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  • 1
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    Alterations of social interaction through genetic and environmental manipulation of the 22q11.2 gene Sept5 in the mouse brain (2012)
    Oxford University Press
    Details
    Publication Date: 2012-07-10
    Description: Social behavior dysfunction is a symptomatic element of schizophrenia and autism spectrum disorder (ASD). Although altered activities in numerous brain regions are associated with defective social cognition and perception, the causative relationship between these altered activities and social cognition and perception—and their genetic underpinnings—are not known in humans. To address these issues, we took advantage of the link between hemizygous deletion of human chromosome 22q11.2 and high rates of social behavior dysfunction, schizophrenia and ASD. We genetically manipulated Sept5 , a 22q11.2 gene, and evaluated its role in social interaction in mice. Sept5 deficiency, against a high degree of homogeneity in a congenic genetic background, selectively impaired active affiliative social interaction in mice. Conversely, virally guided overexpression of Sept5 in the hippocampus or, to a lesser extent, the amygdala elevated levels of active affiliative social interaction in C57BL/6J mice. Congenic knockout mice and mice overexpressing Sept5 in the hippocampus or amygdala were indistinguishable from control mice in novelty and olfactory responses, anxiety or motor activity. Moreover, post-weaning individual housing, an environmental condition designed to reduce stress in male mice, selectively raised levels of Sept5 protein in the amygdala and increased active affiliative social interaction in C57BL/6J mice. These findings identify this 22q11.2 gene in the hippocampus and amygdala as a determinant of social interaction and suggest that defective social interaction seen in 22q11.2-associated schizophrenia and ASD can be genetically and environmentally modified by altering this 22q11.2 gene.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 2
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    Neonatal helper-dependent adenoviral vector gene therapy mediates correction of hemophilia A and tolerance to human factor VIII [Medical Sciences] (2011)
    National Academy of Sciences
    Details
    Publication Date: 2011-02-02
    Description: Neonatal gene therapy is a promising strategy for treating a number of congenital diseases diagnosed shortly after birth as expression of therapeutic proteins during postnatal life may limit the pathologic consequences and result in a potential “cure.” Hemophilia A is often complicated by the development of antibodies to recombinant protein resulting in treatment failure. Neonatal administration of vectors may avoid inhibitory antibody formation to factor VIII (FVIII) by taking advantage of immune immaturity. A helper-dependent adenoviral vector expressing human factor VIII was administered i.v. to neonatal hemophilia A knockout mice. Three days later, mice produced high levels of FVIII. Levels declined rapidly with animal growth to 5 wk of age with stable factor VIII expression thereafter to 〉1 y of age. Decline in factor VIII expression was not related to cell-mediated or humoral responses with lack of development of antibodies to capsid or human factor VIII proteins. Subsequent readministration and augmentation of expression was possible as operational tolerance was established to factor VIII without development of inhibitors; however, protective immunity to adenovirus remained.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 3
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    Evolution of self-compatibility in Arabidopsis by a mutation in the male specificity gene (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-04-20
    Description: Ever since Darwin's pioneering research, the evolution of self-fertilisation (selfing) has been regarded as one of the most prevalent evolutionary transitions in flowering plants. A major mechanism to prevent selfing is the self-incompatibility (SI) recognition system, which consists of male and female specificity genes at the S-locus and SI modifier genes. Under conditions that favour selfing, mutations disabling the male recognition component are predicted to enjoy a relative advantage over those disabling the female component, because male mutations would increase through both pollen and seeds whereas female mutations would increase only through seeds. Despite many studies on the genetic basis of loss of SI in the predominantly selfing plant Arabidopsis thaliana, it remains unknown whether selfing arose through mutations in the female specificity gene (S-receptor kinase, SRK), male specificity gene (S-locus cysteine-rich protein, SCR; also known as S-locus protein 11, SP11) or modifier genes, and whether any of them rose to high frequency across large geographic regions. Here we report that a disruptive 213-base-pair (bp) inversion in the SCR gene (or its derivative haplotypes with deletions encompassing the entire SCR-A and a large portion of SRK-A) is found in 95% of European accessions, which contrasts with the genome-wide pattern of polymorphism in European A. thaliana. Importantly, interspecific crossings using Arabidopsis halleri as a pollen donor reveal that some A. thaliana accessions, including Wei-1, retain the female SI reaction, suggesting that all female components including SRK are still functional. Moreover, when the 213-bp inversion in SCR was inverted and expressed in transgenic Wei-1 plants, the functional SCR restored the SI reaction. The inversion within SCR is the first mutation disrupting SI shown to be nearly fixed in geographically wide samples, and its prevalence is consistent with theoretical predictions regarding the evolutionary advantage of mutations in male components.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tsuchimatsu, Takashi -- Suwabe, Keita -- Shimizu-Inatsugi, Rie -- Isokawa, Sachiyo -- Pavlidis, Pavlos -- Stadler, Thomas -- Suzuki, Go -- Takayama, Seiji -- Watanabe, Masao -- Shimizu, Kentaro K -- England -- Nature. 2010 Apr 29;464(7293):1342-6. doi: 10.1038/nature08927. Epub 2010 Apr 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Plant Biology, University Research Priority Program in Systems Biology/Functional Genomics & Zurich-Basel Plant Science Center, University of Zurich, Zollikerstrasse 107, CH-8008 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20400945" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis/chemistry/classification/*genetics/*physiology ; *Biological Evolution ; Crosses, Genetic ; Genes, Plant/*genetics ; Haplotypes/genetics ; Hybridization, Genetic/genetics ; Molecular Sequence Data ; Mutation/*genetics ; Pollen/physiology ; Pollination ; Reproduction/genetics/physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 4
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    Trans-acting small RNA determines dominance relationships in Brassica self-incompatibility (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-08-21
    Description: A diploid organism has two copies of each gene, one inherited from each parent. The expression of two inherited alleles is sometimes biased by the effects known as dominant/recessive relationships, which determine the final phenotype of the organism. To explore the mechanisms underlying these relationships, we have examined the monoallelic expression of S-locus protein 11 genes (SP11), which encode the male determinants of self-incompatibility in Brassica. We previously reported that SP11 expression was monoallelic in some S heterozygotes, and that the promoter regions of recessive SP11 alleles were specifically methylated in the anther tapetum. Here we show that this methylation is controlled by trans-acting small non-coding RNA (sRNA). We identified inverted genomic sequences that were similar to the recessive SP11 promoters in the flanking regions of dominant SP11 alleles. These sequences were specifically expressed in the anther tapetum and processed into 24-nucleotide sRNA, named SP11 methylation inducer (Smi). Introduction of the Smi genomic region into the recessive S homozygotes triggered the methylation of the promoter of recessive SP11 alleles and repressed their transcription. This is an example showing sRNA encoded in the flanking region of a dominant allele acts in trans to induce transcriptional silencing of the recessive allele. Our finding may provide new insights into the widespread monoallelic gene expression systems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tarutani, Yoshiaki -- Shiba, Hiroshi -- Iwano, Megumi -- Kakizaki, Tomohiro -- Suzuki, Go -- Watanabe, Masao -- Isogai, Akira -- Takayama, Seiji -- England -- Nature. 2010 Aug 19;466(7309):983-6. doi: 10.1038/nature09308.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma 630-0192, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20725042" target="_blank"〉PubMed〈/a〉
    Keywords: *Alleles ; Base Sequence ; Brassica/*genetics/physiology ; DNA Methylation ; Diploidy ; Flowers/genetics ; Gene Expression Regulation, Plant/genetics ; *Gene Silencing ; Genes, Dominant/*genetics ; Genes, Plant/*genetics ; Genes, Recessive/genetics ; Haplotypes/genetics ; Heterozygote ; Homozygote ; Molecular Sequence Data ; Phenotype ; Plant Infertility/*genetics/physiology ; Plant Proteins/genetics ; Plants, Genetically Modified ; Pollen/genetics/metabolism ; Pollination/genetics ; Promoter Regions, Genetic/genetics ; RNA, Plant/*genetics ; RNA, Untranslated/*genetics ; Reproduction/genetics/physiology ; Transcription, Genetic/genetics ; Transgenes/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 5
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    A yeast prion, Mod5, promotes acquired drug resistance and cell survival under environmental stress (2012)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2012-04-21
    Description: Prion conversion from a soluble protein to an aggregated state may be involved in the cellular adaptation of yeast to the environment. However, it remains unclear whether and how cells actively use prion conversion to acquire a fitness advantage in response to environmental stress. We identified Mod5, a yeast transfer RNA isopentenyltransferase lacking glutamine/asparagine-rich domains, as a yeast prion protein and found that its prion conversion in yeast regulated the sterol biosynthetic pathway for acquired cellular resistance against antifungal agents. Furthermore, selective pressure by antifungal drugs on yeast facilitated the de novo appearance of Mod5 prion states for cell survival. Thus, phenotypic changes caused by active prion conversion under environmental selection may contribute to cellular adaptation in living organisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Suzuki, Genjiro -- Shimazu, Naoyuki -- Tanaka, Motomasa -- New York, N.Y. -- Science. 2012 Apr 20;336(6079):355-9. doi: 10.1126/science.1219491.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory for Protein Conformation Diseases, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22517861" target="_blank"〉PubMed〈/a〉
    Keywords: Alkyl and Aryl Transferases/*chemistry/genetics/*metabolism ; Antifungal Agents/*pharmacology ; Biosynthetic Pathways ; Crosses, Genetic ; Drug Resistance, Fungal ; Ergosterol/biosynthesis ; Fluorouracil/pharmacology ; Microbial Viability ; Prions/*chemistry/genetics/metabolism ; Protein Conformation ; Protein Structure, Tertiary ; RNA, Fungal/metabolism ; RNA, Transfer/metabolism ; Recombinant Fusion Proteins/chemistry/metabolism ; Saccharomyces cerevisiae/chemistry/*drug effects/genetics/*physiology ; Saccharomyces cerevisiae Proteins/*chemistry/genetics/*metabolism ; Selection, Genetic ; Solubility ; *Stress, Physiological
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 6
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    A single female-specific piRNA is the primary determiner of sex in the silkworm (2014)
    Nature Publishing Group (NPG)
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    Publication Date: 2014-05-16
    Description: The silkworm Bombyx mori uses a WZ sex determination system that is analogous to the one found in birds and some reptiles. In this system, males have two Z sex chromosomes, whereas females have Z and W sex chromosomes. The silkworm W chromosome has a dominant role in female determination, suggesting the existence of a dominant feminizing gene in this chromosome. However, the W chromosome is almost fully occupied by transposable element sequences, and no functional protein-coding gene has been identified so far. Female-enriched PIWI-interacting RNAs (piRNAs) are the only known transcripts that are produced from the sex-determining region of the W chromosome, but the function(s) of these piRNAs are unknown. Here we show that a W-chromosome-derived, female-specific piRNA is the feminizing factor of B. mori. This piRNA is produced from a piRNA precursor which we named Fem. Fem sequences were arranged in tandem in the sex-determining region of the W chromosome. Inhibition of Fem-derived piRNA-mediated signalling in female embryos led to the production of the male-specific splice variants of B. mori doublesex (Bmdsx), a gene which acts at the downstream end of the sex differentiation cascade. A target gene of Fem-derived piRNA was identified on the Z chromosome of B. mori. This gene, which we named Masc, encoded a CCCH-type zinc finger protein. We show that the silencing of Masc messenger RNA by Fem piRNA is required for the production of female-specific isoforms of Bmdsx in female embryos, and that Masc protein controls both dosage compensation and masculinization in male embryos. Our study characterizes a single small RNA that is responsible for primary sex determination in the WZ sex determination system.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kiuchi, Takashi -- Koga, Hikaru -- Kawamoto, Munetaka -- Shoji, Keisuke -- Sakai, Hiroki -- Arai, Yuji -- Ishihara, Genki -- Kawaoka, Shinpei -- Sugano, Sumio -- Shimada, Toru -- Suzuki, Yutaka -- Suzuki, Masataka G -- Katsuma, Susumu -- England -- Nature. 2014 May 29;509(7502):633-6. doi: 10.1038/nature13315. Epub 2014 May 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Agricultural and Environmental Biology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan. ; 1] Department of Agricultural and Environmental Biology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan [2]. ; Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan. ; Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24828047" target="_blank"〉PubMed〈/a〉
    Keywords: Alternative Splicing/genetics ; Animals ; Base Sequence ; Bombyx/embryology/*genetics ; Dosage Compensation, Genetic ; Female ; Male ; Molecular Sequence Data ; RNA, Small Interfering/*genetics ; *Sex Characteristics ; Sex Chromosomes/genetics ; Sex Determination Processes/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 7
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    Minor zygotic gene activation is essential for mouse preimplantation development [Developmental Biology] (2018)
    National Academy of Sciences
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    Publication Date: 2018-07-18
    Description: In mice, transcription initiates at the mid-one-cell stage and transcriptional activity dramatically increases during the two-cell stage, a process called zygotic gene activation (ZGA). Associated with ZGA is a marked change in the pattern of gene expression that occurs after the second round of DNA replication. To distinguish ZGA before...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 8
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    A metric space for Type Ia supernova spectra (2014)
    Oxford University Press
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    Publication Date: 2014-12-27
    Description: We develop a new framework for use in exploring Type Ia supernovae (SNe Ia) spectra. Combining principal component analysis (PCA) and partial least square (PLS) analysis we are able to establish correlations between the principal components (PCs) and spectroscopic/photometric SNe Ia features. The technique was applied to ~120 SN and ~800 spectra from the Nearby Supernova Factory. The ability of PCA to group together SNe Ia with similar spectral features, already explored in previous studies, is greatly enhanced by two important modifications: (1) the initial data matrix is built using derivatives of spectra over the wavelength, which increases the weight of weak lines and discards extinction, and (2) we extract time evolution information through the use of entire spectral sequences concatenated in each line of the input data matrix. These allow us to define a stable PC parameter space which can be used to characterize synthetic SN Ia spectra by means of real SN features. Using PLS, we demonstrate that the information from important previously known spectral indicators (namely the pseudo-equivalent width of Si ii 5972 Å/Si ii 6355 Å and the line velocity of S ii 5640 Å/Si ii 6355 Å) at a given epoch is contained within the PC space and can be determined through a linear combination of the most important PCs. We also show that the PC space encompasses photometric features like B / V magnitudes, B  – V colours and salt2 parameters c and x 1 . The observed colours and magnitudes, which are heavily affected by extinction, cannot be reconstructed using this technique alone. All the above-mentioned applications allowed us to construct a metric space for comparing synthetic SN Ia spectra with observations.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 9
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    A metric space for Type Ia supernova spectra (2014)
    Oxford University Press
    Details
    Publication Date: 2014-12-29
    Description: We develop a new framework for use in exploring Type Ia supernovae (SNe Ia) spectra. Combining principal component analysis (PCA) and partial least square (PLS) analysis we are able to establish correlations between the principal components (PCs) and spectroscopic/photometric SNe Ia features. The technique was applied to ~120 SN and ~800 spectra from the Nearby Supernova Factory. The ability of PCA to group together SNe Ia with similar spectral features, already explored in previous studies, is greatly enhanced by two important modifications: (1) the initial data matrix is built using derivatives of spectra over the wavelength, which increases the weight of weak lines and discards extinction, and (2) we extract time evolution information through the use of entire spectral sequences concatenated in each line of the input data matrix. These allow us to define a stable PC parameter space which can be used to characterize synthetic SN Ia spectra by means of real SN features. Using PLS, we demonstrate that the information from important previously known spectral indicators (namely the pseudo-equivalent width of Si ii 5972 Å/Si ii 6355 Å and the line velocity of S ii 5640 Å/Si ii 6355 Å) at a given epoch is contained within the PC space and can be determined through a linear combination of the most important PCs. We also show that the PC space encompasses photometric features like B / V magnitudes, B  – V colours and salt2 parameters c and x 1 . The observed colours and magnitudes, which are heavily affected by extinction, cannot be reconstructed using this technique alone. All the above-mentioned applications allowed us to construct a metric space for comparing synthetic SN Ia spectra with observations.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 10
    Electronic Resource
    Electronic Resource
    Magnetic order and suppression of superconductivity around x=0.12 in La"2"-"xSr"xCuO"4 and La"2"-"xBa"xCuO"4
    Amsterdam : Elsevier
    Physica C: Superconductivity and its applications 235-240 (1994), S. 1715-1716 
    Details
    ISSN: 0921-4534
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0921-4534(94)92079-6
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