differences between murine and human action potentials (APs. As previously described, these species-specific traits can be partly overcome by application of a cell-type transforming clamp (CTC to anthropomorphize the murine cardiac AP. CTC is a hybrid experimental-computational dynamic clamp technique, in which a computationally calculated time-dependent current is inserted into a cell in real time, to compensate for the differences between sarcolemmal currents of that cell (e.g., murine and the desired species (e.g., human. For effective CTC performance, mismatch between the measured cell and a mathematical model used to mimic the measured AP must be minimal. We have developed a genetic algorithm (GA approach that rapidly tunes a mathematical model to reproduce the AP of the murine cardiac myocyte under study. Compared to a prior implementation that used a template-based model selection approach, we show that GA optimization to a cell-specific model results in a much better recapitulation of the desired AP morphology with CTC. This improvement was more pronounced when anthropomorphizing neonatal mouse cardiomyocytes to human-like APs than to guinea pig APs. CTC may be useful for a wide range of applications, from screening effects of pharmaceutical compounds on ion channel activity, to exploring variations in the mouse or human genome. Rapid GA optimization of a cell-specific mathematical model improves CTC performance and may therefore expand the applicability and usage of the CTC technique.

  4. The functional landscape of mouse gene expression

    Directory of Open Access Journals (Sweden)

    Zhang Wen

    2004-12-01

    Full Text Available Abstract Background Large-scale quantitative analysis of transcriptional co-expression has been used to dissect regulatory networks and to predict the functions of new genes discovered by genome sequencing in model organisms such as yeast. Although the idea that tissue-specific expression is indicative of gene function in mammals is widely accepted, it has not been objectively tested nor compared with the related but distinct strategy of correlating gene co-expression as a means to predict gene function. Results We generated microarray expression data for nearly 40,000 known and predicted mRNAs in 55 mouse tissues, using custom-built oligonucleotide arrays. We show that quantitative transcriptional co-expression is a powerful predictor of gene function. Hundreds of functional categories, as defined by Gene Ontology 'Biological Processes', are associated with characteristic expression patterns across all tissues, including categories that bear no overt relationship to the tissue of origin. In contrast, simple tissue-specific restriction of expression is a poor predictor of which genes are in which functional categories. As an example, the highly conserved mouse gene PWP1 is widely expressed across different tissues but is co-expressed with many RNA-processing genes; we show that the uncharacterized yeast homolog of PWP1 is required for rRNA biogenesis. Conclusions We conclude that 'functional genomics' strategies based on quantitative transcriptional co-expression will be as fruitful in mammals as they have been in simpler organisms, and that transcriptional control of mammalian physiology is more modular than is generally appreciated. Our data and analyses provide a public resource for mammalian functional genomics.

  5. Ultra low power full adder topologies

    DEFF Research Database (Denmark)

    Moradi, Farshad; Wisland, Dag T.; Mahmoodi, Hamid

    In this paper several low power full adder topologies are presented. The main idea of these circuits is based on the sense energy recovery full adder (SERF) design and the GDI (gate diffusion input) technique. These subthreshold circuits are employed for ultra low power applications. While...

  6. Education, Wechler's Full Scale IQ and "g."

    Science.gov (United States)

    Colom, Roberto; Abad, Francisco J.; Garcia, Luis F.; Juan-Espinosa, Manuel

    2002-01-01

    Investigated whether average Full Scale IQ (FSIQ) differences can be attributed to "g" using the Spanish standardization sample of the Wechsler Adult Intelligence Scale III (WAIS III) (n=703 females and 666 men). Results support the conclusion that WAIS III FSIQ does not directly or exclusively measure "g" across the full range…

  7. Why Online Education Will Attain Full Scale

    Science.gov (United States)

    Sener, John

    2010-01-01

    Online higher education has attained scale and is poised to take the next step in its growth. Although significant obstacles to a full scale adoption of online education remain, we will see full scale adoption of online higher education within the next five to ten years. Practically all higher education students will experience online education in…

  8. About Reformulation in Full-Text IRS.

    Science.gov (United States)

    Debili, Fathi; And Others

    1989-01-01

    Analyzes different kinds of reformulations used in information retrieval systems where full text databases are accessed through natural language queries. Tests of these reformulations on large full text databases managed by the Syntactic and Probabilistic Indexing and Retrieval of Information in Texts (SPIRIT) system are described, and an expert…

  9. Adulthood and mental illness in full inclusion

    Directory of Open Access Journals (Sweden)

    Claus Dieter Stobäus

    2012-08-01

    Full Text Available The article reweaves the information included in Bins’ Master Dissertation discussions with his guide Stobäus and with Mosquera, centered in interfaces between Special Education and Full Inclusion, more in direction of the constitution of adult with mental deficiency and the relationship with learning, at the modality of teaching at Adolescent and Adult Education.

  10. Full averaging of fuzzy impulsive differential inclusions

    Directory of Open Access Journals (Sweden)

    Natalia V. Skripnik

    2010-09-01

    Full Text Available In this paper the substantiation of the method of full averaging for fuzzy impulsive differential inclusions is studied. We extend the similar results for impulsive differential inclusions with Hukuhara derivative (Skripnik, 2007, for fuzzy impulsive differential equations (Plotnikov and Skripnik, 2009, and for fuzzy differential inclusions (Skripnik, 2009.

  11. Genome-wide expression profiling of five mouse models identifies similarities and differences with human psoriasis.

    Directory of Open Access Journals (Sweden)

    William R Swindell

    Full Text Available Development of a suitable mouse model would facilitate the investigation of pathomechanisms underlying human psoriasis and would also assist in development of therapeutic treatments. However, while many psoriasis mouse models have been proposed, no single model recapitulates all features of the human disease, and standardized validation criteria for psoriasis mouse models have not been widely applied. In this study, whole-genome transcriptional profiling is used to compare gene expression patterns manifested by human psoriatic skin lesions with those that occur in five psoriasis mouse models (K5-Tie2, imiquimod, K14-AREG, K5-Stat3C and K5-TGFbeta1. While the cutaneous gene expression profiles associated with each mouse phenotype exhibited statistically significant similarity to the expression profile of psoriasis in humans, each model displayed distinctive sets of similarities and differences in comparison to human psoriasis. For all five models, correspondence to the human disease was strong with respect to genes involved in epidermal development and keratinization. Immune and inflammation-associated gene expression, in contrast, was more variable between models as compared to the human disease. These findings support the value of all five models as research tools, each with identifiable areas of convergence to and divergence from the human disease. Additionally, the approach used in this paper provides an objective and quantitative method for evaluation of proposed mouse models of psoriasis, which can be strategically applied in future studies to score strengths of mouse phenotypes relative to specific aspects of human psoriasis.

  12. Jumping Stand Apparatus Reveals Rapidly Specific Age-Related Cognitive Impairments in Mouse Lemur Primates.

    Directory of Open Access Journals (Sweden)

    Jean-Luc Picq

    Full Text Available The mouse lemur (Microcebus murinus is a promising primate model for investigating normal and pathological cerebral aging. The locomotor behavior of this arboreal primate is characterized by jumps to and from trunks and branches. Many reports indicate insufficient adaptation of the mouse lemur to experimental devices used to evaluate its cognition, which is an impediment to the efficient use of this animal in research. In order to develop cognitive testing methods appropriate to the behavioral and biological traits of this species, we adapted the Lashley jumping stand apparatus, initially designed for rats, to the mouse lemur. We used this jumping stand apparatus to compare performances of young (n = 12 and aged (n = 8 adults in acquisition and long-term retention of visual discriminations. All mouse lemurs completed the tasks and only 25 trials, on average, were needed to master the first discrimination problem with no age-related differences. A month later, all mouse lemurs made progress for acquiring the second discrimination problem but only the young group reached immediately the criterion in the retention test of the first discrimination problem. This study shows that the jumping stand apparatus allows rapid and efficient evaluation of cognition in mouse lemurs and demonstrates that about half of the old mouse lemurs display a specific deficit in long-term retention but not in acquisition of visual discrimination.

  13. SPC-Cre-ERT2 transgenic mouse for temporal gene deletion in alveolar epithelial cells.

    Directory of Open Access Journals (Sweden)

    Yao-Song Gui

    Full Text Available Although several Cre-loxP-based gene knockout mouse models have been generated for the study of gene function in alveolar epithelia in the lung, their applications are still limited. In this study, we developed a SPC-Cre-ER(T2 mouse model, in which a tamoxifen-inducible Cre recombinase (Cre-ER(T2 is under the control of the human surfactant protein C (SPC promoter. The specificity and efficiency of Cre-ER(T2 activity was first evaluated by crossing SPC-Cre-ER(T2 mouse with ROSA26R mouse, a β-galactosidase reporter strain. We found that Cre-ER(T2 was expressed in 30.7% type II alveolar epithelial cells of SPC-Cre-ER(T2/ROSA26R mouse lung tissues in the presence of tamoxifen. We then tested the tamoxifen-inducible recombinase activity of Cre-ER(T2 in a mouse strain bearing TSC1 conditional knockout alleles (TSC1(fx/fx. TSC1 deletion was detected in the lungs of tamoxifen treated SPC-Cre-ER(T2/TSC1(fx/fx mice. Therefore this SPC-Cre-ER(T2 mouse model may be a valuable tool to investigate functions of genes in lung development, physiology and disease.

  14. Mouse allergen, lung function, and atopy in Puerto Rican children.

    Directory of Open Access Journals (Sweden)

    Erick Forno

    Full Text Available To examine the relation between mouse allergen exposure and asthma in Puerto Rican children.Mus m 1, Der p 1, Bla g 2, and Fel d 1 allergens were measured in dust samples from homes of Puerto Rican children with (cases and without (controls asthma in Hartford, CT (n = 449 and San Juan (SJ, Puerto Rico (n = 678. Linear or logistic regression was used for the multivariate analysis of mouse allergen (Mus m 1 and lung function (FEV(1 and FEV(1/FVC and allergy (total IgE and skin test reactivity (STR to ≥1 allergen measures.Homes in SJ had lower mouse allergen levels than those in Hartford. In multivariate analyses, mouse allergen was associated with higher FEV(1 in cases in Hartford (+70.6 ml, 95% confidence interval (CI = 8.6-132.7 ml, P = 0.03 and SJ (+45.1 ml, 95% CI =  -0.5 to 90.6 ml, P = 0.05. In multivariate analyses of controls, mouse allergen was inversely associated with STR to ≥1 allergen in non-sensitized children (odds ratio [OR] for each log-unit increment in Mus m 1 = 0.7, 95% CI = 0.5-0.9, P<0.01. In a multivariate analysis including all children at both study sites, each log-increment in mouse allergen was positively associated with FEV(1 (+28.3 ml, 95% CI = 1.4-55.2 ml, P = 0.04 and inversely associated with STR to ≥1 allergen (OR for each log-unit increment in Mus m 1 = 0.8, 95% CI = 0.6-0.9, P<0.01.Mouse allergen is associated with a higher FEV(1 and lower odds of STR to ≥1 allergen in Puerto Rican children. This may be explained by the allergen itself or correlated microbial exposures.

  15. Mouse models of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Marta Herreros-Villanueva; Elizabeth Hijona; Angel Cosme; Luis Bujanda

    2012-01-01

    Pancreatic cancer is one of the most lethal of human malignancies ranking 4th among cancer-related death in the western world and in the United States,and potent therapeutic options are lacking.Although during the last few years there have been important advances in the understanding of the molecular events responsible for the development of pancreatic cancer,currently specific mechanisms of treatment resistance remain poorly understood and new effective systemic drugs need to be developed and probed.In vivo models to study pancreatic cancer and approach this issue remain limited and present different molecular features that must be considered in the studies depending on the purpose to fit special research themes.In the last few years,several genetically engineered mouse models of pancreatic exocrine neoplasia have been developed.These models mimic the disease as they reproduce genetic alterations implicated in the progression of pancreatic cancer.Genetic alterations such as activating mutations in KRas,or TGFb and/or inactivation of tumoral suppressors such as p53,INK4A/ARF BRCA2 and Smad4 are the most common drivers to pancreatic carcinogenesis and have been used to create transgenic mice.These mouse models have a spectrum of pathologic changes,from pancreatic intraepithelial neoplasia to lesions that progress histologically culminating in fully invasive and metastatic disease and represent the most useful preclinical model system.These models can characterize the cellular and molecular pathology of pancreatic neoplasia and cancer and constitute the best tool to investigate new therapeutic approaches,chemopreventive and/or anticancer treatments.Here,we review and update the current mouse models that reproduce different stages of human pancreatic ductal adenocarcinoma and will have clinical relevance in future pancreatic cancer developments.

  16. Production and Purification of a Polyclonal Antibody Against Purified Mouse IgG2b in Rabbits Towards Designing Mouse Monoclonal Isotyping Kits

    Directory of Open Access Journals (Sweden)

    Sadeq Eivazi

    2015-03-01

    Full Text Available Purpose: Mouse IgG subclasses containing IgG1, IgG2a, IgG2b and IgG3 have been defined and described both physiochemically and immunologically. Methods: Sepharose beads conjugated with protein A affinity chromatography was used for purification of mouse IgG2b. Sodium citrate buffer (0.1 M, pH: 3.5 was used for separation of mouse IgG2b. Verification of the purified fractions was monitored by SDS-PAGE (polyacrylamide gel electrophoresis in reducing condition. Immunized rabbit serum was collected and precipitated at the final concentration of 50% ammonium sulfate. After dialysis against tris-phosphate buffer (pH: 8.1 ion exchange chromatography column was used for purification of rabbit anti-mouse IgG2b. The periodate method was performed for conjugation with some variations. After conjugation, direct ELISA was used to determine the titer of HRP conjugated rabbit IgG against mouse IgG2b. Results: The titer of rabbit anti-mouse IgG2b that determined by ELISA was 32000. The purity of rabbit anti-mouse IgG2b was about 95%. The optimum dilution of prepared HRP conjugated IgG was 1:10000. This study showed that ion-exchange chromatography and affinity chromatography could be appropriate techniques for purification of mouse IgG and IgG subclasses respectively. Conclusion: This study showed that affinity chromatography could be an appropriate method for purification of IgG2b antibodies.

  17. Therapeutic cloning in the mouse

    Science.gov (United States)

    Mombaerts, Peter

    2003-01-01

    Nuclear transfer technology can be applied to produce autologous differentiated cells for therapeutic purposes, a concept termed therapeutic cloning. Countless articles have been published on the ethics and politics of human therapeutic cloning, reflecting the high expectations from this new opportunity for rejuvenation of the aging or diseased body. Yet the research literature on therapeutic cloning, strictly speaking, is comprised of only four articles, all in the mouse. The efficiency of derivation of embryonic stem cell lines via nuclear transfer is remarkably consistent among these reports. However, the efficiency is so low that, in its present form, the concept is unlikely to become widespread in clinical practice. PMID:12949262

  18. Preclinical Mouse Models of Neurofibromatosis

    Science.gov (United States)

    2007-10-01

    arachnoidal cells is rate-limiting for meningioma development in the mouse. Genes & Development, 2002, 16:1060-1065. Kissil JL, Johnson KC, Eckman MS and...doubly mutant Nf1 and Wv hematopoietic cells. Blood 2003; 101: 1984-1986. Shannon, K.M. 35 Kissil JL, Wilker EW, Johnson KC, Eckman MS, Yaffe M, and... Paul E. McKeever, Shannon, K.M. 38 Megan Lim, Simon J. Conway, Luis F. Parada, Yuan Zhu, and Sean J. Morrison. 2007. The loss of Nf1 transiently

  19. Can mouse imaging studies bring order to autism connectivity chaos?

    Directory of Open Access Journals (Sweden)

    Adam Liska

    2016-11-01

    Full Text Available Functional Magnetic Resonance Imaging (fMRI has consistently highlighted impaired or aberrant functional connectivity across brain regions of autism spectrum disorder (ASD patients. However, the manifestation and neural substrates of these alterations are highly heterogeneous and often conflicting. Moreover, their neurobiological underpinnings and etiopathological significance remain largely unknown. A deeper understanding of the complex pathophysiological cascade leading to aberrant connectivity in ASD can greatly benefit from the use of model organisms where individual pathophysiological or phenotypic components of ASD can be recreated and investigated via approaches that are either off limits or confounded by clinical heterogeneity. Despite some obvious limitations in reliably modelling the full phenotypic spectrum of a complex developmental disorder like ASD, mouse models have played a central role in advancing our basic mechanistic and molecular understanding of this syndrome. Recent progress in mouse brain connectivity mapping via resting-state fMRI (rsfMRI offers the opportunity to generate and test mechanistic hypotheses about the elusive origin and significance of connectional aberrations observed in autism. Here we discuss recent progress towards this goal, and illustrate initial examples of how the approach can be employed to establish causal links between ASD-related mutations, developmental processes, and brain connectional architecture. As the spectrum of genetic and pathophysiological components of ASD modelled in the mouse is rapidly expanding, the use of rsfMRI can advance our mechanistic understanding of the origin and significance of the connectional alterations associated with autism, and their heterogeneous expression across patient cohorts.

  20. Compact muon solenoid magnet reaches full field

    CERN Multimedia

    2006-01-01

    Scientist of the U.S. Department of Energy in Fermilab and collaborators of the US/CMS project announced that the world's largest superconducting solenoid magnet has reached full field in tests at CERN. (1 apge)

  1. QXT-full Automatic Saccharify Instrument

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    QXT is a full automatic saccharify instrument of eight holes . The instrument use process control technology of micro-computer. It can realize automatic of saccharify full process correctly. Due to adapt control mode of high precision expert PID and digit automatic calibration technology of fill micro computer, not only ensure precision of linear raising temperature region (1 ℃ /min) and constant temperature region (temperature error ±0.2 ℃), but also overcome the disturbance

  2. Is Full Employment Possible Under Globalization? (revised)

    OpenAIRE

    Robert Pollin

    2008-01-01

    To honor the life work of Professor Sumner Rosen, this lecture examines approaches to promoting full employment at decent jobs within our contemporary era of globalization. The lecture briefly summarizes the theories of unemployment of Marx, Friedman, Keynes and Kalecki. It then addresses the meaning of full employment within the alternative theories and under different historical and country settings. It next considers the issue of the inflation/unemployment trade-off, and the Meidner-Rehn S...

  3. Drug overdose and the full moon.

    Science.gov (United States)

    Sharfman, M

    1980-02-01

    This study assessed the relationship between the phase of the full moon and the incidence of overdose as reported in five metropolitan Phoenix hospitals and the Maricopa County Medical Examiner over the 15-mo. period from January 1, 1976, through and including March 31, 1977. A chi-squared analysis was performed and no significant difference between the distribution of cases occurring during the full moon phase and that outside of these periods was found.

  4. Full Spectrum Crashworthiness Criteria for Rotorcraft

    Science.gov (United States)

    2011-12-01

    C0-C1). The maximum Nij Full Spectrum Crashworthiness Criteria October 2011 Page 97 as measured at the cervical vertebrae (C7-T1) is 1.5 (Table...regions including the head, neck, cervical spine, upper extremities, thorax, abdomen, thoracic lumbar spine, lower extremities, and general. The body...injury mechanisms, such as fractured vertebra , ruptured spleen, or lower leg fracture are not included. Full Spectrum Crashworthiness Criteria

  5. Practical, real-time, full duplex wireless

    KAUST Repository

    Jain, Mayank

    2011-01-01

    This paper presents a full duplex radio design using signal inversion and adaptive cancellation. Signal inversion uses a simple design based on a balanced/unbalanced (Balun) transformer. This new design, unlike prior work, supports wideband and high power systems. In theory, this new design has no limitation on bandwidth or power. In practice, we find that the signal inversion technique alone can cancel at least 45dB across a 40MHz bandwidth. Further, combining signal inversion cancellation with cancellation in the digital domain can reduce self-interference by up to 73dB for a 10MHz OFDM signal. This paper also presents a full duplex medium access control (MAC) design and evaluates it using a testbed of 5 prototype full duplex nodes. Full duplex reduces packet losses due to hidden terminals by up to 88%. Full duplex also mitigates unfair channel allocation in AP-based networks, increasing fairness from 0.85 to 0.98 while improving downlink throughput by 110% and uplink throughput by 15%. These experimental results show that a re- design of the wireless network stack to exploit full duplex capability can result in significant improvements in network performance. © 2011 ACM.

  6. Generation of an Oocyte-Specific Cas9 Transgenic Mouse for Genome Editing.

    Directory of Open Access Journals (Sweden)

    Linlin Zhang

    Full Text Available The CRISPR/Cas9 system has been developed as an easy-handle and multiplexable approach for engineering eukaryotic genomes by zygote microinjection of Cas9 and sgRNA, while preparing Cas9 for microinjection is laborious and introducing inconsistency into the experiment. Here, we describe a modified strategy for gene targeting through using oocyte-specific Cas9 transgenic mouse. With this mouse line, we successfully achieve precise gene targeting by injection of sgRNAs only into one-cell-stage embryos. Through comprehensive analysis, we also show allele complexity and off-target mutagenesis induced by this strategy is obviously lower than Cas9 mRNA/sgRNA injection. Thus, injection of sgRNAs into oocyte-specific Cas9 transgenic mouse embryo provides a convenient, efficient and reliable approach for mouse genome editing.

  7. Fast and Reliable Mouse Picking Using Graphics Hardware

    Directory of Open Access Journals (Sweden)

    Hanli Zhao

    2009-01-01

    Full Text Available Mouse picking is the most commonly used intuitive operation to interact with 3D scenes in a variety of 3D graphics applications. High performance for such operation is necessary in order to provide users with fast responses. This paper proposes a fast and reliable mouse picking algorithm using graphics hardware for 3D triangular scenes. Our approach uses a multi-layer rendering algorithm to perform the picking operation in linear time complexity. The objectspace based ray-triangle intersection test is implemented in a highly parallelized geometry shader. After applying the hardware-supported occlusion queries, only a small number of objects (or sub-objects are rendered in subsequent layers, which accelerates the picking efficiency. Experimental results demonstrate the high performance of our novel approach. Due to its simplicity, our algorithm can be easily integrated into existing real-time rendering systems.

  8. Computerized assessment of social approach behavior in mouse

    Directory of Open Access Journals (Sweden)

    Damon T Page

    2009-11-01

    Full Text Available Altered sociability is a core feature of a variety of human neurological disorders, including autism. Social behaviors may be tested in animal models, such as mice, to study the biological bases of sociability and how this is altered in neurodevelopmental disorders. An easily quantifiable social behavior frequently used to assess sociability in the mouse is the tendency to approach and interact with an unfamiliar mouse. Here we present a novel computer-assisted method for scoring social approach behavior in mice using a three-chambered apparatus. We find consistent results between data scored using the computer assisted method and a human observer, making computerized assessment a reliable, low cost, high-throughput method for testing sociability.

  9. Flexible Piezoelectric Energy Harvesting from Mouse Click Motions

    Directory of Open Access Journals (Sweden)

    Youngsu Cha

    2016-07-01

    Full Text Available In this paper, we study energy harvesting from the mouse click motions of a robot finger and a human index finger using a piezoelectric material. The feasibility of energy harvesting from mouse click motions is experimentally and theoretically assessed. The fingers wear a glove with a pocket for including the piezoelectric material. We model the energy harvesting system through the inverse kinematic framework of parallel joints in a finger and the electromechanical coupling equations of the piezoelectric material. The model is validated through energy harvesting experiments in the robot and human fingers with the systematically varying load resistance. We find that energy harvesting is maximized at the matched load resistance to the impedance of the piezoelectric material, and the harvested energy level is tens of nJ.

  10. Current Concepts: Mouse Models of Sjögren's Syndrome

    Directory of Open Access Journals (Sweden)

    Tegan N. Lavoie

    2011-01-01

    Full Text Available Sjögren's syndrome (SjS is a complex chronic autoimmune disease of unknown etiology which primarily targets the exocrine glands, resulting in eventual loss of secretory function. The disease can present as either primary SjS or secondary SjS, the latter of which occurs concomitantly with another autoimmune disease such as rheumatoid arthritis, systemic lupus erythematosus, scleroderma, or primary biliary cirrhosis. Current advancements in therapeutic prevention and treatment for SjS are impeded by lack of understanding in the pathophysiological and clinical progression of the disease. Development of appropriate mouse models for both primary and secondary SjS is needed in order to advance knowledge of this disease. This paper details important features, advantages, and pitfalls of current animal models of SjS, including spontaneous, transgenic, knockout, immunization, and transplantation chimera mouse models, and emphasizes the need for a better model in representing the human SjS phenotype.

  11. Vascular development and hemodynamic force in the mouse yolk sac

    Directory of Open Access Journals (Sweden)

    Monica D Garcia

    2014-08-01

    Full Text Available Vascular remodeling of the mouse embryonic yolk sac is a highly dynamic process dependent on multiple genetic signaling pathways as well as biomechanical factors regulating proliferation, differentiation, migration, cell-cell and cell-matrix interactions. During this early developmental window, the initial primitive vascular network of the yolk sac undergoes a dynamic remodeling process concurrent with the onset of blood flow, in which endothelial cells establish a branched, hierarchical structure of large vessels and smaller capillary beds. In this review, we will describe the molecular and biomechanical regulators which guide vascular remodeling in the mouse embryonic yolk sac, as well as live imaging methods for characterizing endothelial cell and hemodynamic function in cultured embryos.

  12. Isotropic Optical Mouse Placement for Mobile Robot Velocity Estimation

    Directory of Open Access Journals (Sweden)

    Sungbok Kim

    2014-06-01

    Full Text Available This paper presents the isotropic placement of multiple optical mice for the velocity estimation of a mobile robot. It is assumed that there can be positional restriction on the installation of optical mice at the bottom of a mobile robot. First, the velocity kinematics of a mobile robot with an array of optical mice is obtained and the resulting Jacobian matrix is analysed symbolically. Second, the isotropic, anisotropic and singular optical mouse placements are identified, along with the corresponding characteristic lengths. Third, the least squares mobile robot velocity estimation from the noisy optical mouse velocity measurements is discussed. Finally, simulation results for several different placements of three optical mice are given.

  13. Genetic Mouse Models of Huntington's Disease: Focus on Electrophysiological Mechanisms

    Directory of Open Access Journals (Sweden)

    Carlos Cepeda

    2010-03-01

    Full Text Available The discovery of the HD (Huntington's disease gene in 1993 led to the creation of genetic mouse models of the disease and opened the doors for mechanistic studies. In particular, the early changes and progression of the disease could be followed and examined systematically. The present review focuses on the contribution of these genetic mouse models to the understanding of functional changes in neurons as the HD phenotype progresses, and concentrates on two brain areas: the striatum, the site of most conspicuous pathology in HD, and the cortex, a site that is becoming increasingly important in understanding the widespread behavioural abnormalities. Mounting evidence points to synaptic abnormalities in communication between the cortex and striatum and cell-cell interactions as major determinants of HD symptoms, even in the absence of severe neuronal degeneration and death.

  14. Transgenic mouse - Methods and protocols, 2nd edition

    Directory of Open Access Journals (Sweden)

    Carlo Alberto Redi

    2011-09-01

    Full Text Available Marten H. Hofner (from the Dept. of Pathology of the Groningen University and Jan M. van Deursen (from the Mayo College of Medicine at Rochester, MN, USA provided us with the valuable second edition of Transgenic mouse: in fact, eventhough we are in the –omics era and already equipped with the state-of-the-art techniques in whatsoever field, still we need to have gene(s functional analysis data to understand common and complex deseases. Transgenesis is still an irreplaceable method and protocols to well perform it are more than welcome. Here, how to get genetic modified mice (the quintessential model of so many human deseases considering how much of the human genes are conserved in the mouse and the great block of genic synteny existing between the two genomes is analysed in deep and presented in clearly detailed step by step protocols....

  15. Dissecting Alzheimer disease in Down syndrome using mouse models

    Directory of Open Access Journals (Sweden)

    Xun Yu eChoong

    2015-10-01

    Full Text Available Down syndrome (DS is a common genetic condition caused by the presence of three copies of chromosome 21 (trisomy 21. This greatly increases the risk for Alzheimer disease (AD, but although virtually all people with DS have AD neuropathology by 40 years of age, not all develop dementia. To dissect the genetic contribution of trisomy 21 to DS phenotypes including those relevant to AD, a range of DS mouse models has been generated which are trisomic for chromosome segments syntenic to human chromosome 21. Here, we consider key characteristics of human AD in DS (AD-DS, and our current state of knowledge on related phenotypes in AD and DS mouse models. We go on to review important features needed in future models of AD-DS, to understand this type of dementia and so highlight pathogenic mechanisms relevant to all populations at risk of AD.

  16. Mouse models of ciliopathies: the state of the art

    Directory of Open Access Journals (Sweden)

    Dominic P. Norris

    2012-05-01

    Full Text Available The ciliopathies are an apparently disparate group of human diseases that all result from defects in the formation and/or function of cilia. They include disorders such as Meckel-Grüber syndrome (MKS, Joubert syndrome (JBTS, Bardet-Biedl syndrome (BBS and Alström syndrome (ALS. Reflecting the manifold requirements for cilia in signalling, sensation and motility, different ciliopathies exhibit common elements. The mouse has been used widely as a model organism for the study of ciliopathies. Although many mutant alleles have proved lethal, continued investigations have led to the development of better models. Here, we review current mouse models of a core set of ciliopathies, their utility and future prospects.

  17. Mapping of the Mouse Actin Capping Protein Beta Subunit Gene

    Directory of Open Access Journals (Sweden)

    Cooper John A

    2000-07-01

    Full Text Available Abstract Background Capping protein (CP, a heterodimer of α and β subunits, is found in all eukaryotes. CP binds to the barbed ends of actin filaments in vitro and controls actin assembly and cell motility in vivo. Vertebrates have three isoforms of CPβ produced by alternatively splicing from one gene; lower organisms have one gene and one isoform. Results We isolated genomic clones corresponding to the β subunit of mouse CP and identified its chromosomal location by interspecies backcross mapping. Conclusions The CPβ gene (Cappb1 mapped to Chromosome 4 between Cdc42 and D4Mit312. Three mouse mutations, snubnose, curly tail, and cribriform degeneration, map in the vicinity of the β gene.

  18. Zicam-induced damage to mouse and human nasal tissue.

    Directory of Open Access Journals (Sweden)

    Jae H Lim

    Full Text Available Intranasal medications are used to treat various nasal disorders. However, their effects on olfaction remain unknown. Zicam (zinc gluconate; Matrixx Initiatives, Inc, a homeopathic substance marketed to alleviate cold symptoms, has been implicated in olfactory dysfunction. Here, we investigated Zicam and several common intranasal agents for their effects on olfactory function. Zicam was the only substance that showed significant cytotoxicity in both mouse and human nasal tissue. Specifically, Zicam-treated mice had disrupted sensitivity of olfactory sensory neurons to odorant stimulation and were unable to detect novel odorants in behavioral testing. These findings were long-term as no recovery of function was observed after two months. Finally, human nasal explants treated with Zicam displayed significantly elevated extracellular lactate dehydrogenase levels compared to saline-treated controls, suggesting severe necrosis that was confirmed on histology. Our results demonstrate that Zicam use could irreversibly damage mouse and human nasal tissue and may lead to significant smell dysfunction.

  19. Transcriptomic profiling of trichloroethylene exposure in male mouse liver

    Directory of Open Access Journals (Sweden)

    Yan Jiang

    2015-03-01

    Full Text Available Chronic Trichloroethylene (TCE exposure could induce hepatocellular carcinoma in mice, and occupational exposure in humans was suggested to be associated with liver cancer. To understand the role of non-genotoxic mechanism(s for TCE action, we examined the gene expression and DNA methylation changes in the liver of B6C3F1 mice orally administered with TCE for 5 days. As a beginning step, we profiled gene expression alterations induced by the TCE in mouse livers. Here we describe in detail the experimental methods, quality controls, and other information associated with our data deposited into Gene Expression Omnibus (GEO under GSE58819. Our data provide useful information for gene expression responses to TCE in mouse liver.

  20. Mouse models of myeloproliferative neoplasms: JAK of all grades

    Directory of Open Access Journals (Sweden)

    Juan Li

    2011-05-01

    Full Text Available In 2005, several groups identified a single gain-of-function point mutation in the JAK2 kinase that was present in the majority of patients with myeloproliferative neoplasms (MPNs. Since this discovery, much effort has been dedicated to understanding the molecular consequences of the JAK2V617F mutation in the haematopoietic system. Three waves of mouse models have been produced recently (bone marrow transplantation, transgenic and targeted knock-in, which have facilitated the understanding of the molecular pathogenesis of JAK2V617F-positive MPNs, providing potential platforms for designing and validating novel therapies in humans. This Commentary briefly summarises the first two types of mouse models and then focuses on the more recently generated knock-in models.

  1. Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human.

    Directory of Open Access Journals (Sweden)

    Maryam Rakhshandehroo

    Full Text Available BACKGROUND: Studies in mice have shown that PPARalpha is an important regulator of hepatic lipid metabolism and the acute phase response. However, little information is available on the role of PPARalpha in human liver. Here we set out to compare the function of PPARalpha in mouse and human hepatocytes via analysis of target gene regulation. METHODOLOGY/PRINCIPAL FINDINGS: Primary hepatocytes from 6 human and 6 mouse donors were treated with PPARalpha agonist Wy14643 and gene expression profiling was performed using Affymetrix GeneChips followed by a systems biology analysis. Baseline PPARalpha expression was similar in human and mouse hepatocytes. Depending on species and time of exposure, Wy14643 significantly induced the expression of 362-672 genes. Surprisingly minor overlap was observed between the Wy14643-regulated genes from mouse and human, although more substantial overlap was observed at the pathway level. Xenobiotics metabolism and apolipoprotein synthesis were specifically regulated by PPARalpha in human hepatocytes, whereas glycolysis-gluconeogenesis was regulated specifically in mouse hepatocytes. Most of the genes commonly regulated in mouse and human were involved in lipid metabolism and many represented known PPARalpha targets, including CPT1A, HMGCS2, FABP1, ACSL1, and ADFP. Several genes were identified that were specifically induced by PPARalpha in human (MBL2, ALAS1, CYP1A1, TSKU or mouse (Fbp2, lgals4, Cd36, Ucp2, Pxmp4. Furthermore, several putative novel PPARalpha targets were identified that were commonly regulated in both species, including CREB3L3, KLF10, KLF11 and MAP3K8. CONCLUSIONS/SIGNIFICANCE: Our results suggest that PPARalpha activation has a major impact on gene regulation in human hepatocytes. Importantly, the role of PPARalpha as master regulator of hepatic lipid metabolism is generally well-conserved between mouse and human. Overall, however, PPARalpha regulates a mostly divergent set of genes in mouse and

  2. Comparative stereology of mouse atria.

    Science.gov (United States)

    Bossen, E H; Sommer, J R; Waugh, R A

    1981-01-01

    The left and right atria of the mouse were compared to each other and to the mouse left ventricle using stereologic techniques. The volume fraction (Vv) and surface area per unit cell volume (Sv) of the interior junctional sarcoplasmic reticulum (IJSR), total JSR and extended JSR were greater in the left atrium than in right. The Vv and Sv of the free SR, transverse tubules, and mitochondria were similar in the two atria. It is suggested that the differences in junctional sarcoplasmic reticulum between the atria can be accounted for by a difference in distribution of two types of cells whose anatomy is analogous to working and conducting fibers in the ventricle. The Sv and Vv of the transverse tubules, mitochondria, and all the components of the sarcoplasmic reticulum except for the free SR were greater in the left ventricle than in either atrium. The greater calcium content and sensitivity to extracellular calcium of the atria may explain the greater volume of free SR in the atria as compared to the left ventricle. The Sv of the plasmalemma of the atria and of the Sv of the plasmalemma of the transverse tubules of the left ventricles supports the suggestion of others that there is a constant ratio of surface area to cell volume in cardiac cells.

  3. Take care of your mouse!

    CERN Multimedia

    IT Department

    2011-01-01

    “Stop --- Think --- Click" is the basic recommendation for securely browsing the Internet and for securely reading e-mails. Users who have followed this recommendation in the past were less likely to have their computer infected or their computing account compromised. We would like to thank all those who donated their mouse to the CERN Animal Shelter for Computer Mice (http://cern.ch/c-a-s). For those who still use a mouse, please stay vigilant and  alert: do not click on links whose origin you do not trust or which look like gibberish. Do not install untrusted software or plug-ins, since software from untrusted sources may infect or compromise your computer, or violate copyrights. Finally, take particular care with e-mails: Do not open unexpected or suspicious e-mails or attachments. Delete them if they do not concern you or if they appear strange. If in doubt, or if you have questions, please do not hesitate to contact Computer.Security@cern.ch

  4. Replication of a hepatitis C virus replicon clone in mouse cells

    Directory of Open Access Journals (Sweden)

    Chisari Francis V

    2006-10-01

    Full Text Available Abstract Background Hepatitis C Virus (HCV is a significant public health burden and small animal models are needed to study the pathology and immunobiology of the virus. In effort to develop experimental HCV mouse models, we screened a panel of HCV replicons to identify clones capable of replicating in mouse hepatocytes. Results We report the establishment of stable HCV replication in mouse hepatocyte and fibroblast cell lines using replicons derived from the JFH-1 genotype 2a consensus sequence. Viral RNA replication efficiency in mouse cells was comparable to that observed in human Huh-7 replicon cells, with negative-strand HCV RNA and the viral NS5A protein being readily detected by Northern and Western Blot analysis, respectively. Although HCV replication was established in the absence of adaptive mutations that might otherwise compromise the in vitro infectivity of the JFH-1 clone, no infectious virus was detected when the culture medium from full length HCV RNA replicating mouse cells was titrated on Huh-7 cells, suggesting that the mouse cells were unable to support production of infectious progeny viral particles. Consistent with an additional block in viral entry, infectious JFH-1 particles produced in Huh-7 cells were not able to establish detectable HCV RNA replication in naïve mouse cells. Conclusion Thus, this report expands the repertoire of HCV replication systems and possibly represents a step toward developing mouse models of HCV replication, but it also highlights that other species restrictions might continue to make the development of a purely murine HCV infectious model challenging.

  5. Full Boltzmann equations for leptogenesis including scattering

    CERN Document Server

    Hahn-Woernle, F; Wong, Y Y Y

    2009-01-01

    We study the evolution of a cosmological baryon asymmetry produced via leptogenesis by means of the full classical Boltzmann equations, without the assumption of kinetic equilibrium and including all quantum statistical factors. Beginning with the full mode equations we derive the usual equations of motion for the right-handed neutrino number density and integrated lepton asymmetry, and show explicitly the impact of each assumption on these quantities. For the first time, we investigate also the effects of scattering of the right-handed neutrino with the top quark to leading order in the Yukawa couplings by means of the full Boltzmann equations. We find that in our full Boltzmann treatment the final lepton asymmetry can be suppressed by as much as a factor of 1.5 in the weak wash-out regime (K1), the full Boltzmann treatment and the integrated approach give nearly identical final lepton asymmetries (within 10 % of each other at K>3). Finally, we show that the opposing effects of quantum statistics on decays/i...

  6. Full profile incoherent scatter analysis at Jicamarca

    Directory of Open Access Journals (Sweden)

    D. L. Hysell

    2008-02-01

    Full Text Available Incoherent scatter data from a hybrid long-pulse/double-pulse experiment at Jicamarca are analyzed using a full-profile analysis similar to the one implemented by Holt et al. (1992. In this case, plasma density, electron and ion temperatures, and light ion composition profiles in the topside are estimated simultaneously. Full-profile analysis is crucial at Jicamarca, since the long correlation time of the incoherent scatter signal at 50 MHz invalidates conventional gated analysis. Results for a 24 h interval in April of 2006 are presented, covering altitudes through 1600 km with 10 min time resolution, and compared with results from the NRL ionospheric model SAMI2. The analysis provides the first comprehensive assessment of ionospheric conditions over Jicamarca at sunrise as well as the first 24-h record of helium ion layers. Possible refinements to the experiment and the algorithm are discussed.

  7. Full quivers of representations of algebras

    CERN Document Server

    Belov-Kanel, Alexei; Vishne, Uzi

    2011-01-01

    We introduce the notion of the full quiver of a representation of an algebra, which is a cover of the (classical) quiver, but which captures properties of the representation itself. Gluing of vertices and of arrows enables one to study subtle combinatorial aspects of algebras which are lost in the classical quiver. Full quivers of representations apply especially well to \\Zcd\\ algebras, which have properties very like those of finite dimensional algebras over fields. By choosing the representation appropriately, one can restrict the gluing to two main types: {\\it Frobenius} (along the diagonal) and, more generally {\\it proportional} Frobenius gluing (above the diagonal), and our main result is that any representable algebra has a faithful representation described completely by such a full quiver. Further reductions are considered, which bear on the polynomial identities.

  8. A physical map of the mouse genome

    NARCIS (Netherlands)

    Gregory, SG; Sekhon, M; Schein, J; Zhao, SY; Osoegawa, K; Scott, CE; Evans, RS; Burridge, PW; Cox, TV; Fox, CA; Hutton, RD; Mullenger, IR; Phillips, KJ; Smith, J; Stalker, J; Threadgold, GJ; Birney, E; Wylie, K; Chinwalla, A; Wallis, J; Hillier, L; Carter, J; Gaige, T; Jaeger, S; Kremitzki, C; Layman, D; McGrane, R; Mead, K; Walker, R; Jones, S; Smith, M; Asano, J; Bosdet, I; Chan, S; Chittaranjan, S; Chiu, R; Fjell, C; Fuhrmann, D; Girn, N; Gray, C; Guin, R; Hsiao, L; Krzywinski, M; Kutsche, R; Lee, SS; Mathewson, C; McLeavy, C; Messervier, S; Ness, S; Pandoh, P; Prabhu, AL; Saeedi, P; Smailus, D; Spence, L; Stott, J; Taylor, S; Terpstra, W; Tsai, M; Vardy, J; Wye, N; Yang, G; Shatsman, S; Ayodeji, B; Geer, K; Tsegaye, G; Shvartsbeyn, A; Gebregeorgis, E; Krol, M; Russell, D; Overton, L; Malek, JA; Holmes, M; Heaney, M; Shetty, J; Feldblyum, T; Nierman, WC; Catanese, JJ; Hubbard, T; Waterston, RH; Rogers, J; de Jong, PJ; Fraser, CM; Marra, M; McPherson, JD; Bentley, DR

    2002-01-01

    A physical map of a genome is an essential guide for navigation, allowing the location of any gene or other landmark in the chromosomal DNA. We have constructed a physical map of the mouse genome that contains 296 contigs of overlapping bacterial clones and 16,992 unique markers. The mouse contigs w

  9. The wobbler mouse, an ALS animal model

    DEFF Research Database (Denmark)

    Moser, Jakob Maximilian; Bigini, Paolo; Schmitt-John, Thomas

    2013-01-01

    This review article is focused on the research progress made utilizing the wobbler mouse as animal model for human motor neuron diseases, especially the amyotrophic lateral sclerosis (ALS). The wobbler mouse develops progressive degeneration of upper and lower motor neurons and shows striking...

  10. A physical map of the mouse genome

    NARCIS (Netherlands)

    Gregory, SG; Sekhon, M; Schein, J; Zhao, SY; Osoegawa, K; Scott, CE; Evans, RS; Burridge, PW; Cox, TV; Fox, CA; Hutton, RD; Mullenger, IR; Phillips, KJ; Smith, J; Stalker, J; Threadgold, GJ; Birney, E; Wylie, K; Chinwalla, A; Wallis, J; Hillier, L; Carter, J; Gaige, T; Jaeger, S; Kremitzki, C; Layman, D; McGrane, R; Mead, K; Walker, R; Jones, S; Smith, M; Asano, J; Bosdet, I; Chan, S; Chittaranjan, S; Chiu, R; Fjell, C; Fuhrmann, D; Girn, N; Gray, C; Guin, R; Hsiao, L; Krzywinski, M; Kutsche, R; Lee, SS; Mathewson, C; McLeavy, C; Messervier, S; Ness, S; Pandoh, P; Prabhu, AL; Saeedi, P; Smailus, D; Spence, L; Stott, J; Taylor, S; Terpstra, W; Tsai, M; Vardy, J; Wye, N; Yang, G; Shatsman, S; Ayodeji, B; Geer, K; Tsegaye, G; Shvartsbeyn, A; Gebregeorgis, E; Krol, M; Russell, D; Overton, L; Malek, JA; Holmes, M; Heaney, M; Shetty, J; Feldblyum, T; Nierman, WC; Catanese, JJ; Hubbard, T; Waterston, RH; Rogers, J; de Jong, PJ; Fraser, CM; Marra, M; McPherson, JD; Bentley, DR

    2002-01-01

    A physical map of a genome is an essential guide for navigation, allowing the location of any gene or other landmark in the chromosomal DNA. We have constructed a physical map of the mouse genome that contains 296 contigs of overlapping bacterial clones and 16,992 unique markers. The mouse contigs w

  11. Are You a Man or a Mouse?

    DEFF Research Database (Denmark)

    Herrmann, Janne Rothmar

    2008-01-01

    Are you a man or a mouse? This expression is used to encourage someone to be brave when they are frightened of doing something. It is also an expression which bears associations to John Steinbeck's novella Of Mice and Men, the title of which is taken from Robert Burns' poem To a Mouse, which is o...

  12. A catalog of the mouse gut metagenome

    DEFF Research Database (Denmark)

    Xiao, Liang; Feng, Qiang; Liang, Suisha;

    2015-01-01

    We established a catalog of the mouse gut metagenome comprising ∼2.6 million nonredundant genes by sequencing DNA from fecal samples of 184 mice. To secure high microbiome diversity, we used mouse strains of diverse genetic backgrounds, from different providers, kept in different housing laborato...

  13. A critique of full reserve banking

    OpenAIRE

    Montagnoli, A; S Dow; Johnsen, G.

    2015-01-01

    Proposals for full reserve banking have been put forward as a radical way of preventing further financial crises. They rest on the argument that crises are caused by excessive money supply growth brought about by inadequately controlled bank credit creation. Our aim is to provide a critique of the theoretical assumptions underlying the plans for full reserve banking. In particular some of the plans rely on the view that the money supply is a key causal variable and that it is feasible for cen...

  14. Curvilinear coordinates for full-core atoms

    Science.gov (United States)

    Putrino, Anna; Bachelet, Giovanni B.

    1998-03-01

    Curvilinear coordinates, first introduced by F. Gygi for valence-only electronic systems within the local-density functional theory (F. Gygi, Europhysics Letters 19), 617 (1992)., can be used to describe both core and valence electrons in electronic-structure calculations. A simple and quite general coordinate transformation results in a large, yet affordable plane-wave energy cutoff for full-core systems (e.g., ~= 120 Ryd for carbon or silicon) within the local-density functional theory, and in a reduced correlation time for full-core variational Monte Carlo calculations. Numerical examples will be presented.

  15. The Mouse Genome Database (MGD): from genes to mice--a community resource for mouse biology.

    Science.gov (United States)

    Eppig, Janan T; Bult, Carol J; Kadin, James A; Richardson, Joel E; Blake, Judith A; Anagnostopoulos, A; Baldarelli, R M; Baya, M; Beal, J S; Bello, S M; Boddy, W J; Bradt, D W; Burkart, D L; Butler, N E; Campbell, J; Cassell, M A; Corbani, L E; Cousins, S L; Dahmen, D J; Dene, H; Diehl, A D; Drabkin, H J; Frazer, K S; Frost, P; Glass, L H; Goldsmith, C W; Grant, P L; Lennon-Pierce, M; Lewis, J; Lu, I; Maltais, L J; McAndrews-Hill, M; McClellan, L; Miers, D B; Miller, L A; Ni, L; Ormsby, J E; Qi, D; Reddy, T B K; Reed, D J; Richards-Smith, B; Shaw, D R; Sinclair, R; Smith, C L; Szauter, P; Walker, M B; Walton, D O; Washburn, L L; Witham, I T; Zhu, Y

    2005-01-01

    The Mouse Genome Database (MGD) forms the core of the Mouse Genome Informatics (MGI) system (http://www.informatics.jax.org), a model organism database resource for the laboratory mouse. MGD provides essential integration of experimental knowledge for the mouse system with information annotated from both literature and online sources. MGD curates and presents consensus and experimental data representations of genotype (sequence) through phenotype information, including highly detailed reports about genes and gene products. Primary foci of integration are through representations of relationships among genes, sequences and phenotypes. MGD collaborates with other bioinformatics groups to curate a definitive set of information about the laboratory mouse and to build and implement the data and semantic standards that are essential for comparative genome analysis. Recent improvements in MGD discussed here include the enhancement of phenotype resources, the re-development of the International Mouse Strain Resource, IMSR, the update of mammalian orthology datasets and the electronic publication of classic books in mouse genetics.

  16. On the Specification of Full Contracts

    DEFF Research Database (Denmark)

    Okika, Joseph; Ravn, Anders Peter; Fenech, Stephen;

    2009-01-01

    Contracts specify properties of an interface to a software component. We consider the problem of de ning a full contract that speci es not only the normal behaviour, but also special cases and tolerated exceptions. In this paper we focus on the behavioural properties of use cases taken from the C...

  17. Live a Full Life with Fibro

    Science.gov (United States)

    ... Live a Full Life with Fibro Page Content Fibromyalgia is a chronic pain condition that affects 10 million Americans, but it is often misunderstood. According to a survey conducted by the American Osteopathic Association, many patients delay diagnosis and treatment because of a fear that they ...

  18. Freestart collision for full SHA-1

    NARCIS (Netherlands)

    Stevens, M.M.J.; Karpman, P.; Peyrin, T.

    2015-01-01

    We present in this article a freestart collision example for SHA-1, i.e., a collision for its internal compression function. This is the first practical break of the full SHA-1, reaching all 80 out of 80 steps, while only 10 days of computation on a 64 GPU cluster were necessary to perform the attac

  19. Super-Kamiokande worth full restoration

    CERN Multimedia

    Mishima, I

    2002-01-01

    While prospects are good that the SuperKamiokande facility will be partially repaired after an accident last November, the government has yet to confirm whether it will spend the estimated 2.5 billion yen needed for a full-scale restoration (1 page).

  20. Generalized Full-Information Item Bifactor Analysis

    Science.gov (United States)

    Cai, Li; Yang, Ji Seung; Hansen, Mark

    2011-01-01

    Full-information item bifactor analysis is an important statistical method in psychological and educational measurement. Current methods are limited to single-group analysis and inflexible in the types of item response models supported. We propose a flexible multiple-group item bifactor analysis framework that supports a variety of…

  1. Full and Partial Cloaking in Electromagnetic Scattering

    Science.gov (United States)

    Deng, Youjun; Liu, Hongyu; Uhlmann, Gunther

    2017-01-01

    In this paper, we consider two regularized transformation-optics cloaking schemes for electromagnetic (EM) waves. Both schemes are based on the blowup construction with the generating sets being, respectively, a generic curve and a planar subset. We derive sharp asymptotic estimates in assessing the cloaking performances of the two constructions in terms of the regularization parameters and the geometries of the cloaking devices. The first construction yields an approximate full-cloak, whereas the second construction yields an approximate partial-cloak. Moreover, by incorporating properly chosen conducting layers, both cloaking constructions are capable of nearly cloaking arbitrary EM contents. This work complements the existing results in Ammari et al. (SIAM J Appl Math 73:2055-2076, 2013), Bao and Liu (SIAM J Appl Math 74:724-742, 2014), Bao et al. (J Math Pure Appl (9) 101:716-733, 2014) on approximate EM cloaks with the generating set being a singular point, and it also extends Deng et al. (On regularized full- and partial-cloaks in acoustic scat- tering. Preprint, arXiv:1502.01174, 2015), Li et al. (Commun Math Phys, 335:671-712, 2015) on regularized full and partial cloaks for acoustic waves governed by the Helmholtz system to the more challenging EM case governed by the full Maxwell system.

  2. Pseudomembranous candidiasis in patient wearing full denture

    Directory of Open Access Journals (Sweden)

    Nurdiana Nurdiana

    2009-06-01

    Full Text Available Background: Oral candidiasis is a common opportunistic infection of the oral cavity caused by an overgrowth of Candida species, the commonest being Candida albicans. Candida albicans is a harmless commensal organism inhabiting the mouths but it can change into pathogen and invade tissue and cause acute and chronic disease. Dentures predispose to infection with Candida in as many as 65% of elderly people wearing full upper dentures. Purpose: The purpose of this case report is to discuss thrush in patient wearing full denture which rapidly developed. Case: This paper report a case of 57 year-old man who came to the Oral Medicine Clinic Faculty of Dentistry Airlangga University with clinical appearance of pseudomembranous candidiasis (thrush. Case Management: Diagnosis of this case is confirmed with microbiology examination. Patient was wearing full upper dentures, and from anamnesis known that patient wearing denture for 24 hours and he had poor oral hygiene. Patient was treated with topical (nystatin oral suspension and miconazole oral gel and systemic (ketoconazole antifungal. Patient also instructed not to wear his denture and cleaned white pseudomembrane on his mouth with soft toothbrush. Conclusion: Denture, habit of wearing denture for 24 hours, and poor oral hygiene are predisposing factors of thrush and it can healed completely after treated with topical and systemic antifungal.

  3. Resolution analysis in full waveform inversion

    NARCIS (Netherlands)

    Fichtner, A.; Trampert, J.

    2011-01-01

    We propose a new method for the quantitative resolution analysis in full seismic waveform inversion that overcomes the limitations of classical synthetic inversions while being computationally more efficient and applicable to any misfit measure. The method rests on (1) the local quadratic approximat

  4. Selecting Full-Text Undergraduate Periodicals Databases.

    Science.gov (United States)

    Still, Julie M.; Kassabian, Vibiana

    1999-01-01

    Examines how libraries and librarians can compare full-text general periodical indices, using ProQuest Direct, Periodical Abstracts (via Ovid), and EBSCOhost as examples. Explores breadth and depth of coverage; manipulation of results (email/download/print); ease of use (searching); and indexing quirks. (AEF)

  5. Reconfigurable Full-Page Braille Displays

    Science.gov (United States)

    Garner, H. Douglas

    1994-01-01

    Electrically actuated braille display cells of proposed type arrayed together to form full-page braille displays. Like other braille display cells, these provide changeable patterns of bumps driven by digitally recorded text stored on magnetic tapes or in solid-state electronic memories. Proposed cells contain electrorheological fluid. Viscosity of such fluid increases in strong electrostatic field.

  6. Full Text Journal Subscriptions: An Evolutionary Process.

    Science.gov (United States)

    Luther, Judy

    1997-01-01

    Provides an overview of companies offering Web accessible subscriptions to full text electronic versions of scientific, technical, and medical journals (Academic Press, Blackwell, EBSCO, Elsevier, Highwire Press, Information Quest, Institute of Physics, Johns Hopkins University Press, OCLC, OVID, Springer, and SWETS). Also lists guidelines for…

  7. Introducing DartMouse: The Mouse Speed Congenic Facility at Dartmouth Medical School

    Science.gov (United States)

    Trask, H.; Tomlinson, C.; Fiering, S.; Gorham, J.D.; Muirhead, K.

    2010-01-01

    CF-9 DartMouse™ is the Mouse Speed Congenic Facility at Dartmouth Medical School. Use of DartMouse allows for the rapid introgression of modified genes onto any inbred strain of mouse. Speed congenic strains of mice are achievable in 5 generations (1 to 1.5 years), versus 10 generations (∼3 years) required by conventional back-crossing. The application of DartMouse services saves both money and time for researchers using the laboratory mouse for any number of pre-clinical disease models. DartMouse is a complete service facility that works closely with clients at and outside of Dartmouth, helping to design appropriate breeding schemes to optimize back-crossing speed and efficiency. Clients supply mouse tail snips. DartMouse isolates genomic DNA, performs and analyzes complete genome-wide scans, and returns data in graphical and spreadsheet formats. DartMouse discusses results with clients and makes specific recommendations on breeder selection. DartMouse uses “SNP-Chip” technology on an Illumina BeadStation 500 Platform. Chips use a 377 SNP array covering the mouse genome with an average interval density of <7 cM. Turnaround time from receipt of tails to results is typically <2 weeks. One of DartMouse's most popular services is the “background check” in which the genetic background of supposedly fully back-crossed mice can be thoroughly assessed across all chromosomes. DartMouse was inaugurated in the summer of 2008, and received ARRA-funding in the fall of 2009. Our plans are to make DartMouse a regional and national core facility for the generation of speed congenic mice and for the verification of genetic background for conventionally back-crossed mice.

  8. Posterolateral inter-transverse lumbar fusion in a mouse model

    Directory of Open Access Journals (Sweden)

    Bobyn Justin

    2013-01-01

    Full Text Available Abstract Background Spinal fusion is a common orthopaedic procedure that has been previously modeled using canine, lapine, and rodent subjects. Despite the increasing availability of genetically modified mouse strains, murine models have only been infrequently described. Purpose To present an efficient and minimally traumatic procedure for achieving spinal fusion in a mouse model and determine the optimal rhBMP-2 dose to achieve sufficient fusion mass. Method MicroCT reconstructions of the unfused mouse spine and human spine were compared to design a surgical approach. In phase 1, posterolateral lumbar spine fusion in the mouse was evaluated using 18 animals allocated to three experimental groups. Group 1 received decortication only (n = 3, Group 2 received 10 μg rhBMP-2 in a collagen sponge bilaterally (n = 6, and Group 3 received 10 μg rhBMP-2 + decortication (n = 9. The surgical technique was assessed for intra-operative safety, efficacy, access and reproducibility. Spines were harvested for analysis at 3 weeks (Groups 1, 2 and 1, 2, and 3 weeks (Group 3. In phase 2, a dose response study was carried out in an additional 18 animals with C57BL6 mice receiving sponges containing 0, 0.5, 1, 2.5, 5 μg of rhBMP-2 per sponge bilaterally. Results The operative procedure via midline access was rapid and reproducible, and fusion of the murine articular processes was found to be analogous to the human procedure. Unlike reports from other species, decortication alone (Group 1 yielded no new bone formation. Addition of rhBMP-2 (Groups 2 and 3 yielded a significant bone mass that bridged the L4-L6 vertebrae. The subsequent dose response experiment revealed that 0.5 μg rhBMP-2 per sponge was sufficient to create a fusion mass. Conclusion We describe a new approach for mouse lumbar spine fusion that is safe, efficient, and highly reproducible. The technique we employed is analogous to the human midline procedure and may be highly

  9. The mouse forced swim test.

    Science.gov (United States)

    Can, Adem; Dao, David T; Arad, Michal; Terrillion, Chantelle E; Piantadosi, Sean C; Gould, Todd D

    2012-01-29

    The forced swim test is a rodent behavioral test used for evaluation of antidepressant drugs, antidepressant efficacy of new compounds, and experimental manipulations that are aimed at rendering or preventing depressive-like states. Mice are placed in an inescapable transparent tank that is filled with water and their escape related mobility behavior is measured. The forced swim test is straightforward to conduct reliably and it requires minimal specialized equipment. Successful implementation of the forced swim test requires adherence to certain procedural details and minimization of unwarranted stress to the mice. In the protocol description and the accompanying video, we explain how to conduct the mouse version of this test with emphasis on potential pitfalls that may be detrimental to interpretation of results and how to avoid them. Additionally, we explain how the behaviors manifested in the test are assessed.

  10. Apoptotic signaling in mouse odontogenesis.

    Science.gov (United States)

    Matalova, Eva; Svandova, Eva; Tucker, Abigail S

    2012-01-01

    Apoptosis is an important morphogenetic event in embryogenesis as well as during postnatal life. In the last 2 decades, apoptosis in tooth development (odontogenesis) has been investigated with gradually increasing focus on the mechanisms and signaling pathways involved. The molecular machinery responsible for apoptosis exhibits a high degree of conservation but also organ and tissue specific patterns. This review aims to discuss recent knowledge about apoptotic signaling networks during odontogenesis, concentrating on the mouse, which is often used as a model organism for human dentistry. Apoptosis accompanies the entire development of the tooth and corresponding remodeling of the surrounding bony tissue. It is most evident in its role in the elimination of signaling centers within developing teeth, removal of vestigal tooth germs, and in odontoblast and ameloblast organization during tooth mineralization. Dental apoptosis is caspase dependent and proceeds via mitochondrial mediated cell death with possible amplification by Fas-FasL signaling modulated by Bcl-2 family members.

  11. Full Gradient Solution to Adaptive Hybrid Control

    Science.gov (United States)

    Bean, Jacob; Schiller, Noah H.; Fuller, Chris

    2017-01-01

    This paper focuses on the adaptation mechanisms in adaptive hybrid controllers. Most adaptive hybrid controllers update two filters individually according to the filtered reference least mean squares (FxLMS) algorithm. Because this algorithm was derived for feedforward control, it does not take into account the presence of a feedback loop in the gradient calculation. This paper provides a derivation of the proper weight vector gradient for hybrid (or feedback) controllers that takes into account the presence of feedback. In this formulation, a single weight vector is updated rather than two individually. An internal model structure is assumed for the feedback part of the controller. The full gradient is equivalent to that used in the standard FxLMS algorithm with the addition of a recursive term that is a function of the modeling error. Some simulations are provided to highlight the advantages of using the full gradient in the weight vector update rather than the approximation.

  12. Mesoscopic full counting statistics and exclusion models

    Science.gov (United States)

    Roche, P.-E.; Derrida, B.; Douçot, B.

    2005-02-01

    We calculate the distribution of current fluctuations in two simple exclusion models. Although these models are classical, we recover even for small systems such as a simple or a double barrier, the same distibution of current as given by traditional formalisms for quantum mesoscopic conductors. Due to their simplicity, the full counting statistics in exclusion models can be reduced to the calculation of the largest eigenvalue of a matrix, the size of which is the number of internal configurations of the system. As examples, we derive the shot noise power and higher order statistics of current fluctuations (skewness, full counting statistics, ....) of various conductors, including multiple barriers, diffusive islands between tunnel barriers and diffusive media. A special attention is dedicated to the third cumulant, which experimental measurability has been demonstrated lately.

  13. Full-deautonomisation of a lattice equation

    Science.gov (United States)

    Willox, R.; Mase, T.; Ramani, A.; Grammaticos, B.

    2016-07-01

    In this letter we report on the unexpected possibility of applying the full-deautonomisation approach we recently proposed for predicting the algebraic entropy of second-order birational mappings, to discrete lattice equations. Moreover, we show, on two examples, that the full-deautonomisation technique can in fact also be successfully applied to reductions of these lattice equations to mappings with orders higher than 2. In particular, we apply this technique to a recently discovered lattice equation that has confined singularities while being nonintegrable, and we show that our approach accurately predicts this nonintegrable character. Finally, we demonstrate how our method can even be used to predict the algebraic entropy for some nonconfining higher order mappings.

  14. Full truckload vehicle routing problem with profits

    Directory of Open Access Journals (Sweden)

    Jian Li

    2014-04-01

    Full Text Available A new variant of the full truckload vehicle routing problem is studied. In this problem there are more than one delivery points corresponding to the same pickup point, and one order is allowed to be served several times by the same vehicle or different vehicles. For the orders which cannot be assigned because of resource constraint, the logistics company outsources them to other logistics companies at a certain cost. To maximize its profits, logistics company decides which to be transported by private fleet and which to be outsourced. The mathematical model is constructed for the problem. Since the problem is NP-hard and it is difficult to solve the large-scale problems with an exact algorithm, a hybrid genetic algorithm is proposed. Computational results show the effectiveness of the hybrid genetic algorithm.

  15. Full traveltime inversion in source domain

    KAUST Repository

    Liu, Lu

    2017-06-01

    This paper presents a new method of source-domain full traveltime inversion (FTI). The objective of this study is automatically building near-surface velocity using the early arrivals of seismic data. This method can generate the inverted velocity that can kinetically best match the reconstructed plane-wave source of early arrivals with true source in source domain. It does not require picking first arrivals for tomography, which is one of the most challenging aspects of ray-based tomographic inversion. Besides, this method does not need estimate the source wavelet, which is a necessity for receiver-domain wave-equation velocity inversion. Furthermore, we applied our method on one synthetic dataset; the results show our method could generate a reasonable background velocity even when shingling first arrivals exist and could provide a good initial velocity for the conventional full waveform inversion (FWI).

  16. Full revivals in 2D quantum walks

    Energy Technology Data Exchange (ETDEWEB)

    Stefanak, M; Jex, I [Department of Physics, FJFI CVUT v Praze, Brehova 7, 115 19 Praha 1-Stare Mesto (Czech Republic); Kollar, B; Kiss, T, E-mail: martin.stefanak@fjfi.cvut.c [Department of Quantum Optics and Quantum Information, Research Institute for Solid State Physics and Optics, Hungarian Academy of Sciences, Konkoly-Thege M. u. 29-33, H-1121 Budapest (Hungary)

    2010-09-01

    Recurrence of a random walk is described by the Polya number. For quantum walks, recurrence is understood as the return of the walker to the origin, rather than the full revival of its quantum state. Localization for two-dimensional quantum walks is known to exist in the sense of non-vanishing probability distribution in the asymptotic limit. We show, on the example of the 2D Grover walk, that one can exploit the effect of localization to construct stationary solutions. Moreover, we find full revivals of a quantum state with a period of two steps. We prove that there cannot be longer cycles for a four-state quantum walk. Stationary states and revivals result from interference, which has no counterpart in classical random walks.

  17. Ultralow Thermal Conductivity in Full Heusler Semiconductors

    Science.gov (United States)

    He, Jiangang; Amsler, Maximilian; Xia, Yi; Naghavi, S. Shahab; Hegde, Vinay I.; Hao, Shiqiang; Goedecker, Stefan; OzoliĆš, Vidvuds; Wolverton, Chris

    2016-07-01

    Semiconducting half and, to a lesser extent, full Heusler compounds are promising thermoelectric materials due to their compelling electronic properties with large power factors. However, intrinsically high thermal conductivity resulting in a limited thermoelectric efficiency has so far impeded their widespread use in practical applications. Here, we report the computational discovery of a class of hitherto unknown stable semiconducting full Heusler compounds with ten valence electrons (X2Y Z , X =Ca , Sr, and Ba; Y =Au and Hg; Z =Sn , Pb, As, Sb, and Bi) through high-throughput ab initio screening. These new compounds exhibit ultralow lattice thermal conductivity κL close to the theoretical minimum due to strong anharmonic rattling of the heavy noble metals, while preserving high power factors, thus resulting in excellent phonon-glass electron-crystal materials.

  18. La estructura social de Full Monty

    Directory of Open Access Journals (Sweden)

    Javier Sánchez Herrera

    2004-01-01

    Full Text Available Full Monty forma parte de un tipo de cine alejado de la estética y las propuestas comerciales de Hollywood, que deja ver tras historias en apariencia simples unas problemáticas sociales, políticas y económicas de personas o colectivos inscritos en una sociedad en particular. Para el caso específico de este film, la sociedad en la cual se inscribe la historia está sometida a diferentes tensiones producto de fenómenos como el neoliberalismo, la globalización, los problemas de la mujer o los nuevos estilos de vida, entre otros, tal como queda en evidencia en esta cinta.

  19. On Boolean matrices with full factor rank

    Energy Technology Data Exchange (ETDEWEB)

    Shitov, Ya [National Research University " Higher School of Economics" , Moscow (Russian Federation)

    2013-11-30

    It is demonstrated that every (0,1)-matrix of size n×m having Boolean rank n contains a column with at least √n/2−1 zero entries. This bound is shown to be asymptotically optimal. As a corollary, it is established that the size of a full-rank Boolean matrix is bounded from above by a function of its tropical and determinantal ranks. Bibliography: 16 titles.

  20. Laser Resurfacing: Full Field and Fractional.

    Science.gov (United States)

    Pozner, Jason N; DiBernardo, Barry E

    2016-07-01

    Laser resurfacing is a very popular procedure worldwide. Full field and fractional lasers are used in many aesthetic practices. There have been significant advances in laser resurfacing in the past few years, which make patient treatments more efficacious and with less downtime. Erbium and carbon dioxide and ablative, nonablative, and hybrid fractional lasers are all extremely effective and popular tools that have a place in plastic surgery and dermatology offices.

  1. The Full Cost of Intercity Highway Transportation

    OpenAIRE

    David Levinson; David Gillen

    1997-01-01

    In this paper we review the theoretical and empirical literature on the cost structure of the provision of intercity highway transportation and specify and estimate our own cost functions . We develop a full cost model which identifies the key cost components and then estimate costs component by component: user costs, infrastructure costs, time and congestion costs, noise costs, accident costs, and pollution costs. The total long run average cost is $0.34 per vehicle kilometer traveled. The s...

  2. Neoclassical physics in full distribution function gyrokinetics

    Science.gov (United States)

    Dif-Pradalier, G.; Diamond, P. H.; Grandgirard, V.; Sarazin, Y.; Abiteboul, J.; Garbet, X.; Ghendrih, Ph.; Latu, G.; Strugarek, A.; Ku, S.; Chang, C. S.

    2011-06-01

    Treatment of binary Coulomb collisions when the full gyrokinetic distribution function is evolved is discussed here. A spectrum of different collision operators is presented, differing through both the physics that can be addressed and the numerics they are based on. Eulerian-like (semi-Lagrangian) and particle in cell (PIC) (Monte-Carlo) schemes are successfully cross-compared, and a detailed confrontation to neoclassical theory is shown.

  3. Toward Full Spatiotemporal Control on the Nanoscale

    Science.gov (United States)

    Durach, Maxim; Rusina, Anastasia; Stockman, Mark I.; Nelson, Keith

    2007-10-01

    We introduce an approach to implement full coherent control on nanometer length scales. It is based on spatio-temporal modulation of the surface plasmon polariton (SPP) fields at the thick edge of a nanowedge. The SPP wavepackets propagating toward the sharp edge of this nanowedge are compressed and adiabatically concentrated at a nanofocus, forming an ultrashort pulse of local fields. The one-dimensional spatial profile and temporal waveform of this pulse are completely coherently controlled.

  4. The Full Function Test Explosive Generator

    Energy Technology Data Exchange (ETDEWEB)

    Reisman, D B; Javedani, J B; Griffith, L V; Ellsworth, G F; Kuklo, R M; Goerz, D A; White, A D; Tallerico, L J; Gidding, D A; Murphy, M J; Chase, J B

    2009-12-13

    We have conducted three tests of a new pulsed power device called the Full Function Test (FFT). These tests represented the culmination of an effort to establish a high energy pulsed power capability based on high explosive pulsed power (HEPP) technology. This involved an extensive computational modeling, engineering, fabrication, and fielding effort. The experiments were highly successful and a new US record for magnetic energy was obtained.

  5. A Reconsideration of Full-Cost Pricing

    OpenAIRE

    Nubbemeyer, Elmar

    2010-01-01

    The wide use of full-cost pricing techniques remains an explanandum in both economics and management accounting theory. This work surveys and develops possible theoretical explanations of this industrial pricing behaviour and analyses some of its implications. By recognition of the widespread use of imperfect cost-plus pricing heuristics, observable pricing behaviour, as well as empirical market-level phenomena, can be explained. Furthermore, methodological aspects of marginalist price the...

  6. Database Citation in Full Text Biomedical Articles

    OpenAIRE

    Şenay Kafkas; Jee-Hyub Kim; Johanna R. McEntyre

    2013-01-01

    Molecular biology and literature databases represent essential infrastructure for life science research. Effective integration of these data resources requires that there are structured cross-references at the level of individual articles and biological records. Here, we describe the current patterns of how database entries are cited in research articles, based on analysis of the full text Open Access articles available from Europe PMC. Focusing on citation of entries in the European Nucleoti...

  7. Full-waveform inversion: Filling the gaps

    KAUST Repository

    Beydoun, Wafik B.

    2015-09-01

    After receiving an outstanding response to its inaugural workshop in 2013, SEG once again achieved great success with its 2015 SEG Middle East Workshop, “Full-waveform inversion: Filling the gaps,” which took place 30 March–1 April 2015 in Abu Dhabi, UAE. The workshop was organized by SEG, and its partner sponsors were Saudi Aramco (gold sponsor), ExxonMobil, and CGG. Read More: http://library.seg.org/doi/10.1190/tle34091106.1

  8. Treatment plan evaluation for interstitial photodynamic therapy in a mouse model by Monte Carlo simulation with FullMonte

    Science.gov (United States)

    Cassidy, Jeffrey; Betz, Vaughn; Lilge, Lothar

    2015-02-01

    Monte Carlo (MC) simulation is recognized as the “gold standard” for biophotonic simulation, capturing all relevant physics and material properties at the perceived cost of high computing demands. Tetrahedral-mesh-based MC simulations particularly are attractive due to the ability to refine the mesh at will to conform to complicated geometries or user-defined resolution requirements. Since no approximations of material or light-source properties are required, MC methods are applicable to the broadest set of biophotonic simulation problems. MC methods also have other implementation features including inherent parallelism, and permit a continuously-variable quality-runtime tradeoff. We demonstrate here a complete MC-based prospective fluence dose evaluation system for interstitial PDT to generate dose-volume histograms on a tetrahedral mesh geometry description. To our knowledge, this is the first such system for general interstitial photodynamic therapy employing MC methods and is therefore applicable to a very broad cross-section of anatomy and material properties. We demonstrate that evaluation of dose-volume histograms is an effective variance-reduction scheme in its own right which greatly reduces the number of packets required and hence runtime required to achieve acceptable result confidence. We conclude that MC methods are feasible for general PDT treatment evaluation and planning, and considerably less costly than widely believed.

  9. Full duplex communication using visible light

    CERN Document Server

    Yang, Yongchao; Li, Yuanhang; Gao, Xumin; Yuan, Jialei; Zhu, Hongbo; Wang, Yongjin

    2016-01-01

    In this work, we propose, fabricate and characterize a full duplex communication system using visible light on a single chip. Both the suspended p-n junction InGaN/GaN multiple quantum well (MQW) devices and the suspended waveguides are obtained on a GaN-on-silicon platform by wafer-level processing. Two suspended p-n junction InGaN/GaN MQW devices that can both emit and detect light simultaneously are connected using suspended waveguides to form an in-plane visible light communication (VLC) system. The light that is emitted from one suspended p-n junction InGaN/GaN MQW device can induce a current in the device located at the other end of the waveguide via in-plane light coupling, thus leading to full duplex communication using visible light. This proof-of-concept in-plane VLC system paves the way towards the implementation of a full duplex communications system operating at the same frequency using visible light on a single chip.

  10. On the full Boltzmann equations for Leptogenesis

    CERN Document Server

    Garayoa, J; Pinto, T; Rius, N; Vives, O

    2009-01-01

    We consider the full Boltzmann equations for standard and soft leptogenesis, instead of the usual integrated Boltzmann equations which assume kinetic equilibrium for all species. Decays and inverse decays may be inefficient for thermalising the heavy-(s)neutrino distribution function, leading to significant deviations from kinetic equilibrium. We analyse the impact of using the full kinetic equations in the case of a previously generated lepton asymmetry, and find that the washout of this initial asymmetry due to the interactions of the right-handed neutrino is larger than when calculated via the integrated equations. We also solve the full Boltzmann equations for soft leptogenesis, where the lepton asymmetry induced by the soft SUSY-breaking terms in sneutrino decays is a purely thermal effect, since at T=0 the asymmetry in leptons cancels the one in sleptons. In this case, we obtain that in the weak washout regime (K ~< 1) the final lepton asymmetry can change up to a factor four with respect to previous...

  11. On the full Boltzmann equations for leptogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Garayoa, J.; Pastor, S.; Pinto, T.; Rius, N.; Vives, O., E-mail: garayoa@ific.uv.es, E-mail: pastor@ific.uv.es, E-mail: teguayco@gmail.com, E-mail: nuria@ific.uv.es, E-mail: vives@ific.uv.es [Depto. de Física Teórica and IFIC, Universidad de Valencia-CSIC, Edificio de Institutos de Paterna, Apt. 22085, 46071 Valencia (Spain)

    2009-09-01

    We consider the full Boltzmann equations for standard and soft leptogenesis, instead of the usual integrated Boltzmann equations which assume kinetic equilibrium for all species. Decays and inverse decays may be inefficient for thermalising the heavy-(s)neutrino distribution function, leading to significant deviations from kinetic equilibrium. We analyse the impact of using the full kinetic equations in the case of a previously generated lepton asymmetry, and find that the washout of this initial asymmetry due to the interactions of the right-handed neutrino is larger than when calculated via the integrated equations. We also solve the full Boltzmann equations for soft leptogenesis, where the lepton asymmetry induced by the soft SUSY-breaking terms in sneutrino decays is a purely thermal effect, since at T = 0 the asymmetry in leptons cancels the one in sleptons. In this case, we obtain that in the weak washout regime (K ∼< 1) the final lepton asymmetry can change up to a factor four with respect to previous estimates.

  12. Full waveform inversion for ultrasonic flaw identification

    Science.gov (United States)

    Seidl, Robert; Rank, Ernst

    2017-02-01

    Ultrasonic Nondestructive Testing is concerned with detecting flaws inside components without causing physical damage. It is possible to detect flaws using ultrasound measurements but usually no additional details about the flaw like position, dimension or orientation are available. The information about these details is hidden in the recorded experimental signals. The idea of full waveform inversion is to adapt the parameters of an initial simulation model of the undamaged specimen by minimizing the discrepancy between these simulated signals and experimentally measured signals of the flawed specimen. Flaws in the structure are characterized by a change or deterioration in the material properties. Commonly, full waveform inversion is mostly applied in seismology on a larger scale to infer mechanical properties of the earth. We propose to use acoustic full waveform inversion for structural parameters to visualize the interior of the component. The method is adapted to US NDT by combining multiple similar experiments on the test component as the typical small amount of sensors is not sufficient for a successful imaging. It is shown that the combination of simulations and multiple experiments can be used to detect flaws and their position, dimension and orientation in emulated simulation cases.

  13. CURRENT WAYS TO HARVEST ENERGY USING A COMPUTER MOUSE

    Directory of Open Access Journals (Sweden)

    Frantisek Horvat

    2014-02-01

    Full Text Available This paper deals with the idea of an energy harvesting (EH system that uses the mechanical energy from finger presses on the buttons of a computer mouse by means of a piezomaterial (PVF2. The piezomaterial is placed in the mouse at the interface between the button and the body. This paper reviews the parameters of the PVF2 piezomaterial and tests their possible implementation into EH systems utilizing these types of mechanical interactions. The paper tests the viability of two EH concepts: a battery management system, and a semi-autonomous system. A statistical estimate of the button operations is performed for various computer activities, showing that an average of up to 3300 mouse clicks per hour was produced for gaming applications, representing a tip frequency of 0.91 Hz on the PVF2 member. This frequency is tested on the PVF2 system, and an assessment of the two EH systems is reviewed. The results show that fully autonomous systems are not suitable for capturing low-frequency mechanical interactions, due to the parameters of current piezomaterials, and the resulting very long startup phase. However, a hybrid EH system which uses available power to initiate the circuit and eliminate the startup phase may be explored for future studies.

  14. Sex effects in mouse prion disease incubation time.

    Directory of Open Access Journals (Sweden)

    Shaheen Akhtar

    Full Text Available Prion disease incubation time in mice is determined by many factors including PrP expression level, Prnp alleles, genetic background, prion strain and route of inoculation. Sex differences have been described in age of onset for vCJD and in disease duration for both vCJD and sporadic CJD and have also been shown in experimental models. The sex effects reported for mouse incubation times are often contradictory and detail only one strain of mice or prions, resulting in broad generalisations and a confusing picture. To clarify the effect of sex on prion disease incubation time in mice we have compared male and female transmission data from twelve different inbred lines of mice inoculated with at least two prion strains, representing both mouse-adapted scrapie and BSE. Our data show that sex can have a highly significant difference on incubation time. However, this is limited to particular mouse and prion strain combinations. No sex differences were seen in endogenous PrP(C levels nor in the neuropathological markers of prion disease: PrP(Sc distribution, spongiosis, neuronal loss and gliosis. These data suggest that when comparing incubation times between experimental groups, such as testing the effects of modifier genes or therapeutics, single sex groups should be used.

  15. Influence of age, irradiation and humanization on NSG mouse phenotypes

    Directory of Open Access Journals (Sweden)

    Jaclyn S. Knibbe-Hollinger

    2015-10-01

    Full Text Available Humanized mice are frequently utilized in bench to bedside therapeutic tests to combat human infectious, cancerous and degenerative diseases. For the fields of hematology-oncology, regenerative medicine, and infectious diseases, the immune deficient mice have been used commonly in basic research efforts. Obstacles in true translational efforts abound, as the relationship between mouse and human cells in disease pathogenesis and therapeutic studies requires lengthy investigations. The interplay between human immunity and mouse biology proves ever more complicated when aging, irradiation, and human immune reconstitution are considered. All can affect a range of biochemical and behavioral functions. To such ends, we show age- and irradiation-dependent influences for the development of macrocytic hyper chromic anemia, myelodysplasia, blood protein reductions and body composition changes. Humanization contributes to hematologic abnormalities. Home cage behavior revealed day and dark cycle locomotion also influenced by human cell reconstitutions. Significant age-related day-to-day variability in movement, feeding and drinking behaviors were observed. We posit that this data serves to enable researchers to better design translational studies in this rapidly emerging field of mouse humanization.

  16. Imaging of functional connectivity in the mouse brain.

    Directory of Open Access Journals (Sweden)

    Brian R White

    Full Text Available Functional neuroimaging (e.g., with fMRI has been difficult to perform in mice, making it challenging to translate between human fMRI studies and molecular and genetic mechanisms. A method to easily perform large-scale functional neuroimaging in mice would enable the discovery of functional correlates of genetic manipulations and bridge with mouse models of disease. To satisfy this need, we combined resting-state functional connectivity mapping with optical intrinsic signal imaging (fcOIS. We demonstrate functional connectivity in mice through highly detailed fcOIS mapping of resting-state networks across most of the cerebral cortex. Synthesis of multiple network connectivity patterns through iterative parcellation and clustering provides a comprehensive map of the functional neuroarchitecture and demonstrates identification of the major functional regions of the mouse cerebral cortex. The method relies on simple and relatively inexpensive camera-based equipment, does not require exogenous contrast agents and involves only reflection of the scalp (the skull remains intact making it minimally invasive. In principle, fcOIS allows new paradigms linking human neuroscience with the power of molecular/genetic manipulations in mouse models.

  17. Characteristics of transposable element exonization within human and mouse.

    Directory of Open Access Journals (Sweden)

    Noa Sela

    Full Text Available Insertion of transposed elements within mammalian genes is thought to be an important contributor to mammalian evolution and speciation. Insertion of transposed elements into introns can lead to their activation as alternatively spliced cassette exons, an event called exonization. Elucidation of the evolutionary constraints that have shaped fixation of transposed elements within human and mouse protein coding genes and subsequent exonization is important for understanding of how the exonization process has affected transcriptome and proteome complexities. Here we show that exonization of transposed elements is biased towards the beginning of the coding sequence in both human and mouse genes. Analysis of single nucleotide polymorphisms (SNPs revealed that exonization of transposed elements can be population-specific, implying that exonizations may enhance divergence and lead to speciation. SNP density analysis revealed differences between Alu and other transposed elements. Finally, we identified cases of primate-specific Alu elements that depend on RNA editing for their exonization. These results shed light on TE fixation and the exonization process within human and mouse genes.

  18. Enhancement of NMRI Mouse Embryo Development In vitro

    Directory of Open Access Journals (Sweden)

    Abedini, F.

    2013-12-01

    Full Text Available Most of the systematic studies used in the development of human embryo culture media have been done first on mouse embryos. The general use of NMRI outbred mice is a model for toxicology, teratology and pharmacology. NMRI mouse embryo exhibit the two-cell block in vitro. The objective of this study was to evaluate and compare the effects of four kinds of culture media on the development of zygotes (NMRI after embryo vitrification. One-cell mouse embryos were obtained from NMRI mice after superovulation and mating with adult male NMRI mice. And then randomly divided into 4 groups for culture in four different cultures media including: M16 (A, DMEM/Ham, F-12 (B, DMEM/Ham's F-12 co-culture with Vero cells(C and DMEM/Ham's F-12 co-culture with MEF cells (D. Afterward all of the embryos were vitrified in EFS40 solution and collected. Results of our study revealed, more blastocysts significantly were developed with co-culture with MEF cells in DMEM/Ham's F-12 medium. More research needed to understand the effect of other components of culture medium, and co-culture on NMRI embryo development.

  19. Mouse models of estrogen receptor-positive breast cancer

    Directory of Open Access Journals (Sweden)

    Shakur Mohibi

    2011-01-01

    Full Text Available Breast cancer is the most frequent malignancy and second leading cause of cancer-related deaths among women. Despite advances in genetic and biochemical analyses, the incidence of breast cancer and its associated mortality remain very high. About 60 - 70% of breast cancers are Estrogen Receptor alpha (ER-α positive and are dependent on estrogen for growth. Selective estrogen receptor modulators (SERMs have therefore provided an effective targeted therapy to treat ER-α positive breast cancer patients. Unfortunately, development of resistance to endocrine therapy is frequent and leads to cancer recurrence. Our understanding of molecular mechanisms involved in the development of ER-α positive tumors and their resistance to ER antagonists is currently limited due to lack of experimental models of ER-α positive breast cancer. In most mouse models of breast cancer, the tumors that form are typically ER-negative and independent of estrogen for their growth. However, in recent years more attention has been given to develop mouse models that develop different subtypes of breast cancers, including ER-positive tumors. In this review, we discuss the currently available mouse models that develop ER-α positive mammary tumors and their potential use to elucidate the molecular mechanisms of ER-α positive breast cancer development and endocrine resistance.

  20. Update of human and mouse forkhead box (FOX gene families

    Directory of Open Access Journals (Sweden)

    Jackson Brian C

    2010-06-01

    Full Text Available Abstract The forkhead box (FOX proteins are transcription factors that play complex and important roles in processes from development and organogenesis to regulation of metabolism and the immune system. There are 50 FOX genes in the human genome and 44 in the mouse, divided into 19 subfamilies. All human FOX genes have close mouse orthologues, with one exception: the mouse has a single Foxd4, whereas the human gene has undergone a recent duplication to a total of seven (FOXD4 and FOXD4L1 → FOXD4L6. Evolutionarily ancient family members can be found as far back as the fungi and metazoans. The DNA-binding domain, the forkhead domain, is an example of the winged-helix domain, and is very well conserved across the FOX family and across species, with a few notable exceptions in which divergence has created new functionality. Mutations in FOX genes have been implicated in at least four familial human diseases, and differential expression may play a role in a number of other pathologies -- ranging from metabolic disorders to autoimmunity. Furthermore, FOX genes are differentially expressed in a large number of cancers; their role can be either as an oncogene or tumour suppressor, depending on the family member and cell type. Although some drugs that target FOX gene expression or activity, notably proteasome inhibitors, appear to work well, much more basic research is needed to unlock the complex interplay of upstream and downstream interactions with FOX family transcription factors.

  1. Female presence and estrous state influence mouse ultrasonic courtship vocalizations.

    Directory of Open Access Journals (Sweden)

    Jessica L Hanson

    Full Text Available The laboratory mouse is an emerging model for context-dependent vocal signaling and reception. Mouse ultrasonic vocalizations are robustly produced in social contexts. In adults, male vocalization during courtship has become a model of interest for signal-receiver interactions. These vocalizations can be grouped into syllable types that are consistently produced by different subspecies and strains of mice. Vocalizations are unique to individuals, vary across development, and depend on social housing conditions. The behavioral significance of different syllable types, including the contexts in which different vocalizations are made and the responses listeners have to different types of vocalizations, is not well understood. We examined the effect of female presence and estrous state on male vocalizations by exploring the use of syllable types and the parameters of syllables during courtship. We also explored correlations between vocalizations and other behaviors. These experimental manipulations produced four main findings: 1 vocalizations varied among males, 2 the production of USVs and an increase in the use of a specific syllable type were temporally related to mounting behavior, 3 the frequency (kHz, bandwidth, and duration of syllables produced by males were influenced by the estrous phase of female partners, and 4 syllable types changed when females were removed. These findings show that mouse ultrasonic courtship vocalizations are sensitive to changes in female phase and presence, further demonstrating the context-sensitivity of these calls.

  2. How informative is the mouse for human gut microbiota research?

    Directory of Open Access Journals (Sweden)

    Thi Loan Anh Nguyen

    2015-01-01

    Full Text Available The microbiota of the human gut is gaining broad attention owing to its association with a wide range of diseases, ranging from metabolic disorders (e.g. obesity and type 2 diabetes to autoimmune diseases (such as inflammatory bowel disease and type 1 diabetes, cancer and even neurodevelopmental disorders (e.g. autism. Having been increasingly used in biomedical research, mice have become the model of choice for most studies in this emerging field. Mouse models allow perturbations in gut microbiota to be studied in a controlled experimental setup, and thus help in assessing causality of the complex host-microbiota interactions and in developing mechanistic hypotheses. However, pitfalls should be considered when translating gut microbiome research results from mouse models to humans. In this Special Article, we discuss the intrinsic similarities and differences that exist between the two systems, and compare the human and murine core gut microbiota based on a meta-analysis of currently available datasets. Finally, we discuss the external factors that influence the capability of mouse models to recapitulate the gut microbiota shifts associated with human diseases, and investigate which alternative model systems exist for gut microbiota research.

  3. Txndc9 Is Required for Meiotic Maturation of Mouse Oocytes

    Directory of Open Access Journals (Sweden)

    Fanhua Ma

    2017-01-01

    Full Text Available Txndc9 (thioredoxin domain containing protein 9 has been shown to be involved in mammalian mitosis; however, its function in mammalian oocyte meiosis remains unclear. In this study, we initially found that Txndc9 is expressed during meiotic maturation of mouse oocytes and higher expression of Txndc9 mRNA and protein occurred in germinal vesicle (GV stage. By using confocal scanning, we observed that Txndc9 localized at both nucleus and cytoplasm, especially at spindle microtubules. Specific depletion of Txndc9 by siRNA in mouse oocyte resulted in decreasing the rate of first polar body extrusion and increasing abnormal spindle assemble. Moreover, knockdown of Txndc9 in germinal vesicle (GV stage oocytes led to higher level of reactive oxygen species (ROS and lower level of antioxidant glutathione (GSH as compared with control oocytes, which indicated that Txndc9 may be involved in mediating the redox balance. In summary, our results demonstrated that Txndc9 is crucial for mouse oocyte maturation by regulating spindle assembly, polar body extrusion, and redox status.

  4. Screening for Stress Resistance Mutations in the Mouse

    Directory of Open Access Journals (Sweden)

    Wallace S Chick

    2014-09-01

    Full Text Available Longevity is correlated with stress resistance in many animal models. However, previous efforts through the boosting of the antioxidant defense system did not extend life span, suggesting that longevity related stress resistance is mediated by other uncharacterized pathways. We have developed a high-throughput platform for screening and rapid identification of novel genetic mutants in the mouse that are stress-resistant. Selection for resistance to stressors occurs in mutagenized mouse embryonic stem (ES cells, which are carefully treated so as to maintain pluripotency for mouse production. Initial characterization of these mutant ES cells revealed mutations in Pigl, Tiam1, and Rffl, among others. These genes are implicated in glycosylphosphatidylinositol biosynthesis, NADPH oxidase function, and inflammation. These mutants: (1 are resistant to two different oxidative stressors, paraquat and the omission of 2-mercaptoethanol, (2 have reduced levels of endogenous reactive oxygen species (ROS, (3 are capable of generating live mice, and (4 transmit the stress resistance phenotype to the mice. This strategy offers an efficient way to select for new mutants expressing a stress resistance phenotype, to rapidly identify the causative genes, and to develop mice for in vivo studies.

  5. Proteomic interactions in the mouse vitreous-retina complex.

    Directory of Open Access Journals (Sweden)

    Jessica M Skeie

    Full Text Available PURPOSE: Human vitreoretinal diseases are due to presumed abnormal mechanical interactions between the vitreous and retina, and translational models are limited. This study determined whether nonstructural proteins and potential retinal biomarkers were expressed by the normal mouse vitreous and retina. METHODS: Vitreous and retina samples from mice were collected by evisceration and analyzed by liquid chromatography-tandem mass spectrometry. Identified proteins were further analyzed for differential expression and functional interactions using bioinformatic software. RESULTS: We identified 1,680 unique proteins in the retina and 675 unique proteins in the vitreous. Unbiased clustering identified protein pathways that distinguish retina from vitreous including oxidative phosphorylation and neurofilament cytoskeletal remodeling, whereas the vitreous expressed oxidative stress and innate immunology pathways. Some intracellular protein pathways were found in both retina and vitreous, such as glycolysis and gluconeogenesis and neuronal signaling, suggesting proteins might be shuttled between the retina and vitreous. We also identified human disease biomarkers represented in the mouse vitreous and retina, including carbonic anhydrase-2 and 3, crystallins, macrophage inhibitory factor, glutathione peroxidase, peroxiredoxins, S100 precursors, and von Willebrand factor. CONCLUSIONS: Our analysis suggests the vitreous expresses nonstructural proteins that functionally interact with the retina to manage oxidative stress, immune reactions, and intracellular proteins may be exchanged between the retina and vitreous. This novel proteomic dataset can be used for investigating human vitreoretinopathies in mouse models. Validation of vitreoretinal biomarkers for human ocular diseases will provide a critical tool for diagnostics and an avenue for therapeutics.

  6. The Mouse Universal Genotyping Array: From Substrains to Subspecies

    Directory of Open Access Journals (Sweden)

    Andrew P. Morgan

    2016-02-01

    Full Text Available Genotyping microarrays are an important resource for genetic mapping, population genetics, and monitoring of the genetic integrity of laboratory stocks. We have developed the third generation of the Mouse Universal Genotyping Array (MUGA series, GigaMUGA, a 143,259-probe Illumina Infinium II array for the house mouse (Mus musculus. The bulk of the content of GigaMUGA is optimized for genetic mapping in the Collaborative Cross and Diversity Outbred populations, and for substrain-level identification of laboratory mice. In addition to 141,090 single nucleotide polymorphism probes, GigaMUGA contains 2006 probes for copy number concentrated in structurally polymorphic regions of the mouse genome. The performance of the array is characterized in a set of 500 high-quality reference samples spanning laboratory inbred strains, recombinant inbred lines, outbred stocks, and wild-caught mice. GigaMUGA is highly informative across a wide range of genetically diverse samples, from laboratory substrains to other Mus species. In addition to describing the content and performance of the array, we provide detailed probe-level annotation and recommendations for quality control.

  7. Computer simulations of the mouse spermatogenic cycle

    Directory of Open Access Journals (Sweden)

    Debjit Ray

    2014-12-01

    Full Text Available The spermatogenic cycle describes the periodic development of germ cells in the testicular tissue. The temporal–spatial dynamics of the cycle highlight the unique, complex, and interdependent interaction between germ and somatic cells, and are the key to continual sperm production. Although understanding the spermatogenic cycle has important clinical relevance for male fertility and contraception, there are a number of experimental obstacles. For example, the lengthy process cannot be visualized through dynamic imaging, and the precise action of germ cells that leads to the emergence of testicular morphology remains uncharacterized. Here, we report an agent-based model that simulates the mouse spermatogenic cycle on a cross-section of the seminiferous tubule over a time scale of hours to years, while considering feedback regulation, mitotic and meiotic division, differentiation, apoptosis, and movement. The computer model is able to elaborate the germ cell dynamics in a time-lapse movie format, allowing us to trace individual cells as they change state and location. More importantly, the model provides mechanistic understanding of the fundamentals of male fertility, namely how testicular morphology and sperm production are achieved. By manipulating cellular behaviors either individually or collectively in silico, the model predicts causal events for the altered arrangement of germ cells upon genetic or environmental perturbations. This in silico platform can serve as an interactive tool to perform long-term simulation and to identify optimal approaches for infertility treatment and contraceptive development.

  8. Mouse Model Resources for Vision Research

    Directory of Open Access Journals (Sweden)

    Jungyeon Won

    2011-01-01

    Full Text Available The need for mouse models, with their well-developed genetics and similarity to human physiology and anatomy, is clear and their central role in furthering our understanding of human disease is readily apparent in the literature. Mice carrying mutations that alter developmental pathways or cellular function provide model systems for analyzing defects in comparable human disorders and for testing therapeutic strategies. Mutant mice also provide reproducible, experimental systems for elucidating pathways of normal development and function. Two programs, the Eye Mutant Resource and the Translational Vision Research Models, focused on providing such models to the vision research community are described herein. Over 100 mutant lines from the Eye Mutant Resource and 60 mutant lines from the Translational Vision Research Models have been developed. The ocular diseases of the mutant lines include a wide range of phenotypes, including cataracts, retinal dysplasia and degeneration, and abnormal blood vessel formation. The mutations in disease genes have been mapped and in some cases identified by direct sequencing. Here, we report 3 novel alleles of Crxtvrm65, Rp1tvrm64, and Rpe65tvrm148 as successful examples of the TVRM program, that closely resemble previously reported knockout models.

  9. Full cycle rapid scan EPR deconvolution algorithm

    Science.gov (United States)

    Tseytlin, Mark

    2017-08-01

    Rapid scan electron paramagnetic resonance (RS EPR) is a continuous-wave (CW) method that combines narrowband excitation and broadband detection. Sinusoidal magnetic field scans that span the entire EPR spectrum cause electron spin excitations twice during the scan period. Periodic transient RS signals are digitized and time-averaged. Deconvolution of absorption spectrum from the measured full-cycle signal is an ill-posed problem that does not have a stable solution because the magnetic field passes the same EPR line twice per sinusoidal scan during up- and down-field passages. As a result, RS signals consist of two contributions that need to be separated and postprocessed individually. Deconvolution of either of the contributions is a well-posed problem that has a stable solution. The current version of the RS EPR algorithm solves the separation problem by cutting the full-scan signal into two half-period pieces. This imposes a constraint on the experiment; the EPR signal must completely decay by the end of each half-scan in order to not be truncated. The constraint limits the maximum scan frequency and, therefore, the RS signal-to-noise gain. Faster scans permit the use of higher excitation powers without saturating the spin system, translating into a higher EPR sensitivity. A stable, full-scan algorithm is described in this paper that does not require truncation of the periodic response. This algorithm utilizes the additive property of linear systems: the response to a sum of two inputs is equal the sum of responses to each of the inputs separately. Based on this property, the mathematical model for CW RS EPR can be replaced by that of a sum of two independent full-cycle pulsed field-modulated experiments. In each of these experiments, the excitation power equals to zero during either up- or down-field scan. The full-cycle algorithm permits approaching the upper theoretical scan frequency limit; the transient spin system response must decay within the scan

  10. An improved protocol for isolation and culture of mesenchymal stem cells from mouse bone marrow

    Directory of Open Access Journals (Sweden)

    Shuo Huang

    2015-01-01

    Full Text Available Mesenchymal stem cells (MSCs from bone marrow are main cell source for tissue repair and engineering, and vehicles of cell-based gene therapy. Unlike other species, mouse bone marrow derived MSCs (BM-MSCs are difficult to harvest and grow due to the low MSCs yield. We report here a standardised, reliable, and easy-to-perform protocol for isolation and culture of mouse BM-MSCs. There are five main features of this protocol. (1 After flushing bone marrow out of the marrow cavity, we cultured the cells with fat mass without filtering and washing them. Our method is simply keeping the MSCs in their initial niche with minimal disturbance. (2 Our culture medium is not supplemented with any additional growth factor. (3 Our method does not need to separate cells using flow cytometry or immunomagnetic sorting techniques. (4 Our method has been carefully tested in several mouse strains and the results are reproducible. (5 We have optimised this protocol, and list detailed potential problems and trouble-shooting tricks. Using our protocol, the isolated mouse BM-MSCs were strongly positive for CD44 and CD90, negative CD45 and CD31, and exhibited tri-lineage differentiation potentials. Compared with the commonly used protocol, our protocol had higher success rate of establishing the mouse BM-MSCs in culture. Our protocol may be a simple, reliable, and alternative method for culturing MSCs from mouse bone marrow tissues.

  11. Mutagenicity testing with transgenic mice. Part I: Comparison with the mouse bone marrow micronucleus test

    Directory of Open Access Journals (Sweden)

    Wahnschaffe U

    2005-01-01

    Full Text Available Abstract As part of a larger literature study on transgenic animals in mutagenicity testing, test results from the transgenic mutagenicity assays (lacI model; commercially available as the Big Blue® mouse, and the lacZ model; commercially available as the Muta™Mouse, were compared with the results on the same substances in the more traditional mouse bone marrow micronucleus test. 39 substances were found which had been tested in the micronucleus assay and in the above transgenic mouse systems. Although, the transgenic animal mutation assay is not directly comparable with the micronucleus test, because different genetic endpoints are examined: chromosome aberration versus gene mutation, the results for the majority of substances were in agreement. Both test systems, the transgenic mouse assay and the mouse bone marrow micronucleus test, have advantages and they complement each other. However, the transgenic animal assay has some distinct advantages over the micronucleus test: it is not restricted to one target organ and detects systemic as well as local mutagenic effects.

  12. Olfaction in three genetic and two MPTP-induced Parkinson's disease mouse models.

    Directory of Open Access Journals (Sweden)

    Stefan Kurtenbach

    Full Text Available Various genetic or toxin-induced mouse models are frequently used for investigation of early PD pathology. Although olfactory impairment is known to precede motor symptoms by years, it is not known whether it is caused by impairments in the brain, the olfactory epithelium, or both. In this study, we investigated the olfactory function in three genetic Parkinson's disease (PD mouse models and mice treated with MPTP intraperitoneally and intranasally. To investigate olfactory function, we performed electro-olfactogram recordings (EOGs and an olfactory behavior test (cookie-finding test. We show that neither a parkin knockout mouse strain, nor intraperitoneal MPTP treated animals display any olfactory impairment in EOG recordings and the applied behavior test. We also found no difference in the responses of the olfactory epithelium to odorants in a mouse strain over-expressing doubly mutated α-synuclein, while this mouse strain was not suitable to test olfaction in a cookie-finding test as it displays a mobility impairment. A transgenic mouse expressing mutated α-synuclein in dopaminergic neurons performed equal to control animals in the cookie-finding test. Further we show that intranasal MPTP application can cause functional damage of the olfactory epithelium.

  13. Cloning of rat sp56, the homologue of mouse sperm ZP3 receptor-sp56

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Mouse sp56 is considered as one of the candidates for mouse zona pellucida 3 (mZP3) receptor. Up to date, its homologue has only been cloned from guinea pig, namely AM67. Based on the cDNA sequence of mouse sp56, we designed a pair of primer to amplify its homologue from rat testis cDNA. Using RT-PCR,two fragments of 743 bp and 938 bp were amplified. The PCR products show very high homology to mouse sp56. However, the 743 bp product completely lacks one of the seven Sushi domains of mouse sp56. Using the 743 bp product as the probe to detect the expression profile of sp56 in rat tissues, Northern blot shows that a ~2.0 kb mRNA expresses specifically in testis. Employed the RACE method, two full cDNA sequences of rat sp56 were obtained. A Mr ~42 KD band was detected in denatured and non-reducing protein sample of rat testis and sperm with anti-mouse sp56 monoclonal antibody by Western blot method. Rat sp56was localized on rat sperm head by the indirect immunofiuorescence method. Rat sp56 immunoreactivitywas detected from the early pachytene spermatocytes and throughout the spermatogenesis. Its cloning willfurther our understanding of the mechanism of the sperm-egg recognition and binding.

  14. Redirection of Human Cancer Cells upon the Interaction with the Regenerating Mouse Mammary Gland Microenvironment

    Directory of Open Access Journals (Sweden)

    Sonia M. Rosenfield

    2013-01-01

    Full Text Available Tumorigenesis is often described as a result of accumulated mutations that lead to growth advantage and clonal expansion of mutated cells. There is evidence in the literature that cancer cells are influenced by the microenvironment. Our previous studies demonstrated that the mouse mammary gland is capable of redirecting mouse cells of non-mammary origins as well as Mouse Mammary Tumor Virus (MMTV-neu transformed cells toward normal mammary epithelial cell fate during gland regeneration. Interestingly, the malignant phenotype of MMTV-neu transformed cells was suppressed during serial transplantation experiments. Here, we discuss our studies that demonstrated the potential of the regenerating mouse mammary gland to redirect cancer cells of different species into a functional tumor-free mammary epithelial cell progeny. Immunochemistry for human specific CD133, mitochondria, cytokeratins as well as milk proteins and FISH for human specific probe identified human epithelial cell progeny in ducts, lobules, and secretory acini. Fluorescent In Situ Hybridization (FISH for human centromeric DNA and FACS analysis of propidium iodine staining excluded the possibility of mouse-human cell fusion. To our knowledge this is the first evidence that human cancer cells of embryonic or somatic origins respond to developmental signals generated by the mouse mammary gland microenvironment during gland regeneration in vivo.

  15. Mouse ENU Mutagenesis to Understand Immunity to Infection: Methods, Selected Examples, and Perspectives

    Directory of Open Access Journals (Sweden)

    Grégory Caignard

    2014-09-01

    Full Text Available Infectious diseases are responsible for over 25% of deaths globally, but many more individuals are exposed to deadly pathogens. The outcome of infection results from a set of diverse factors including pathogen virulence factors, the environment, and the genetic make-up of the host. The completion of the human reference genome sequence in 2004 along with technological advances have tremendously accelerated and renovated the tools to study the genetic etiology of infectious diseases in humans and its best characterized mammalian model, the mouse. Advancements in mouse genomic resources have accelerated genome-wide functional approaches, such as gene-driven and phenotype-driven mutagenesis, bringing to the fore the use of mouse models that reproduce accurately many aspects of the pathogenesis of human infectious diseases. Treatment with the mutagen N-ethyl-N-nitrosourea (ENU has become the most popular phenotype-driven approach. Our team and others have employed mouse ENU mutagenesis to identify host genes that directly impact susceptibility to pathogens of global significance. In this review, we first describe the strategies and tools used in mouse genetics to understand immunity to infection with special emphasis on chemical mutagenesis of the mouse germ-line together with current strategies to efficiently identify functional mutations using next generation sequencing. Then, we highlight illustrative examples of genes, proteins, and cellular signatures that have been revealed by ENU screens and have been shown to be involved in susceptibility or resistance to infectious diseases caused by parasites, bacteria, and viruses.

  16. Spontaneous Movements of a Computer Mouse Reveal Egoism and In-group Favoritism.

    Science.gov (United States)

    Maliszewski, Norbert; Wojciechowski, Łukasz; Suszek, Hubert

    2017-01-01

    The purpose of the project was to assess whether the first spontaneous movements of a computer mouse, when making an assessment on a scale presented on the screen, may express a respondent's implicit attitudes. In Study 1, the altruistic behaviors of 66 students were assessed. The students were led to believe that the task they were performing was also being performed by another person and they were asked to distribute earnings between themselves and the partner. The participants performed the tasks under conditions with and without distractors. With the distractors, in the first few seconds spontaneous mouse movements on the scale expressed a selfish distribution of money, while later the movements gravitated toward more altruism. In Study 2, 77 Polish students evaluated a painting by a Polish/Jewish painter on a scale. They evaluated it under conditions of full or distracted cognitive abilities. Spontaneous movements of the mouse on the scale were analyzed. In addition, implicit attitudes toward both Poles and Jews were measured with the Implicit Association Test (IAT). A significant association between implicit attitudes (IAT) and spontaneous evaluation of images using a computer mouse was observed in the group with the distractor. The participants with strong implicit in-group favoritism of Poles revealed stronger preference for the Polish painter's work in the first few seconds of mouse movement. Taken together, these results suggest that spontaneous mouse movements may reveal egoism (in-group favoritism), i.e., processes that were not observed in the participants' final decisions (clicking on the scale).

  17. Ultrasound biomicroscopy in mouse cardiovascular development

    Science.gov (United States)

    Turnbull, Daniel H.

    2004-05-01

    The mouse is the preferred animal model for studying mammalian cardiovascular development and many human congenital heart diseases. Ultrasound biomicroscopy (UBM), utilizing high-frequency (40-50-MHz) ultrasound, is uniquely capable of providing in vivo, real-time microimaging and Doppler blood velocity measurements in mouse embryos and neonates. UBM analyses of normal and abnormal mouse cardiovascular function will be described to illustrate the power of this microimaging approach. In particular, real-time UBM images have been used to analyze dimensional changes in the mouse heart from embryonic to neonatal stages. UBM-Doppler has been used recently to examine the precise timing of onset of a functional circulation in early-stage mouse embryos, from the first detectable cardiac contractions. In other experiments, blood velocity waveforms have been analyzed to characterize the functional phenotype of mutant mouse embryos having defects in cardiac valve formation. Finally, UBM has been developed for real-time, in utero image-guided injection of mouse embryos, enabling cell transplantation and genetic gain-of-function experiments with transfected cells and retroviruses. In summary, UBM provides a unique and powerful approach for in vivo analysis and image-guided manipulation in normal and genetically engineered mice, over a wide range of embryonic to neonatal developmental stages.

  18. Conditional Expression of Human 15-Lipoxygenase-1 in Mouse Prostate Induces Prostatic Intraepithelial Neoplasia: The FLiMP Mouse Model

    Directory of Open Access Journals (Sweden)

    Uddhav P. Kelavkar

    2006-06-01

    Full Text Available The incidence and mortality of prostate cancer (PCa vary greatly in different geographic regions, for which lifestyle factors, such as dietary fat intake, have been implicated. Human 15-lipoxygenase-1 (h15-LO-1, which metabolizes polyunsaturated fatty acids, is a highly regulated, tissue-specific, lipid-peroxidating enzyme that functions in physiological membrane remodeling and in the pathogenesis of atherosclerosis, inflammation, and carcinogenesis. We have shown that aberrant overexpression of 15-LO-1 occurs in human PCa, particularly high-grade PCa, and in high-grade prostatic intraepithelial neoplasia (HGPIN, and that the murine orthologue is increased in SV40-based genetically engineered mouse (GEM models of PCa, such as LADY and TRansgenic Adenocarcinoma of Mouse Prostate. To further define the role of 15-LO-1 in prostate carcinogenesis, we established a novel GEM model with targeted overexpression of h15-LO-1 in the prostate [human fifteen lipoxygenase-1 in mouse prostate (FLiMP]. We used a Cre- mediated and a loxP-mediated recombination strategy to target h15-LO-1 specifically to the prostate of C57BL/6 mice. Wild-type (wt, FLiMP+/-, and FLiMP+/+ mice aged 7 to 21, 24 to 28, and 35 weeks were characterized by histopathology, immunohistochemistry (IHC, and DNA/RNA and enzyme analyses. Compared to wt mice, h15-LO-1 enzyme activity was increased similarly in both homozygous FLiMP+/+ and hemizygous FLiMP+/- prostates. Dorsolateral and ventral prostates of FLiMP mice showed focal and progressive epithelial hyperplasia with nuclear atypia, indicative of the definition of mouse prostatic intraepithelial neoplasia (mPIN according to the National Cancer Institute. These foci showed increased proliferation by Ki-67 IHC. No progression to invasive PCa was noted up to 35 weeks. By IHC, h15-LO-1 expression was limited to luminal epithelial cells, with increased expression in mPIN foci (similar to human HGPIN. In summary, targeted overexpression of h

  19. Mechanism of testosterone deficiency in the transgenic sickle cell mouse.

    Directory of Open Access Journals (Sweden)

    Biljana Musicki

    Full Text Available Testosterone deficiency is associated with sickle cell disease (SCD, but its underlying mechanism is not known. We investigated the possible occurrence and mechanism of testosterone deficiency in a mouse model of human SCD. Transgenic sickle male mice (Sickle exhibited decreased serum and intratesticular testosterone and increased luteinizing hormone (LH levels compared with wild type (WT mice, indicating primary hypogonadism in Sickle mice. LH-, dbcAMP-, and pregnenolone- (but not 22-hydroxycholesterol- stimulated testosterone production by Leydig cells isolated from the Sickle mouse testis was decreased compared to that of WT mice, implying defective Leydig cell steroidogenesis. There also was reduced protein expression of steroidogenic acute regulatory protein (STAR, but not cholesterol side-chain cleavage enzyme (P450scc, in the Sickle mouse testis. These data suggest that the capacity of P450scc to support testosterone production may be limited by the supply of cholesterol to the mitochondria in Sickle mice. The sickle mouse testis exhibited upregulated NADPH oxidase subunit gp91phox and increased oxidative stress, measured as 4-hydroxy-2-nonenal, and unchanged protein expression of an antioxidant glutathione peroxidase-1. Mice heterozygous for the human sickle globin (Hemi exhibited intermediate hypogonadal changes between those of WT and Sickle mice. These results demonstrate that testosterone deficiency occurs in Sickle mice, mimicking the human condition. The defects in the Leydig cell steroidogenic pathway in Sickle mice, mainly due to reduced availability of cholesterol for testosterone production, may be related to NADPH oxidase-derived oxidative stress. Our findings suggest that targeting testicular oxidative stress or steroidogenesis mechanisms in SCD offers a potential treatment for improving phenotypic changes associated with testosterone deficiency in this disease.

  20. Cholesterol depletion disorganizes oocyte membrane rafts altering mouse fertilization.

    Directory of Open Access Journals (Sweden)

    Jorgelina Buschiazzo

    Full Text Available Drastic membrane reorganization occurs when mammalian sperm binds to and fuses with the oocyte membrane. Two oocyte protein families are essential for fertilization, tetraspanins and glycosylphosphatidylinositol-anchored proteins. The firsts are associated to tetraspanin-enriched microdomains and the seconds to lipid rafts. Here we report membrane raft involvement in mouse fertilization assessed by cholesterol modulation using methyl-β-cyclodextrin. Cholesterol removal induced: (1 a decrease of the fertilization rate and index; and (2 a delay in the extrusion of the second polar body. Cholesterol repletion recovered the fertilization ability of cholesterol-depleted oocytes, indicating reversibility of these effects. In vivo time-lapse analyses using fluorescent cholesterol permitted to identify the time-point at which the probe is mainly located at the plasma membrane enabling the estimation of the extent of the cholesterol depletion. We confirmed that the mouse oocyte is rich in rafts according to the presence of the raft marker lipid, ganglioside GM1 on the membrane of living oocytes and we identified the coexistence of two types of microdomains, planar rafts and caveolae-like structures, by terms of two differential rafts markers, flotillin-2 and caveolin-1, respectively. Moreover, this is the first report that shows characteristic caveolae-like invaginations in the mouse oocyte identified by electron microscopy. Raft disruption by cholesterol depletion disturbed the subcellular localization of the signal molecule c-Src and the inhibition of Src kinase proteins prevented second polar body extrusion, consistent with a role of Src-related kinases in fertilization via signaling complexes. Our data highlight the functional importance of intact membrane rafts for mouse fertilization and its dependence on cholesterol.

  1. Delimiting species without nuclear monophyly in Madagascar's mouse lemurs.

    Directory of Open Access Journals (Sweden)

    David W Weisrock

    Full Text Available BACKGROUND: Speciation begins when populations become genetically separated through a substantial reduction in gene flow, and it is at this point that a genetically cohesive set of populations attain the sole property of species: the independent evolution of a population-level lineage. The comprehensive delimitation of species within biodiversity hotspots, regardless of their level of divergence, is important for understanding the factors that drive the diversification of biota and for identifying them as targets for conservation. However, delimiting recently diverged species is challenging due to insufficient time for the differential evolution of characters--including morphological differences, reproductive isolation, and gene tree monophyly--that are typically used as evidence for separately evolving lineages. METHODOLOGY: In this study, we assembled multiple lines of evidence from the analysis of mtDNA and nDNA sequence data for the delimitation of a high diversity of cryptically diverged population-level mouse lemur lineages across the island of Madagascar. Our study uses a multi-faceted approach that applies phylogenetic, population genetic, and genealogical analysis for recognizing lineage diversity and presents the most thoroughly sampled species delimitation of mouse lemur ever performed. CONCLUSIONS: The resolution of a large number of geographically defined clades in the mtDNA gene tree provides strong initial evidence for recognizing a high diversity of population-level lineages in mouse lemurs. We find additional support for lineage recognition in the striking concordance between mtDNA clades and patterns of nuclear population structure. Lineages identified using these two sources of evidence also exhibit patterns of population divergence according to genealogical exclusivity estimates. Mouse lemur lineage diversity is reflected in both a geographically fine-scaled pattern of population divergence within established and

  2. Graded Maximal Exercise Testing to Assess Mouse Cardio-Metabolic Phenotypes.

    Directory of Open Access Journals (Sweden)

    Jennifer M Petrosino

    Full Text Available Functional assessments of cardiovascular fitness (CVF are needed to establish animal models of dysfunction, test the effects of novel therapeutics, and establish the cardio-metabolic phenotype of mice. In humans, the graded maximal exercise test (GXT is a standardized diagnostic for assessing CVF and mortality risk. These tests, which consist of concurrent staged increases in running speed and inclination, provide diagnostic cardio-metabolic parameters, such as, VO2max, anaerobic threshold, and metabolic crossover. Unlike the human-GXT, published mouse treadmill tests have set, not staged, increases in inclination as speed progress until exhaustion (PXT. Additionally, they often lack multiple cardio-metabolic parameters. Here, we developed a mouse-GXT with the intent of improving mouse-exercise testing sensitivity and developing translatable parameters to assess CVF in healthy and dysfunctional mice. The mouse-GXT, like the human-GXT, incorporated staged increases in inclination, speed, and intensity; and, was designed by considering imitations of the PXT and differences between human and mouse physiology. The mouse-GXT and PXTs were both tested in healthy mice (C57BL/6J, FVBN/J to determine their ability to identify cardio-metabolic parameters (anaerobic threshold, VO2max, metabolic crossover observed in human-GXTs. Next, theses assays were tested on established diet-induced (obese-C57BL/6J and genetic (cardiac isoform Casq2-/- models of cardiovascular dysfunction. Results showed that both tests reported VO2max and provided reproducible data about performance. Only the mouse-GXT reproducibly identified anaerobic threshold, metabolic crossover, and detected impaired CVF in dysfunctional models. Our findings demonstrated that the mouse-GXT is a sensitive, non-invasive, and cost-effective method for assessing CVF in mice. This new test can be used as a functional assessment to determine the cardio-metabolic phenotype of various animal models or

  3. Lineage-specific biology revealed by a finished genome assembly of the mouse.

    Directory of Open Access Journals (Sweden)

    Deanna M Church

    2009-05-01

    Full Text Available The mouse (Mus musculus is the premier animal model for understanding human disease and development. Here we show that a comprehensive understanding of mouse biology is only possible with the availability of a finished, high-quality genome assembly. The finished clone-based assembly of the mouse strain C57BL/6J reported here has over 175,000 fewer gaps and over 139 Mb more of novel sequence, compared with the earlier MGSCv3 draft genome assembly. In a comprehensive analysis of this revised genome sequence, we are now able to define 20,210 protein-coding genes, over a thousand more than predicted in the human genome (19,042 genes. In addition, we identified 439 long, non-protein-coding RNAs with evidence for transcribed orthologs in human. We analyzed the complex and repetitive landscape of 267 Mb of sequence that was missing or misassembled in the previously published assembly, and we provide insights into the reasons for its resistance to sequencing and assembly by whole-genome shotgun approaches. Duplicated regions within newly assembled sequence tend to be of more recent ancestry than duplicates in the published draft, correcting our initial understanding of recent evolution on the mouse lineage. These duplicates appear to be largely composed of sequence regions containing transposable elements and duplicated protein-coding genes; of these, some may be fixed in the mouse population, but at least 40% of segmentally duplicated sequences are copy number variable even among laboratory mouse strains. Mouse lineage-specific regions contain 3,767 genes drawn mainly from rapidly-changing gene families associated with reproductive functions. The finished mouse genome assembly, therefore, greatly improves our understanding of rodent-specific biology and allows the delineation of ancestral biological functions that are shared with human from derived functions that are not.

  4. A pink mouse reports the switch from red to green fluorescence upon Cre-mediated recombination

    Directory of Open Access Journals (Sweden)

    Hartwich Heiner

    2012-06-01

    Full Text Available Abstract Background Targeted genetic modification in the mouse becomes increasingly important in biomedical and basic science. This goal is most often achieved by use of the Cre/loxP system and numerous Cre-driver mouse lines are currently generated. Their initial characterization requires reporter mouse lines to study the in vivo spatiotemporal activity of Cre. Findings Here, we report a dual fluorescence reporter mouse line, which switches expression from the red fluorescent protein mCherry to eGFP after Cre-mediated recombination. Both fluorescent proteins are expressed from the ubiquitously active and strong CAGGS promoter. Among the founders, we noticed a pink mouse line, expressing high levels of the red fluorescent protein mCherry throughout the entire body. Presence of mCherry in the living animal as well as in almost all organs was clearly visible without optical equipment. Upon Cre-activity, mCherry expression was switched to eGFP, demonstrating functionality of this reporter mouse line. Conclusions The pink mouse presented here is an attractive novel reporter line for fluorescence-based monitoring of Cre-activity. The high expression of mCherry, which is visible to the naked eye, facilitates breeding and crossing, as no genotyping is required to identify mice carrying the reporter allele. The presence of two fluorescent proteins allows in vivo monitoring of recombined and non-recombined cells. Finally, the pink mouse is an eye-catching animal model to demonstrate the power of transgenic techniques in teaching courses.

  5. Combination restoration in full mouth rehabilitation

    Directory of Open Access Journals (Sweden)

    Sanjna Nayar

    2015-01-01

    Full Text Available Successful restoration of the dentition requires plenty of contemporary and conventional treatment techniques and planning and attachment retained partial dentures are one such kind of treatment modality in prosthodontics. Satisfactory restoration in a patient with a partially edentulous situation can be challenging especially when unilateral or bilateral posterior segment of teeth is missing. One such treatment modality is attachment-retained cast partial dentures. The purpose of this article is to provide an overview of a case with maxillary complete denture and opposing cast partial denture with precision attachment.

  6. A World of Full of Voices

    Directory of Open Access Journals (Sweden)

    Carolyn Kenny

    2006-07-01

    Full Text Available For several hundred years now, the primary research method in anthropology has been ethnography. One does not see many experimental studies that use randomized clinical trials in the study of culture. And there is a very practical reason for this. Culture is far too complex to control variables. Culture cannot be studied in a lab. Culture is its own unique kind of container with implied signals that are difficult to observe. Culture is lived within a context, but not in a laboratory. So we have thick descriptions to help us find knowledge and truth about the lives lived within these contexts. We have stories.

  7. Full Scale Experiment with Interactive Urban Lighting

    DEFF Research Database (Denmark)

    Poulsen, Esben Skouboe; Andersen, Hans Jørgen; Jensen, Ole B.

    2012-01-01

    This paper presents and discusses the results of a full-scale interactive urban illumination experiment. The experiment investigates how human motion intensities can be used as input for controlling the illumination of a town square in the city of Aalborg in Denmark. The trajectory, velocity...... changed according to their presence or actions, whereas people watching from the outside noticed to a larger degree the interaction between the illumination and the immersed persons. We seek to develop new knowledge about the experience of responsive environments and to explore technical, social...

  8. The PS Booster's ejection kicker: full house.

    CERN Multimedia

    1971-01-01

    The modules of the Booster's four-storied full-aperture kicker pretty much fill their vacuum tank (front cover removed). In the original 800 MeV version, the delay-type modules were pulsed at 30 kV from a Pulse-Forming-Network (PFN), yielding a field risetime as short as 60 ns. The fieldstrength was 0.1 T at a current of 1200 A. The modules are made from steel plates and ferrite slabs. The ferrite's high initial outgassing rate presented a serious vacuum problem for a long time.

  9. A Representation of Permutations with Full Cycle

    CERN Document Server

    Cesmelioglu, Ayca

    2010-01-01

    For q > 2, Carlitz proved that the group of permutation polynomials (PPs) over F_q is generated by linear polynomials and x^{q-2}. Based on this result, this note points out a simple method for representing all PPs with full cycle over the prime field F_p, where p is an odd prime. We use the isomorphism between the symmetric group S_p of p elements and the group of PPs over F_p, and the well-known fact that permutations in S_p have the same cycle structure if and only if they are conjugate.

  10. Brownian semistationary processes and conditional full support

    CERN Document Server

    Pakkanen, Mikko S

    2010-01-01

    In this note, we study the infinite-dimensional conditional laws of Brownian semistationary processes. Motivated by the fact that these processes are typically not semimartingales, we present sufficient conditions ensuring that a Brownian semistationary process has conditional full support, a property introduced by Guasoni, R\\'asonyi, and Schachermayer [Ann. Appl. Probab., 18 (2008) pp. 491--520]. By the results of Guasoni, R\\'asonyi, and Schachermayer, this property has two important implications. It ensures, firstly, that the process admits no free lunches under proportional transaction costs, and secondly, that it can be approximated pathwise (in the sup norm) by semimartingales that admit equivalent martingale measures.

  11. Full spectrum millimeter-wave modulation.

    Science.gov (United States)

    Macario, Julien; Yao, Peng; Shi, Shouyuan; Zablocki, Alicia; Harrity, Charles; Martin, Richard D; Schuetz, Christopher A; Prather, Dennis W

    2012-10-01

    In recent years, the development of new lithium niobate electro-optic modulator designs and material processing techniques have contributed to support the increasing need for faster optical networks by considerably extending the operational bandwidth of modulators. In an effort to provide higher bandwidths for future generations of networks, we have developed a lithium niobate electro-optic phase modulator based on a coplanar waveguide ridged structure that operates up to 300 GHz. By thinning the lithium niobate substrate down to less than 39 µm, we are able to eliminate substrate modes and observe optical sidebands over the full millimeter-wave spectrum.

  12. Full Elasticity Tensor from Thermal Diffuse Scattering

    Science.gov (United States)

    Wehinger, Björn; Mirone, Alessandro; Krisch, Michael; Bosak, Alexeï

    2017-01-01

    We present a method for the precise determination of the full elasticity tensor from a single crystal diffraction experiment using monochromatic x rays. For the two benchmark systems calcite and magnesium oxide, we show that the measurement of thermal diffuse scattering in the proximity of Bragg reflections provides accurate values of the complete set of elastic constants. This approach allows for a reliable and model-free determination of the elastic properties and can be performed together with crystal structure investigation in the same experiment.

  13. Full-field wafer warpage measurement technique

    Science.gov (United States)

    Hsieh, H. L.; Lee, J. Y.; Huang, Y. G.; Liang, A. J.; Sun, B. Y.

    2017-06-01

    An innovative moiré technique for full-field wafer warpage measurement is proposed in this study. The wafer warpage measurement technique is developed based on moiré method, Talbot effect, scanning profiling method, stroboscopic, instantaneous phase-shift method, as well as four-step phase shift method, high resolution, high stability and full-field measurement capabilities can be easily achieved. According to the proposed full-field optical configuration, a laser beam is expanded into a collimated beam with a 2-inch diameter and projected onto the wafer surface. The beam is reflected by the wafer surface and forms a moiré fringe image after passing two circular gratings, which is then focused and captured on a CCD camera for computation. The corresponding moiré fringes reflected from the wafer surface are obtained by overlapping the images of the measuring grating and the reference grating. The moiré fringes will shift when wafer warpage occurs. The phase of the moiré fringes will change proportionally to the degree of warpage in the wafer, which can be measured by detecting variations in the phase shift of the moiré fringes in each detection points on the surface of the entire wafer. The phase shift variations of each detection points can be calculated via the instantaneous phase-shift method and the four-step phase-shift method. By adding up the phase shift variations of each detection points along the radii of the circular gratings, the warpage value and surface topography of the wafer can be obtained. Experiments show that the proposed method is capable of obtaining test results similar to that of a commercial sensor, as well as performing accurate measurements under high speed rotation of 1500rpm. As compared to current warpage measurement methods such as the beam optical method, confocal microscopy, laser interferometry, shadow moiré method, and structured light method, this proposed technique has the advantage of full-field measurement, high

  14. Optimal Transport for Seismic Full Waveform Inversion

    CERN Document Server

    Engquist, Bjorn; Yang, Yunan

    2016-01-01

    Full waveform inversion is a successful procedure for determining properties of the earth from surface measurements in seismology. This inverse problem is solved by a PDE constrained optimization where unknown coefficients in a computed wavefield are adjusted to minimize the mismatch with the measured data. We propose using the Wasserstein metric, which is related to optimal transport, for measuring this mismatch. Several advantageous properties are proved with regards to convexity of the objective function and robustness with respect to noise. The Wasserstein metric is computed by solving a Monge-Ampere equation. We describe an algorithm for computing its Frechet gradient for use in the optimization. Numerical examples are given.

  15. Forty Defective Criticisms of Full Reserve Banking

    OpenAIRE

    Musgrave, Ralph S.

    2016-01-01

    Abstract. The basics of full reserve banking (FR) are set out below, followed by forty defective criticisms of FR. Each of those forty sections has: 1. A heading. 2. Where the heading does not adequately capture the nature of the criticism, there is a paragraph below the heading starting “I.e…”, which expands on the heading. 3. There are references to one or more economists who have put the relevant criticism. 4. The answer to each criticism which starts with a paragraph beginning with the wo...

  16. [Dogs, man-wolves and full moon].

    Science.gov (United States)

    Goddemeier, Christof

    2002-06-01

    According to a study of the British Medical Journal in England the incidence of dog bites increases at the time of a full moon. The following article first passes the myths dealing with the werewolf. By changing from delinquent to patient during the Enlightenment the werewolf gets important to the history of medicine and psychiatry. From the anthropological point of view the so-called Lycorexia may be understood as an unconscious effort to undo evolution by transformation into beast. By the figure of the "Huckup" in recent variants concerning the werewolf subject a psychological turn of the legend is expressed.

  17. Lithium compensation for full cell operation

    Science.gov (United States)

    Xiao, Jie; Zheng, Jianming; Chen, Xilin; Lu, Dongping; Liu, Jun; Jiguang, Jiguang

    2016-05-17

    Disclosed herein are embodiments of a lithium-ion battery system comprising an anode, an anode current collector, and a layer of lithium metal in contact with the current collector, but not in contact with the anode. The lithium compensation layer dissolves into the electrolyte to compensate for the loss of lithium ions during usage of the full cell. The specific placement of the lithium compensation layer, such that there is no direct physical contact between the lithium compensation layer and the anode, provides certain advantages.

  18. Towards the integration of mouse databases - definition and implementation of solutions to two use-cases in mouse functional genomics

    Directory of Open Access Journals (Sweden)

    Schofield Paul

    2010-01-01

    Full Text Available Abstract Background The integration of information present in many disparate biological databases represents a major challenge in biomedical research. To define the problems and needs, and to explore strategies for database integration in mouse functional genomics, we consulted the biologist user community and implemented solutions to two user-defined use-cases. Results We organised workshops, meetings and used a questionnaire to identify the needs of biologist database users in mouse functional genomics. As a result, two use-cases were developed that can be used to drive future designs or extensions of mouse databases. Here, we present the use-cases and describe some initial computational solutions for them. The application for the gene-centric use-case, "MUSIG-Gen" starts from a list of gene names and collects a wide range of data types from several distributed databases in a "shopping cart"-like manner. The iterative user-driven approach is a response to strongly articulated requests from users, especially those without computational biology backgrounds. The application for the phenotype-centric use-case, "MUSIG-Phen", is based on a similar concept and starting from phenotype descriptions retrieves information for associated genes. Conclusion The use-cases created, and their prototype software implementations should help to better define biologists' needs for database integration and may serve as a starting point for future bioinformatics solutions aimed at end-user biologists.

  19. Radiosensitivity of cultured human and mouse keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    Parkinson, E.K.; Hume, W.J.; Potten, C.S.

    1986-10-01

    Clonogenic survival assays after ..gamma..-radiation in vitro were performed on freshly isolated and subcultured keratinocytes from mouse skin, mouse tongue and human skin. Survival curves were constructed by fitting the data to a multi-target model of cell survival. When subcultured, keratinocytes from all sites produced survival curves which showed a reduced shoulder region and an increased D/sub 0/ when compared with their freshly isolated counterparts. Freshly isolated human skin keratinocytes were more radiosensitive than mouse keratinocytes from either skin or tongue.

  20. ROSA full-core and DNBR capabilities

    Energy Technology Data Exchange (ETDEWEB)

    Gibcus, H.P.M.; Verhagen, F.C.M.; Wakker, P.H. [NRG, Arnhem (Netherlands)

    2012-11-01

    This paper presents the latest developments of the ROSA (Reloading Optimization by Simulated Annealing) code system with an emphasis on the first full-core version and the minimum DNBR (Departure from Nucleate Boiling Ratio) as a new optimization parameter. Designing the core loading pattern of nuclear power plants is becoming a more and more complex task. This task becomes even more complicated if asymmetries in the core loading pattern arise, for instance due to damaged fuel assemblies. For over almost two decades ROSA, NRG's (Nuclear Research and consultancy Group) loading pattern optimization code system for PWRs, has proven to be a valuable tool to reactor operators in accomplishing this task. To improve the use of ROSA for designing asymmetric loading patterns, NRG has developed a full-core version of ROSA besides the original quarter-core version which requires rotational symmetry in the computational domain. The extension of ROSA with DNBR as an optimization parameter is part of ROSA's continuous development. (orig.)

  1. ROSA full-core and DNBR capabilities

    Energy Technology Data Exchange (ETDEWEB)

    Gibcus, H.P.M.; Verhagen, F.C.M.; Wakker, P.H. [NRG, Arnhem (Netherlands)

    2013-06-15

    The latest developments of the ROSA (Reloading Optimization by Simulated Annealing) code system with an emphasis on the first full-core version and the minimum DNBR (Departure from Nucleate Boiling Ratio) as a new optimization parameter are presented. Designing the core loading pattern of nuclear power plants is becoming a more and more complex task. This task becomes even more complicated if asymmetries in the core loading pattern arise, for instance due to damaged fuel assemblies. For over almost 2 decades ROSA, NRG's (Nuclear Research and consultancy Group) loading pattern optimization code system for PWRs, has proven to be a valuable tool to reactor operators in accomplishing this task. To improve the use of ROSA for designing asymmetric loading patterns, NRG has developed a full-core version of ROSA besides the original quarter-core version which requires rotational symmetry in the computational domain. The extension of ROSA with DNBR as an optimization parameter is part of ROSA's continuous development. (orig.)

  2. Full-color holographic 3D printer

    Science.gov (United States)

    Takano, Masami; Shigeta, Hiroaki; Nishihara, Takashi; Yamaguchi, Masahiro; Takahashi, Susumu; Ohyama, Nagaaki; Kobayashi, Akihiko; Iwata, Fujio

    2003-05-01

    A holographic 3D printer is a system that produces a direct hologram with full-parallax information using the 3-dimensional data of a subject from a computer. In this paper, we present a proposal for the reproduction of full-color images with the holographic 3D printer. In order to realize the 3-dimensional color image, we selected the 3 laser wavelength colors of red (λ=633nm), green (λ=533nm), and blue (λ=442nm), and we built a one-step optical system using a projection system and a liquid crystal display. The 3-dimensional color image is obtained by synthesizing in a 2D array the multiple exposure with these 3 wavelengths made on each 250mm elementary hologram, and moving recording medium on a x-y stage. For the natural color reproduction in the holographic 3D printer, we take the approach of the digital processing technique based on the color management technology. The matching between the input and output colors is performed by investigating first, the relation between the gray level transmittance of the LCD and the diffraction efficiency of the hologram and second, by measuring the color displayed by the hologram to establish a correlation. In our first experimental results a non-linear functional relation for single and multiple exposure of the three components were found. These results are the first step in the realization of a natural color 3D image produced by the holographic color 3D printer.

  3. NASA project 1: Full-body dynamometer

    Science.gov (United States)

    Lu, Li-Dai

    1993-01-01

    In space, where the body does only a fraction of work it does on earth, muscle atrophy is a major concern. The bones and the muscles will begin to deteriorate after a short stay in weightlessness. Bone decalcification appears to be a major problem with extensive living in microgravity. Resistance exercise is not only essential to prevent muscle atrophy in space, it also helps to keep bone decalcification in check. For a space station, where the astronauts are expected to live for months at a time, exercise is especially important. Experts recommend about an hour and a half to two hours of exercise per day to keep the muscles in good condition in microgravity. The exercises will not only keep the astronauts in excellent physical condition, it will also make it easier for them to readjust to earth's gravity on return. The stationary bicycle and the treadmill have been the astronauts' primary sources of exercise since the 1970's. The major problem with both the stationary bicycle and the treadmill is that while they may keep the leg muscles from deteriorating in microgravity, they do little for muscles in the upper body. The National Aeronautics and Space Administration (NASA) is currently developing a full-body dynamometer (FBD), which will provide the astronauts with a full-body workout. It will also test the astronauts for muscle atrophy and rehabilitate the weakened muscle. The specification and the function structure for the FBD is presented.

  4. Cryptanalysis of the full Spritz stream cipher

    DEFF Research Database (Denmark)

    Banik, Subhadeep; Isobe, Takanori

    2016-01-01

    Spritz is a stream cipher proposed by Rivest and Schuldt at the rump session of CRYPTO 2014. It is intended to be a replacement of the popular RC4 stream cipher. In this paper we propose distinguishing attacks on the full Spritz, based on a short-term bias in the first two bytes of a keystream...... and a long-term bias in the first two bytes of every cycle of N keystream bytes, where N is the size of the internal permutation. Our attacks are able to distinguish a keystream of the full Spritz from a random sequence with samples of first two bytes produced by 244.8 multiple key-IV pairs or 260.......8 keystream bytes produced by a single key- IV pair. These biases are also useful in the event of plaintext recovery in a broadcast attack. In the second part of the paper, we look at a state recovery attack on Spritz, in a special situation when the cipher enters a class of weak states. We determine...

  5. ARKTOS full-scale evacuation tests

    Energy Technology Data Exchange (ETDEWEB)

    Seligman, B.; Hatfield, P. [ARKTOS Developments Ltd., Surrey, BC (Canada); Bercha, F. [Bercha Group, Calgary, AB (Canada)

    2008-09-15

    The ARKTOS amphibious vehicle can be used for evacuation operations in both open water and ice conditions. It is approved as an evacuation system by various regulators, such as the United States Coast Guard, and is operational in several marine cold regions as an escape, evacuation, and rescue (EER) system. An EER research project was performed in 2006 that provided a general reliability evaluation of the ARKTOS system. However, the project did not have the benefit of detailed full-scale tests in order to validate the associated computer model in drill or non-life threatening evacuation conditions. This paper described a follow-up set of full-scale evacuation tests designed to provide more detailed information and validation data for the reliability that the computer model described in the 2006 research project. A description and photographic illustrations of the ARKTOS system were presented. The tests and subsequent analyses were described. Specifically, the paper described the observations, and presented the statistical results from the data collected, and compared observed results with predicted results of a probabilistic EER simulation computer model. Conclusions and recommendations for reliability improvements were also provided. It was concluded that under the benign conditions, the drill performance was satisfactory in all aspects, both in the evacuation activities and the rescue or de-boarding activities. 3 refs., 1 tab., 17 figs.

  6. Wind Turbine Experiments at Full Dynamic Similarity

    Science.gov (United States)

    Miller, Mark; Kiefer, Janik; Westergaard, Carsten; Hultmark, Marcus

    2015-11-01

    Performing experiments with scaled-down wind turbines has traditionally been difficult due to the matching requirements of the two driving non-dimensional parameters, the Tip Speed Ratio (TSR) and the Reynolds number. Typically, full-size turbines must be used to provide the baseline cases for engineering models and computer simulations where flow similarity is required. We present a new approach to investigating wind turbine aerodynamics at full dynamic similarity by employing a high-pressure wind tunnel at Princeton University known as the High Reynolds number Test Facility (or HRTF). This facility allows for Reynolds numbers of up to 3 million (based on chord and velocity at the tip) while still matching the TSR, on a geometrically similar, small-scale model. The background development of this project is briefly presented including the design and manufacture of a model turbine. Following this the power, thrust and wake data are discussed, in particular the scaling dependence on the Reynolds number. Supported under NSF grant CBET-1435254 (program manager Gregory Rorrer).

  7. Cloning and characterization of mouse growth hormone-releasing hormone (GRH) complementary DNA: increased GRH messenger RNA levels in the growth hormone-deficient lit/lit mouse.

    Science.gov (United States)

    Frohman, M A; Downs, T R; Chomczynski, P; Frohman, L A

    1989-10-01

    We have isolated and cloned the full length cDNA for mouse GH-releasing hormone (mGRH) from mouse hypothalamus using a recently described strategy involving the polymerase chain reaction technique (PCR). Degenerate oligonucleotide primers were selected based on short (six amino acids) conserved regions in the human and rat GRH peptides that would recognize DNA sequences encoding similar amino acids regardless of codon usage. Primer-extended cDNA was amplified by PCR on cDNA templates prepared by reverse transcribing total mouse hypothalamic RNA. After cloning and sequencing the initial product, the 3' and 5' ends of mGRH were generated using a separate PCR strategy (RACE protocol). The mGRH cDNA encodes a 103-amino acid reading frame, structurally similar to the human and rat GRH genes, containing a signal sequence, a 42-residue GRH peptide, and a 31-residue C-terminal region. Although the structures of mouse and rat GRH are highly conserved in the signal peptide and C-terminal region, there is considerable diversity in the GRH region, which exhibits nearly comparable homology with the rat (68%) and human (62%) structures. Differences between mouse and rat GRH were also found in the amino acid cleavage sites at the 5' and 3' ends of the mature peptide and at the polyadenylation signal.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Selective expression of myosin IC Isoform A in mouse and human cell lines and mouse prostate cancer tissues.

    Directory of Open Access Journals (Sweden)

    Ivanna Ihnatovych

    Full Text Available Myosin IC is a single headed member of the myosin superfamily. We recently identified a novel isoform and showed that the MYOIC gene in mammalian cells encodes three isoforms (isoforms A, B, and C. Furthermore, we demonstrated that myosin IC isoform A but not isoform B exhibits a tissue specific expression pattern. In this study, we extended our analysis of myosin IC isoform expression patterns by analyzing the protein and mRNA expression in various mammalian cell lines and in various prostate specimens and tumor tissues from the transgenic mouse prostate (TRAMP model by immunoblotting, qRT-PCR, and by indirect immunohistochemical staining of paraffin embedded prostate specimen. Analysis of a panel of mammalian cell lines showed an increased mRNA and protein expression of specifically myosin IC isoform A in a panel of human and mouse prostate cancer cell lines but not in non-cancer prostate or other (non-prostate- cancer cell lines. Furthermore, we demonstrate that myosin IC isoform A expression is significantly increased in TRAMP mouse prostate samples with prostatic intraepithelial neoplasia (PIN lesions and in distant site metastases in lung and liver when compared to matched normal tissues. Our observations demonstrate specific changes in the expression of myosin IC isoform A that are concurrent with the occurrence of prostate cancer in the TRAMP mouse prostate cancer model that closely mimics clinical prostate cancer. These data suggest that elevated levels of myosin IC isoform A may be a potential marker for the detection of prostate cancer.

  9. Full-Scale Tunnel (FST) model

    Science.gov (United States)

    1929-01-01

    Model of Full-Scale Tunnel (FST) under construction. On June 26, 1929, Elton W. Miller wrote to George W. Lewis proposing the construction of a model of the full-scale tunnel . 'The excellent energy ratio obtained in the new wind tunnel of the California Institute of Technology suggests that before proceeding with our full scale tunnel design, we ought to investigate the effect on energy ratio of such factors as: 1. Small included angle for the exit cone; 2. Carefully designed return passages of circular section as far as possible, without sudden changes in cross sections; 3. Tightness of walls. It is believed that much useful information can be obtained by building a model of about 1/16 scale, that is, having a closed throat of 2 ft. by 4 ft. The outside dimensions would be about 12 ft. by 25 ft. in plan and the height 4 ft. Two propellers will be required about 28 in. in diameter, each to be driven by direct current motor at a maximum speed of 4500 R.P.M. Provision can be made for altering the length of certain portions, particularly the exit cone, and possibly for the application of boundary layer control in order to effect satisfactory air flow. This model can be constructed in a comparatively short time, using 2 by 4 framing with matched sheathing inside, and where circular sections are desired they can be obtained by nailing sheet metal to wooden ribs, which can be cut on the band saw. It is estimated that three months will be required for the construction and testing of such a model and that the cost will be approximately three thousand dollars, one thousand dollars of which will be for the motors. No suitable location appears to exist in any of our present buildings, and it may be necessary to build it outside and cover it with a roof.' George Lewis responded immediately (June 27) granting the authority to proceed. He urged Langley to expedite construction and to employ extra carpenters if necessary. Funds for the model came from the FST project. In a 1979

  10. Towards Full-Waveform Ambient Noise Inversion

    Science.gov (United States)

    Sager, Korbinian; Ermert, Laura; Afanasiev, Michael; Boehm, Christian; Fichtner, Andreas

    2017-04-01

    Noise tomography usually works under the assumption that the inter-station ambient noise correlation is equal to a scaled version of the Green function between the two receivers. This assumption, however, is only met under specific conditions, e.g. wavefield diffusivity and equipartitioning, or the isotropic distribution of both mono- and dipolar uncorrelated noise sources. These assumptions are typically not satisfied in the Earth. This inconsistency inhibits the exploitation of the full waveform information contained in noise correlations in order to constrain Earth structure and noise generation. To overcome this limitation, we attempt to develop a method that consistently accounts for the distribution of noise sources, 3D heterogeneous Earth structure and the full seismic wave propagation physics. This is intended to improve the resolution of tomographic images, to refine noise source distribution, and thereby to contribute to a better understanding of both Earth structure and noise generation. First, we develop an inversion strategy based on a 2D finite-difference code using adjoint techniques. To enable a joint inversion for noise sources and Earth structure, we investigate the following aspects: i) the capability of different misfit functionals to image wave speed anomalies and source distribution and ii) possible source-structure trade-offs, especially to what extent unresolvable structure can be mapped into the inverted noise source distribution and vice versa. In anticipation of real-data applications, we present an extension of the open-source waveform modelling and inversion package Salvus (http://salvus.io). It allows us to compute correlation functions in 3D media with heterogeneous noise sources at the surface and the corresponding sensitivity kernels for the distribution of noise sources and Earth structure. By studying the effect of noise sources on correlation functions in 3D, we validate the aforementioned inversion strategy and prepare the

  11. Alterations in Striatal Synaptic Transmission are Consistent across Genetic Mouse Models of Huntington's Disease

    Directory of Open Access Journals (Sweden)

    Damian M Cummings

    2010-05-01

    Full Text Available Since the identification of the gene responsible for HD (Huntington's disease, many genetic mouse models have been generated. Each employs a unique approach for delivery of the mutated gene and has a different CAG repeat length and background strain. The resultant diversity in the genetic context and phenotypes of these models has led to extensive debate regarding the relevance of each model to the human disorder. Here, we compare and contrast the striatal synaptic phenotypes of two models of HD, namely the YAC128 mouse, which carries the full-length huntingtin gene on a yeast artificial chromosome, and the CAG140 KI*** (knock-in mouse, which carries a human/mouse chimaeric gene that is expressed in the context of the mouse genome, with our previously published data obtained from the R6/2 mouse, which is transgenic for exon 1 mutant huntingtin. We show that striatal MSNs (medium-sized spiny neurons in YAC128 and CAG140 KI mice have similar electrophysiological phenotypes to that of the R6/2 mouse. These include a progressive increase in membrane input resistance, a reduction in membrane capacitance, a lower frequency of spontaneous excitatory postsynaptic currents and a greater frequency of spontaneous inhibitory postsynaptic currents in a subpopulation of striatal neurons. Thus, despite differences in the context of the inserted gene between these three models of HD, the primary electrophysiological changes observed in striatal MSNs are consistent. The outcomes suggest that the changes are due to the expression of mutant huntingtin and such alterations can be extended to the human condition.

  12. Alterations in striatal synaptic transmission are consistent across genetic mouse models of Huntington's disease

    Directory of Open Access Journals (Sweden)

    Damian M Cummings

    2010-06-01

    Full Text Available Since the identification of the gene responsible for HD (Huntington's disease, many genetic mouse models have been generated. Each employs a unique approach for delivery of the mutated gene and has a different CAG repeat length and background strain. The resultant diversity in the genetic context and phenotypes of these models has led to extensive debate regarding the relevance of each model to the human disorder. Here, we compare and contrast the striatal synaptic phenotypes of two models of HD, namely the YAC128 mouse, which carries the full-length huntingtin gene on a yeast artificial chromosome, and the CAG140 KI (knock-in mouse, which carries a human/mouse chimaeric gene that is expressed in the context of the mouse genome, with our previously published data obtained from the R6/2 mouse, which is transgenic for exon 1 mutant huntingtin. We show that striatal MSNs (medium-sized spiny neurons in YAC128 and CAG140 KI mice have similar electrophysiological phenotypes to that of the R6/2 mouse. These include a progressive increase in membrane input resistance, a reduction in membrane capacitance, a lower frequency of spontaneous excitatory postsynaptic currents and a greater frequency of spontaneous inhibitory postsynaptic currents in a subpopulation of striatal neurons. Thus, despite differences in the context of the inserted gene between these three models of HD, the primary electrophysiological changes observed in striatal MSNs are consistent. The outcomes suggest that the changes are due to the expression of mutant huntingtin and such alterations can be extended to the human condition.

  13. Narrow-Bicliques: Cryptanalysis of Full IDEA

    DEFF Research Database (Denmark)

    Khovratovich, D.; Leurent, G.; Rechberger, C.

    2012-01-01

    We apply and extend the recently introduced biclique framework to IDEA and for the first time describe an approach to noticeably speed-up key-recovery for the full 8.5 round IDEA.We also show that the biclique approach to block cipher cryptanalysis not only obtains results on more rounds, but also...... improves time and data complexities over existing attacks. We consider the first 7.5 rounds of IDEA and demonstrate a variant of the approach that works with practical data complexity. The conceptual contribution is the narrow-bicliques technique: the recently introduced independent-biclique approach...... the practical use of IDEA in any way, yet the techniques are practically verified to a large extent....

  14. Full Rotational Control of Levitated Silicon Nanorods

    CERN Document Server

    Kuhn, Stefan; Stickler, Benjamin A; Patolsky, Fernando; Hornberger, Klaus; Arndt, Markus; Millen, James

    2016-01-01

    We study a nanofabricated silicon rod levitated in an optical trap. By manipulating the polarization of the light we gain full control over the ro-translational dynamics of the rod. We are able to trap both its centre-of-mass and align it along the linear polarization of the laser field. The rod can be set into rotation at a tuned frequency by exploiting the radiation pressure exerted by elliptically polarized light. The rotational motion of the rod dynamically modifies the optical potential, which allows tuning of the rotational frequency over hundreds of Kilohertz. This ability to trap and control the motion and alignment of nanoparticles opens up the field of rotational optomechanics, rotational ground state cooling and the study of rotational thermodynamics in the underdamped regime.

  15. Full-term pregnancy in umbilical hernia

    Directory of Open Access Journals (Sweden)

    Damien Punguyire

    2011-01-01

    Full Text Available While umbilical hernias frequently occur during pregnancy, the few reported cases of uterine or fibroid incarceration in ventral hernias during pregnancy all involved incisional abdominal wall defects from prior laparotomies and Cesarean sections; none involved umbilical hernias. We discuss the case of a 42-year-old well-developed, well-nourished grand multiparous woman (G8P7 with a huge umbilical hernia containing a 38-week gravid uterus, as well as her management and the avoidance of known complications that have occurred in similar incisional hernia cases. Successful pregnancy outcomes can occur in cases of pregnancies in ventral hernias, even in resource-poor settings that have Cesarean section capabilities

  16. Full-color OLED on silicon microdisplay

    Science.gov (United States)

    Ghosh, Amalkumar P.

    2002-02-01

    eMagin has developed numerous enhancements to organic light emitting diode (OLED) technology, including a unique, up- emitting structure for OLED-on-silicon microdisplay devices. Recently, eMagin has fabricated full color SVGA+ resolution OLED microdisplays on silicon, with over 1.5 million color elements. The display is based on white light emission from OLED followed by LCD-type red, green and blue color filters. The color filters are patterned directly on OLED devices following suitable thin film encapsulation and the drive circuits are built directly on single crystal silicon. The resultant color OLED technology, with hits high efficiency, high brightness, and low power consumption, is ideally suited for near to the eye applications such as wearable PCS, wireless Internet applications and mobile phone, portable DVD viewers, digital cameras and other emerging applications.

  17. The fullness of empathy: reflections and illustrations.

    Science.gov (United States)

    Peloquin, S M

    1995-01-01

    Seven core values are said to undergird the profession of occupational therapy, with empathy serving as a hallmark of one of those values-personal dignity. This inquiry explores the meaning of empathy within a practice that holds occupation at its center. The literature on empathy in both philosophy and the behavioral sciences yields cogent thoughts about the fullness of empathy and its characteristics actions. The Healing Heart, the biography of a pioneer therapist, Ora Ruggles, shows the manner in which occupational therapists can be empathic in their practice. These reflections and illustrations serve to sharpen the vision of occupational therapists as persons who reach for both the hands and the hearts of others.

  18. Recent Advancements towards Full-Systems Microfluidics

    Directory of Open Access Journals (Sweden)

    Amine Miled

    2017-07-01

    Full Text Available Microfluidics is quickly becoming a key technology in an expanding range of fields, such as medical sciences, biosensing, bioactuation, chemical synthesis, and more. This is helping its transformation from a promising R&D tool to commercially viable technology. Fuelling this expansion is the intensified focus on automation and enhanced functionality through integration of complex electrical control, mechanical properties, in situ sensing and flow control. Here we highlight recent contributions to the Sensors Special Issue series called “Microfluidics-Based Microsystem Integration Research” under the following categories: (i Device fabrication to support complex functionality; (ii New methods for flow control and mixing; (iii Towards routine analysis and point of care applications; (iv In situ characterization; and (v Plug and play microfluidics.

  19. Full-wave current conveyor precision rectifier

    Directory of Open Access Journals (Sweden)

    Đukić Slobodan R.

    2008-01-01

    Full Text Available A circuit that provides precision rectification of small signal with low temperature sensitivity for frequencies up to 100 kHz without waveform distortion is presented. It utilizes an improved second type current conveyor based on current-steering output stage and biased silicon diodes. The use of a DC current source to bias the rectifying diodes provides higher temperature stability and lower DC offset level at the output. Proposed design of the precision rectifier ensures good current transfer linearity in the range that satisfy class A of the amplifier and good voltage transfer characteristic for low level signals. Distortion during the zero crossing of the input signal is practically eliminated. Design of the proposed rectifier is realized with standard components.

  20. Facies Constrained Elastic Full Waveform Inversion

    KAUST Repository

    Zhang, Z.

    2017-05-26

    Current efforts to utilize full waveform inversion (FWI) as a tool beyond acoustic imaging applications, for example for reservoir analysis, face inherent limitations on resolution and also on the potential trade-off between elastic model parameters. Adding rock physics constraints does help to mitigate these issues. However, current approaches to add such constraints are based on averaged type rock physics regularization terms. Since the true earth model consists of different facies, averaging over those facies naturally leads to smoothed models. To overcome this, we propose a novel way to utilize facies based constraints in elastic FWI. A so-called confidence map is calculated and updated at each iteration of the inversion using both the inverted models and the prior information. The numerical example shows that the proposed method can reduce the cross-talks and also can improve the resolution of inverted elastic properties.

  1. Full spectrum neurorestoratology: enhancing neuroresponse to disasters

    Directory of Open Access Journals (Sweden)

    Andrews RJ

    2014-07-01

    Full Text Available Russell J Andrews,1 Leonidas Quintana2 1Ames Research Center, Nanotechnology and Smart Systems, National Aeronautics and Space Administration, Moffett Field, CA, USA; 2Department of Neurosurgery, Valparaiso University School of Medicine, Valparaiso, Chile Abstract: With more than 200,000 deaths in some years from earthquakes alone, disasters, both natural and manmade, are a major challenge for neurorestoratology. To minimize permanent neurological injury and death, it is essential for treatment to begin immediately, within minutes ideally, but certainly within 24 hours. Fortunately, the humanitarian and medical response to disasters removes the socioeconomic, legal, and political barriers that can hinder the treatment of neurological disorders under normal (nondisaster situations. Here we review the resources and equipment already available as well as in development to enhance prompt treatment of neurological injuries arising from disasters. To be sustainable, the response to disasters must be integrated into the ongoing daily health care delivery systems worldwide, from medical education and specialty training (resident/registrar to acute and subacute intensive care to long-term rehabilitation. The "trauma center" concept developed in the USA and elsewhere for nonmass casualty response is an example of a program developed within the existing health care training and delivery infrastructure. We therefore propose a model for worldwide disaster response that integrates disaster neurorestoratology into health care delivery systems worldwide, both governmental and nongovernmental, and national and international. An overall blueprint is presented for the full spectrum of disaster neurorestoratology, from prevention of nervous system injury, to comprehensive and immediate acute care, to long-term neurorehabilitation. Such a comprehensive response to disasters would overcome the geographic, socioeconomic, and political barriers that presently impair

  2. Preconditioning Strategies in Elastic Full Waveform Inversion.

    Science.gov (United States)

    Matharu, G.; Sacchi, M. D.

    2016-12-01

    Elastic full waveform inversion (FWI) is inherently more non-linear than its acoustic counterpart, a property that stems from the increased model space of the problem. Whereas acoustic media can be parametrized by density and P-wave velocity, visco-elastic media are parametrized by density, attenuation and 21 independent coefficients of the elastic tensor. Imposing assumptions of isotropy and perfect elasticity to simplify the physics, reduces the number of independent parameters required to characterize a medium. Isotropic, elastic media can be parametrized in terms of density and the Lamé parameters. The different parameters can exhibit trade-off that manifest as attributes in the data. In the context of FWI, this means that certain parameters cannot be uniquely resolved. An ideal model update in full waveform inversion is equivalent to a Newton step. Explicit computation of the Hessian and its inverse is not computationally feasible in elastic FWI. The inverse Hessian scales the gradients to account for trade-off between parameters as well as compensating for inadequate illumination related to source-receiver coverage. Gradient preconditioners can be applied to mimic the action of the inverse Hessian and partially correct for inaccuracies in the gradient. In this study, we investigate the effects of model reparametrization by recasting a regularized form of the least-squares waveform misfit into a preconditioned formulation. New model parameters are obtained by applying invertible weighting matrices to the model vector. The weighting matrices are related to estimates of the prior model covariance matrix and incorporate information about spatially variant correlations of model parameters as well as correlations between independent parameters. We compare the convergence of conventional FWI to FWI after model reparametrization.

  3. Full Life Wind Turbine Gearbox Lubricating Fluids

    Energy Technology Data Exchange (ETDEWEB)

    Lutz, Glenn A.; Jungk, Manfred; Bryant, Jonathan J.; Lauer, Rebecca S.; Chobot, Anthony; Mayer, Tyler; Palmer, Shane; Kauffman, Robert E.

    2012-02-28

    Industrial gear box lubricants typically are hydrocarbon based mineral oils with considerable amounts of additives to overcome the lack of base fluid properties like wear protection, oxidation stability, load carrying capacity, low temperature solidification and drop of viscosity at higher temperatures. For today's wind turbine gearboxes, the requirements are more severe and synthetic hydrocarbon oils are used to improve on this, but all such hydrocarbon based lubricants require significant amounts of Extreme Pressure (EP) additives to meet performance requirements. Perfluoropolyether (PFPE) fluids provide load carrying capacity as an inherent property. During the course of the project with the main tasks of 'Establish a Benchmark', 'Lubricant Evaluation', 'Full Scale Gearbox Trial' and 'Economic Evaluation', the PAO Reference oil exhibited significant changes after laboratory gear testing, in service operation in the field and full scale gearbox trial. Four hydrocarbon base oils were selected for comparison in the benchmarking exercise and showed variation with respect to meeting the requirements for the laboratory micro-pitting tests, while the PFPE fluid exceeded the requirements even with the material taken after the full scale gear box trial. This is remarkable for a lubricant without EP additives. Laboratory bearing tests performed on the PFPE fluids before and after the full scale gear box trial showed the results met requirements for the industry standard. The PFPE fluid successfully completed the full scale gear box test program which included baseline and progressive staged load testing. The evaluation of gears showed no micro-pitting or objectionable wear. By the final stage, lubricant film thickness had been reduced to just 21% of its original value, this was by design and resulted in a lambda ratio of well below 1. This test design scenario of a low lambda ratio is a very undesirable lubrication condition

  4. Full Life Wind Turbine Gearbox Lubricating Fluids

    Energy Technology Data Exchange (ETDEWEB)

    Lutz, Glenn A.; Jungk, Manfred; Bryant, Jonathan J.; Lauer, Rebecca S.; Chobot, Anthony; Mayer, Tyler; Palmer, Shane; Kauffman, Robert E.

    2012-02-28

    Industrial gear box lubricants typically are hydrocarbon based mineral oils with considerable amounts of additives to overcome the lack of base fluid properties like wear protection, oxidation stability, load carrying capacity, low temperature solidification and drop of viscosity at higher temperatures. For today's wind turbine gearboxes, the requirements are more severe and synthetic hydrocarbon oils are used to improve on this, but all such hydrocarbon based lubricants require significant amounts of Extreme Pressure (EP) additives to meet performance requirements. Perfluoropolyether (PFPE) fluids provide load carrying capacity as an inherent property. During the course of the project with the main tasks of 'Establish a Benchmark', 'Lubricant Evaluation', 'Full Scale Gearbox Trial' and 'Economic Evaluation', the PAO Reference oil exhibited significant changes after laboratory gear testing, in service operation in the field and full scale gearbox trial. Four hydrocarbon base oils were selected for comparison in the benchmarking exercise and showed variation with respect to meeting the requirements for the laboratory micro-pitting tests, while the PFPE fluid exceeded the requirements even with the material taken after the full scale gear box trial. This is remarkable for a lubricant without EP additives. Laboratory bearing tests performed on the PFPE fluids before and after the full scale gear box trial showed the results met requirements for the industry standard. The PFPE fluid successfully completed the full scale gear box test program which included baseline and progressive staged load testing. The evaluation of gears showed no micro-pitting or objectionable wear. By the final stage, lubricant film thickness had been reduced to just 21% of its original value, this was by design and resulted in a lambda ratio of well below 1. This test design scenario of a low lambda ratio is a very undesirable lubrication condition

  5. Integration of Mouse Phenome Data Resources

    Energy Technology Data Exchange (ETDEWEB)

    Hancock, John M [MRC Mammalian Genetics Unit, Harwell, Oxfordshire, UK; Adams, Neils [Wellcome Trust Sanger Institute, United Kingdom; Aidinis, Vassilis [MRC Mammalian Genetics Unit, Harwell, Oxfordshire, UK; Blake, Judith A [Jackson Laboratory, The, Bar Harbor, ME; Bogue, Molly [Jackson Laboratory, The, Bar Harbor, ME; Brown, Steve D M [MRC Mammalian Genetics Unit, Harwell, Oxfordshire, UK; Chesler, Elissa J [ORNL; Davidson, Duncan [MRC Human Genetics Unit, Edinburgh, UK; Duran, Christopher [MRC Mammalian Genetics Unit, Harwell, Oxfordshire, UK; Eppig, Janan T [Jackson Laboratory, The, Bar Harbor, ME; Gailus-Durner, Valerie [Institute of Experimental Genetics, Neuherberg, Germany; Gkoutos, Georgios V [University of Cambridge; Greenaway, Simon [MRC Mammalian Genetics Unit, Harwell, Oxfordshire, UK; Angelis, Martin Hrabe de [Institute of Experimental Genetics, Neuherberg, Germany; Kollias, George [BSRC Fleming, Athens, Greece; Leblanc, Sophie [Institut Clinique de la Souris, Cedex, France; Lee, Kirsty [MRC Human Genetics Unit, Edinburgh, UK; Lengger, Christoph [Institute of Experimental Genetics, Neuherberg, Germany; Maier, Holger [Institute of Experimental Genetics, Neuherberg, Germany; Mallon, Ann-Marie [MRC Mammalian Genetics Unit, Harwell, Oxfordshire, UK; Masuya, Hiroshi [RIKEN, Japan; Melvin, David [Wellcome Trust Sanger Institute, United Kingdom; Muller, Werner [Faculty of Life Sciences, Manchester, UK; Parkinson, Helen [European Bioinformatics Institute, Wellcome Trust Genome Campus; Proctor, Glenn [European Bioinformatics Institute, Wellcome Trust Genome Campus; Reuveni, Eli [Mouse Biology Unit, Rome, Italy; Schofield, Paul [University of Cambridge; Shukla, Aadya [University of Oxford; Smith, Cynthia [Jackson Laboratory, The, Bar Harbor, ME; Toyoda, Tetsuro [RIKEN, Japan; Vasseur, Laurent [Institut Clinique de la Souris, Cedex, France; Wakana, Shigeharu [RIKEN, Japan; Walling, Alison [MRC Mary Lyon Centre, Oxfordshire, UK; White, Jacqui [Wellcome Trust Sanger Institute, United Kingdom; Wood, Joe [MRC Mary Lyon Centre, Oxfordshire, UK; Zouberakis, Michalis [BSRC Fleming, Athens, Greece

    2008-01-01

    Understanding the functions encoded in the mouse genome will be central to an understanding of the genetic basis of human disease. To achieve this it will be essential to be able to characterise the phenotypic consequences of variation and alterations in individual genes. Data on the phenotypes of mouse strains are currently held in a number of different forms (detailed descriptions of mouse lines, first line phenotyping data on novel mutations, data on the normal features of inbred lines, etc.) at many sites worldwide. For the most efficient use of these data sets, we have set in train a process to develop standards for the description of phenotypes (using ontologies), and file formats for the description of phenotyping protocols and phenotype data sets. This process is ongoing, and needs to be supported by the wider mouse genetics and phenotyping communities to succeed. We invite interested parties to contact us as we develop this process further.

  6. The Mouse Genome Database (MGD): facilitating mouse as a model for human biology and disease.

    Science.gov (United States)

    Eppig, Janan T; Blake, Judith A; Bult, Carol J; Kadin, James A; Richardson, Joel E

    2015-01-01

    The Mouse Genome Database (MGD, http://www.informatics.jax.org) serves the international biomedical research community as the central resource for integrated genomic, genetic and biological data on the laboratory mouse. To facilitate use of mouse as a model in translational studies, MGD maintains a core of high-quality curated data and integrates experimentally and computationally generated data sets. MGD maintains a unified catalog of genes and genome features, including functional RNAs, QTL and phenotypic loci. MGD curates and provides functional and phenotype annotations for mouse genes using the Gene Ontology and Mammalian Phenotype Ontology. MGD integrates phenotype data and associates mouse genotypes to human diseases, providing critical mouse-human relationships and access to repositories holding mouse models. MGD is the authoritative source of nomenclature for genes, genome features, alleles and strains following guidelines of the International Committee on Standardized Genetic Nomenclature for Mice. A new addition to MGD, the Human-Mouse: Disease Connection, allows users to explore gene-phenotype-disease relationships between human and mouse. MGD has also updated search paradigms for phenotypic allele attributes, incorporated incidental mutation data, added a module for display and exploration of genes and microRNA interactions and adopted the JBrowse genome browser. MGD resources are freely available to the scientific community. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  7. The International Mouse Phenotyping Consortium: past and future perspectives on mouse phenotyping

    Science.gov (United States)

    Moore, Mark W.

    2013-01-01

    Determining the function of all mammalian genes remains a major challenge for the biomedical science community in the 21st century. The goal of the International Mouse Phenotyping Consortium (IMPC) over the next 10 years is to undertake broad-based phenotyping of 20,000 mouse genes, providing an unprecedented insight into mammalian gene function. This short article explores the drivers for large-scale mouse phenotyping and provides an overview of the aims and processes involved in IMPC mouse production and phenotyping. PMID:22940749

  8. Mouse cell culture: methods and protocols

    OpenAIRE

    Elvira M. Guerra Shinohara

    2010-01-01

    The mouse is, out of any doubt, the experimental animal par excellence for many many colleagues within the scientific community, notably for those working in mammalian biology (in a broad sense, from basic genetic to modeling human diseases), starting at least from 1664 Robert Hooke experiments on air’s propertyn. Not surprising then that mouse cell cultures is a well established field of research itself and that there are several handbooks devoted to this discipline. Here, Andrew Ward ...

  9. Aging, Breast Cancer and the Mouse Model

    Science.gov (United States)

    2005-05-01

    Presenescent or senescent hBF (1.2 or 18x×10 4/well, respectively) [M, Stampfer , P. Yaswen, Lawrence Berkeley National Laboratory wdre suspended in 60 l cold...2.8 1 2.8 Inducing a human-like senescent phenotype in mouse fibroblasts Jean-Philihoo Copp , Simona Parrinello, Ana Krtolica, Christopher K. Patil...MAMMARY EPITHELIAL CELL PROLIFERATION AND TUMORIGENESIS: A MOUSE MODEL FOR HUMAN AGING. Jean-Philippe Coppe, Simona Parrinello, Ana Krtolica, Christopher

  10. Neuronal mechanism of epileptogenesis in EL mouse

    OpenAIRE

    2013-01-01

    The convulsions of the EL mouse (EL) were described by Imaizumi et al. in 1954 and were established as epilepsy by Suzuki in 1976. The EL mouse has been kept as an inbred strain and is considered one of the best animal models originated in Japan. The mode of inheritance is autosomal dominant, and environmental risk factors for seizure occurrence are hypothesised to contribute to the polygenic background. Paroxysmal activities in the EL brain arise from the parietal cortex (PCX) and are augmen...

  11. Senescent mouse cells fail to overtly regulate the HIRA histone chaperone and do not form robust Senescence Associated Heterochromatin Foci

    Directory of Open Access Journals (Sweden)

    Enders Greg H

    2010-06-01

    Full Text Available Abstract Background Cellular senescence is a permanent growth arrest that occurs in response to cellular stressors, such as telomere shortening or activation of oncogenes. Although the process of senescence growth arrest is somewhat conserved between mouse and human cells, there are some critical differences in the molecular pathways of senescence between these two species. Recent studies in human fibroblasts have defined a cell signaling pathway that is initiated by repression of a specific Wnt ligand, Wnt2. This, in turn, activates a histone chaperone HIRA, and culminates in formation of specialized punctate domains of facultative heterochromatin, called Senescence-Associated Heterochromatin Foci (SAHF, that are enriched in the histone variant, macroH2A. SAHF are thought to repress expression of proliferation-promoting genes, thereby contributing to senescence-associated proliferation arrest. We asked whether this Wnt2-HIRA-SAHF pathway is conserved in mouse fibroblasts. Results We show that mouse embryo fibroblasts (MEFs and mouse skin fibroblasts, do not form robust punctate SAHF in response to an activated Ras oncogene or shortened telomeres. However, senescent MEFs do exhibit elevated levels of macroH2A staining throughout the nucleus as a whole. Consistent with their failure to fully activate the SAHF assembly pathway, the Wnt2-HIRA signaling axis is not overtly regulated between proliferating and senescent mouse cells. Conclusions In addition to the previously defined differences between mouse and human cells in the mechanisms and phenotypes associated with senescence, we conclude that senescent mouse and human fibroblasts also differ at the level of chromatin and the signaling pathways used to regulate chromatin. These differences between human and mouse senescence may contribute to the increased propensity of mouse fibroblasts (and perhaps other mouse cell types to become immortalized and transformed, compared to human cells.

  12. Ethical Considerations in Mouse Experiments.

    Science.gov (United States)

    Baertschi, Bernard; Gyger, Marcel

    2011-03-01

    Mice count morally because they can be harmed. This raises a moral issue in animal experimentation. Three main ethical attitudes towards animals are reviewed here. The Kantian view denies moral value to animals because they lack reason. The second view, by Singer, considers animals as sentient creatures (i.e., able to suffer). Finally, Regan considers that animals are subjects of their own life; they are autonomous and therefore have moral rights. Singer is a reformist and allows animal experimentation under certain conditions. Regan is abolitionist, saying that animals have moral rights that cannot be negotiated. Current animal protection legislation strives to put in balance the human and animal interests to decide whether an animal experiment is morally justified or not. An ethical evaluation process is conducted based on the harm-benefit assessment of the experiment. The researcher has to implement the 3Rs (Replacement, Reduction, Refinement) to minimize the harms to the animals and make sure that the outcomes are scientifically significant and that the quality of the science is high, in order to maximize benefits to humans and animals. Curr. Protoc. Mouse Biol. 1:155-167. © 2011 by John Wiley & Sons, Inc.

  13. Mouse behavioral endophenotypes for schizophrenia.

    Science.gov (United States)

    Amann, Laura C; Gandal, Michael J; Halene, Tobias B; Ehrlichman, Richard S; White, Samantha L; McCarren, Hilary S; Siegel, Steven J

    2010-09-30

    An endophenotype is a heritable trait that is generally considered to be more highly, associated with a gene-based neurological deficit than a disease phenotype itself. Such, endophenotypic deficits may therefore be observed in the non-affected relatives of disease patients. Once endophenotypes have been established for a given illness, such as schizophrenia, mechanisms of, action may then be established and treatment options developed in order to target such measures. The, current paper describes and assesses the merits and limitations of utilizing behavioral and, electrophysiological endophenotypes of schizophrenia in mice. Such endophenotypic deficits include: decreased auditory event related potential (ERP) amplitude and gating (specifically, that of the P20, N40, P80 and P120); impaired mismatch negativity (MMN); changes in theta and gamma frequency, analyses; decreased pre-pulse inhibition (PPI); impaired working and episodic memories (for instance, novel object recognition [NOR], contextual and cued fear conditioning, latent inhibition, Morris and, radial arm maze identification and nose poke); sociability; and locomotor activity. A variety of, pharmacological treatments, including ketamine, MK-801 and phencyclidine (PCP) can be used to, induce some of the deficits described above, and numerous transgenic mouse strains have been, developed to address the mechanisms responsible for such endophenotypic differences. We also, address the viability and validity of using such measures regarding their potential clinical implications, and suggest several practices that could increase the translatability of preclinical data.

  14. Mouse models of intracranial aneurysm.

    Science.gov (United States)

    Wang, Yutang; Emeto, Theophilus I; Lee, James; Marshman, Laurence; Moran, Corey; Seto, Sai-wang; Golledge, Jonathan

    2015-05-01

    Subarachnoid hemorrhage secondary to rupture of an intracranial aneurysm is a highly lethal medical condition. Current management strategies for unruptured intracranial aneurysms involve radiological surveillance and neurosurgical or endovascular interventions. There is no pharmacological treatment available to decrease the risk of aneurysm rupture and subsequent subarachnoid hemorrhage. There is growing interest in the pathogenesis of intracranial aneurysm focused on the development of drug therapies to decrease the incidence of aneurysm rupture. The study of rodent models of intracranial aneurysms has the potential to improve our understanding of intracranial aneurysm development and progression. This review summarizes current mouse models of intact and ruptured intracranial aneurysms and discusses the relevance of these models to human intracranial aneurysms. The article also reviews the importance of these models in investigating the molecular mechanisms involved in the disease. Finally, potential pharmaceutical targets for intracranial aneurysm suggested by previous studies are discussed. Examples of potential drug targets include matrix metalloproteinases, stromal cell-derived factor-1, tumor necrosis factor-α, the renin-angiotensin system and the β-estrogen receptor. An agreed clear, precise and reproducible definition of what constitutes an aneurysm in the models would assist in their use to better understand the pathology of intracranial aneurysm and applying findings to patients.

  15. Full resolution hologram-like autostereoscopic display

    Science.gov (United States)

    Eichenlaub, Jesse B.; Hutchins, Jamie

    1995-01-01

    Under this program, Dimension Technologies Inc. (DTI) developed a prototype display that uses a proprietary illumination technique to create autostereoscopic hologram-like full resolution images on an LCD operating at 180 fps. The resulting 3D image possesses a resolution equal to that of the LCD along with properties normally associated with holograms, including change of perspective with observer position and lack of viewing position restrictions. Furthermore, this autostereoscopic technique eliminates the need to wear special glasses to achieve the parallax effect. Under the program a prototype display was developed which demonstrates the hologram-like full resolution concept. To implement such a system, DTI explored various concept designs and enabling technologies required to support those designs. Specifically required were: a parallax illumination system with sufficient brightness and control; an LCD with rapid address and pixel response; and an interface to an image generation system for creation of computer graphics. Of the possible parallax illumination system designs, we chose a design which utilizes an array of fluorescent lamps. This system creates six sets of illumination areas to be imaged behind an LCD. This controlled illumination array is interfaced to a lenticular lens assembly which images the light segments into thin vertical light lines to achieve the parallax effect. This light line formation is the foundation of DTI's autostereoscopic technique. The David Sarnoff Research Center (Sarnoff) was subcontracted to develop an LCD that would operate with a fast scan rate and pixel response. Sarnoff chose a surface mode cell technique and produced the world's first large area pi-cell active matrix TFT LCD. The device provided adequate performance to evaluate five different perspective stereo viewing zones. A Silicon Graphics' Iris Indigo system was used for image generation which allowed for static and dynamic multiple perspective image rendering

  16. Full Waveform Inversion Using Nonlinearly Smoothed Wavefields

    KAUST Repository

    Li, Y.

    2017-05-26

    The lack of low frequency information in the acquired data makes full waveform inversion (FWI) conditionally converge to the accurate solution. An initial velocity model that results in data with events within a half cycle of their location in the observed data was required to converge. The multiplication of wavefields with slightly different frequencies generates artificial low frequency components. This can be effectively utilized by multiplying the wavefield with itself, which is nonlinear operation, followed by a smoothing operator to extract the artificially produced low frequency information. We construct the objective function using the nonlinearly smoothed wavefields with a global-correlation norm to properly handle the energy imbalance in the nonlinearly smoothed wavefield. Similar to the multi-scale strategy, we progressively reduce the smoothing width applied to the multiplied wavefield to welcome higher resolution. We calculate the gradient of the objective function using the adjoint-state technique, which is similar to the conventional FWI except for the adjoint source. Examples on the Marmousi 2 model demonstrate the feasibility of the proposed FWI method to mitigate the cycle-skipping problem in the case of a lack of low frequency information.

  17. Habermas's Expressivist Theology: Chalice Half-Full?

    Directory of Open Access Journals (Sweden)

    Felmon John Davis

    2012-01-01

    Full Text Available The article addresses the question of the respect owed to believers and their faiths and states that a demand for respect for the person of the believer does not imply a demand for respect for their faith. However, being 'respect' a complex and ambiguous notion, the article studies some arguments that go in the direction of justifying the move from respect for persons to respect for their beliefs. According to Habermas, there is a respect citizens of a democracy owe each other that requires taking each other's opinions seriously, including their religiously motivated opinions. What is more, Habermas claims that we all have something to learn from each other. The articles argues against this line of thought and states there is no obligation to respect anything about people's moral claims except their right to make them. The article argues against Habermas's approach by showing its epistemological and ontological inconsistency and concludes that respect for persons as moral reason-givers or as fellow-citizens does not lead to any substantial respect for the contents of their claims.

  18. Automated full matrix capture for industrial processes

    Science.gov (United States)

    Brown, Roy H.; Pierce, S. Gareth; Collison, Ian; Dutton, Ben; Dziewierz, Jerzy; Jackson, Joseph; Lardner, Timothy; MacLeod, Charles; Morozov, Maxim

    2015-03-01

    Full matrix capture (FMC) ultrasound can be used to generate a permanent re-focusable record of data describing the geometry of a part; a valuable asset for an inspection process. FMC is a desirable acquisition mode for automated scanning of complex geometries, as it allows compensation for surface shape in post processing and application of the total focusing method. However, automating the delivery of such FMC inspection remains a significant challenge for real industrial processes due to the high data overhead associated with the ultrasonic acquisition. The benefits of NDE delivery using six-axis industrial robots are well versed when considering complex inspection geometries, but such an approach brings additional challenges to scanning speed and positional accuracy when combined with FMC inspection. This study outlines steps taken to optimize the scanning speed and data management of a process to scan the diffusion bonded membrane of a titanium test plate. A system combining a KUKA robotic arm and a reconfigurable FMC phased array controller is presented. The speed and data implications of different scanning methods are compared, and the impacts on data visualization quality are discussed with reference to this study. For the 0.5 m2 sample considered, typical acquisitions of 18 TB/m2 were measured for a triple back wall FMC acquisition, illustrating the challenge of combining high data throughput with acceptable scanning speeds.

  19. Full STEAM Ahead: From Earth to Ploonoids

    Science.gov (United States)

    Runyon, C. R.; Hall, C.; Blackman, C. L.; Royle, M.; Williams, M. N.

    2015-12-01

    What the heck is a plunoid, you ask? The NASA Solar System Exploration Research Virtual Institute's Education/Public Engagement (EPE) program,from two SSERVI teams (SEEED at Brown/MIT and CLASS at University of Central Florida), is moving full STEAM ahead, engaging the public in the exciting discoveries being made around small bodies, including PLanetary mOONs and asterOIDS (i.e ploonoids). The team has incorporated the arts, from visual representations, storytelling, and music into every facet of the program, to stimulate an affective and personal connection to the content. This past year, the SSERVI STEAM team has participated in numerous public science events, including International Observe the Moon Night, two Astronomy Nights at a local baseball venue, Dark Skies at the US and Canadian National Parks, and Space Day at Camp Happy Days, a camp for children with cancer. Through these events, the team reached over 10000 members of the general public, showcasing current NASA SSERVI research, dispelling myths about our landing and exploring the moon, demonstrating the excitement of STEM through hands-on interactive displays, and providing an outlet for creativity by having multiple ways of representing and explaining scientific information through the arts. Join us on our "ed"venture through the solar system ploonoids.

  20. Habermas's Expressivist Theology: Chalice Half-Full?

    Directory of Open Access Journals (Sweden)

    Felmon John Davis

    2015-07-01

    Full Text Available The article addresses the question of the respect owed to believers and their faiths and states that a demand for respect for the person of the believer does not imply a demand for respect for their faith. However, being 'respect' a complex and ambiguous notion, the article studies some arguments that go in the direction of justifying the move from respect for persons to respect for their beliefs. According to Habermas, there is a respect citizens of a democracy owe each other that requires taking each other's opinions seriously, including their religiously motivated opinions. What is more, Habermas claims that we all have something to learn from each other. The articles argues against this line of thought and states there is no obligation to respect anything about people's moral claims except their right to make them. The article argues against Habermas's approach by showing its epistemological and ontological inconsistency and concludes that respect for persons as moral reason-givers or as fellow-citizens does not lead to any substantial respect for the contents of their claims.

  1. Schottky Heterodyne Receivers With Full Waveguide Bandwidth

    Science.gov (United States)

    Hesler, Jeffrey; Crowe, Thomas

    2011-01-01

    Compact THz receivers with broad bandwidth and low noise have been developed for the frequency range from 100 GHz to 1 THz. These receivers meet the requirements for high-resolution spectroscopic studies of planetary atmospheres (including the Earth s) from spacecraft, as well as airborne and balloon platforms. The ongoing research is significant not only for the development of Schottky mixers, but also for the creation of a receiver system, including the LO chain. The new receivers meet the goals of high sensitivity, compact size, low total power requirement, and operation across complete waveguide bands. The exceptional performance makes these receivers ideal for the broader range of scientific and commercial applications. These include the extension of sophisticated test and measurement equipment to 1 THz and the development of low-cost imaging systems for security applications and industrial process monitoring. As a particular example, a WR-1.9SHM (400-600 GHz) has been developed (see Figure 1), with state-of-the-art noise temperature ranging from 1,000-1,800 K (DSB) over the full waveguide band. Also, a Vector Network Analyzer extender has been developed (see Figure 2) for the WR1.5 waveguide band (500 750 GHz) with 100-dB dynamic range.

  2. Full Waveform Inversion of Solar Interior Flows

    CERN Document Server

    Hanasoge, Shravan M

    2014-01-01

    The inference of flows of material in the interior of the Sun is a subject of major interest in helioseismology. Here we apply techniques of Full Waveform Inversion (FWI) to synthetic data to test flow inversions. In this idealized setup, we do not model seismic realization noise, training the focus entirely on the problem of whether a chosen supergranulation flow model can be seismically recovered. We define the misfit functional as a sum of L_2 norm deviations in travel times between prediction and observation, as measured using short-distance f and p_1 filtered and large-distance unfiltered $p$ modes. FWI allows for the introduction of measurements of choice and iteratively improving the background model, while monitoring the evolution of the misfit in all desired categories. Although the misfit is seen to uniformly reduce in all categories, convergence to the true model is very slow, possibly because it is trapped in a local minimum. The primary source of error is inaccurate depth localization, which, owi...

  3. "Full moon" endoscopic sign in intraventricular neurocysticercosis.

    Science.gov (United States)

    Ramos-Zúñiga, R; de La Cruz-Ramírez, J; Casillas-Espinosa, P M; Sánchez-Prieto, J A; López-Hernández, M D S

    2011-04-01

    Despite improvements in sanitation, diagnosis and treatment, neurocysticercosis is still a public health problem in many countries. In symptomatic patients, there is a broad spectrum of clinical manifestations. When cysticerci are lodged in the ventricles or the subarachnoid space, the flow of cerebrospinal fluid can be obstructed and lead to hydrocephalus and intracranial hypertension. The endoscopic view may be useful as a diagnostic tool. This report clearly shows a common endoscopic pattern in 4 selected patients with ventricular cysticercosis (2 third ventricle/2 lateral ventricle). The endoscopic view of the cysts in the ventricles resembles a "full moon". This analogy helped to identify the features of cysticerci with intact walls and the vesicular stage, malleable due to its cystic content and having an irregular surface, as evidence of the microscopic structure of the cyst wall in a cysticercus. This finding is not seen in other intraventricular cysts or tumors that can actually be considered as an additional diagnostic criterion among the definitive findings to establish the diagnosis of cysticercosis, since it involves direct endoscopic visualization of a cysticercus under histopathological demonstration. Additionally, the endoscopic approach can be used as primary treatment for these cases, following the minimally invasive approach principle. © Georg Thieme Verlag KG Stuttgart · New York.

  4. Exhibitors: Full of Confidence Adequate Preparation

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    From March 26th,three most important trade fairs for Chinese textile industry opened successively inBeijing.Several exhibitors showed their confidence and preparation to TA Weekly. Bosideng:CHIC is an everlasting marketing chance"We’ll definitely participate in CHIC 2009,with even moreinvestment."Gao Dekang,the President of Bosideng Co.,Ltd said,"Bosideng is going to make full use of this trade fair for furtherdevelopment."According to the organizer of CHIC 2009,Bosidengreserved 1000 square meters for its show."CHIC witnessed the blooming development of Chinese clothingindustry for the last ten years.CHIC has made a progress to catch upwith the world trend as well as in the social influence.It has becomethe pioneer of fashion and is regarded as the releasing center,innovation center and brand center."As a long-term participant,Bosideng has the right to say these words.It is in this fair,Bosideng

  5. Source Estimation by Full Wave Form Inversion

    Energy Technology Data Exchange (ETDEWEB)

    Sjögreen, Björn [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Center for Applied Scientific Computing; Petersson, N. Anders [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Center for Applied Scientific Computing

    2013-08-07

    Given time-dependent ground motion recordings at a number of receiver stations, we solve the inverse problem for estimating the parameters of the seismic source. The source is modeled as a point moment tensor source, characterized by its location, moment tensor components, the start time, and frequency parameter (rise time) of its source time function. In total, there are 11 unknown parameters. We use a non-linear conjugate gradient algorithm to minimize the full waveform misfit between observed and computed ground motions at the receiver stations. An important underlying assumption of the minimization problem is that the wave propagation is accurately described by the elastic wave equation in a heterogeneous isotropic material. We use a fourth order accurate finite difference method, developed in [12], to evolve the waves forwards in time. The adjoint wave equation corresponding to the discretized elastic wave equation is used to compute the gradient of the misfit, which is needed by the non-linear conjugated minimization algorithm. A new source point moment source discretization is derived that guarantees that the Hessian of the misfit is a continuous function of the source location. An efficient approach for calculating the Hessian is also presented. We show how the Hessian can be used to scale the problem to improve the convergence of the non-linear conjugated gradient algorithm. Numerical experiments are presented for estimating the source parameters from synthetic data in a layer over half-space problem (LOH.1), illustrating rapid convergence of the proposed approach.

  6. Full-Automatic Parking registration and payment

    DEFF Research Database (Denmark)

    Agerholm, Niels; Lahrmann, Harry; Jørgensen, Brian

    2014-01-01

    As part of ITS Platform North Denmark, a full-automatic GNSS-based parking payment (PP) system was developed (PP app). On the basis of the parking position and parking time, the PP app can determine the price of parking and collect the amount from the car owner’s bank account. The driver...... is informed about any initiation of PP via SMS message. If the driver finds the payment erroneous, it can be cancelled via SMS message. Parking attendants can check if the car in question has an ongoing payment for parking. To handle the problems with GNSS-based positioning in densely built-up areas......, an advanced map matching algorithm was integrated in the PP app. 24 of the participating vehicles used the PP app, and 58 parking payments were carried out without errors. In a few cases, the wrong parking area was selected. This was due to lack of information in the map rather than errors in the map matching...

  7. Transcript annotation in FANTOM3: mouse gene catalog based on physical cDNAs.

    Directory of Open Access Journals (Sweden)

    Norihiro Maeda

    2006-04-01

    Full Text Available The international FANTOM consortium aims to produce a comprehensive picture of the mammalian transcriptome, based upon an extensive cDNA collection and functional annotation of full-length enriched cDNAs. The previous dataset, FANTOM2, comprised 60,770 full-length enriched cDNAs. Functional annotation revealed that this cDNA dataset contained only about half of the estimated number of mouse protein-coding genes, indicating that a number of cDNAs still remained to be collected and identified. To pursue the complete gene catalog that covers all predicted mouse genes, cloning and sequencing of full-length enriched cDNAs has been continued since FANTOM2. In FANTOM3, 42,031 newly isolated cDNAs were subjected to functional annotation, and the annotation of 4,347 FANTOM2 cDNAs was updated. To accomplish accurate functional annotation, we improved our automated annotation pipeline by introducing new coding sequence prediction programs and developed a Web-based annotation interface for simplifying the annotation procedures to reduce manual annotation errors. Automated coding sequence and function prediction was followed with manual curation and review by expert curators. A total of 102,801 full-length enriched mouse cDNAs were annotated. Out of 102,801 transcripts, 56,722 were functionally annotated as protein coding (including partial or truncated transcripts, providing to our knowledge the greatest current coverage of the mouse proteome by full-length cDNAs. The total number of distinct non-protein-coding transcripts increased to 34,030. The FANTOM3 annotation system, consisting of automated computational prediction, manual curation, and final expert curation, facilitated the comprehensive characterization of the mouse transcriptome, and could be applied to the transcriptomes of other species.

  8. On chip electrofusion of single human B cells and mouse myeloma cells for efficient hybridoma generation

    NARCIS (Netherlands)

    Kemna, Evelien; Wolbers, F.; van den Berg, Albert; Vermes, I.

    2011-01-01

    This article describes the development and full characterization of a microfluidic chip for electrofusion of human peripheral blood B-cells and mouse myeloma (NS-1) cells to generate hybridomas. The chip consists of an array of 783 traps, with dimensions that were optimized to obtain a final cell

  9. Hyperelastic Material Properties of Mouse Skin under Compression.

    Directory of Open Access Journals (Sweden)

    Yuxiang Wang

    Full Text Available The skin is a dynamic organ whose complex material properties are capable of withstanding continuous mechanical stress while accommodating insults and organism growth. Moreover, synchronized hair cycles, comprising waves of hair growth, regression and rest, are accompanied by dramatic fluctuations in skin thickness in mice. Whether such structural changes alter skin mechanics is unknown. Mouse models are extensively used to study skin biology and pathophysiology, including aging, UV-induced skin damage and somatosensory signaling. As the skin serves a pivotal role in the transfer function from sensory stimuli to neuronal signaling, we sought to define the mechanical properties of mouse skin over a range of normal physiological states. Skin thickness, stiffness and modulus were quantitatively surveyed in adult, female mice (Mus musculus. These measures were analyzed under uniaxial compression, which is relevant for touch reception and compression injuries, rather than tension, which is typically used to analyze skin mechanics. Compression tests were performed with 105 full-thickness, freshly isolated specimens from the hairy skin of the hind limb. Physiological variables included body weight, hair-cycle stage, maturity level, skin site and individual animal differences. Skin thickness and stiffness were dominated by hair-cycle stage at young (6-10 weeks and intermediate (13-19 weeks adult ages but by body weight in mature mice (26-34 weeks. Interestingly, stiffness varied inversely with thickness so that hyperelastic modulus was consistent across hair-cycle stages and body weights. By contrast, the mechanics of hairy skin differs markedly with anatomical location. In particular, skin containing fascial structures such as nerves and blood vessels showed significantly greater modulus than adjacent sites. Collectively, this systematic survey indicates that, although its structure changes dramatically throughout adult life, mouse skin at a given

  10. Going Full Circle With Teacher Feedback

    Directory of Open Access Journals (Sweden)

    Jo-Anne L. Manswell Butty

    2015-07-01

    Full Text Available Research on the evaluation of early childhood programs focuses mainly on its outcomes rather than its process with often little attention given to the role that feedback to teachers in pre-kindergarten (pre-k programs plays in the larger cycle of the evaluation process. This article provides a case example of a multiyear evaluation of community-based pre-k programs serving about 360 three- and four-year old children over a 5-year period in the District of Columbia. The Closing the Loop Evaluation Model proposed represents a responsive evaluation approach that illustrates the interconnected interactions between teacher feedback during the evaluation process and two supporting evaluation methodologies that emphasize social justice and utility. Findings from the case example highlight the responsive evaluation approach, feedback process, and ensuing conceptual and instrumental changes that occurred among stakeholders from whole-group feedback to small-group “report card” meetings with add-ons such as technical assistance, teacher-generated action plans, and teacher follow-up and feedback to close the evaluation loop. The authors discuss lessons learned about the evaluation process from the case example around aspects of feedback, including timing, audience, and function. Findings highlight the importance of feedback being timely and prompt, high quality in focus and content, non-punitive, collaborative, concise, and useful. The authors conclude that an evaluation process that includes teacher feedback, couched in social justice and utility, can have positive outcomes for all stakeholders and will likely lead to higher quality early childhood education programs.

  11. ADAPTIVE FULL-SPECTRUM SOLOR ENERGY SYSTEMS

    Energy Technology Data Exchange (ETDEWEB)

    Byard D. Wood

    2004-04-01

    This RD&D project is a three year team effort to develop a hybrid solar lighting (HSL) system that transports solar light from a paraboloidal dish concentrator to a luminaire via a large core polymer fiber optic. The luminaire can be a device to distribute sunlight into a space for the production of algae or it can be a device that is a combination of solar lighting and electric lighting. A benchmark prototype system has been developed to evaluate the HSL system. Sunlight is collected using a one-meter paraboloidal concentrator dish with two-axis tracking. A secondary mirror consisting of eight planar-segmented mirrors directs the visible part of the spectrum to eight fibers (receiver) and subsequently to eight luminaires. This results in about 8,200 lumens incident at each fiber tip. Each fiber can illuminate about 16.7 m{sup 2} (180 ft{sup 2}) of office space. The IR spectrum is directed to a thermophotovoltaic (TPV) array to produce electricity. During this reporting period, the project team made advancements in the design of the second generation (Alpha) system. For the Alpha system, the eight individual 12 mm fibers have been replaced with a centralized bundle of 3 mm fibers. The TRNSYS Full-Spectrum Solar Energy System model has been updated and new components have been added. The TPV array and nonimaging device have been tested and progress has been made in the fiber transmission models. A test plan was developed for both the high-lumen tests and the study to determine the non-energy benefits of daylighting. The photobioreactor team also made major advancements in the testing of model scale and bench top lab-scale systems.

  12. Full system decontamination experience in BWR

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, N.; Sugai, K.; Katayouse, N.; Fujimori, A.; Iida, K.; Hayashi, K. [Tokyo Electric Power Company, Tokyo (Japan); Kanasaki, T.; Inami, I. [Toshiba Corporation, Yokohama (Japan); Strohmer, F. [Framatome ANP Gmbh, Eelangen (Germany)

    2002-07-01

    At the Fukushima Daiichi Nuclear Power Station unit 3, unit 2, unit 5 and unit 1 of Tokyo Electric Power Company (TEPCO), the replacement of the core shroud and internals has been conducted since 1997 in this order. The welded core internals in operating BWR plants were replaced to improve stress corrosion cracking (SCC) resistance. At present these units are operating smoothly. The developed technology concept is to restore those internals in open air inside the reactor pressure vessel (RPV). To reduce the radiation dose rate inside the RPV, not only a shielding method was applied to cut the radiation from the irradiated structures but also a chemical decontamination method was applied to dissolve the radioactive crud deposited on the surface by using chemical agents. The calculated decontamination factor (DF) at the RPV bottom reached 35-117. As result, the dose rate decreased to approximately 0.1 mSv/h under water. Before and after the installation of the in-vessel shielding, a mechanical cleaning was extensively applied inside the RPV to remove the residual crud as well as the swarf, chips from cutting. As a result, the dose rate at the RPV bottom decreased to ranging from 0.2 to 0.4 mSv/h in air. A working environment for human access, which was better than expected, was established inside the RPV, resulting in 70, 140, 50 and 70 man-Sv (estimated) saving respectively at unit 3 (1F-3), unit 2(1F-2), unit 5(1F-5) and unit 1(1F-1). All four full system decontamination (FSDs) contributed to the successful realization of the core shroud replacement project under the dry condition in RPV.

  13. Human more complex than mouse at cellular level.

    Directory of Open Access Journals (Sweden)

    Alexander E Vinogradov

    Full Text Available The family of transcription factors with the C2H2 zinc finger domain is expanding in the evolution of vertebrates, reaching its highest numbers in the mammals. The question arises: whether an increased amount of these transcription factors is related to embryogenesis, nervous system, pathology or more of them are expressed in individual cells? Among mammals, the primates have a more complex anatomical structure than the rodents (e.g., brain. In this work, I show that a greater number of C2H2-ZF genes are expressed in the human cells than in the mouse cells. The effect is especially pronounced for C2H2-ZF genes accompanied with the KRAB domain. The relative difference between the numbers of C2H2-ZF(-KRAB genes in the human and mouse cellular transcriptomes even exceeds their difference in the genomes (i.e. a greater subset of existing in the genome genes is expressed in the human cellular transcriptomes compared to the mouse transcriptomes. The evolutionary turnover of C2H2-ZF(-KRAB genes acts in the direction of the revealed phenomenon, i.e. gene duplication and loss enhances the difference in the relative number of C2H2-ZF(-KRAB genes between human and mouse cellular transcriptomes. A higher amount of these genes is expressed in the brain and embryonic cells (compared with other tissues, whereas a lower amount--in the cancer cells. It is specifically the C2H2-ZF transcription factors whose repertoire is poorer in the cancer and richer in the brain (other transcription factors taken together do not show this trend. These facts suggest that increase of anatomical complexity is accompanied by a more complex intracellular regulation involving these transcription factors. Malignization is associated with simplification of this regulation. These results agree with the known fact that human cells are more resistant to oncogenic transformation than mouse cells. The list of C2H2-ZF genes whose suppression might be involved in malignization is provided.

  14. Full Waveform Inversion Using Waveform Sensitivity Kernels

    Science.gov (United States)

    Schumacher, Florian; Friederich, Wolfgang

    2013-04-01

    We present a full waveform inversion concept for applications ranging from seismological to enineering contexts, in which the steps of forward simulation, computation of sensitivity kernels, and the actual inversion are kept separate of each other. We derive waveform sensitivity kernels from Born scattering theory, which for unit material perturbations are identical to the Born integrand for the considered path between source and receiver. The evaluation of such a kernel requires the calculation of Green functions and their strains for single forces at the receiver position, as well as displacement fields and strains originating at the seismic source. We compute these quantities in the frequency domain using the 3D spectral element code SPECFEM3D (Tromp, Komatitsch and Liu, 2008) and the 1D semi-analytical code GEMINI (Friederich and Dalkolmo, 1995) in both, Cartesian and spherical framework. We developed and implemented the modularized software package ASKI (Analysis of Sensitivity and Kernel Inversion) to compute waveform sensitivity kernels from wavefields generated by any of the above methods (support for more methods is planned), where some examples will be shown. As the kernels can be computed independently from any data values, this approach allows to do a sensitivity and resolution analysis first without inverting any data. In the context of active seismic experiments, this property may be used to investigate optimal acquisition geometry and expectable resolution before actually collecting any data, assuming the background model is known sufficiently well. The actual inversion step then, can be repeated at relatively low costs with different (sub)sets of data, adding different smoothing conditions. Using the sensitivity kernels, we expect the waveform inversion to have better convergence properties compared with strategies that use gradients of a misfit function. Also the propagation of the forward wavefield and the backward propagation from the receiver

  15. The recombinational anatomy of a mouse chromosome.

    Directory of Open Access Journals (Sweden)

    Kenneth Paigen

    2008-07-01

    Full Text Available Among mammals, genetic recombination occurs at highly delimited sites known as recombination hotspots. They are typically 1-2 kb long and vary as much as a 1,000-fold or more in recombination activity. Although much is known about the molecular details of the recombination process itself, the factors determining the location and relative activity of hotspots are poorly understood. To further our understanding, we have collected and mapped the locations of 5,472 crossover events along mouse Chromosome 1 arising in 6,028 meioses of male and female reciprocal F1 hybrids of C57BL/6J and CAST/EiJ mice. Crossovers were mapped to a minimum resolution of 225 kb, and those in the telomere-proximal 24.7 Mb were further mapped to resolve individual hotspots. Recombination rates were evolutionarily conserved on a regional scale, but not at the local level. There was a clear negative-exponential relationship between the relative activity and abundance of hotspot activity classes, such that a small number of the most active hotspots account for the majority of recombination. Females had 1.2x higher overall recombination than males did, although the sex ratio showed considerable regional variation. Locally, entirely sex-specific hotspots were rare. The initiation of recombination at the most active hotspot was regulated independently on the two parental chromatids, and analysis of reciprocal crosses indicated that parental imprinting has subtle effects on recombination rates. It appears that the regulation of mammalian recombination is a complex, dynamic process involving multiple factors reflecting species, sex, individual variation within species, and the properties of individual hotspots.

  16. Distribution of cytoglobin in the mouse brain

    Directory of Open Access Journals (Sweden)

    Stefan eReuss

    2016-04-01

    Full Text Available Cytoglobin (Cygb is a vertebrate globin with so far poorly defined function. It is expressed in the fibroblast cell-lineage but has also been found in neurons. Here we provide, using immunohistochemistry, a detailed study on the distribution of Cygb in the mouse brain. While Cygb is a cytoplasmic protein in active cells of the supportive tissue, in neurons it is located in the cytoplasm and the nucleus. We found the expression of Cygb in all brain regions, although only a fraction of the neurons was Cygb-positive. Signals were of different intensity ranging from faint to very intense. Telencephalic neurons in all laminae of the cerebral cortex, in the olfactory bulb (in particular periglomerular cells, in the hippocampal formation (strongly stained pyramidal cells with long processes, basal ganglia (scattered multipolar neurons in the dorsal striatum, dorsal and ventral pallidum, and in the amygdala (neurons with unlabeled processes were labeled by the antibody. In the diencephalon, we observed Cygb-positive neurons of moderate intensity in various nuclei of the dorsal thalamus, in the hypothalamus, metathalamus (geniculate nuclei, epithalamus with strong labeling of habenular nucleus neurons and no labeling of pineal cells, and in the ventral thalamus. Tegmental neurons stood out by strongly stained somata with long processes in, e.g., the laterodorsal nucleus. In the tectum, faintly labeled neurons and fibers were detected in the superior colliculus. The cerebellum exhibited unlabeled Purkinje-neurons but signs of strong afferent cortical innervation. Neurons in the gray matter of the spinal cord showed moderate immunofluorescence. Peripheral ganglia were not labeled by the antibody. The Meynert-fascicle and the olfactory and optic nerves/tracts were the only Cygb-immunoreactive fiber systems. Notably, we found a remarkable level of colocalization of Cygb and neuronal nitric oxide-synthase in neurons, which supports a functional association.

  17. TRPM3 expression in mouse retina.

    Directory of Open Access Journals (Sweden)

    R Lane Brown

    Full Text Available Transient receptor potential (TRP channels constitute a large family of cation permeable ion channels that serve crucial functions in sensory systems by transducing environmental changes into cellular voltage and calcium signals. Within the retina, two closely related members of the melastatin TRP family, TRPM1 and TRPM3, are highly expressed. TRPM1 has been shown to be required for the depolarizing response to light of ON-bipolar cells, but the role of TRPM3 in the retina is unknown. Immunohistochemical staining of mouse retina with an antibody directed against the C-terminus of TRPM3 labeled the inner plexiform layer (IPL and a subset of cells in the ganglion cell layer. Within the IPL, TRPM3 immunofluorescence was markedly stronger in the OFF sublamina than in the ON sublamina. Electroretinogram recordings showed that the scotopic and photopic a- and b-waves of TRPM3(-/- mice are normal indicating that TRPM3 does not play a major role in visual processing in the outer retina. TRPM3 activity was measured by calcium imaging and patch-clamp recording of immunopurified retinal ganglion cells. Application of the TRPM3 agonist, pregnenolone sulfate (PS, stimulated increases in intracellular calcium in ~40% of cells from wild type and TRPM1(‑/‑ mice, and the PS-stimulated increases in calcium were blocked by co-application of mefenamic acid, a TRPM3 antagonist. No PS-stimulated changes in fluorescence were observed in ganglion cells from TRPM3(-/- mice. Similarly, PS-stimulated currents that could be blocked by mefenamic acid were recorded from wild type retinal ganglion cells but were absent in ganglion cells from TRPM3-/- mice.

  18. Carcinogenic effects in a phenylketonuria mouse model.

    Directory of Open Access Journals (Sweden)

    Neil Sidell

    Full Text Available Phenylketonuria (PKU is a metabolic disorder caused by impaired phenylalanine hydroxylase (PAH. This condition results in hyperphenylalaninemia and elevated levels of abnormal phenylalanine metabolites, among which is phenylacetic acid/phenylacetate (PA. In recent years, PA and its analogs were found to have anticancer activity against a variety of malignancies suggesting the possibility that PKU may offer protection against cancer through chronically elevated levels of PA. We tested this hypothesis in a genetic mouse model of PKU (PAH(enu2 which has a biochemical profile that closely resembles that of human PKU. Plasma levels of phenylalanine in homozygous (HMZ PAH(enu2 mice were >12-fold those of heterozygous (HTZ littermates while tyrosine levels were reduced. Phenylketones, including PA, were also markedly elevated to the range seen in the human disease. Mice were subjected to 7,12 dimethylbenz[a]anthracene (DMBA carcinogenesis, a model which is sensitive to the anticancer effects of the PA derivative 4-chlorophenylacetate (4-CPA. Tumor induction by DMBA was not significantly different between the HTZ and HMZ mice, either in total tumor development or in the type of cancers that arose. HMZ mice were then treated with 4-CPA as positive controls for the anticancer effects of PA and to evaluate its possible effects on phenylalanine metabolism in PKU mice. 4-CPA had no effect on the plasma concentrations of phenylalanine, phenylketones, or tyrosine. Surprisingly, the HMZ mice treated with 4-CPA developed an unexplained neuromuscular syndrome which precluded its use in these animals as an anticancer agent. Together, these studies support the use of PAH(enu2 mice as a model for studying human PKU. Chronically elevated levels of PA in the PAH(enu2 mice were not protective against cancer.

  19. Characterization of a pneumococcal meningitis mouse model

    Directory of Open Access Journals (Sweden)

    Mook-Kanamori Barry

    2012-03-01

    Full Text Available Abstract Background S. pneumoniae is the most common causative agent of meningitis, and is associated with high morbidity and mortality. We aimed to develop an integrated and representative pneumococcal meningitis mouse model resembling the human situation. Methods Adult mice (C57BL/6 were inoculated in the cisterna magna with increasing doses of S. pneumoniae serotype 3 colony forming units (CFU; n = 24, 104, 105, 106 and 107 CFU and survival studies were performed. Cerebrospinal fluid (CSF, brain, blood, spleen, and lungs were collected. Subsequently, mice were inoculated with 104 CFU S. pneumoniae serotype 3 and sacrificed at 6 (n = 6 and 30 hours (n = 6. Outcome parameters were bacterial outgrowth, clinical score, and cytokine and chemokine levels (using Luminex® in CSF, blood and brain. Meningeal inflammation, neutrophil infiltration, parenchymal and subarachnoidal hemorrhages, microglial activation and hippocampal apoptosis were assessed in histopathological studies. Results Lower doses of bacteria delayed onset of illness and time of death (median survival CFU 104, 56 hrs; 105, 38 hrs, 106, 28 hrs. 107, 24 hrs. Bacterial titers in brain and CSF were similar in all mice at the end-stage of disease independent of inoculation dose, though bacterial outgrowth in the systemic compartment was less at lower inoculation doses. At 30 hours after inoculation with 104 CFU of S. pneumoniae, blood levels of KC, IL6, MIP-2 and IFN- γ were elevated, as were brain homogenate levels of KC, MIP-2, IL-6, IL-1β and RANTES. Brain histology uniformly showed meningeal inflammation at 6 hours, and, neutrophil infiltration, microglial activation, and hippocampal apoptosis at 30 hours. Parenchymal and subarachnoidal and cortical hemorrhages were seen in 5 of 6 and 3 of 6 mice at 6 and 30 hours, respectively. Conclusion We have developed and validated a murine model of pneumococcal meningitis.

  20. Extensive Hair Shaft Growth after Mouse Whisker Follicle Isolation, Cryopreservation and Transplantation in Nude Mice.

    Directory of Open Access Journals (Sweden)

    Wenluo Cao

    Full Text Available We previously demonstrated that whole hair follicles could be cryopreserved to maintain their stem-cells differentation potential. In the present study, we demonstrated that cryopreserved mouse whisker hair follicles maintain their hair growth potential. DMSO better cryopreserved mouse whisker follicles compared to glycerol. Cryopreserved hair follicles also maintained the hair follicle-associated-pluripotent (HAP stem cells, evidenced by P75NTR expression. Subcutaneous transplantation of DMSO-cryopreserved hair follicles in nude mice resulted in extensive hair fiber growth over 8 weeks, indicating the functional recovery of hair shaft growth of cryopreserved hair follicles.

  1. Preliminar toxicological assesement of Ruta graveolens, Origanum vulgare and Persea americana on the preimplantational mouse embryos

    Directory of Open Access Journals (Sweden)

    V. Benavides

    2014-06-01

    Full Text Available The growing interest in natural medicine makes it necessary to study plant properties as well as their possible secondary effects. In recent years the toxic effects of many medicinal plants on the preimplantational mouse embryo development have been studied. Many of them produce malformations and alterations in the embryonic development. Ruta graveolens "ruda", Origanum vulgare "oregano" and Persea americana "palta" are used in rural areas to menstrual colic and to provoke abortion (estrella, 1995. This study is aimed at assessing "in vivd'the effect of extracts of "oregano", "ruda" and "palta" to 20% on the morphology and growth of preimplantational mouse embryos.

  2. Reprogramming of mouse amniotic fluid cells using a PiggyBac transposon system

    Directory of Open Access Journals (Sweden)

    E. Bertin

    2015-11-01

    Full Text Available Induced pluripotent stem (iPS cells are generated from mouse and human somatic cells by forced expression of defined transcription factors using different methods. Amniotic fluid (AF cells are easy to obtain from routinely scheduled procedures for prenatal diagnosis and iPS cells have been generated from human AF. Here, we generated iPS cells from mouse AF cells, using a non-viral-based approach constituted by the PiggyBac (PB transposon system. All iPS cell lines obtained exhibited characteristics of pluripotent cells, including the ability to differentiate toward derivatives of all three germ layers in vitro and in vivo.

  3. Surfing the internet with a BCI mouse

    Science.gov (United States)

    Yu, Tianyou; Li, Yuanqing; Long, Jinyi; Gu, Zhenghui

    2012-06-01

    In this paper, we present a new web browser based on a two-dimensional (2D) brain-computer interface (BCI) mouse, where our major concern is the selection of an intended target in a multi-target web page. A real-world web page may contain tens or even hundreds of targets, including hyperlinks, input elements, buttons, etc. In this case, a target filter designed in our system can be used to exclude most of those targets of no interest. Specifically, the user filters the targets of no interest out by inputting keywords with a P300-based speller, while keeps those containing the keywords. Such filtering largely facilitates the target selection task based on our BCI mouse. When there are only several targets in a web page (either an original sparse page or a target-filtered page), the user moves the mouse toward the target of interest using his/her electroencephalographic signal. The horizontal movement and vertical movement are controlled by motor imagery and P300 potential, respectively. If the mouse encounters a target of no interest, the user rejects it and continues to move the mouse. Otherwise the user selects the target and activates it. With the collaboration of the target filtering and a series of mouse movements and target selections/rejections, the user can select an intended target in a web page. Based on our browser system, common navigation functions, including history rolling forward and backward, hyperlink selection, page scrolling, text input, etc, are available. The system has been tested on seven subjects. Experimental results not only validated the efficacy of the proposed method, but also showed that free internet surfing with a BCI mouse is feasible.

  4. Systematic analysis, comparison, and integration of disease based human genetic association data and mouse genetic phenotypic information

    Directory of Open Access Journals (Sweden)

    Wang S Alex

    2010-01-01

    Full Text Available Abstract Background The genetic contributions to human common disorders and mouse genetic models of disease are complex and often overlapping. In common human diseases, unlike classical Mendelian disorders, genetic factors generally have small effect sizes, are multifactorial, and are highly pleiotropic. Likewise, mouse genetic models of disease often have pleiotropic and overlapping phenotypes. Moreover, phenotypic descriptions in the literature in both human and mouse are often poorly characterized and difficult to compare directly. Methods In this report, human genetic association results from the literature are summarized with regard to replication, disease phenotype, and gene specific results; and organized in the context of a systematic disease ontology. Similarly summarized mouse genetic disease models are organized within the Mammalian Phenotype ontology. Human and mouse disease and phenotype based gene sets are identified. These disease gene sets are then compared individually and in large groups through dendrogram analysis and hierarchical clustering analysis. Results Human disease and mouse phenotype gene sets are shown to group into disease and phenotypically relevant groups at both a coarse and fine level based on gene sharing. Conclusion This analysis provides a systematic and global perspective on the genetics of common human disease as compared to itself and in the context of mouse genetic models of disease.

  5. A human-like senescence-associated secretory phenotype is conserved in mouse cells dependent on physiological oxygen.

    Directory of Open Access Journals (Sweden)

    Jean-Philippe Coppé

    Full Text Available Cellular senescence irreversibly arrests cell proliferation in response to oncogenic stimuli. Human cells develop a senescence-associated secretory phenotype (SASP, which increases the secretion of cytokines and other factors that alter the behavior of neighboring cells. We show here that "senescent" mouse fibroblasts, which arrested growth after repeated passage under standard culture conditions (20% oxygen, do not express a human-like SASP, and differ from similarly cultured human cells in other respects. However, when cultured in physiological (3% oxygen and induced to senesce by radiation, mouse cells more closely resemble human cells, including expression of a robust SASP. We describe two new aspects of the human and mouse SASPs. First, cells from both species upregulated the expression and secretion of several matrix metalloproteinases, which comprise a conserved genomic cluster. Second, for both species, the ability to promote the growth of premalignant epithelial cells was due primarily to the conserved SASP factor CXCL-1/KC/GRO-alpha. Further, mouse fibroblasts made senescent in 3%, but not 20%, oxygen promoted epithelial tumorigenesis in mouse xenographs. Our findings underscore critical mouse-human differences in oxygen sensitivity, identify conditions to use mouse cells to model human cellular senescence, and reveal novel conserved features of the SASP.

  6. Insights on Foxn1 Biological Significance and Usages of the “Nude” Mouse in Studies of T-Lymphopoiesis

    Directory of Open Access Journals (Sweden)

    Zhijie Zhang, Preston Burnley, Brandon Coder, Dong-Ming Su

    2012-01-01

    Full Text Available Mutation in the “nude” gene, i.e. the FoxN1 gene, induces a hairless phenotype and a rudimentary thymus gland in mice (nude mouse and humans (T-cell related primary immunodeficiency. Conventional FoxN1 gene knockout and transgenic mouse models have been generated for studies of FoxN1 gene function related to skin and immune diseases, and for cancer models. It appeared that FoxN1's role was fully understood and the nude mouse model was fully utilized. However, in recent years, with the development of inducible gene knockout/knockin mouse models with the loxP-Cre(ERT and diphtheria toxin receptor-induced cell abolished systems, it appears that the complete repertoire of FoxN1's roles and deep-going usage of nude mouse model in immune function studies have just begun. Here we summarize the research progress made by several recent works studying the role of FoxN1 in the thymus and utilizing nude and “second (conditional nude” mouse models for studies of T-cell development and function. We also raise questions and propose further consideration of FoxN1 functions and utilizing this mouse model for immune function studies.

  7. Conditionally reprogrammed normal and transformed mouse mammary epithelial cells display a progenitor-cell-like phenotype.

    Directory of Open Access Journals (Sweden)

    Francisco R Saenz

    Full Text Available Mammary epithelial (ME cells cultured under conventional conditions senesce after several passages. Here, we demonstrate that mouse ME cells isolated from normal mammary glands or from mouse mammary tumor virus (MMTV-Neu-induced mammary tumors, can be cultured indefinitely as conditionally reprogrammed cells (CRCs on irradiated fibroblasts in the presence of the Rho kinase inhibitor Y-27632. Cell surface progenitor-associated markers are rapidly induced in normal mouse ME-CRCs relative to ME cells. However, the expression of certain mammary progenitor subpopulations, such as CD49f+ ESA+ CD44+, drops significantly in later passages. Nevertheless, mouse ME-CRCs grown in a three-dimensional extracellular matrix gave rise to mammary acinar structures. ME-CRCs isolated from MMTV-Neu transgenic mouse mammary tumors express high levels of HER2/neu, as well as tumor-initiating cell markers, such as CD44+, CD49f+, and ESA+ (EpCam. These patterns of expression are sustained in later CRC passages. Early and late passage ME-CRCs from MMTV-Neu tumors that were implanted in the mammary fat pads of syngeneic or nude mice developed vascular tumors that metastasized within 6 weeks of transplantation. Importantly, the histopathology of these tumors was indistinguishable from that of the parental tumors that develop in the MMTV-Neu mice. Application of the CRC system to mouse mammary epithelial cells provides an attractive model system to study the genetics and phenotype of normal and transformed mouse epithelium in a defined culture environment and in vivo transplant studies.

  8. Increased apoptosis and hypomyelination in cerebral white matter of macular mutant mouse brain

    Directory of Open Access Journals (Sweden)

    Shoichi Takikita

    2015-09-01

    Full Text Available Hypomyelination in developing brain is often accompanied by congenital metabolic disorders. Menkes kinky hair disease is an X-linked neurodegenerative disease of impaired copper transport, resulting from a mutation of the Menkes disease gene, a transmembrane copper-transporting p-type ATPase gene (ATP7A. In a macular mutant mouse model, the murine ortholog of Menkes gene (mottled gene is mutated, and widespread neurodegeneration and subsequent death are observed. Although some biochemical analysis of myelin protein in macular mouse has been reported, detailed histological study of myelination in this mouse model is currently lacking. Since myelin abnormality is one of the neuropathologic findings of human Menkes disease, in this study early myelination in macular mouse brain was evaluated by immunohistochemistry. Two-week-old macular mice and normal littermates were perfused with 4% paraformaldehyde. Immunohistochemical staining of paraffin embedded and vibratome sections was performed using antibodies against either CNPase, cleaved caspase-3 or O4 (marker of immature oligodendrocytes. This staining showed that cerebral myelination in macular mouse was generally hypoplastic and that hypomyelination was remarkable in internal capsule, corpus callosum, and cingulate cortex. In addition, an increased number of cleaved caspase-3 positive cells were observed in corpus callosum and internal capsule. Copper deficiency induced by low copper diet has been reported to induce oligodendrocyte dysfunction and leads to hypomyelination in this mouse model. Taken together, hypomyelination observed in this study in a mouse model of Menkes disease is assumed to be induced by increased apoptosis of immature oligodendrocytes in developing cerebrum, through deficient intracellular copper metabolism.

  9. Determination of reference genes for circadian studies in different tissues and mouse strains

    Directory of Open Access Journals (Sweden)

    Kosir Rok

    2010-08-01

    Full Text Available Abstract Background Circadian rhythms have a profound effect on human health. Their disruption can lead to serious pathologies, such as cancer and obesity. Gene expression studies in these pathologies are often studied in different mouse strains by quantitative real time polymerase chain reaction (qPCR. Selection of reference genes is a crucial step of qPCR experiments. Recent studies show that reference gene stability can vary between species and tissues, but none has taken circadian experiments into consideration. Results In the present study the expression of ten candidate reference genes (Actb, Eif2a, Gapdh, Hmbs, Hprt1, Ppib, Rn18s, Rplp0, Tbcc and Utp6c was measured in 131 liver and 97 adrenal gland samples taken from three mouse strains (C57BL/6JOlaHsd, 129Pas plus C57BL/6J and Crem KO on 129Pas plus C57BL/6J background every 4 h in a 24 h period. Expression stability was evaluated by geNorm and NormFinder programs. Differences in ranking of the most stable reference genes were observed both between individual mouse strains as well as between tissues within each mouse strain. We show that selection of reference gene (Actb that is often used for analyses in individual mouse strains leads to errors if used for normalization when different mouse strains are compared. We identified alternative reference genes that are stable in these comparisons. Conclusions Genetic background and circadian time influence the expression stability of reference genes. Differences between mouse strains and tissues should be taken into consideration to avoid false interpretations. We show that the use of a single reference gene can lead to false biological conclusions. This manuscript provides a useful reference point for researchers that search for stable reference genes in the field of circadian biology.

  10. Mouse T-cells restrict replication of human immunodeficiency virus at the level of integration

    Directory of Open Access Journals (Sweden)

    Goffinet Christine

    2008-07-01

    Full Text Available Abstract Background The development of an immunocompetent, genetically modified mouse model to study HIV-1 pathogenesis and to test antiviral strategies has been hampered by the fact that cells from native mice do not or only inefficiently support several steps of the HIV-1 replication cycle. Upon HIV-1 infection, mouse T-cell lines fail to express viral proteins, but the underlying replication barrier has thus far not been unambiguously identified. Here, we performed a kinetic and quantitative assessment of consecutive steps in the early phase of the HIV-1 replication cycle in T-cells from mice and humans. Results Both T-cell lines and primary T-cells from mice harbor a severe post-entry defect that is independent of potential species-specTR transactivation. Reverse transcription occurred efficiently following VSV-G-mediated entry of virions into mouse T-cells, and abundant levels of 2-LTR circles indicated successful nuclear import of the pre-integration complex. To probe the next step in the retroviral replication cycle, i.e. the integration of HIV-1 into the host cell genome, we established and validated a nested real-time PCR to specifically quantify HIV-1 integrants exploiting highly repetitive mouse B1 elements. Importantly, we demonstrate that the frequency of integrant formation is diminished 18- to > 305-fold in mouse T-cell lines compared to a human counterpart, resulting in a largely abortive infection. Moreover, differences in transgene expression from residual vector integrants, the transcription off which is cyclin T1-independent, provided evidence for an additional, peri-integrational deficit in certain mouse T-cell lines. Conclusion In contrast to earlier reports, we find that mouse T-cells efficiently support early replication steps up to and including nuclear import, but restrict HIV-1 at the level of chromosomal integration.

  11. Isolation and characterization of multipotential mesenchymal cells from the mouse synovium.

    Directory of Open Access Journals (Sweden)

    Ippei Futami

    Full Text Available The human synovium contains mesenchymal stem cells (MSCs, which are multipotential non-hematopoietic progenitor cells that can differentiate into a variety of mesenchymal lineages and they may therefore be a candidate cell source for tissue repair. However, the molecular mechanisms by which this can occur are still largely unknown. Mouse primary cell culture enables us to investigate the molecular mechanisms underlying various phenomena because it allows for relatively easy gene manipulation, which is indispensable for the molecular analysis. However, mouse synovial mesenchymal cells (SMCs have not been established, although rabbit, cow, and rat SMCs are available, in addition to human MSCs. The aim of this study was to establish methods to harvest the synovium and to isolate and culture primary SMCs from mice. As the mouse SMCs were not able to be harvested and isolated using the same protocol for human, rat and rabbit SMCs, the protocol for humans was modified for SMCs from the Balb/c mouse knee joint. The mouse SMCs obtained showed superior proliferative potential, growth kinetics and colony formation compared to cells derived from muscle and bone marrow. They expressed PDGFRá and Sca-1 detected by flow cytometry, and showed an osteogenic, adipogenic and chondrogenic potential similar or superior to the cells derived from muscle and bone marrow by demonstrating in vitro osteogenesis, adipogenesis and chondrogenesis. In conclusion, we established a primary mouse synovial cell culture method. The cells derived from the mouse synovium demonstrated both the ability to proliferate and multipotentiality similar or superior to the cells derived from muscle and bone marrow.

  12. Manual annotation and analysis of the defensin gene cluster in the C57BL/6J mouse reference genome

    Directory of Open Access Journals (Sweden)

    Dougan Gordon

    2009-12-01

    Full Text Available Abstract Background Host defense peptides are a critical component of the innate immune system. Human alpha- and beta-defensin genes are subject to copy number variation (CNV and historically the organization of mouse alpha-defensin genes has been poorly defined. Here we present the first full manual genomic annotation of the mouse defensin region on Chromosome 8 of the reference strain C57BL/6J, and the analysis of the orthologous regions of the human and rat genomes. Problems were identified with the reference assemblies of all three genomes. Defensins have been studied for over two decades and their naming has become a critical issue due to incorrect identification of defensin genes derived from different mouse strains and the duplicated nature of this region. Results The defensin gene cluster region on mouse Chromosome 8 A2 contains 98 gene loci: 53 are likely active defensin genes and 22 defensin pseudogenes. Several TATA box motifs were found for human and mouse defensin genes that likely impact gene expression. Three novel defensin genes belonging to the Cryptdin Related Sequences (CRS family were identified. All additional mouse defensin loci on Chromosomes 1, 2 and 14 were annotated and unusual splice variants identified. Comparison of the mouse alpha-defensins in the three main mouse reference gene sets Ensembl, Mouse Genome Informatics (MGI, and NCBI RefSeq reveals significant inconsistencies in annotation and nomenclature. We are collaborating with the Mouse Genome Nomenclature Committee (MGNC to establish a standardized naming scheme for alpha-defensins. Conclusions Prior to this analysis, there was no reliable reference gene set available for the mouse strain C57BL/6J defensin genes, demonstrating that manual intervention is still critical for the annotation of complex gene families and heavily duplicated regions. Accurate gene annotation is facilitated by the annotation of pseudogenes and regulatory elements. Manually curated gene

  13. Defining the role of polyamines in colon carcinogenesis using mouse models

    Directory of Open Access Journals (Sweden)

    Natalia A Ignatenko

    2011-01-01

    Full Text Available Genetics and diet are both considered important risk determinants for colorectal cancer, a leading cause of death in the US and worldwide. Genetically engineered mouse (GEM models have made a significant contribution to the characterization of colorectal cancer risk factors. Reliable, reproducible, and clinically relevant animal models help in the identification of the molecular events associated with disease progression and in the development of effictive treatment strategies. This review is focused on the use of mouse models for studying the role of polyamines in colon carcinogenesis. We describe how the available mouse models of colon cancer such as the multiple intestinal neoplasia (Min mice and knockout genetic models facilitate understanding of the role of polyamines in colon carcinogenesis and help in the development of a rational strategy for colon cancer chemoprevention.

  14. Genome-scale analysis of positional clustering of mouse testis-specific genes

    Directory of Open Access Journals (Sweden)

    Lee Bernett TK

    2005-01-01

    Full Text Available Abstract Background Genes are not randomly distributed on a chromosome as they were thought even after removal of tandem repeats. The positional clustering of co-expressed genes is known in prokaryotes and recently reported in several eukaryotic organisms such as Caenorhabditis elegans, Drosophila melanogaster, and Homo sapiens. In order to further investigate the mode of tissue-specific gene clustering in higher eukaryotes, we have performed a genome-scale analysis of positional clustering of the mouse testis-specific genes. Results Our computational analysis shows that a large proportion of testis-specific genes are clustered in groups of 2 to 5 genes in the mouse genome. The number of clusters is much higher than expected by chance even after removal of tandem repeats. Conclusion Our result suggests that testis-specific genes tend to cluster on the mouse chromosomes. This provides another piece of evidence for the hypothesis that clusters of tissue-specific genes do exist.

  15. Understanding mammalian genetic systems: the challenge of phenotyping in the mouse.

    Directory of Open Access Journals (Sweden)

    Steve D M Brown

    2006-08-01

    Full Text Available Understanding mammalian genetic systems is predicated on the determination of the relationship between genetic variation and phenotype. Several international programmes are under way to deliver mutations in every gene in the mouse genome. The challenge for mouse geneticists is to develop approaches that will provide comprehensive phenotype datasets for these mouse mutant libraries. Several factors are critical to success in this endeavour. It will be important to catalogue assay and environment and where possible to adopt standardised procedures for phenotyping tests along with common environmental conditions to ensure comparable datasets of phenotypes. Moreover, the scale of the task underlines the need to invest in technological development improving both the speed and cost of phenotyping platforms. In addition, it will be necessary to develop new informatics standards that capture the phenotype assay as well as other factors, genetic and environmental, that impinge upon phenotype outcome.

  16. Bio-Inspired PVDF-Based, Mouse Whisker Mimicking, Tactile Sensor

    Directory of Open Access Journals (Sweden)

    Mohsin Islam Tiwana

    2016-10-01

    Full Text Available The design and fabrication of a Polyvinylidene fluoride (PVDF based, mouse (or rodent whisker mimicking, tactile sensor is presented. Unlike previous designs reported in the literature, this sensor mimics the mouse whisker not only mechanically, but it also makes macro movements just like a real mouse whisker in a natural environment. We have developed a mathematical model and performed finite element analysis using COMSOL, in order to optimise the whisker to have the same natural frequency as that of a biological whisker. Similarly, we have developed a control system that enables the whisker mimicking sensor to vibrate at variable frequencies and conducted practical experiments to validate the response of the sensor. The natural frequency of the whisker can be designed anywhere between 35 and 110 Hz, the same as a biological whisker, by choosing different materials and physical dimensions. The control system of this sensor enables the whisker to vibrate between 5 and 236 Hz.

  17. Virtual histology of transgenic mouse embryos for high-throughput phenotyping.

    Directory of Open Access Journals (Sweden)

    John T Johnson

    2006-04-01

    Full Text Available A bold new effort to disrupt every gene in the mouse genome necessitates systematic, interdisciplinary approaches to analyzing patterning defects in the mouse embryo. We present a novel, rapid, and inexpensive method for obtaining high-resolution virtual histology for phenotypic assessment of mouse embryos. Using osmium tetroxide to differentially stain tissues followed by volumetric X-ray computed tomography to image whole embryos, isometric resolutions of 27 mum or 8 mum were achieved with scan times of 2 h or 12 h, respectively, using mid-gestation E9.5-E12.5 embryos. The datasets generated by this method are immediately amenable to state-of-the-art computational methods of organ patterning analysis. This technique to assess embryo anatomy represents a significant improvement in resolution, time, and expense for the quantitative, three-dimensional analysis of developmental patterning defects attributed to genetically engineered mutations and chemically induced embryotoxicity.

  18. Mouse models in male fertility research

    Institute of Scientific and Technical Information of China (English)

    Duangporn Jamsai; Moira K O'Bryan

    2011-01-01

    Limited knowledge of the genetic causes of male infertility has resulted in few treatment and targeted therapeutic options.Although the ideal approach to identify infertility causing mutations is to conduct studies in the human population,this approach has progressed slowly due to the limitations described herein.Given the complexity of male fertility,the entire process cannot be modeled in vitro.As such,animal models,in particular mouse models,provide a valuable alternative for gene identification and experimentation.Since the introduction of molecular biology and recent advances in animal model production,there has been a substantial acceleration in the identification and characterization of genes associated with many diseases,including infertility.Three major types of mouse models are commonly used in biomedical research,including knockout/knockin/gene-trapped,transgenic and chemical-induced point mutant mice.Using these mouse models,over 400 genes essential for male fertility have been revealed.It has,however,been estimated that thousands of genes are involved in the regulation of the complex process of male fertility,as many such genes remain to be characterized.The current review is by no means a comprehensive list of these mouse models,rather it contains examples of how mouse models have advanced our knowledge of post-natal germ cell development and male fertility regulation.

  19. Asymmetric Reprogramming Capacity of Parental Pronuclei in Mouse Zygotes

    Directory of Open Access Journals (Sweden)

    Wenqiang Liu

    2014-03-01

    Full Text Available It has been demonstrated that reprogramming factors are sequestered in the pronuclei of zygotes after fertilization, because zygotes enucleated at the M phase instead of interphase of the first mitosis can support the development of cloned embryos. However, the contribution of the parental pronucleus derived from either the sperm or the oocyte in reprogramming remains elusive. Here, we demonstrate that the parental pronuclei have asymmetric reprogramming capacities and that the reprogramming factors reside predominantly in the male pronucleus. As a result, only female pronucleus-depleted (FPD mouse zygotes can reprogram somatic cells to a pluripotent state and support the full-term development of cloned embryos; male pronucleus-depleted (MPD zygotes fail to support somatic cell reprogramming. We further demonstrate that fusion of an additional male pronucleus into a zygote greatly enhances reprogramming efficiency. Our data provide a clue to further identify critical reprogramming factors in the male pronucleus.

  20. Characterization of a male reproductive transcriptome for Peromyscus eremicus (Cactus mouse

    Directory of Open Access Journals (Sweden)

    Lauren L. Kordonowy

    2016-10-01

    Full Text Available Rodents of the genus Peromyscus have become increasingly utilized models for investigations into adaptive biology. This genus is particularly powerful for research linking genetics with adaptive physiology or behaviors, and recent research has capitalized on the unique opportunities afforded by the ecological diversity of these rodents. Well characterized genomic and transcriptomic data is intrinsic to explorations of the genetic architecture responsible for ecological adaptations. Therefore, this study characterizes the transcriptome of three male reproductive tissues (testes, epididymis and vas deferens of Peromyscus eremicus (Cactus mouse, a desert specialist. The transcriptome assembly process was optimized in order to produce a high quality and substantially complete annotated transcriptome. This composite transcriptome was generated to characterize the expressed transcripts in the male reproductive tract of P. eremicus, which will serve as a crucial resource for future research investigating our hypothesis that the male Cactus mouse possesses an adaptive reproductive phenotype to mitigate water-loss from ejaculate. This study reports genes under positive selection in the male Cactus mouse reproductive transcriptome relative to transcriptomes from Peromyscus maniculatus (deer mouse and Mus musculus. Thus, this study expands upon existing genetic research in this species, and we provide a high quality transcriptome to enable further explorations of our proposed hypothesis for male Cactus mouse reproductive adaptations to minimize seminal fluid loss.

  1. Human and mouse mononuclear phagocyte networks: a tale of two species?

    Directory of Open Access Journals (Sweden)

    Gary eReynolds

    2015-06-01

    Full Text Available Dendritic cells (DCs, monocytes and macrophages are a heterogeneous population of mononuclear phagocytes that are involved in antigen processing and presentation to initiate and regulate immune responses to pathogens, vaccines, tumour and tolerance to self. In addition to their afferent sentinel function, DCs and macrophages are also critical as effectors and coordinators of inflammation and homeostasis in peripheral tissues. Harnessing DCs and macrophages for therapeutic purposes has major implications for infectious disease, vaccination, transplantation, tolerance induction, inflammation and cancer immunotherapy. There has been a paradigm shift in our understanding of the developmental origin and function of the cellular constituents of the mononuclear phagocyte system. Significant progress has been made in tandem in both human and mouse mononuclear phagocyte biology. This progress has been accelerated by comparative biology analysis between mouse and human, which has proved to be an exceptionally fruitful strategy to harmonise findings across species. Such analyses have provided unexpected insights and facilitated productive reciprocal and iterative processes to inform our understanding of human and mouse mononuclear phagocytes. In this review, we discuss the strategies, power and utility of comparative biology approaches to integrate recent advances in human and mouse mononuclear phagocyte biology and its potential to drive forward clinical translation of this knowledge. We also present a functional framework on the parallel organisation of human and mouse mononuclear phagocyte networks.

  2. Histopathological characteristics of a novel knock-in mouse prostate cancer model

    Directory of Open Access Journals (Sweden)

    G. Wu

    2006-06-01

    Full Text Available Prostate cancer is relatively unique to man. There is no naturally occurring prostate cancer in the mouse. Pre-clinical studies involve the establishment of a genetically engineered mouse prostate cancer model with features close to those of the human situation. A new knock-in mouse adenocarcinoma prostate (KIMAP model was established, which showed close-to-human kinetics of tumor development. In order to determine if the similar kinetics is associated with heterogeneous tumor architecture similar to the human situation, we utilized a new mouse histological grading system (Gleason analogous grading system similar to the Gleason human grading system and flow cytometry DNA analysis to measure and compare the adenocarcinoma of the KIMAP model with human prostate cancer. Sixty KIMAP prostate cancer samples from 60 mice were measured and compared with human prostate cancer. Flow cytometry DNA analysis was performed on malignant prostate tissues obtained from KIMAP models. Mice with prostate cancer from KIMAP models showed a 53.3% compound histological score rate, which was close to the human clinical average (50% and showed a significant correlation with age (P = 0.001. Flow cytometry analyses demonstrated that most KIMAP tumor tissues were diploid, analogous to the human situation. The similarities of the KIMAP mouse model with tumors of the human prostate suggest the use of this experimental model to complement studies of human prostate cancer.

  3. Topical Application of Oleuropein Induces Anagen Hair Growth in Telogen Mouse Skin.

    Directory of Open Access Journals (Sweden)

    Tao Tong

    Full Text Available Oleuropein promoted cultured human follicle dermal papilla cell proliferation and induced LEF1 and Cyc-D1 mRNA expression and β-catenin protein expression in dermal papilla cells. Nuclear accumulation of β-catenin in dermal papilla cells was observed after oleuropein treatment. Topical application of oleuropein (0.4 mg/mouse/day to C57BL/6N mice accelerated the hair-growth induction and increased the size of hair follicles in telogenic mouse skin. The oleuropein-treated mouse skin showed substantial upregulation of Wnt10b, FZDR1, LRP5, LEF1, Cyc-D1, IGF-1, KGF, HGF, and VEGF mRNA expression and β-catenin protein expression.These results demonstrate that topical oleuroepin administration induced anagenic hair growth in telogenic C57BL/6N mouse skin. The hair-growth promoting effect of oleuropein in mice appeared to be associated with the stimulation of the Wnt10b/β-catenin signaling pathway and the upregulation of IGF-1, KGF, HGF, and VEGF gene expression in mouse skin tissue.

  4. Two pore channel 2 differentially modulates neural differentiation of mouse embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Zhe-Hao Zhang

    Full Text Available Nicotinic acid adenine dinucleotide phosphate (NAADP is an endogenous Ca(2+ mobilizing nucleotide presented in various species. NAADP mobilizes Ca(2+ from acidic organelles through two pore channel 2 (TPC2 in many cell types and it has been previously shown that NAADP can potently induce neuronal differentiation in PC12 cells. Here we examined the role of TPC2 signaling in the neural differentiation of mouse embryonic stem (ES cells. We found that the expression of TPC2 was markedly decreased during the initial ES cell entry into neural progenitors, and the levels of TPC2 gradually rebounded during the late stages of neurogenesis. Correspondingly, TPC2 knockdown accelerated mouse ES cell differentiation into neural progenitors but inhibited these neural progenitors from committing to neurons. Overexpression of TPC2, on the other hand, inhibited mouse ES cell from entering the early neural lineage. Interestingly, TPC2 knockdown had no effect on the differentiation of astrocytes and oligodendrocytes of mouse ES cells. Taken together, our data indicate that TPC2 signaling plays a temporal and differential role in modulating the neural lineage entry of mouse ES cells, in that TPC2 signaling inhibits ES cell entry to early neural progenitors, but is required for late neuronal differentiation.

  5. Sildenafil enhances neurogenesis and oligodendrogenesis in ischemic brain of middle-aged mouse.

    Directory of Open Access Journals (Sweden)

    Rui Lan Zhang

    Full Text Available Adult neural stem cells give rise to neurons, oligodendrocytes and astrocytes. Aging reduces neural stem cells. Using an inducible nestin-CreER(T2/R26R-yellow fluorescent protein (YFP mouse, we investigated the effect of Sildenafil, a phosphodiesterase type 5 (PDE5 inhibitor, on nestin lineage neural stem cells and their progeny in the ischemic brain of the middle-aged mouse. We showed that focal cerebral ischemia induced nestin lineage neural stem cells in the subventricular zone (SVZ of the lateral ventricles and nestin expressing NeuN positive neurons and adenomatous polyposis coli (APC positive mature oligodendrocytes in the ischemic striatum and corpus callosum in the aged mouse. Treatment of the ischemic middle-aged mouse with Sildenafil increased nestin expressing neural stem cells, mature neurons, and oligodendrocytes by 33, 75, and 30%, respectively, in the ischemic brain. These data indicate that Sildenafil amplifies nestin expressing neural stem cells and their neuronal and oligodendrocyte progeny in the ischemic brain of the middle-aged mouse.

  6. Identification of a set of genes showing regionally enriched expression in the mouse brain

    Directory of Open Access Journals (Sweden)

    Marra Marco A

    2008-07-01

    Full Text Available Abstract Background The Pleiades Promoter Project aims to improve gene therapy by designing human mini-promoters ( Results We have utilized LongSAGE to identify regionally enriched transcripts in the adult mouse brain. As supplemental strategies, we also performed a meta-analysis of published literature and inspected the Allen Brain Atlas in situ hybridization data. From a set of approximately 30,000 mouse genes, 237 were identified as showing specific or enriched expression in 30 target regions of the mouse brain. GO term over-representation among these genes revealed co-involvement in various aspects of central nervous system development and physiology. Conclusion Using a multi-faceted expression validation approach, we have identified mouse genes whose human orthologs are good candidates for design of mini-promoters. These mouse genes represent molecular markers in several discrete brain regions/cell-types, which could potentially provide a mechanistic explanation of unique functions performed by each region. This set of markers may also serve as a resource for further studies of gene regulatory elements influencing brain expression.

  7. Comparative Proteomics of Mouse Tears and Saliva: Evidence from Large Protein Families for Functional Adaptation

    Directory of Open Access Journals (Sweden)

    Robert C. Karn

    2015-09-01

    Full Text Available We produced a tear proteome of the genome mouse, C57BL/6, that contained 139 different protein identifications: 110 from a two-dimensional (2D gel with subsequent trypsin digestion, 19 from a one-dimensional (1D gel with subsequent trypsin digestion and ten from a 1D gel with subsequent Asp-N digestion. We compared this tear proteome with a C57BL/6 mouse saliva proteome produced previously. Sixteen of the 139 tear proteins are shared between the two proteomes, including six proteins that combat microbial growth. Among the 123 other tear proteins, were members of four large protein families that have no counterparts in humans: Androgen-binding proteins (ABPs with different members expressed in the two proteomes, Exocrine secreted peptides (ESPs expressed exclusively in the tear proteome, major urinary proteins (MUPs expressed in one or both proteomes and the mouse-specific Kallikreins (subfamily b KLKs expressed exclusively in the saliva proteome. All four families have members with suggested roles in mouse communication, which may influence some aspect of reproductive behavior. We discuss this in the context of functional adaptation involving tear and saliva proteins in the secretions of mouse lacrimal and salivary glands, respectively.

  8. Pancreatic cancer study based on full field OCT and dynamic full field OCT (Conference Presentation)

    Science.gov (United States)

    Apelian, Clement; Camus, Marine; Prat, Frederic; Boccara, A. Claude

    2017-02-01

    Pancreatic cancer is one of the most feared cancer types due to high death rates and the difficulty to perform surgery. This cancer outcome could benefit from recent technological developments for diagnosis. We used a combination of standard Full Field OCT and Dynamic Full Field OCT to capture both morphological features and metabolic functions of rodents pancreas in normal and cancerous conditions with and without chemotherapy. Results were compared to histology to evaluate the performances and the specificities of the method. The comparison highlighted the importance of a number of endogenous markers like immune cells, fibrous development, architecture and more.

  9. Comment on “Full spin flipping in the presence of full Siberian Snake”

    Directory of Open Access Journals (Sweden)

    S. R. Mane

    2009-09-01

    Full Text Available Bai and Roser {Phys. Rev. ST Accel. Beams 11, 091001 (2008PRABFM1098-440210.1103/PhysRevSTAB.11.091001 [Phys. Rev. ST Accel. Beams 12, 019901(E (2009]PRABFM1098-440210.1103/PhysRevSTAB.12.019901} have published an idea for a design of a spin flipper, consisting of two radial field rf dipoles with correlated phases, to operate with full strength Siberian Snakes, at a spin tune of 1/2. Some details of their design analysis are oversimplified.

  10. Application of functional genomics to the chimeric mouse model of HCV infection: optimization of microarray protocols and genomics analysis

    Directory of Open Access Journals (Sweden)

    Smith Maria W

    2006-05-01

    Full Text Available Abstract Background Many model systems of human viral disease involve human-mouse chimeric tissue. One such system is the recently developed SCID-beige/Alb-uPA mouse model of hepatitis C virus (HCV infection which involves a human-mouse chimeric liver. The use of functional genomics to study HCV infection in these chimeric tissues is complicated by the potential cross-hybridization of mouse mRNA on human oligonucleotide microarrays. To identify genes affected by mouse liver mRNA hybridization, mRNA from identical human liver samples labeled with either Cy3 or Cy5 was compared in the presence and absence of known amounts of mouse liver mRNA labeled in only one dye. Results The results indicate that hybridization of mouse mRNA to the corresponding human gene probe on Agilent Human 22 K oligonucleotide microarray does occur. The number of genes affected by such cross-hybridization was subsequently reduced to approximately 300 genes both by increasing the hybridization temperature and using liver samples which contain at least 80% human tissue. In addition, Real Time quantitative RT-PCR using human specific probes was shown to be a valid method to verify the expression level in human cells of known cross-hybridizing genes. Conclusion The identification of genes affected by cross-hybridization of mouse liver RNA on human oligonucleotide microarrays makes it feasible to use functional genomics approaches to study the chimeric SCID-beige/Alb-uPA mouse model of HCV infection. This approach used to study cross-species hybridization on oligonucleotide microarrays can be adapted to other chimeric systems of viral disease to facilitate selective analysis of human gene expression.

  11. Identification of 9 uterine genes that are regulated during mouse pregnancy and exhibit abnormal levels in the cyclooxygenase-1 knockout mouse

    Directory of Open Access Journals (Sweden)

    Soper Jessica

    2007-07-01

    Full Text Available Abstract Background Preterm birth is the leading cause of all infant mortality. In 2004, 12.5% of all births were preterm. In order to understand preterm labor, we must first understand normal labor. Since many of the myometrial changes that occur during pregnancy are similar in mice and humans and mouse gestation is short, we have studied the uterine genes that change in the mouse during pregnancy. Here, we used microarray analysis to identify uterine genes in the gravid mouse that are differentially regulated in the cyclooxygenase-1 knockout mouse model of delayed parturition. Methods Gestational d18.0 uteri (n = 4 were collected from pregnant wild-type and cyclooxygenase-1 knockout mice. Part of the uterus was used for frozen sections and RNA was isolated from the remainder. Microarray analysis was performed at the Indiana University School of Medicine Genomic Core and analyzed using the Microarray Data Portal. Northern analysis was performed to confirm microarray data and the genes localized in the gravid uterus by in situ hybridization. Results We identified 277 genes that are abnormally expressed in the gravid d18.0 cyclooxygenase-1 knockout mouse. Nine of these genes are also regulated in the normal murine uterus during the last half of gestation. Many of these genes are involved in the immune response, consistent with an important role of the immune system in parturition. Expression of 4 of these genes; arginase I, IgJ, Tnfrsf9 and troponin; was confirmed by Northern analysis to be mis-regulated during pregnancy in the knockout mouse. In situ hybridization of these genes demonstrated a similar location in the gravid wild-type and Cox-1 knockout mouse uteri. Conclusion To our knowledge, this is the first work to demonstrate the uterine location of these 4 genes in the mouse during late pregnancy. There are several putative transcription factor binding sites that are shared by many of the 9 genes identified here including; estrogen and

  12. Mouse Simulation Using Two Coloured Tapes

    CERN Document Server

    Kumar, Vikram; Mahe, Swapnil; Vyawahare, Swapnil; 10.5121/ijist.2012.2206

    2012-01-01

    In this paper, we present a novel approach for Human Computer Interaction (HCI) where, we control cursor movement using a real-time camera. Current methods involve changing mouse parts such as adding more buttons or changing the position of the tracking ball. Instead, our method is to use a camera and computer vision technology, such as image segmentation and gesture recognition, to control mouse tasks (left and right clicking, double-clicking, and scrolling) and we show how it can perform everything as current mouse devices can. The software will be developed in JAVA language. Recognition and pose estimation in this system are user independent and robust as we will be using colour tapes on our finger to perform actions. The software can be used as an intuitive input interface to applications that require multi-dimensional control e.g. computer games etc.

  13. Contemporary approaches for modifying the mouse genome

    Science.gov (United States)

    Adams, David J.; van der Weyden, Louise

    2008-01-01

    The mouse is a premiere experimental organism that has contributed significantly to our understanding of vertebrate biology. Manipulation of the mouse genome via embryonic stem (ES) cell technology makes it possible to engineer an almost limitless repertoire of mutations to model human disease and assess gene function. In this review we outline recent advances in mouse experimental genetics and provide a “how-to” guide for those people wishing to access this technology. We also discuss new technologies, such as transposon-mediated mutagenesis, and resources of targeting vectors and ES cells, which are likely to dramatically accelerate the pace with which we can assess gene function in vivo, and the progress of forward and reverse genetic screens in mice. PMID:18559964

  14. Peripheral Neuropathy in Mouse Models of Diabetes.

    Science.gov (United States)

    Jolivalt, Corinne G; Frizzi, Katie E; Guernsey, Lucie; Marquez, Alex; Ochoa, Joseline; Rodriguez, Maria; Calcutt, Nigel A

    2016-09-01

    Peripheral neuropathy is a frequent complication of chronic diabetes that most commonly presents as a distal degenerative polyneuropathy with sensory loss. Around 20% to 30% of such patients may also experience neuropathic pain. The underlying pathogenic mechanisms are uncertain, and therapeutic options are limited. Rodent models of diabetes have been used for more than 40 years to study neuropathy and evaluate potential therapies. For much of this period, streptozotocin-diabetic rats were the model of choice. The emergence of new technologies that allow relatively cheap and routine manipulations of the mouse genome has prompted increased use of mouse models of diabetes to study neuropathy. In this article, we describe the commonly used mouse models of type 1 and type 2 diabetes, and provide protocols to phenotype the structural, functional, and behavioral indices of peripheral neuropathy, with a particular emphasis on assays pertinent to the human condition. © 2016 by John Wiley & Sons, Inc.

  15. Citrobacter rodentium mouse model of bacterial infection.

    Science.gov (United States)

    Crepin, Valerie F; Collins, James W; Habibzay, Maryam; Frankel, Gad

    2016-10-01

    Infection of mice with Citrobacter rodentium is a robust model to study bacterial pathogenesis, mucosal immunology, the health benefits of probiotics and the role of the microbiota during infection. C. rodentium was first isolated by Barthold from an outbreak of mouse diarrhea in Yale University in 1972 and was 'rediscovered' by Falkow and Schauer in 1993. Since then the use of the model has proliferated, and it is now the gold standard for studying virulence of the closely related human pathogens enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC, respectively). Here we provide a detailed protocol for various applications of the model, including bacterial growth, site-directed mutagenesis, mouse inoculation (from cultured cells and after cohabitation), monitoring of bacterial colonization, tissue extraction and analysis, immune responses, probiotic treatment and microbiota analysis. The main protocol, from mouse infection to clearance and analysis of tissues and host responses, takes ∼5 weeks to complete.

  16. Biotransformation in Egyptian spiny mouse Acomys cahirinus.

    Science.gov (United States)

    Watkins, J B; LaFollette, J W; Sanders, R A

    1995-01-01

    The activities of several representative biotransformation enzymes were determined in male and female spiny mouse tissues. Cytochrome P450 monooxygenase activity toward benzo(a)pyrene was significantly greater in female spiny mouse intestine than in males. Activity toward benzphetamine in both sexes was high in the liver, with little activity in the kidney and intestine. Sulfotransferase activity was high in kidney and intestine of female spiny mice but undetectable in the same tissues in males. Hepatic glutathione S-transferase activity towards 1-chloro-2,4-dinitrobenzene in females was significantly higher than in males. UDP-Glucuronosyltransferase activity toward 1-naphthol in both sexes in the kidney was significantly higher than hepatic and intestinal activity. Intestinal N-acetyltransferase activity towards 2-aminofluorene and beta-naphthylamine was significantly greater in females than males. No consistent relation appeared to exist between biotransformation activities in spiny mouse and those in other related rodent species.

  17. OCT guided microinjections for mouse embryonic research

    Science.gov (United States)

    Larin, Kirill V.; Syed, Saba H.; Coughlin, Andrew J.; Wang, Shang; West, Jennifer L.; Dickinson, Mary E.; Larina, Irina V.

    2013-02-01

    Optical coherence tomography (OCT) is gaining popularity as live imaging tool for embryonic research in animal models. Recently we have demonstrated that OCT can be used for live imaging of cultured early mouse embryos (E7.5-E10) as well as later stage mouse embryos in utero (E12.5 to the end of gestation). Targeted delivery of signaling molecules, drugs, and cells is a powerful approach to study normal and abnormal development, and image guidance is highly important for such manipulations. Here we demonstrate that OCT can be used to guide microinjections of gold nanoshell suspensions in live mouse embryos. This approach can potentially be used for variety of applications such as guided injections of contrast agents, signaling molecules, pharmacological agents, cell transplantation and extraction, as well as other image-guided micromanipulations. Our studies also reveal novel potential for gold nanoshells in embryonic research.

  18. Differential Gene Expression in Chemically Induced Mouse Lung Adenomas

    Directory of Open Access Journals (Sweden)

    Ruisheng Yao

    2003-01-01

    Full Text Available Because of similarities in histopathology and tumor progression stages between mouse and human lung adenocarcinomas, the mouse lung tumor model with lung adenomas as the endpoint has been used extensively to evaluate the efficacy of putative lung cancer chemopreventive agents. In this study, a competitive cDNA library screening (CCLS was employed to determine changes in the expression of mRNA in chemically induced lung adenomas compared with paired normal lung tissues. A total of 2555 clones having altered expression in tumors were observed following competitive hybridization between normal lung and lung adenomas after primary screening of over 160,000 clones from a mouse lung cDNA library. Among the 755 clones confirmed by dot blot hybridization, 240 clones were underexpressed, whereas 515 clones were overexpressed in tumors. Sixty-five clones with the most frequently altered expression in six individual tumors were confirmed by semiquantitative RT-PCR. When examining the 58 known genes, 39 clones had increased expression and 19 had decreased expression, whereas the 7 novel genes showed overexpression. A high percentage (>60% of overexpressed or underexpressed genes was observed in at least two or three of the lesions. Reproducibly overexpressed genes included ERK-1, JAK-1, surfactant proteins A, B, and C, NFAT1, α-1 protease inhibitor, helix-loop-helix ubiquitous kinase (CHUK, α-adaptin, α-1 PI2, thioether S-methyltransferase, and CYP2C40. Reproducibly underexpressed genes included paroxanase, ALDH II, CC10, von Ebner salivary gland protein, and α- and β-globin. In addition, CCLS identified several novel genes or genes not previously associated with lung carcinogenesis, including a hypothetical protein (FLJ11240 and a guanine nucleotide exchange factor homologue. This study shows the efficacy of this methodology for identifying genes with altered expression. These genes may prove to be helpful in our understanding of the genetic basis of

  19. A method for the immortalization of newborn mouse skin keratinocytes

    Directory of Open Access Journals (Sweden)

    Brianna O Hammiller

    2015-07-01

    Full Text Available Isolation and culture of mouse primary epidermal keratinocytes is a common technique that allows for easy genetic and environmental manipulation. However, due to their limited lifespan in culture, experiments utilizing primary keratinocytes require large numbers of animals, and are time consuming and expensive. To avoid these issues, we developed a method for the immortalization of primary mouse epidermal keratinocytes. Upon isolation of newborn epidermal keratinocytes according to established methods, the cells were cultured long-term in keratinocyte growth factor-containing medium. The cells senesced within a few weeks and eventually, small, slowly growing colonies emerged. After they regained confluency, the cells were passaged and slowly refilled the dish. With several rounds of subculture, the cells adapted to culture conditions, were easily subcultured, maintained normal morphology, and were apparently immortal. The immortalized cells retained the ability to differentiate with increased calcium concentrations, and were maintained to high passage numbers, while maintaining a relatively stable karyotype. Analysis of multiple immortalized cell lines as well as primary keratinocyte cultures, revealed increased numbers of chromosomes, especially in the primary keratinocytes, and chromosomal aberrations in most of the immortalized cultures and in the primary keratinocytes. Orthotopic grafting of immortalized keratinocytes together with fibroblasts onto nude mouse hosts produced skin while v-rasHa infection of the immortalized keratinocytes prior to grafting produced squamous cell carcinoma. In summary, this method of cell line generation allows for decreased use of animals, reduces the expense and time involved in research, and provides a useful model for cutaneous keratinocyte experimentation.

  20. Adaptive optics retinal imaging in the living mouse eye.

    Science.gov (United States)

    Geng, Ying; Dubra, Alfredo; Yin, Lu; Merigan, William H; Sharma, Robin; Libby, Richard T; Williams, David R

    2012-04-01

    Correction of the eye's monochromatic aberrations using adaptive optics (AO) can improve the resolution of in vivo mouse retinal images [Biss et al., Opt. Lett. 32(6), 659 (2007) and Alt et al., Proc. SPIE 7550, 755019 (2010)], but previous attempts have been limited by poor spot quality in the Shack-Hartmann wavefront sensor (SHWS). Recent advances in mouse eye wavefront sensing using an adjustable focus beacon with an annular beam profile have improved the wavefront sensor spot quality [Geng et al., Biomed. Opt. Express 2(4), 717 (2011)], and we have incorporated them into a fluorescence adaptive optics scanning laser ophthalmoscope (AOSLO). The performance of the instrument was tested on the living mouse eye, and images of multiple retinal structures, including the photoreceptor mosaic, nerve fiber bundles, fine capillaries and fluorescently labeled ganglion cells were obtained. The in vivo transverse and axial resolutions of the fluorescence channel of the AOSLO were estimated from the full width half maximum (FWHM) of the line and point spread functions (LSF and PSF), and were found to be better than 0.79 μm ± 0.03 μm (STD)(45% wider than the diffraction limit) and 10.8 μm ± 0.7 μm (STD)(two times the diffraction limit), respectively. The axial positional accuracy was estimated to be 0.36 μm. This resolution and positional accuracy has allowed us to classify many ganglion cell types, such as bistratified ganglion cells, in vivo.

  1. Characterization of a spontaneous retinal neovascular mouse model.

    Directory of Open Access Journals (Sweden)

    Eiichi Hasegawa

    Full Text Available BACKGROUND: Vision loss due to vascular disease of the retina is a leading cause of blindness in the world. Retinal angiomatous proliferation (RAP is a subgroup of neovascular age-related macular degeneration (AMD, whereby abnormal blood vessels develop in the retina leading to debilitating vision loss and eventual blindness. The novel mouse strain, neoretinal vascularization 2 (NRV2, shows spontaneous fundus changes associated with abnormal neovascularization. The purpose of this study is to characterize the induction of pathologic angiogenesis in this mouse model. METHODS: The NRV2 mice were examined from postnatal day 12 (p12 to 3 months. The phenotypic changes within the retina were evaluated by fundus photography, fluorescein angiography, optical coherence tomography, and immunohistochemical and electron microscopic analysis. The pathological neovascularization was imaged by confocal microscopy and reconstructed using three-dimensional image analysis software. RESULTS: We found that NRV2 mice develop multifocal retinal depigmentation in the posterior fundus. Depigmented lesions developed vascular leakage observed by fluorescein angiography. The spontaneous angiogenesis arose from the retinal vascular plexus at postnatal day (p15 and extended toward retinal pigment epithelium (RPE. By three months of age, histological analysis revealed encapsulation of the neovascular lesion by the RPE in the photoreceptor cell layer and subretinal space. CONCLUSIONS: The NRV2 mouse strain develops early neovascular lesions within the retina, which grow downward towards the RPE beginning at p15. This retinal neovascularization model mimics early stages of human retinal angiomatous proliferation (RAP and will likely be a useful in elucidating targeted therapeutics for patients with ocular neovascular disease.

  2. Mouse Hepatic Tumor Vascular Imaging by Experimental Selective Angiography.

    Directory of Open Access Journals (Sweden)

    Sang Kyum Kim

    Full Text Available Human hepatocellular carcinoma (HCC has unique vascular features, which require selective imaging of hepatic arterial perfusion and portal venous perfusion with vascular catheterization for sufficient evaluation. Unlike in humans, vessels in mice are too small to catheterize, and the importance of separately imaging the feeding vessels of tumors is frequently overlooked in hepatic tumor models. The purpose of this study was to perform selective latex angiography in several mouse liver tumor models and assess their suitability.In several ectopic (Lewis lung carcinoma, B16/F10 melanoma cell lines and spontaneous liver tumor (Albumin-Cre/MST1fl/fl/MST2fl/fl, Albumin-Cre/WW45fl/fl, and H-ras12V genetically modified mouse models, the heart left ventricle and/or main portal vein of mice was punctured, and latex dye was infused to achieve selective latex arteriography and/or portography.H-ras12V transgenic mice (a HCC and hepatic adenoma model developed multiple liver nodules that displayed three different perfusion patterns (portal venous or hepatic artery perfusion predominant, mixed perfusion, indicating intra-tumoral vascular heterogeneity. Selective latex angiography revealed that the Lewis lung carcinoma implant model and the Albumin-Cre/WW45fl/fl model reproduced conventional angiography findings of human HCC. Specifically, these mice developed tumors with abundant feeding arteries but no portal venous perfusion.Different hepatic tumor models showed different tumor vessel characteristics that influence the suitability of the model and that should be considered when designing translational experiments. Selective latex angiography applied to certain mouse tumor models (both ectopic and spontaneous closely simulated typical characteristics of human HCC vascular imaging.

  3. Proteomic analysis of regenerating mouse liver following 50% partial hepatectomy

    Directory of Open Access Journals (Sweden)

    Pan Xiaoping

    2009-12-01

    Full Text Available Abstract Background Although 70% (or 2/3 partial hepatectomy (PH is the most studied model for liver regeneration, the hepatic protein expression profile associated with lower volume liver resection (such as 50% PH has not yet been reported. Therefore, the aim of this study was to determine the global protein expression profile of the regenerating mouse liver following 50% PH by differential proteomics, and thereby gaining some insights into the hepatic regeneration mechanism(s under this milder but clinically more relevant condition. Results Proteins from sham-operated mouse livers and livers regenerating for 24 h after 50% PH were separated by SDS-PAGE and analyzed by nanoUPLC-Q-Tof mass spectrometry. Compared to sham-operated group, there were totally 87 differentially expressed proteins (with 50 up-regulated and 37 down-regulated ones identified in the regenerating mouse livers, most of which have not been previously related to liver regeneration. Remarkably, over 25 differentially expressed proteins were located at mitochondria. Several of the mitochondria-resident proteins which play important roles in citric acid cycle, oxidative phosphorylation and ATP production were found to be down-regulated, consistent with the recently-proposed model in which the reduction of ATP content in the remnant liver gives rise to early stress signals that contribute to the onset of liver regeneration. Pathway analysis revealed a central role of c-Myc in the regulation of liver regeneration. Conclusions Our study provides novel evidence for mitochondria as a pivotal organelle that is connected to liver regeneration, and lays the foundation for further studies on key factors and pathways involved in liver regeneration following 50% PH, a condition frequently used for partial liver transplantation and conservative liver resection.

  4. Full-Rate Full-Diversity Achieving MIMO Precoding with Partial CSIT

    CERN Document Server

    Dutta, Biswajit; Chockalingam, A

    2011-01-01

    In this paper, we consider a $n_t\\times n_r$ multiple-input multiple-output (MIMO) channel subjected to block fading. Reliability (in terms of achieved diversity order) and rate (in number of symbols transmitted per channel use) are of interest in such channels. We propose a new precoding scheme which achieves both full diversity ($n_tn_r$th order diversity) as well as full rate ($n_t$ symbols per channel use) using partial channel state information at the transmitter (CSIT), applicable in MIMO systems including $n_rfull diversity and improved coding gain through an optimization over the choice of constellation sets. The optimization maximizes $d_{min}^2$ for our precoding scheme subject to an energy constraint. The scheme requires feedback of $n_t-1$ angle parameter values, compared to $2n_tn_r$ real coefficients in case of full CSIT. Error rate performance results for $3\\times 1$, $3\\times 2$, $4\\times 1$, $8\\times 1$ precoded MIMO systems (with $n_t=3,...

  5. The German Mouse Clinic: a platform for systemic phenotype analysis of mouse models.

    Science.gov (United States)

    Fuchs, H; Gailus-Durner, V; Adler, T; Pimentel, J A Aguilar; Becker, L; Bolle, I; Brielmeier, M; Calzada-Wack, J; Dalke, C; Ehrhardt, N; Fasnacht, N; Ferwagner, B; Frischmann, U; Hans, W; Hölter, S M; Hölzlwimmer, G; Horsch, M; Javaheri, A; Kallnik, M; Kling, E; Lengger, C; Maier, H; Mossbrugger, I; Mörth, C; Naton, B; Nöth, U; Pasche, B; Prehn, C; Przemeck, G; Puk, O; Racz, I; Rathkolb, B; Rozman, J; Schäble, K; Schreiner, R; Schrewe, A; Sina, C; Steinkamp, R; Thiele, F; Willershäuser, M; Zeh, R; Adamski, J; Busch, D H; Beckers, J; Behrendt, H; Daniel, H; Esposito, I; Favor, J; Graw, J; Heldmaier, G; Höfler, H; Ivandic, B; Katus, H; Klingenspor, M; Klopstock, T; Lengeling, A; Mempel, M; Müller, W; Neschen, S; Ollert, M; Quintanilla-Martinez, L; Rosenstiel, P; Schmidt, J; Schreiber, S; Schughart, K; Schulz, H; Wolf, E; Wurst, W; Zimmer, A; Hrabé de Angelis, M

    2009-02-01

    The German Mouse Clinic (GMC) is a large scale phenotyping center where mouse mutant lines are analyzed in a standardized and comprehensive way. The result is an almost complete picture of the phenotype of a mouse mutant line--a systemic view. At the GMC, expert scientists from various fields of mouse research work in close cooperation with clinicians side by side at one location. The phenotype screens comprise the following areas: allergy, behavior, clinical chemistry, cardiovascular analyses, dysmorphology, bone and cartilage, energy metabolism, eye and vision, host-pathogen interactions, immunology, lung function, molecular phenotyping, neurology, nociception, steroid metabolism, and pathology. The German Mouse Clinic is an open access platform that offers a collaboration-based phenotyping to the scientific community (www.mouseclinic.de). More than 80 mutant lines have been analyzed in a primary screen for 320 parameters, and for 95% of the mutant lines we have found new or additional phenotypes that were not associated with the mouse line before. Our data contributed to the association of mutant mouse lines to the corresponding human disease. In addition, the systemic phenotype analysis accounts for pleiotropic gene functions and refines previous phenotypic characterizations. This is an important basis for the analysis of underlying disease mechanisms. We are currently setting up a platform that will include environmental challenge tests to decipher genome-environmental interactions in the areas nutrition, exercise, air, stress and infection with different standardized experiments. This will help us to identify genetic predispositions as susceptibility factors for environmental influences.

  6. Sphingolipid metabolism in organotypic mouse keratinocyte cultures

    Energy Technology Data Exchange (ETDEWEB)

    Madison, K.C.; Swartzendruber, D.C.; Wertz, P.W.; Downing, D.T. (Univ. of Iowa College of Medicine, Iowa City (USA))

    1990-12-01

    Ceramides are the dominant component of the stratum corneum intercellular lipid lamellae, which constitute the epidermal permeability barrier. Only pig and human epidermal ceramides have been extensively characterized and the structures of the ceramides of cultured keratinocytes have not been previously investigated. In the present studies, we have characterized the ceramides synthesized by organotypic lifted mouse keratinocyte cultures for the first time and compared them to the ceramides of intact mouse epidermis. Both mouse epidermis and cultures contained five ceramides, ceramide 1 being the least polar and ceramide 5 the most polar. Ceramide 1 was a group of acylceramides, i.e., very-long-chain omega-hydroxyceramides with an ester-linked nonhydroxy fatty acid. Ceramide 2 contained medium-length saturated nonhydroxy fatty acids. (In culture, the ceramide 2 band was split into two parts with the slightly more polar ceramide 2' containing short-chain saturated nonhydroxy fatty acids.) Ceramide 5 contained short-chain alpha-hydroxy fatty acids. The structures of ceramides 1, 2, and 5 were analagous to those of pig and human epidermis. Mouse epidermal ceramide 3 was quite unusual, containing beta-hydroxy fatty acids, a structure not previously identified among mammalian ceramides. In contrast, culture ceramide 3 was composed of omega-hydroxy fatty acids with a chain-length distribution similar to that of ceramide 1. Mouse ceramide 4 was composed of fatty acids with chromatographic mobility similar to hydroxy fatty acids but with different chemical reactivity; it remains only partially characterized. Culture ceramide 4 was present in quantities too small for analysis. All ceramides in mouse epidermis and cultures contained only sphingosine bases, whereas pig and human ceramides also contain phytosphingosine.

  7. Primary 3-dimensional culture of mouse hepatocytes

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Complex 3-dimensional structures with good functions have been obtained under the primary mixcoculture of mouse hepatocytes with mouse liver fibroblasts without serum. Albumin secretion is kept above 10 μg/106 cells and urea synthesis reaches 25 μg/106 on the 7th day of culture. Avoiding serum affection, liver fibroblasts' effects on hepatocytes' viability, functions and 3-dimensional structure forming in primary serum-free culture have been studied. Important effects of the mesenchyma, especially the direct adherence of fibroblasts to hepatocytes, are shown.

  8. Automated classification of mouse pup isolation syllables: from cluster analysis to an Excel based ‘mouse pup syllable classification calculator’

    Directory of Open Access Journals (Sweden)

    Jasmine eGrimsley

    2013-01-01

    Full Text Available Mouse pups vocalize at high rates when they are cold or isolated from the nest. The proportions of each syllable type produced carry information about disease state and are being used as behavioral markers for the internal state of animals. Manual classifications of these vocalizations identified ten syllable types based on their spectro-temporal features. However, manual classification of mouse syllables is time consuming and vulnerable to experimenter bias. This study uses an automated cluster analysis to identify acoustically distinct syllable types produced by CBA/CaJ mouse pups, and then compares the results to prior manual classification methods. The cluster analysis identified two syllable types, based on their frequency bands, that have continuous frequency-time structure, and two syllable types featuring abrupt frequency transitions. Although cluster analysis computed fewer syllable types than manual classification, the clusters represented well the probability distributions of the acoustic features within syllables. These probability distributions indicate that some of the manually classified syllable types are not statistically distinct. The characteristics of the four classified clusters were used to generate a Microsoft Excel-based mouse syllable classifier that rapidly categorizes syllables, with over a 90% match, into the syllable types determined by cluster analysis.

  9. Mouse polyoma virus and adenovirus replication in mouse cells temperature-sensitive in DNA synthesis.

    Science.gov (United States)

    Sheinin, R; Fabbro, J; Dubsky, M

    1985-01-01

    Mouse adenovirus multiplies, apparently without impediment, in temperature-inactivated ts A1S9, tsC1 and ts2 mouse fibroblasts. Thus, the DNA of mouse adenovirus can replicate in the absence of functional DNA topoisomerase II, a DNA-chain-elongation factor, and a protein required for traverse of the G1/S interface, respectively, encoded in the ts A1S9, tsC1 and ts2 genetic loci. These results are compared with those obtained with polyoma virus.

  10. Recovery Outline: New Mexico Jumping Mouse (Zapus hudsonius luteus)

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The purpose of this recovery outline is to provide an interim strategy to guide the conservation and recovery of the New Mexico meadow jumping mouse (jumping mouse)...

  11. Numerical experiment for nonlinear full-wave tomography. 3; Hisenkei full wave tomography no suchi jikken

    Energy Technology Data Exchange (ETDEWEB)

    Tsuchiya, T. [Dia Consultants Company, Tokyo (Japan)

    1996-10-01

    Nonlinear full-wave tomography (FWT) is under investigation to improve the estimation accuracy of Vp/Vs distributions. Full-wave tomography is one of the underground structure exploration methods mainly using Tarantola`s nonlinear local optimization method (LOM). Numerical experiment for FWT was carried out assuming relatively weak nonlinear underground structure. In the case of inversion by local optimization method, adequate preconditioning is important. Utilization of geological information is also effective in estimating low-frequency components of a model. As far as data are obtained under proper observation arrangement, even in actual field, precise estimation of Vp/Vs distributions is possible by FWT using explosion in a hole as wave source. In full-wave tomography, selection of observation arrangement is essential for both Vp and Vs. However, the proper arrangement is different between Vp and Vs. Approach to different analyses for Vp and Vs is also necessary by using only proper data for Vp and Vs among obtained data sets. 4 figs.

  12. Dantrolene is neuroprotective in Huntington's disease transgenic mouse model

    Directory of Open Access Journals (Sweden)

    Chen Xi

    2011-11-01

    Full Text Available Abstract Background Huntington's disease (HD is a progressive neurodegenerative disorder caused by a polyglutamine expansion in the Huntingtin protein which results in the selective degeneration of striatal medium spiny neurons (MSNs. Our group has previously demonstrated that calcium (Ca2+ signaling is abnormal in MSNs from the yeast artificial chromosome transgenic mouse model of HD (YAC128. Moreover, we demonstrated that deranged intracellular Ca2+ signaling sensitizes YAC128 MSNs to glutamate-induced excitotoxicity when compared to wild type (WT MSNs. In previous studies we also observed abnormal neuronal Ca2+ signaling in neurons from spinocerebellar ataxia 2 (SCA2 and spinocerebellar ataxia 3 (SCA3 mouse models and demonstrated that treatment with dantrolene, a ryanodine receptor antagonist and clinically relevant Ca2+ signaling stabilizer, was neuroprotective in experiments with these mouse models. The aim of the current study was to evaluate potential beneficial effects of dantrolene in experiments with YAC128 HD mouse model. Results The application of caffeine and glutamate resulted in increased Ca2+ release from intracellular stores in YAC128 MSN cultures when compared to WT MSN cultures. Pre-treatment with dantrolene protected YAC128 MSNs from glutamate excitotoxicty, with an effective concentration of 100 nM and above. Feeding dantrolene (5 mg/kg twice a week to YAC128 mice between 2 months and 11.5 months of age resulted in significantly improved performance in the beam-walking and gait-walking assays. Neuropathological analysis revealed that long-term dantrolene feeding to YAC128 mice significantly reduced the loss of NeuN-positive striatal neurons and reduced formation of Httexp nuclear aggregates. Conclusions Our results support the hypothesis that deranged Ca2+ signaling plays an important role in HD pathology. Our data also implicate the RyanRs as a potential therapeutic target for the treatment of HD and demonstrate that Ryan

  13. Interdigitated paralemniscal and lemniscal pathways in the mouse barrel cortex.

    Directory of Open Access Journals (Sweden)

    Ingrid Bureau

    2006-11-01

    Full Text Available Primary sensory cortical areas receive information through multiple thalamic channels. In the rodent whisker system, lemniscal and paralemniscal thalamocortical projections, from the ventral posteromedial nucleus (VPM and posterior medial nucleus (POm respectively, carry distinct types of sensory information to cortex. Little is known about how these separate streams of activity are parsed and integrated within the neocortical microcircuit. We used quantitative laser scanning photostimulation to probe the organization of functional thalamocortical and ascending intracortical projections in the mouse barrel cortex. To map the thalamocortical projections, we recorded from neocortical excitatory neurons while stimulating VPM or POm. Neurons in layers (L4, L5, and L6A received dense input from thalamus (L4, L5B, and L6A from VPM; and L5A from POm, whereas L2/3 neurons rarely received thalamic input. We further mapped the lemniscal and paralemniscal circuits from L4 and L5A to L2/3. Lemniscal L4 neurons targeted L3 within a column. Paralemniscal L5A neurons targeted a superficial band (thickness, 60 mum of neurons immediately below L1, defining a functionally distinct L2 in the mouse barrel cortex. L2 neurons received input from lemniscal L3 cells and paralemniscal L5A cells spread over multiple columns. Our data indicate that lemniscal and paralemniscal information is segregated into interdigitated cortical layers.

  14. The effect of the melatonin on cryopreserved mouse testicular cells

    Directory of Open Access Journals (Sweden)

    Ghasem Saki

    2016-01-01

    Full Text Available Background: After improvements in various cancer treatments, life expectancy has been raised, but success in treatment causes loss of fertility in many of the survived young men. Cryopreservation of immature testicular tissues or cells introduced as the only way to preserve fertility. However, freezing has some harmful effects. Melatonin, a pineal gland hormone, has receptors in reproductive systems of different species. It is assumed that melatonin has free radical scavenger properties. Objective: The aim of this study was to evaluate the effects of melatonin on the cryopreserved testicular cells in mouse. Materials and Methods: Cells from 7- 10 days old NMRI mice testes were isolated using two step enzymatic digestion. The testicular cells were divided into two groups randomly and cryopreserved in two different freezing media with and without the addition of 100 μm melatonin. Finally, apoptosis of the cells was assayed by flow cytometry. Also, lactate dehydrogenase activity test was performed to assess the cytotoxicity. Results: The results of lactate dehydrogenase showed the nearly cytotoxic effect of melatonin. The results of flow cytometry showed increase in apoptosis in the cryopreserved cells in the media containing melatonin compared to the control group. Conclusion: The present study shows that melatonin has an apoptotic effect on cryopreserved mouse testicular cells.

  15. A computational clonal analysis of the developing mouse limb bud.

    Directory of Open Access Journals (Sweden)

    Luciano Marcon

    Full Text Available A comprehensive spatio-temporal description of the tissue movements underlying organogenesis would be an extremely useful resource to developmental biology. Clonal analysis and fate mappings are popular experiments to study tissue movement during morphogenesis. Such experiments allow cell populations to be labeled at an early stage of development and to follow their spatial evolution over time. However, disentangling the cumulative effects of the multiple events responsible for the expansion of the labeled cell population is not always straightforward. To overcome this problem, we develop a novel computational method that combines accurate quantification of 2D limb bud morphologies and growth modeling to analyze mouse clonal data of early limb development. Firstly, we explore various tissue movements that match experimental limb bud shape changes. Secondly, by comparing computational clones with newly generated mouse clonal data we are able to choose and characterize the tissue movement map that better matches experimental data. Our computational analysis produces for the first time a two dimensional model of limb growth based on experimental data that can be used to better characterize limb tissue movement in space and time. The model shows that the distribution and shapes of clones can be described as a combination of anisotropic growth with isotropic cell mixing, without the need for lineage compartmentalization along the AP and PD axis. Lastly, we show that this comprehensive description can be used to reassess spatio-temporal gene regulations taking tissue movement into account and to investigate PD patterning hypothesis.

  16. Expression Divergence of Tandemly Arrayed Genes in Human and Mouse

    Directory of Open Access Journals (Sweden)

    Valia Shoja

    2007-01-01

    Full Text Available Tandemly arrayed genes (TAGs account for about one third of the duplicated genes in eukaryotic genomes, yet there has not been any systematic study of their gene expression patterns. Taking advantage of recently published large-scale microarray data sets, we studied the expression divergence of 361 two-member TAGs in human and 212 two-member TAGs in mouse and examined the effect of sequence divergence, gene orientation, and chromosomal proximity on the divergence of TAG expression patterns. Our results show that there is a weak negative correlation between sequence divergence of TAG members and their expression similarity. There is also a weak negative correlation between chromosomal proximity of TAG members and their expression similarity. We did not detect any significant relationship between gene orientation and expression similarity. We also found that downstream TAG members do not show significantly narrower expression breadth than upstream members, contrary to what we predict based on TAG expression divergence hypothesis that we propose. Finally, we show that both chromosomal proximity and expression correlation in TAGs do not differ significantly from their neighboring non-TAG gene pairs, suggesting that tandem duplication is unlikely to be the cause for the higher-than-random expression association between neighboring genes on a chromosome in human and mouse.

  17. The truth about mouse, human, worms and yeast

    Directory of Open Access Journals (Sweden)

    Nelson David R

    2004-01-01

    Full Text Available Abstract Genome comparisons are behind the powerful new annotation methods being developed to find all human genes, as well as genes from other genomes. Genomes are now frequently being studied in pairs to provide cross-comparison datasets. This 'Noah's Ark' approach often reveals unsuspected genes and may support the deletion of false-positive predictions. Joining mouse and human as the cross-comparison dataset for the first two mammals are: two Drosophila species, D. melanogaster and D. pseudoobscura; two sea squirts, Ciona intestinalis and Ciona savignyi; four yeast (Saccharomyces species; two nematodes, Caenorhabditis elegans and Caenorhabditis briggsae; and two pufferfish (Takefugu rubripes and Tetraodon nigroviridis. Even genomes like yeast and C. elegans, which have been known for more than five years, are now being significantly improved. Methods developed for yeast or nematodes will now be applied to mouse and human, and soon to additional mammals such as rat and dog, to identify all the mammalian protein-coding genes. Current large disparities between human Unigene predictions (127,835 genes and gene-scanning methods (45,000 genes still need to be resolved. This will be the challenge during the next few years.

  18. Mouse cloning and somatic cell reprogramming using electrofused blastomeres

    Institute of Scientific and Technical Information of China (English)

    Amjad Riaz; Xiaoyang Zhao; Xiangpeng Dai; Wei Li; Lei Liu; Haifeng Wan; Yang Yu; Liu Wang; Qi Zhou

    2011-01-01

    Mouse cloning from fertilized eggs can assist development of approaches for the production of "genetically tailored" human embryonic stem(ES)cell lines that are not constrained by the limitations of oocyte availability. However, to date only zygotes have been successfully used as recipients of nuclei from terminally differentiated somatic cell donors leading to ES cell lines. In fertility clinics, embryos of advanced embryonic stages are usually stored for future use, but their ability to support the derivation of ES cell lines via somatic nuclear transfer has not yet been proved.Here, we report that two-cell stage electrofused mouse embryos, arrested in mitosis, can support developmental reprogramming of nuclei from donor cells ranging from blastomeres to somatic cells. Live, full-term cloned pups from embryonic donors, as well as pluripotent ES cell lines from embryonic or somatic donors, were successfully generated from these reconstructed embryos. Advanced stage pre-implantation embryos were unable to develop normally to term after electrofusion and transfer of a somatic cell nucleus, indicating that discarded pre-implantation human embryos could be an important resource for research that minimizes the ethical concerns for human therapeutic cloning. Our approach provides an attractive and practical alternative to therapeutic cloning using donated oocytes for the generation of patient-specific human ES cell lines.

  19. Mouse models of SCN5A-related cardiac arrhythmias

    Directory of Open Access Journals (Sweden)

    Flavien eCharpentier

    2012-06-01

    Full Text Available Mutations of SCN5A gene, which encodes the α-subunit of the voltage-gated Na+ channel NaV1.5, underlie hereditary cardiac arrhythmic syndromes such as the type 3 long QT syndrome, cardiac conduction diseases, the Brugada syndrome, the sick sinus syndrome, atrial standstill and numerous overlap syndromes. Patch-clamp studies in heterologous expression systems have provided important information to understand the genotype-phenotype relationships of these diseases. However, they could not clarify how SCN5A mutations can be responsible for such a large spectrum of diseases, for the late age of onset or the progressiveness of some of these diseases and for the overlapping syndromes. Genetically modified mice rapidly appeared as promising tools for understanding the pathophysiological mechanisms of cardiac SCN5A-related arrhythmic syndromes and several mouse models have been established. This paper reviews some of the results obtained on these models that, for most of them, recapitulate the clinical phenotypes of the patients. It also points out that these models also have their own limitations. Overall, mouse models appear as powerful tools to elucidate the pathophysiological mechanisms of SCN5A-related diseases and offer the opportunity to investigate the secondary cellular consequences of SCN5A mutations such as the expression remodelling of other genes that might participate to the overall phenotype. Finally, they constitute useful tools for addressing the role of genetic and environmental modifiers on cardiac electrical activity.

  20. Prolactin stimulates precursor cells in the adult mouse hippocampus.

    Directory of Open Access Journals (Sweden)

    Tara L Walker

    Full Text Available In the search for ways to combat degenerative neurological disorders, neurogenesis-stimulating factors are proving to be a promising area of research. In this study, we show that the hormonal factor prolactin (PRL can activate a pool of latent precursor cells in the adult mouse hippocampus. Using an in vitro neurosphere assay, we found that the addition of exogenous PRL to primary adult hippocampal cells resulted in an approximate 50% increase in neurosphere number. In addition, direct infusion of PRL into the adult dentate gyrus also resulted in a significant increase in neurosphere number. Together these data indicate that exogenous PRL can increase hippocampal precursor numbers both in vitro and in vivo. Conversely, PRL null mice showed a significant reduction (approximately 80% in the number of hippocampal-derived neurospheres. Interestingly, no deficit in precursor proliferation was observed in vivo, indicating that in this situation other niche factors can compensate for a loss in PRL. The PRL loss resulted in learning and memory deficits in the PRL null mice, as indicated by significant deficits in the standard behavioral tests requiring input from the hippocampus. This behavioral deficit was rescued by direct infusion of recombinant PRL into the hippocampus, indicating that a lack of PRL in the adult mouse hippocampus can be correlated with impaired learning and memory.

  1. Reversible modulation of SIRT1 activity in a mouse strain

    Science.gov (United States)

    Clark-Knowles, Katherine V.; He, Xiaohong; Jardine, Karen; Coulombe, Josée; Dewar-Darch, Danielle; Caron, Annabelle Z.

    2017-01-01

    The SIRT1 protein deacetylase is reported to have a remarkably wide spectrum of biological functions affecting such varied processes as aging, cancer, metabolism, neurodegeneration and immunity. However, the SIRT1 literature is also full of contradictions. To help establish the role(s) of SIRT1 in these and other biological processes, we set out to create a mouse in which the SIRT1 activity could be toggled between on and off states by fusing the estrogen receptor ligand-binding domain (ER) to the C terminus of the SIRT1 protein. We found that the catalytic activity of the SIRT1-ER fusion protein increased 4–5 fold in cells treated with its ligand, 4-hydroxy-tamoxifen (4OHT). The 4OHT-induced activation of SIRT1-ER was due in large part to a 2 to 4-fold increase in abundance of the SIRT1-ER protein in cells in culture and in tissues in vivo. This increase is reversible and is a consequence of 4OHT-induced stabilization of the SIRT1-ER protein. Since changes in SIRT1 level or activity of 2–4 fold are frequently reported to be sufficient to affect its biological functions, this mouse should be helpful in establishing the causal relationships between SIRT1 and the diseases and processes it affects. PMID:28273169

  2. Differential Apoptosis Radiosensitivity of Neural Progenitors in Adult Mouse Hippocampus

    Directory of Open Access Journals (Sweden)

    Yu-Qing Li

    2016-06-01

    Full Text Available Mammalian tissue-specific stem cells and progenitors demonstrate differential DNA damage response. Neural progenitors in dentate gyrus of the hippocampus are known to undergo apoptosis after irradiation. Using a mouse model of hippocampal neuronal development, we characterized the apoptosis sensitivity of the different neural progenitor subpopulations in adult mouse dentate gyrus after irradiation. Two different bromodeoxyuridine incorporation paradigms were used for cell fate mapping. We identified two apoptosis sensitive neural progenitor subpopulations after irradiation. The first represented non-proliferative and non-newborn neuroblasts and immature neurons that expressed doublecortin, calretinin or both. The second consisted of proliferative intermediate neural progenitors. The putative radial glia-like neural stem cells or type-1 cells, regardless of proliferation status, were apoptosis resistant after irradiation. There was no evidence of radiation-induced apoptosis in the absence of the Trp53 (p53 gene but absence of Cdkn1a (p21 did not alter the apoptotic response. Upregulation of nuclear p53 was observed in neuroblasts after irradiation. We conclude that adult hippocampal neural progenitors may demonstrate differential p53-dependent apoptosis sensitivity after irradiation.

  3. Transcriptome analysis of mouse stem cells and early embryos.

    Directory of Open Access Journals (Sweden)

    Alexei A Sharov

    2003-12-01

    Full Text Available Understanding and harnessing cellular potency are fundamental in biology and are also critical to the future therapeutic use of stem cells. Transcriptome analysis of these pluripotent cells is a first step towards such goals. Starting with sources that include oocytes, blastocysts, and embryonic and adult stem cells, we obtained 249,200 high-quality EST sequences and clustered them with public sequences to produce an index of approximately 30,000 total mouse genes that includes 977 previously unidentified genes. Analysis of gene expression levels by EST frequency identifies genes that characterize preimplantation embryos, embryonic stem cells, and adult stem cells, thus providing potential markers as well as clues to the functional features of these cells. Principal component analysis identified a set of 88 genes whose average expression levels decrease from oocytes to blastocysts, stem cells, postimplantation embryos, and finally to newborn tissues. This can be a first step towards a possible definition of a molecular scale of cellular potency. The sequences and cDNA clones recovered in this work provide a comprehensive resource for genes functioning in early mouse embryos and stem cells. The nonrestricted community access to the resource can accelerate a wide range of research, particularly in reproductive and regenerative medicine.

  4. Improvement in Isolation and Identification of Mouse Oogonial Stem Cells

    Directory of Open Access Journals (Sweden)

    Zhiyong Lu

    2016-01-01

    Full Text Available Female germline stem cells (FGSCs or oogonial stem cells (OSCs have the capacity to generate newborn oocytes and thus open a new door to fight ovarian aging and female infertility. However, the production and identification of OSCs are difficult for investigators. Rare amount of these cells in the ovary results in the failure of the acquisition of OSCs. Furthermore, the oocyte formation by OSCs in vivo was usually confirmed using tissue sections by immunofluorescence or immunohistochemistry in previous studies. STO or MEF feeder cells are derived from mouse, not human. In our study, we modified the protocol. The cells were digested from ovaries and cultured for 2-3 days and then were purified by magnetic-activated cell sorting (MACS. The ovaries and fetus of mice injected with EGFP-positive OSCs were prepared and put on the slides to directly visualize oocyte and progeny formation under microscope. Additionally, the human umbilical cord mesenchymal stem cells (hUC-MSCs were also used as feeder cells to support the proliferation of OSCs. The results showed that all the modified procedures can significantly improve and facilitate the generation and characterization of OSCs, and hUC-MSCs as feeder will be useful for isolation and proliferation of human OSCs avoiding contamination from mouse.

  5. Recent advances in mouse models of obesityandnonalcoholic steatohepatitis-associatedhepatocarcinogenesis

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Hepatocellular carcinoma (HCC) is the fifth mostcommon cancer, and obesity has been establishedas a risk factor for HCC development. Nonalcoholicsteatohepatitis (NASH) is apparently the key linkbetween obesity and hepatocarcinogenesis, and obesityalso accelerates HCC development synergistically withother risk factors, such as hepatitis virus infectionand alcohol consumption. As an explanation for thepathogenesis of NASH, the so-called "two-hit" theoryhas been widely accepted, but recently, a better model,the so-called "multiple-hits hypothesis" was proposed,which states that many disease-promoting factors mayoccur in parallel, rather than consecutively. However,the overall mechanism remains largely unknown. Variouscell-cell and organ-organ interactions are involved inthe pathogenesis of NASH, and thus appropriate in vivodisease models are essential for a deeper understanding.However, replicating the full spectrum of human NASHhas been difficult, as NASH involves obesity, insulinresistance, steatohepatitis, fibrosis, and ultimately HCC,and the lack of an appropriate mouse model has beena considerable barrier to determining the missing linksamong obesity, NASH, and HCC. In recent years, severalinnovative mouse models presenting obesity- and NASHassociatedHCC have been established by modifieddiets, chemotoxic agents, genetic manipulation, or acombination of these factors, shedding some light onthis complex network and providing new therapeuticstrategies. Thus, in this paper, I review the mousemodels of obesity- and NASH-associated HCC, especiallyfocusing on recent advances and their clinical relevance.

  6. Web-based analysis of the mouse transcriptome using Genevestigator

    Directory of Open Access Journals (Sweden)

    Gruissem Wilhelm

    2006-06-01

    Full Text Available Abstract Background Gene function analysis often requires a complex and laborious sequence of laboratory and computer-based experiments. Choosing an effective experimental design generally results from hypotheses derived from prior knowledge or experimentation. Knowledge obtained from meta-analyzing compendia of expression data with annotation libraries can provide significant clues in understanding gene and network function, resulting in better hypotheses that can be tested in the laboratory. Description Genevestigator is a microarray database and analysis system allowing context-driven queries. Simple but powerful tools allow biologists with little computational background to retrieve information about when, where and how genes are expressed. We manually curated and quality-controlled 3110 mouse Affymetrix arrays from public repositories. Data queries can be run against an annotation library comprising 160 anatomy categories, 12 developmental stage groups, 80 stimuli, and 182 genetic backgrounds or modifications. The quality of results obtained through Genevestigator is illustrated by a number of biological scenarios that are substantiated by other types of experimentation in the literature. Conclusion The Genevestigator-Mouse database effectively provides biologically meaningful results and can be accessed at https://www.genevestigator.ethz.ch.

  7. MicroRNAs in mouse models of lymphoid malignancies

    Directory of Open Access Journals (Sweden)

    Nicola A. O. Zanesi

    2010-05-01

    Full Text Available The discovery of microRNAs (miRNAs has revealed a new layer of gene expression regulation that affects many normal and pathologic biological systems. Among the malignancies affected by the dysregulation of miRNAs there are cancers of lymphoid origin, in which miRNAs are thought to have tumor suppressive or tumor promoting activities, depending on the nature of their specific targets. In the last 4-5 years, the experimental field that provided the deepest insights into the in vivo biology of miRNAs is that of mouse modeling in which transgenic and knockout animals mimic, respectively, over-expression or down-regulation of specific miRNAs involved in human leukemia/lymphoma. This review discusses recent advances in our understanding of lymphoid malignancies based on the natural and engineered mouse models of three different miRNAs, miR-15a/16-1 cluster, miR-155, and miR-17-92 cluster.

  8. Transgenic mouse models of spinal and bulbar muscular atrophy (SBMA).

    Science.gov (United States)

    Katsuno, M; Adachi, H; Inukai, A; Sobue, G

    2003-01-01

    Spinal and bulbar muscular atrophy (SBMA) is a late-onset motor neuron disease characterized by proximal muscle atrophy, weakness, contraction fasciculations, and bulbar involvement. Only males develop symptoms, while female carriers usually are asymptomatic. A specific treatment for SBMA has not been established. The molecular basis of SBMA is the expansion of a trinucleotide CAG repeat, which encodes the polyglutamine (polyQ) tract, in the first exon of the androgen receptor (AR) gene. The pathologic hallmark is nuclear inclusions (NIs) containing the mutant and truncated AR with expanded polyQ in the residual motor neurons in the brainstem and spinal cord as well as in some other visceral organs. Several transgenic (Tg) mouse models have been created for studying the pathogenesis of SBMA. The Tg mouse model carrying pure 239 CAGs under human AR promoter and another model carrying truncated AR with expanded CAGs show motor impairment and nuclear NIs in spinal motor neurons. Interestingly, Tg mice carrying full-length human AR with expanded polyQ demonstrate progressive motor impairment and neurogenic pathology as well as sexual difference of phenotypes. These models recapitulate the phenotypic expression observed in SBMA. The ligand-dependent nuclear localization of the mutant AR is found to be involved in the disease mechanism, and hormonal therapy is suggested to be a therapeutic approach applicable to SBMA.

  9. Craniofacial characteristics of fragile X syndrome in mouse and man.

    Science.gov (United States)

    Heulens, Inge; Suttie, Michael; Postnov, Andrei; De Clerck, Nora; Perrotta, Concetta S; Mattina, Teresa; Faravelli, Francesca; Forzano, Francesca; Kooy, R Frank; Hammond, Peter

    2013-08-01

    For a disorder as common as fragile X syndrome, the most common hereditary form of cognitive impairment, the facial features are relatively ill defined. An elongated face and prominent ears are the most commonly accepted dysmorphic hallmarks. We analysed 3D facial photographs of 51 males and 15 females with full FMR1 mutations and 9 females with a premutation using dense-surface modelling techniques and a new technique that forms a directed graph with normalized face shapes as nodes and edges linking those with closest dysmorphism. In addition to reconfirming known features, we confirmed the occurrence of some at an earlier age than previously recorded. We also identified as yet unrecorded facial characteristics such as reduced facial depth, hypoplasticity of the nasal bone-cartilage interface and narrow mid-facial width exaggerating ear prominence. As no consistent craniofacial abnormalities had been reported in animal models, we analysed micro-CT images of the fragile X mouse model. Results indicated altered dimensions in the mandible and both outer and inner skull, with the latter potentially reflecting differences in neuroanatomy. We extrapolated the mouse results to face shape differences of the human fragile X face.

  10. Evaluating diabetes and hypertension disease causality using mouse phenotypes

    Directory of Open Access Journals (Sweden)

    Han Jing-Dong J

    2010-07-01

    Full Text Available Abstract Background Genome-wide association studies (GWAS have found hundreds of single nucleotide polymorphisms (SNPs associated with common diseases. However, it is largely unknown what genes linked with the SNPs actually implicate disease causality. A definitive proof for disease causality can be demonstration of disease-like phenotypes through genetic perturbation of the genes or alleles, which is obviously a daunting task for complex diseases where only mammalian models can be used. Results Here we tapped the rich resource of mouse phenotype data and developed a method to quantify the probability that a gene perturbation causes the phenotypes of a disease. Using type II diabetes (T2D and hypertension (HT as study cases, we found that the genes, when perturbed, having high probability to cause T2D and HT phenotypes tend to be hubs in the interactome networks and are enriched for signaling pathways regulating metabolism but not metabolic pathways, even though the genes in these metabolic pathways are often the most significantly changed in expression levels in these diseases. Conclusions Compared to human genetic disease-based predictions, our mouse phenotype based predictors greatly increased the coverage while keeping a similarly high specificity. The disease phenotype probabilities given by our approach can be used to evaluate the likelihood of disease causality of disease-associated genes and genes surrounding disease-associated SNPs.

  11. Dynamic changes of the phosphoproteome in postmortem mouse brains.

    Directory of Open Access Journals (Sweden)

    Tsutomu Oka

    Full Text Available Protein phosphorylation is deeply involved in the pathological mechanism of various neurodegenerative disorders. However, in human pathological samples, phosphorylation can be modified during preservation by postmortem factors such as time and temperature. Postmortem changes may also differ among proteins. Unfortunately, there is no comprehensive database that could support the analysis of protein phosphorylation in human brain samples from the standpoint of postmortem changes. As a first step toward addressing the issue, we performed phosphoproteome analysis with brain tissue dissected from mouse bodies preserved under different conditions. Quantitative whole proteome mass analysis showed surprisingly diverse postmortem changes in phosphoproteins that were dependent on temperature, time and protein species. Twelve hrs postmortem was a critical time point for preservation at room temperature. At 4°C, after the body was cooled down, most phosphoproteins were stable for 72 hrs. At either temperature, increase greater than 2-fold was exceptional during this interval. We found several standard proteins by which we can calculate the postmortem time at room temperature. The information obtained in this study will be indispensable for evaluating experimental data with human as well as mouse brain samples.

  12. Mouse embryonic retina delivers information controlling cortical neurogenesis.

    Directory of Open Access Journals (Sweden)

    Ciro Bonetti

    Full Text Available The relative contribution of extrinsic and intrinsic mechanisms to cortical development is an intensely debated issue and an outstanding question in neurobiology. Currently, the emerging view is that interplay between intrinsic genetic mechanisms and extrinsic information shape different stages of cortical development. Yet, whereas the intrinsic program of early neocortical developmental events has been at least in part decoded, the exact nature and impact of extrinsic signaling are still elusive and controversial. We found that in the mouse developing visual system, acute pharmacological inhibition of spontaneous retinal activity (retinal waves-RWs during embryonic stages increase the rate of corticogenesis (cell cycle withdrawal. Furthermore, early perturbation of retinal spontaneous activity leads to changes of cortical layer structure at a later time point. These data suggest that mouse embryonic retina delivers long-distance information capable of modulating cell genesis in the developing visual cortex and that spontaneous activity is the candidate long-distance acting extrinsic cue mediating this process. In addition, these data may support spontaneous activity to be a general signal coordinating neurogenesis in other developing sensory pathways or areas of the central nervous system.

  13. Corticofugal GABAergic projection neurons in the mouse frontal cortex

    Directory of Open Access Journals (Sweden)

    Ryohei eTomioka

    2015-10-01

    Full Text Available Cortical projection neurons are classified by hodology in corticocortical, commissural and corticofugal subtypes. Although cortical projection neurons had been regarded as only glutamatergic neurons, recently corticocortical GABAergic projection neurons has been also reported in several species. Here we demonstrate corticofugal GABAergic projection neurons in the mouse frontal cortex. We employed viral-vector-mediated anterograde tracing, classical retrograde tracing, and immunohistochemistry to characterize neocortical GABAergic projection neurons. Injections of the Cre-dependent adeno-associated virus into glutamate decarboxylase 67-Cre knock-in mice revealed neocortical GABAergic projections widely to the forebrain, including the cerebral cortices, caudate putamen, ventral pallidum, lateral globus pallidus, nucleus accumbens, and olfactory tubercle. Minor GABAergic projections were also found in the mediodorsal thalamic nucleus, diagonal band of Broca, medial globus pallidus, substantial nigra, and dorsal raphe nucleus. Retrograde tracing studies also demonstrated corticofugal GABAergic projection neurons in the mouse frontal cortex. Further immunohistochemical screening with neurochemical markers revealed the majority of corticostriatal GABAergic projection neurons were positive for somatostatin-immunoreactivity. In contrast, corticothalamic GABAergic projection neurons were not identified by representative neurochemical markers for GABAergic neurons. These findings suggest that corticofugal GABAergic projection neurons are heterogeneous in terms of their neurochemical properties and target nuclei, and provide axonal innervations mainly to the nuclei in the basal ganglia.

  14. ATRX dysfunction induces replication defects in primary mouse cells.

    Directory of Open Access Journals (Sweden)

    David Clynes

    Full Text Available The chromatin remodeling protein ATRX, which targets tandem repetitive DNA, has been shown to be required for expression of the alpha globin genes, for proliferation of a variety of cellular progenitors, for chromosome congression and for the maintenance of telomeres. Mutations in ATRX have recently been identified in tumours which maintain their telomeres by a telomerase independent pathway involving homologous recombination thought to be triggered by DNA damage. It is as yet unknown whether there is a central underlying mechanism associated with ATRX dysfunction which can explain the numerous cellular phenomena observed. There is, however, growing evidence for its role in the replication of various repetitive DNA templates which are thought to have a propensity to form secondary structures. Using a mouse knockout model we demonstrate that ATRX plays a direct role in facilitating DNA replication. Ablation of ATRX alone, although leading to a DNA damage response at telomeres, is not sufficient to trigger the alternative lengthening of telomere pathway in mouse embryonic stem cells.

  15. Mouse for Computer Control from the Joystick of the Wheelchair

    Directory of Open Access Journals (Sweden)

    Roberto Casas

    2012-11-01

    Full Text Available Becoming autonomous is one of the biggest challenges for many people with disabilities. Increasing their autonomy usually involves the use of a wheelchair and any kind of digital assistant, such as a computer or a tablet, to communicate, to work or even for leisure. In such a situation, those people are obliged to use two different human interfaces to move a pointer and to drive the wheelchair. A joystick is the most common option to control a wheelchair. On the other hand, there are many different adapted interfaces to emulate the use of a mouse. This paper presents a system, BJoy Ring mouse, which captures the motion of the joystick on a wheelchair. The captured signal is used to move the cursor or the pointer of any digital device including an USB port. This system avoids any mechanical or electronic change in the joystick to keep its original safety and warranty. Communication between the device and the computer (or any other digital assistant uses the USB protocol, although it could be easily improved to a Bluetooth wireless connection. Validation tests with real users proved this system to be useful aid for people with motor disabilities.

  16. Mouse cloning and somatic cell reprogramming using electrofused blastomeres.

    Science.gov (United States)

    Riaz, Amjad; Zhao, Xiaoyang; Dai, Xiangpeng; Li, Wei; Liu, Lei; Wan, Haifeng; Yu, Yang; Wang, Liu; Zhou, Qi

    2011-05-01

    Mouse cloning from fertilized eggs can assist development of approaches for the production of "genetically tailored" human embryonic stem (ES) cell lines that are not constrained by the limitations of oocyte availability. However, to date only zygotes have been successfully used as recipients of nuclei from terminally differentiated somatic cell donors leading to ES cell lines. In fertility clinics, embryos of advanced embryonic stages are usually stored for future use, but their ability to support the derivation of ES cell lines via somatic nuclear transfer has not yet been proved. Here, we report that two-cell stage electrofused mouse embryos, arrested in mitosis, can support developmental reprogramming of nuclei from donor cells ranging from blastomeres to somatic cells. Live, full-term cloned pups from embryonic donors, as well as pluripotent ES cell lines from embryonic or somatic donors, were successfully generated from these reconstructed embryos. Advanced stage pre-implantation embryos were unable to develop normally to term after electrofusion and transfer of a somatic cell nucleus, indicating that discarded pre-implantation human embryos could be an important resource for research that minimizes the ethical concerns for human therapeutic cloning. Our approach provides an attractive and practical alternative to therapeutic cloning using donated oocytes for the generation of patient-specific human ES cell lines.

  17. Recombinant mouse interferon-gamma regulation of antibody production.

    OpenAIRE

    1983-01-01

    Interferon-gamma produced in monkey cells by transfection with mouse interferon-gamma cDNA suppressed the mouse in vitro antibody response in a manner similar to that of natural mouse interferon-gamma. Significant suppression was obtained with as little as 1 U of interferon. Recombinant human interferon-gamma produced by cloning in a similar fashion was not suppressive. Both the suppressive and the antiviral activities of recombinant interferon-gamma were neutralized by antibodies to mouse na...

  18. Dynamics of muscle fibre growth during postnatal mouse development

    Directory of Open Access Journals (Sweden)

    Gnocchi Viola F

    2010-02-01

    Full Text Available Abstract Background Postnatal growth in mouse is rapid, with total skeletal muscle mass increasing several-fold in the first few weeks. Muscle growth can be achieved by either an increase in muscle fibre number or an increase in the size of individual myofibres, or a combination of both. Where myofibre hypertrophy during growth requires the addition of new myonuclei, these are supplied by muscle satellite cells, the resident stem cells of skeletal muscle. Results Here, we report on the dynamics of postnatal myofibre growth in the mouse extensor digitorum longus (EDL muscle, which is essentially composed of fast type II fibres in adult. We found that there was no net gain in myofibre number in the EDL between P7 and P56 (adulthood. However, myofibre cross-sectional area increased by 7.6-fold, and length by 1.9-fold between these ages, resulting in an increase in total myofibre volume of 14.1-fold: showing the extent of myofibre hypertrophy during the postnatal period. To determine how the number of myonuclei changes during this period of intense muscle fibre hypertrophy, we used two complementary mouse models: 3F-nlacZ-E mice express nlacZ only in myonuclei, while Myf5nlacZ/+ mice have β-galactosidase activity in satellite cells. There was a ~5-fold increase in myonuclear number per myofibre between P3 and P21. Thus myofibre hypertrophy is initially accompanied by a significant addition of myonuclei. Despite this, the estimated myonuclear domain still doubled between P7 and P21 to 9.2 × 103 μm3. There was no further addition of myonuclei from P21, but myofibre volume continued to increase, resulting in an estimated ~3-fold expansion of the myonuclear domain to 26.5 × 103 μm3 by P56. We also used our two mouse models to determine the number of satellite cells per myofibre during postnatal growth. Satellite cell number in EDL was initially ~14 satellite cells per myofibre at P7, but then fell to reach the adult level of ~5 by P21. Conclusions

  19. Communication Framework For the Mionix Naos QG Mouse

    DEFF Research Database (Denmark)

    Wulff-Jensen, Andreas

    2017-01-01

    The Mionix Naos QG mouse has multiple sensors integrated. It can record all the metrics native to mice: being scroll, clicks and mouse movements. Moreover, this mouse has heart rate (HR) and Galvanic Skin Response (GSR) sensors embedded. Through Mionics API [1] WebSocket can be used to access all...

  20. Habitat corridor utilization by the gray mouse lemur, Microcebus ...

    African Journals Online (AJOL)

    the gray mouse lemur, Microcebus murinus, in the littoral forest fragments of south eastern Madagascar. ... and vegetation structure represent suitable habitat for mouse le- ..... ment of tropical forest biodiversity in a human-modified world. Biological .... major histocompatibility complex in the Malagasy mouse lemur, Microce-.

  1. On a new Mouse from Java

    NARCIS (Netherlands)

    Jentink, F.A.

    1910-01-01

    A mouse, collected by Mr. Bartels, April 1903, at an altitude of 6000 feet on the Pangerango-mountain, Java, was presented by that gentleman to our Museum. In comparing it with our Javan Mice I see that the animal differs enough to bestow it with a new specific title. Superficially it reminds my Mus

  2. Genetically engineered mouse models of prostate cancer

    NARCIS (Netherlands)

    Nawijn, Martijn C.; Bergman, Andreas M.; van der Poel, Henk G.

    2008-01-01

    Objectives: Mouse models of prostate cancer are used to test the contribution of individual genes to the transformation process, evaluate the collaboration between multiple genetic lesions observed in a single tumour, and perform preclinical intervention studies in prostate cancer research. Methods:

  3. Pathology of Mouse Models of Accelerated Aging

    NARCIS (Netherlands)

    Harkema, L.; Youssef, S. A.; de Bruin, A.

    2016-01-01

    Progeroid mouse models display phenotypes in multiple organ systems that suggest premature aging and resemble features of natural aging of both mice and humans. The prospect of a significant increase in the global elderly population within the next decades has led to the emergence of geroscience, wh

  4. Pathology of Mouse Models of Accelerated Aging

    NARCIS (Netherlands)

    Harkema, L; Youssef, S A; de Bruin, A|info:eu-repo/dai/nl/304837261

    2016-01-01

    Progeroid mouse models display phenotypes in multiple organ systems that suggest premature aging and resemble features of natural aging of both mice and humans. The prospect of a significant increase in the global elderly population within the next decades has led to the emergence of "geroscience,"

  5. Somatic Cell Nuclear Transfer in the Mouse

    Science.gov (United States)

    Kishigami, Satoshi; Wakayama, Teruhiko

    Somatic cell nuclear transfer (SCNT) has become a unique and powerful tool for epigenetic reprogramming research and gene manipulation in animals since “Dolly,” the first animal cloned from an adult cell was reported in 1997. Although the success rates of somatic cloning have been inefficient and the mechanism of reprogramming is still largely unknown, this technique has been proven to work in more than 10 mammalian species. Among them, the mouse provides the best model for both basic and applied research of somatic cloning because of its abounding genetic resources, rapid sexual maturity and propagation, minimal requirements for housing, etc. This chapter describes a basic protocol for mouse cloning using cumulus cells, the most popular cell type for NT, in which donor nuclei are directly injected into the oocyte using a piezo-actuated micromanipulator. In particular, we focus on a new, more efficient mouse cloning protocol using trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, which increases both in vitro and in vivo developmental rates from twofold to fivefold. This new method including TSA will be helpful to establish mouse cloning in many laboratories.

  6. Pathology of Mouse Models of Accelerated Aging

    NARCIS (Netherlands)

    Harkema, L; Youssef, S A; de Bruin, A

    2016-01-01

    Progeroid mouse models display phenotypes in multiple organ systems that suggest premature aging and resemble features of natural aging of both mice and humans. The prospect of a significant increase in the global elderly population within the next decades has led to the emergence of "geroscience,"

  7. Candida albicans escapes from mouse neutrophils

    DEFF Research Database (Denmark)

    Ermert, David; Niemiec, Maria J; Röhm, Marc

    2013-01-01

    Candida albicans, the most commonly isolated human fungal pathogen, is able to grow as budding yeasts or filamentous forms, such as hyphae. The ability to switch morphology has been attributed a crucial role for the pathogenesis of C. albicans. To mimic disseminated candidiasis in humans, the mouse...

  8. Agglutination of Mouse Erythrocytes by Eperythrozoon coccoides

    OpenAIRE

    Iralu, Vichazelhu; Ganong, Kevin D.

    1983-01-01

    Erythrocytes from blood of mice infected with Eperythrozoon coccoides for 3 or 4 days agglutinated spontaneously. Washed E. coccoides particles agglutinated washed erythrocytes of uninfected mice. E. coccoides-mediated agglutination of normal mouse erythrocytes would be an excellent system for studies of bacterial adhesion.

  9. Progress of gene targeting in mouse

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Gene targeting is a powerful approach of study- ing the genefunction in vivo. Specific genetic modifications, including simple gene disruption, point mutations, large chromosomal deletions and rearrangements, targeted incor- poration of foreign genes, could be introduced into the mouse genome by gene targeting. Recent studies make it possible to do the gene targeting with temporal and spatial control.

  10. Effects of verbenalin on prostatitis mouse model

    Science.gov (United States)

    Miao, Mingsan; Guo, Lin; Yan, Xiaoli; Wang, Tan; Li, Zuming

    2015-01-01

    The aim of this study was to observe the treatment characteristics of verbenalin on a prostatitis mouse model. Give Xiaozhiling injection in the prostate locally to make a prostatitis mouse model. High, medium and low doses of verbenalin were each given to different mouse groups. The amount of water was determined in 14th, 28th. The number of white cells and lecithin corpuscle density in prostatic fluid were determined. Morphological changes in the prostate, testis, epididymis and kidney were detected. Compared with the model control group, the mice treated with high, medium and low doses of verbenalin had significantly increased amounts of water, and prostate white blood cell count and prostate volume density (Vv) were decreased significantly, the density of lecithin corpuscle score increased, and pathologic prostatitis changes were significantly reduced. Pathological change in the testis was significantly reduced and the change in the epididymis was obviously reduced. The thymic cortex thickness and the number of lymphocytes increased significantly and could reduce the renal pathological changes in potential. Verbenalin has a good therapeutic effect on the prostatitis mouse model. PMID:26858560

  11. Hod mice and the mouse set conjecture

    CERN Document Server

    Sargsyan, Grigor

    2015-01-01

    The author develops the theory of Hod mice below AD_{\\mathbb{R}}+ "\\Theta is regular". He uses this theory to show that HOD of the minimal model of AD_{\\mathbb{R}}+ "\\Theta is regular" satisfies GCH. Moreover, he shows that the Mouse Set Conjecture is true in the minimal model of AD_{\\mathbb{R}}+ "\\Theta is regular".

  12. Isolation of Mouse salivary gland stem cells

    NARCIS (Netherlands)

    Pringle, Sarah; Nanduri, Lalitha; van der Zwaag, Marianne; van Os, Ronald; Coppes, Rob

    2011-01-01

    Mature salivary glands of both human and mouse origin comprise a minimum of five cell types, each of which facilitates the production and excretion of saliva into the oral cavity. Serous and mucous acinar cells are the protein and mucous producing factories of the gland respectively, and represent

  13. Having Fun with a Cordless Mouse

    Science.gov (United States)

    Nunn, John

    2016-01-01

    A cordless mouse with an added reed switch is used as a wireless data logger to record every time the wheel of a trolley completes a revolution. The limitations of the system in terms of maximum clicking rate and spatial resolution are considered and data obtained from the descent of a trolley down a ramp at various different angles is analysed in…

  14. Agglutination of Mouse Erythrocytes by Eperythrozoon coccoides

    Science.gov (United States)

    Iralu, Vichazelhu; Ganong, Kevin D.

    1983-01-01

    Erythrocytes from blood of mice infected with Eperythrozoon coccoides for 3 or 4 days agglutinated spontaneously. Washed E. coccoides particles agglutinated washed erythrocytes of uninfected mice. E. coccoides-mediated agglutination of normal mouse erythrocytes would be an excellent system for studies of bacterial adhesion. Images PMID:6832825

  15. Agglutination of Mouse Erythrocytes by Eperythrozoon coccoides

    OpenAIRE

    Iralu, Vichazelhu; Ganong, Kevin D.

    1983-01-01

    Erythrocytes from blood of mice infected with Eperythrozoon coccoides for 3 or 4 days agglutinated spontaneously. Washed E. coccoides particles agglutinated washed erythrocytes of uninfected mice. E. coccoides-mediated agglutination of normal mouse erythrocytes would be an excellent system for studies of bacterial adhesion.

  16. Monovalency Unleashes the Full Therapeutic Potential of the DN-30 Anti-Met Antibody*

    Science.gov (United States)

    Pacchiana, Giovanni; Chiriaco, Cristina; Stella, Maria C.; Petronzelli, Fiorella; De Santis, Rita; Galluzzo, Maria; Carminati, Paolo; Comoglio, Paolo M.; Michieli, Paolo; Vigna, Elisa

    2010-01-01

    Met, the high affinity receptor for hepatocyte growth factor, is one of the most frequently activated tyrosine kinases in human cancer and a validated target for cancer therapy. We previously developed a mouse monoclonal antibody directed against the extracellular portion of Met (DN-30) that induces Met proteolytic cleavage (receptor “shedding”) followed by proteasome-mediated receptor degradation. This translates into inhibition of hepatocyte growth factor/Met-mediated biological activities. However, DN-30 binding to Met also results in partial activation of the Met kinase due to antibody-mediated receptor homodimerization. To safely harness the therapeutic potential of DN-30, its shedding activity must be disassociated from its agonistic activity. Here we show that the DN-30 Fab fragment maintains high affinity Met binding, elicits efficient receptor shedding and down-regulation, and does not promote kinase activation. In Met-addicted tumor cell lines, DN-30 Fab displays potent cytostatic and cytotoxic activity in a dose-dependent fashion. DN-30 Fab also inhibits anchorage-independent growth of several tumor cell lines. In mouse tumorigenesis assays using Met-addicted carcinoma cells, intratumor administration of DN-30 Fab or systemic delivery of a chemically stabilized form of the same molecule results in reduction of Met phosphorylation and inhibition of tumor growth. These data provide proof of concept that monovalency unleashes the full therapeutic potential of the DN-30 antibody and point at DN-30 Fab as a promising tool for Met-targeted therapy. PMID:20833723

  17. Monovalency unleashes the full therapeutic potential of the DN-30 anti-Met antibody.

    Science.gov (United States)

    Pacchiana, Giovanni; Chiriaco, Cristina; Stella, Maria C; Petronzelli, Fiorella; De Santis, Rita; Galluzzo, Maria; Carminati, Paolo; Comoglio, Paolo M; Michieli, Paolo; Vigna, Elisa

    2010-11-12

    Met, the high affinity receptor for hepatocyte growth factor, is one of the most frequently activated tyrosine kinases in human cancer and a validated target for cancer therapy. We previously developed a mouse monoclonal antibody directed against the extracellular portion of Met (DN-30) that induces Met proteolytic cleavage (receptor "shedding") followed by proteasome-mediated receptor degradation. This translates into inhibition of hepatocyte growth factor/Met-mediated biological activities. However, DN-30 binding to Met also results in partial activation of the Met kinase due to antibody-mediated receptor homodimerization. To safely harness the therapeutic potential of DN-30, its shedding activity must be disassociated from its agonistic activity. Here we show that the DN-30 Fab fragment maintains high affinity Met binding, elicits efficient receptor shedding and down-regulation, and does not promote kinase activation. In Met-addicted tumor cell lines, DN-30 Fab displays potent cytostatic and cytotoxic activity in a dose-dependent fashion. DN-30 Fab also inhibits anchorage-independent growth of several tumor cell lines. In mouse tumorigenesis assays using Met-addicted carcinoma cells, intratumor administration of DN-30 Fab or systemic delivery of a chemically stabilized form of the same molecule results in reduction of Met phosphorylation and inhibition of tumor growth. These data provide proof of concept that monovalency unleashes the full therapeutic potential of the DN-30 antibody and point at DN-30 Fab as a promising tool for Met-targeted therapy.

  18. Expression of murine APOBEC3 alleles in different mouse strains and their effect on mouse mammary tumor virus infection.

    Science.gov (United States)

    Okeoma, Chioma M; Petersen, Josiah; Ross, Susan R

    2009-04-01

    Recent work has shown that mouse APOBEC3 restricts infection by mouse mammary tumor virus (MMTV) and murine leukemia virus (MLV) and that there are polymorphic APOBEC3 alleles found in different inbred mouse strains. For example, C57BL/6 mice, which are resistant to Friend MLV (F-MLV), encode a APOBEC3 gene different from that encoded by F-MLV-susceptible BALB/c mice; the predominant RNA produced in C57BL/6 mice lacks exon 5 (mA3(-5)) and encodes a protein with 15 polymorphic amino acids. It has also been reported that BALB/c mice produce only a variant RNA that lacks exon 2 (mA3(-2)). In this study, we examined the effect of these polymorphic APOBEC3 proteins on MMTV infection. We found that the major RNA made in C57BL/6 and B10.BR mice lacks exon 5 but that BALB/c and C3H/HeN mice predominantly express an RNA that contains all nine exons. In addition to producing the splice variant, C57BL/6 and B10.BR cells and tissues had levels of mA3 RNA fivefold higher than those from BALB/c and C3H/HeN mice. A cloned C57BL/6-derived mA3 protein lacking exon 5 inhibited MMTV infection better than a cloned full-length protein derived from 129/Ola RNA when packaged into MMTV virions. We also tested dendritic cells derived from different inbred mouse strains for their abilities to be infected by MMTV and showed that susceptibility to infection correlated with the presence of the exon 5-encoding allele. In vivo susceptibility to infection cosegregated with the inherited mA3 allele in a C57BL/6 x BALB/c backcross analysis. Moreover, virus produced in vivo in the mammary tissue of mA3 knockout and BALB/c mice was more infectious than that produced in the tissue of C57BL/6 mice. These data indicate that mA3 plays a role in the genetics of susceptibility and resistance to MMTV infection.

  19. Phylogeographic Structure of the White-Footed Mouse and the Deer Mouse, Two Lyme Disease Reservoir Hosts in Quebec.

    Directory of Open Access Journals (Sweden)

    Jessica Fiset

    Full Text Available Modification of a species range is one of many consequences of climate change and is driving the emergence of Lyme disease in eastern Canada. The primary reservoir host of the bacteria responsible for Lyme disease, Borrelia burgdorferi, is the white-footed mouse (Peromyscus leucopus, whose range is rapidly shifting north into southern Québec. The deer mouse, P. maniculatus, is occurring over most Québec province and is a less competent host for B. burgdorferi. Here, we compared the phylogeographic structure of both Peromyscus species in Québec. Using a combination of multiple mitochondrial DNA markers and phylogeographic methods, we detected an ongoing and rapid expansion of P. leucopus, while P. maniculatus appears more stable. Haplotype and populations networks indicated that populations of P. maniculatus exhibit more genetic structure than P. leucopus across the study area. Furthermore, significant and consistent genetic divergences between populations of the two species on both sides of the St. Lawrence River suggest that distinct lineages of P. leucopus and P. maniculatus with different ancestral origins colonized Southern Québec following the Last Glacial Maximum. The phylogeographic structure of pathogens is expected to mirror the structure observed in their reservoir hosts. As different strains of Borrelia burgdorferi may be associated with different levels of pathogenicity and immune responses of their hosts, our results are helpful at better understanding the pattern of spread of Lyme disease in a zone of emergence, and associated risk for human populations.

  20. Kinetic properties of mouse pancreatic lipase-related protein-2 suggest the mouse may not model human fat digestion.

    Science.gov (United States)

    Xiao, Xunjun; Ross, Leah E; Miller, Rita A; Lowe, Mark E

    2011-05-01

    Genetically engineered mice have been employed to understand the role of lipases in dietary fat digestion with the expectation that the results can be extrapolated to humans. However, little is known about the properties of mouse pancreatic triglyceride lipase (mPTL) and pancreatic lipase-related protein-2 (mPLRP2). In this study, both lipases were expressed in Pichia Pastoris GS115, purified to near homogeneity, and their properties were characterized. Mouse PTL displayed the kinetics typical of PTL from other species. Like mPTL, mPLRP2 exhibited strong activity against various triglycerides. In contrast to mPTL, mPLRP2 was not inhibited by increasing bile salt concentration. Colipase stimulated mPLRP2 activity 2- to 4-fold. Additionally, mPTL absolutely required colipase for absorption to a lipid interface, whereas mPLRP2 absorbed fully without colipase. mPLRP2 had full activity in the presence of BSA, whereas BSA completely inhibited mPTL unless colipase was present. All of these properties of mPLRP2 differ from the properties of human PLRP2 (hPLRP2). Furthermore, mPLRP2 appears capable of compensating for mPTL deficiency. These findings suggest that the molecular mechanisms of dietary fat digestion may be different in humans and mice. Thus, extrapolation of dietary fat digestion in mice to humans should be done with care.

  1. New routes for transgenesis of the mouse.

    Science.gov (United States)

    Belizário, José E; Akamini, Priscilla; Wolf, Philip; Strauss, Bryan; Xavier-Neto, José

    2012-08-01

    Transgenesis refers to the molecular genetic techniques for directing specific insertions, deletions and point mutations in the genome of germ cells in order to create genetically modified organisms (GMO). Genetic modification is becoming more practicable, efficient and predictable with the development and use of a variety of cell and molecular biology tools and DNA sequencing technologies. A collection of plasmidial and viral vectors, cell-type specific promoters, positive and negative selectable markers, reporter genes, drug-inducible Cre-loxP and Flp/FRT recombinase systems are available which ensure efficient transgenesis in the mouse. The technologies for the insertion and removal of genes by homologous-directed recombination in embryonic stem cells (ES) and generation of targeted gain- and loss-of function alleles have allowed the creation of thousands of mouse models of a variety of diseases. The engineered zinc finger nucleases (ZFNs) and small hairpin RNA-expressing constructs are novel tools with useful properties for gene knockout free of ES manipulation. In this review we briefly outline the different approaches and technologies for transgenesis as well as their advantages and disadvantages. We also present an overview on how the novel integrative mouse and human genomic databases and bioinformatics approaches have been used to understand genotype-phenotype relationships of hundreds of mutated and candidate disease genes in mouse models. The updating and continued improvements of the genomic technologies will eventually help us to unraveling the biological and pathological processes in such a way that they can be translated more efficiently from mouse to human and vise-versa.

  2. A Novel Mouse Model of Diffuse Intrinsic Pontine Glioma Initiated in Pax3-Expressing Cells

    Directory of Open Access Journals (Sweden)

    Katherine L. Misuraca

    2016-01-01

    Full Text Available Diffuse intrinsic pontine glioma (DIPG is a rare and incurable brain tumor that arises predominately in children and involves the pons, a structure that along with the midbrain and medulla makes up the brainstem. We have previously developed genetically engineered mouse models of brainstem glioma using the RCAS/Tv-a system by targeting PDGF-B overexpression, p53 loss, and H3.3K27M mutation to Nestin-expressing brainstem progenitor cells of the neonatal mouse. Here we describe a novel mouse model targeting these same genetic alterations to Pax3-expressing cells, which in the neonatal mouse pons consist of a Pax3+/Nestin+/Sox2+ population lining the fourth ventricle and a Pax3+/NeuN+ parenchymal population. Injection of RCAS-PDGF-B into the brainstem of Pax3-Tv-a mice at postnatal day 3 results in 40% of mice developing asymptomatic low-grade glioma. A mixture of low- and high-grade glioma results from injection of Pax3-Tv-a;p53fl/fl mice with RCAS-PDGF-B and RCAS-Cre, with or without RCAS-H3.3K27M. These tumors are Ki67+, Nestin+, Olig2+, and largely GFAP− and can arise anywhere within the brainstem, including the classic DIPG location of the ventral pons. Expression of the H3.3K27M mutation reduces overall H3K27me3 as compared with tumors without the mutation, similar to what has been previously shown in human and mouse tumors. Thus, we have generated a novel genetically engineered mouse model of DIPG, which faithfully recapitulates the human disease and represents a novel platform with which to study the biology and treatment of this deadly disease.

  3. Essential Role for endogenous siRNAs during meiosis in mouse oocytes.

    Directory of Open Access Journals (Sweden)

    Paula Stein

    2015-02-01

    Full Text Available The RNase III enzyme DICER generates both microRNAs (miRNAs and endogenous short interfering RNAs (endo-siRNAs. Both small RNA species silence gene expression post-transcriptionally in association with the ARGONAUTE (AGO family of proteins. In mammals, there are four AGO proteins (AGO1-4, of which only AGO2 possesses endonucleolytic activity. siRNAs trigger endonucleolytic cleavage of target mRNAs, mediated by AGO2, whereas miRNAs cause translational repression and mRNA decay through association with any of the four AGO proteins. Dicer deletion in mouse oocytes leads to female infertility due to defects during meiosis I. Because mouse oocytes express both miRNAs and endo-siRNAs, this phenotype could be due to the absence of either class of small RNA, or both. However, we and others demonstrated that miRNA function is suppressed in mouse oocytes, which suggested that endo-siRNAs, not miRNAs, are essential for female meiosis. To determine if this was the case we generated mice that express a catalytically inactive knock-in allele of Ago2 (Ago2ADH exclusively in oocytes and thereby disrupted the function of siRNAs. Oogenesis and hormonal response are normal in Ago2ADH oocytes, but meiotic maturation is impaired, with severe defects in spindle formation and chromosome alignment that lead to meiotic catastrophe. The transcriptome of these oocytes is widely perturbed and shows a highly significant correlation with the transcriptome of Dicer null and Ago2 null oocytes. Expression of the mouse transcript (MT, the most abundant transposable element in mouse oocytes, is increased. This study reveals that endo-siRNAs are essential during meiosis I in mouse females, demonstrating a role for endo-siRNAs in mammals.

  4. Multifunctional adaptive NS1 mutations are selected upon human influenza virus evolution in the mouse.

    Directory of Open Access Journals (Sweden)

    Nicole E Forbes

    Full Text Available The role of the NS1 protein in modulating influenza A virulence and host range was assessed by adapting A/Hong Kong/1/1968 (H3N2 (HK-wt to increased virulence in the mouse. Sequencing the NS genome segment of mouse-adapted variants revealed 11 mutations in the NS1 gene and 4 in the overlapping NEP gene. Using the HK-wt virus and reverse genetics to incorporate mutant NS gene segments, we demonstrated that all NS1 mutations were adaptive and enhanced virus replication (up to 100 fold in mouse cells and/or lungs. All but one NS1 mutant was associated with increased virulence measured by survival and weight loss in the mouse. Ten of twelve NS1 mutants significantly enhanced IFN-β antagonism to reduce the level of IFN β production relative to HK-wt in infected mouse lungs at 1 day post infection, where 9 mutants induced viral yields in the lung that were equivalent to or significantly greater than HK-wt (up to 16 fold increase. Eight of 12 NS1 mutants had reduced or lost the ability to bind the 30 kDa cleavage and polyadenylation specificity factor (CPSF30 thus demonstrating a lack of correlation with reduced IFN β production. Mutant NS1 genes resulted in increased viral mRNA transcription (10 of 12 mutants, and protein production (6 of 12 mutants in mouse cells. Increased transcription activity was demonstrated in the influenza mini-genome assay for 7 of 11 NS1 mutants. Although we have shown gain-of-function properties for all mutant NS genes, the contribution of the NEP mutations to phenotypic changes remains to be assessed. This study demonstrates that NS1 is a multifunctional virulence factor subject to adaptive evolution.

  5. Defining the molecular pathologies in cloaca malformation: similarities between mouse and human

    Directory of Open Access Journals (Sweden)

    Laura A. Runck

    2014-04-01

    Full Text Available Anorectal malformations are congenital anomalies that form a spectrum of disorders, from the most benign type with excellent functional prognosis, to very complex, such as cloaca malformation in females in which the rectum, vagina and urethra fail to develop separately and instead drain via a single common channel into the perineum. The severity of this phenotype suggests that the defect occurs in the early stages of embryonic development of the organs derived from the cloaca. Owing to the inability to directly investigate human embryonic cloaca development, current research has relied on the use of mouse models of anorectal malformations. However, even studies of mouse embryos lack analysis of the earliest stages of cloaca patterning and morphogenesis. Here we compared human and mouse cloaca development and retrospectively identified that early mis-patterning of the embryonic cloaca might underlie the most severe forms of anorectal malformation in humans. In mouse, we identified that defective sonic hedgehog (Shh signaling results in early dorsal-ventral epithelial abnormalities prior to the reported defects in septation. This is manifested by the absence of Sox2 and aberrant expression of keratins in the embryonic cloaca of Shh knockout mice. Shh knockout embryos additionally develop a hypervascular stroma, which is defective in BMP signaling. These epithelial and stromal defects persist later, creating an indeterminate epithelium with molecular alterations in the common channel. We then used these animals to perform a broad comparison with patients with mild-to-severe forms of anorectal malformations including cloaca malformation. We found striking parallels with the Shh mouse model, including nearly identical defective molecular identity of the epithelium and surrounding stroma. Our work strongly suggests that early embryonic cloacal epithelial differentiation defects might be the underlying cause of severe forms of anorectal malformations

  6. Bloomsbury report on mouse embryo phenotyping: recommendations from the IMPC workshop on embryonic lethal screening

    Directory of Open Access Journals (Sweden)

    David Adams

    2013-05-01

    Full Text Available Identifying genes that are important for embryo development is a crucial first step towards understanding their many functions in driving the ordered growth, differentiation and organogenesis of embryos. It can also shed light on the origins of developmental disease and congenital abnormalities. Current international efforts to examine gene function in the mouse provide a unique opportunity to pinpoint genes that are involved in embryogenesis, owing to the emergence of embryonic lethal knockout mutants. Through internationally coordinated efforts, the International Knockout Mouse Consortium (IKMC has generated a public resource of mouse knockout strains and, in April 2012, the International Mouse Phenotyping Consortium (IMPC, supported by the EU InfraCoMP programme, convened a workshop to discuss developing a phenotyping pipeline for the investigation of embryonic lethal knockout lines. This workshop brought together over 100 scientists, from 13 countries, who are working in the academic and commercial research sectors, including experts and opinion leaders in the fields of embryology, animal imaging, data capture, quality control and annotation, high-throughput mouse production, phenotyping, and reporter gene analysis. This article summarises the outcome of the workshop, including (1 the vital scientific importance of phenotyping embryonic lethal mouse strains for basic and translational research; (2 a common framework to harmonise international efforts within this context; (3 the types of phenotyping that are likely to be most appropriate for systematic use, with a focus on 3D embryo imaging; (4 the importance of centralising data in a standardised form to facilitate data mining; and (5 the development of online tools to allow open access to and dissemination of the phenotyping data.

  7. The Mouse Genome Database: integration of and access to knowledge about the laboratory mouse.

    Science.gov (United States)

    Blake, Judith A; Bult, Carol J; Eppig, Janan T; Kadin, James A; Richardson, Joel E

    2014-01-01

    The Mouse Genome Database (MGD) (http://www.informatics.jax.org) is the community model organism database resource for the laboratory mouse, a premier animal model for the study of genetic and genomic systems relevant to human biology and disease. MGD maintains a comprehensive catalog of genes, functional RNAs and other genome features as well as heritable phenotypes and quantitative trait loci. The genome feature catalog is generated by the integration of computational and manual genome annotations generated by NCBI, Ensembl and Vega/HAVANA. MGD curates and maintains the comprehensive listing of functional annotations for mouse genes using the Gene Ontology, and MGD curates and integrates comprehensive phenotype annotations including associations of mouse models with human diseases. Recent improvements include integration of the latest mouse genome build (GRCm38), improved access to comparative and functional annotations for mouse genes with expanded representation of comparative vertebrate genomes and new loads of phenotype data from high-throughput phenotyping projects. All MGD resources are freely available to the research community.

  8. Poleward expansion of the white-footed mouse (Peromyscus leucopus under climate change: implications for the spread of lyme disease.

    Directory of Open Access Journals (Sweden)

    Emilie Roy-Dufresne

    Full Text Available The white-footed mouse (Peromyscus leucopus is an important reservoir host for Borrelia burgdorferi, the pathogen responsible for Lyme disease, and its distribution is expanding northward. We used an Ecological Niche Factor Analysis to identify the climatic factors associated with the distribution shift of the white-footed mouse over the last 30 years at the northern edge of its range, and modeled its current and potential future (2050 distributions using the platform BIOMOD. A mild and shorter winter is favouring the northern expansion of the white-footed mouse in Québec. With more favorable winter conditions projected by 2050, the distribution range of the white-footed mouse is expected to expand further northward by 3° latitude. We also show that today in southern Québec, the occurrence of B. burgdorferi is associated with high probability of presence of the white-footed mouse. Changes in the distribution of the white-footed mouse will likely alter the geographical range of B. burgdorferi and impact the public health in northern regions that have yet to be exposed to Lyme disease.

  9. Matrine Inhibits Mouse Sperm Function by Reducing Sperm [Ca2+]i and Phospho-ERK1/2

    Directory of Open Access Journals (Sweden)

    Tao Luo

    2015-01-01

    Full Text Available Background: Matrine is a bioactive alkaloid that has a variety of pharmacological effects and is widely used in Chinese medicine. However, its effects on male reproduction are not well known. In this study, we aimed to investigate the in vitro toxicity of matrine on mature mouse sperm. Methods: Mouse cauda epididymal sperm were exposed to matrine (10-200 µM in vitro. The viability, motility, capacitation, acrosome reaction and fertilization ability of the mouse sperm were examined. Furthermore, the intracellular calcium concentration ([Ca2+]i, calcium (Catsper and potassium (Ksper currents, and phosphorylation of extracellular signal regulated kinases 1/2 (p-ERK1/2 of the sperm were analyzed. Results: After exposure to 100 µM or more of matrine, mouse cauda epididymal sperm exhibited a significant reduction in total motility, progressive motility, linear velocity and acrosome reaction rate induced by Ca2+ ionophore A23187. As a result, the fertilization ability of mouse sperm was remarkably decreased by matrine. Our data further demonstrated that matrine significantly reduced sperm [Ca2+]i and [Ca2+]i-related p-ERK1/2; however, both the CatSper and KSper currents, which are thought to interactively regulate Ca2+ influx in sperm, were not affected by matrine. Conclusion: Our findings indicate that matrine inhibits mouse sperm function by reducing sperm [Ca2+]i and suppressing the phosphorylation of ERK1/2.

  10. Expression of TPM1κ, a Novel Sarcomeric Isoform of the TPM1 Gene, in Mouse Heart and Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Syamalima Dube

    2014-01-01

    Full Text Available We have investigated the expression of TPM1α and TPM1κ in mouse striated muscles. TPM1α and TMP1κ were amplified from the cDNA of mouse heart by using conventional RT-PCR. We have cloned the PCR amplified DNA and determined the nucleotide sequences. Deduced amino acid sequences show that there are three amino acid changes in mouse exon 2a when compared with the human TPM1κ. However, the deduced amino acid sequences of human TPM1α and mouse TPM1α are identical. Conventional RT-PCR data as well as qRT-PCR data, calculating both absolute copy number and relative expression, revealed that the expression of TPM1κ is significantly lower compared to TPM1α in both mouse heart and skeletal muscle. It was also found that the expression level of TPM1κ transcripts in mouse heart is higher than it is in skeletal muscle. To the best of our knowledge, this is the first report of the expression of TPM1κ in mammalian skeletal muscle.

  11. Evaluation of OPEN zinc finger nucleases for direct gene targeting of the ROSA26 locus in mouse embryos.

    Directory of Open Access Journals (Sweden)

    Mario Hermann

    Full Text Available Zinc finger nucleases (ZFNs enable precise genome modification in a variety of organisms and cell types. Commercial ZFNs were reported to enhance gene targeting directly in mouse zygotes, whereas similar approaches using publicly available resources have not yet been described. Here we report precise targeted mutagenesis of the mouse genome using Oligomerized Pool Engineering (OPEN ZFNs. OPEN ZFN can be constructed using publicly available resources and therefore provide an attractive alternative for academic researchers. Two ZFN pairs specific to the mouse genomic locus gt(ROSA26Sor were generated by OPEN selections and used for gene disruption and homology-mediated gene replacement in single cell mouse embryos. One specific ZFN pair facilitated non-homologous end joining (NHEJ-mediated gene disruption when expressed in mouse zygotes. We also observed a single homologous recombination (HR-driven gene replacement event when this ZFN pair was co-injected with a targeting vector. Our experiments demonstrate the feasibility of achieving both gene ablation through NHEJ and gene replacement by HR by using the OPEN ZFN technology directly in mouse zygotes.

  12. Enhanced Reconstitution of Human Erythropoiesis and Thrombopoiesis in an Immunodeficient Mouse Model with KitWv Mutations

    Directory of Open Access Journals (Sweden)

    Ayano Yurino

    2016-09-01

    Full Text Available In human-to-mouse xenograft models, reconstitution of human hematopoiesis is usually B-lymphoid dominant. Here we show that the introduction of homozygous KitWv mutations into C57BL/6.Rag2nullIl2rgnull mice with NOD-Sirpa (BRGS strongly promoted human multi-lineage reconstitution. After xenotransplantation of human CD34+CD38− cord blood cells, these newly generated C57BL/6.Rag2nullIl2rgnullNOD-Sirpa KitWv/Wv (BRGSKWv/Wv mice showed significantly higher levels of human cell chimerism and long-term multi-lineage reconstitution compared with BRGS mice. Strikingly, this mouse displayed a robust reconstitution of human erythropoiesis and thrombopoiesis with terminal maturation in the bone marrow. Furthermore, depletion of host macrophages by clodronate administration resulted in the presence of human erythrocytes and platelets in the circulation. Thus, attenuation of mouse KIT signaling greatly enhances the multi-lineage differentiation of human hematopoietic stem and progenitor cells (HSPCs in mouse bone marrow, presumably by outcompeting mouse HSPCs to occupy suitable microenvironments. The BRGSKWv/Wv mouse model is a useful tool to study human multi-lineage hematopoiesis.

  13. Mouse model of ulcerative colitis using trinitrobenzene sulfonic acid

    Directory of Open Access Journals (Sweden)

    Irfan Ahmad Rather

    2015-12-01

    Full Text Available Animal model of intestinal inflammation is of paramount significance that aids in discerning the pathologies underlying ulcerative colitis and Crohn’s disease, the two clinical presentations of inflammatory bowel disease. The 2,4,6-trinitrobenzene sulfonic acid (TNBS colitis model represents one such intestinal inflammation-prototype that is generated in susceptible strains of mice through intra-rectal instillation of compound TNBS. In this paper, we demonstrate the experimental induction of TNBS-mediated colitis in a susceptible strain of ICR mice. This can be done by the following steps: a acclimation, b induction and c observation. TNBS-mouse model provides the information in shortest possible time and simultaneously represents a cost effective and highly reproducible model method of studying the pathogenesis of inflammatory bowel disease.

  14. Developmental Defects in Trisomy 21 and Mouse Models

    Directory of Open Access Journals (Sweden)

    Jean Maurice Delabar

    2006-01-01

    Full Text Available Aneuploidies have diverse phenotypic consequences, ranging from mental retardation and developmental abnormalities to susceptibility to common phenotypes and various neoplasms. This review focuses on the developmental defects of murine models of a prototype human aneuploidy: trisomy 21 (Down syndrome, DS, T21. Murine models are clearly the best tool for dissecting the phenotypic consequences of imbalances that affect single genes or chromosome segments. Embryos can be studied freely in mice, making murine models particularly useful for the characterization of developmental abnormalities. This review describes the main phenotypic alterations occurring during the development of patients with T21 and the developmental abnormalities observed in mouse models, and investigates phenotypes common to both species.

  15. Mammalian safety of Decaleside II in the laboratory mouse

    Directory of Open Access Journals (Sweden)

    Y. Rajashekar

    2014-01-01

    Full Text Available Decaleside II, a novel trisaccharide isolated from the edible roots of Decalepis hamiltonii, belongs to a new class of natural insecticides. We have evaluated the mammalian safety of Decaleside II in the laboratory mouse. Our results on acute and sub acute toxicity study suggest that Decaleside II is not toxic to the laboratory mice as there were no symptoms of toxicity or mortality up to 2400 mg/kg bw. Haematological profile was unaltered and serum profiles of enzymes were not significantly affected. The lack of toxicity of Decaleside is attributed to the 1,4 α linkage of the sugars which are easily hydrolyzed by the digestive enzymes such as glucosidases. The selective toxicity to insects and mammalian safety of Decaleside II makes them highly suitable for use as novel grain protectants of natural origin.

  16. PET/CT Imaging in Mouse Models of Myocardial Ischemia

    Directory of Open Access Journals (Sweden)

    Sara Gargiulo

    2012-01-01

    Full Text Available Different species have been used to reproduce myocardial infarction models but in the last years mice became the animals of choice for the analysis of several diseases, due to their short life cycle and the possibility of genetic manipulation. Many techniques are currently used for cardiovascular imaging in mice, including X-ray computed tomography (CT, high-resolution ultrasound, magnetic resonance imaging, and nuclear medicine procedures. Cardiac positron emission tomography (PET allows to examine noninvasively, on a molecular level and with high sensitivity, regional changes in myocardial perfusion, metabolism, apoptosis, inflammation, and gene expression or to measure changes in anatomical and functional parameters in heart diseases. Currently hybrid PET/CT scanners for small laboratory animals are available, where CT adds high-resolution anatomical information. This paper reviews mouse models of myocardial infarction and discusses the applications of dedicated PET/CT systems technology, including animal preparation, anesthesia, radiotracers, and images postprocessing.

  17. Mouse Mammary Tumor Virus Molecular Biology and Oncogenesis

    Directory of Open Access Journals (Sweden)

    Susan R. Ross

    2010-09-01

    Full Text Available Mouse mammary tumor virus (MMTV, which was discovered as a milk‑transmitted, infectious cancer-inducing agent in the 1930s, has been used since that time as an animal model for the study of human breast cancer. Like other complex retroviruses, MMTV encodes a number of accessory proteins that both facilitate infection and affect host immune response. In vivo, the virus predominantly infects lymphocytes and mammary epithelial cells. High level infection of mammary epithelial cells ensures efficient passage of virus to the next generation. It also results in mammary tumor induction, since the MMTV provirus integrates into the mammary epithelial cell genome during viral replication and activates cellular oncogene expression. Thus, mammary tumor induction is a by-product of the infection cycle. A number of important oncogenes have been discovered by carrying out MMTV integration site analysis, some of which may play a role in human breast cancer.

  18. Mitochondrial Protection by Exogenous Otx2 in Mouse Retinal Neurons

    Directory of Open Access Journals (Sweden)

    Hyoung-Tai Kim

    2015-11-01

    Full Text Available OTX2 (orthodenticle homeobox 2 haplodeficiency causes diverse defects in mammalian visual systems ranging from retinal dysfunction to anophthalmia. We find that the retinal dystrophy of Otx2+/GFP heterozygous knockin mice is mainly due to the loss of bipolar cells and consequent deficits in retinal activity. Among bipolar cell types, OFF-cone bipolar subsets, which lack autonomous Otx2 gene expression but receive Otx2 proteins from photoreceptors, degenerate most rapidly in Otx2+/GFP mouse retinas, suggesting a neuroprotective effect of the imported Otx2 protein. In support of this hypothesis, retinal dystrophy in Otx2+/GFP mice is prevented by intraocular injection of Otx2 protein, which localizes to the mitochondria of bipolar cells and facilitates ATP synthesis as a part of mitochondrial ATP synthase complex. Taken together, our findings demonstrate a mitochondrial function for Otx2 and suggest a potential therapeutic application of OTX2 protein delivery in human retinal dystrophy.

  19. Fibrosis and inflammation are greater in muscles of beta-sarcoglycan-null mouse than mdx mouse.

    Science.gov (United States)

    Gibertini, Sara; Zanotti, Simona; Savadori, Paolo; Curcio, Maurizio; Saredi, Simona; Salerno, Franco; Andreetta, Francesca; Bernasconi, Pia; Mantegazza, Renato; Mora, Marina

    2014-05-01

    The Sgcb-null mouse, with knocked-down β-sarcoglycan, develops severe muscular dystrophy as in type 2E human limb girdle muscular dystrophy. The mdx mouse, lacking dystrophin, is the most used model for Duchenne muscular dystrophy (DMD). Unlike DMD, the mdx mouse has mild clinical features and shows little fibrosis in limb muscles. To characterize ECM protein deposition and the progression of muscle fibrosis, we evaluated protein and transcript levels of collagens I, III and VI, decorin, and TGF-β1, in quadriceps and diaphragm, at 2, 4, 8, 12, 26, and 52 weeks in Sgcb-null mice, and protein levels at 12, 26, and 52 weeks in mdx mice. In Sgcb-null mice, severe morphological disruption was present from 4 weeks in both quadriceps and diaphragm, and included conspicuous deposition of extracellular matrix components. Histopathological features of Sgcb-null mouse muscles were similar to those of age-matched mdx muscles at all ages examined, but, in the Sgcb-null mouse, the extent of connective tissue deposition was generally greater than mdx. Furthermore, in the Sgcb-null mouse, the amount of all three collagen isoforms increased steadily, while, in the mdx, they remained stable. We also found that, at 12 weeks, macrophages were significantly more numerous in mildly inflamed areas of Sgcb-null quadriceps compared to mdx quadriceps (but not in highly inflamed regions), while, in the diaphragm, macrophages did not differ significantly between the two models, in either region. Osteopontin mRNA was also significantly greater at 12 weeks in laser-dissected highly inflamed areas of the Sgcb-null quadriceps compared to the mdx quadriceps. TGF-β1 was present in areas of degeneration-regeneration, but levels were highly variable and in general did not differ significantly between the two models and controls. The roles of the various subtypes of macrophages in muscle repair and fibrosis in the two models require further study. The Sgcb-null mouse, which develops early fibrosis

  20. Pericentriolar Targeting of the Mouse Mammary Tumor Virus GAG Protein.

    Directory of Open Access Journals (Sweden)

    Guangzhi Zhang

    Full Text Available The Gag protein of the mouse mammary tumor virus (MMTV is the chief determinant of subcellular targeting. Electron microscopy studies show that MMTV Gag forms capsids within the cytoplasm and assembles as immature particles with MMTV RNA and the Y box binding protein-1, required for centrosome maturation. Other betaretroviruses, such as Mason-Pfizer monkey retrovirus (M-PMV, assemble adjacent to the pericentriolar region because of a cytoplasmic targeting and retention signal in the Matrix protein. Previous studies suggest that the MMTV Matrix protein may also harbor a similar cytoplasmic targeting and retention signal. Herein, we show that a substantial fraction of MMTV Gag localizes to the pericentriolar region. This was observed in HEK293T, HeLa human cell lines and the mouse derived NMuMG mammary gland cells. Moreover, MMTV capsids were observed adjacent to centrioles when expressed from plasmids encoding either MMTV Gag alone, Gag-Pro-Pol or full-length virus. We found that the cytoplasmic targeting and retention signal in the MMTV Matrix protein was sufficient for pericentriolar targeting, whereas mutation of the glutamine to alanine at position 56 (D56/A resulted in plasma membrane localization, similar to previous observations from mutational studies of M-PMV Gag. Furthermore, transmission electron microscopy studies showed that MMTV capsids accumulate around centrioles suggesting that, similar to M-PMV, the pericentriolar region may be a site for MMTV assembly. Together, the data imply that MMTV Gag targets the pericentriolar region as a result of the MMTV cytoplasmic targeting and retention signal, possibly aided by the Y box protein-1 required for the assembly of centrosomal microtubules.