ABSTRACT
We show that the dynamic magnetic susceptibility and the superparamagnetic blocking temperature of an Fe(8) single molecule magnet oscillate as a function of the magnetic field H(x) applied along its hard magnetic axis. These oscillations are associated with quantum interferences, tuned by H(x), between different spin tunneling paths linking two excited magnetic states. The oscillation period is determined by the quantum mixing between the ground S=10 and excited multiplets. These experiments enable us to quantify such mixing. We find that the weight of excited multiplets in the magnetic ground state of Fe(8) amounts to approximately 11.6%.
Subject(s)
Iron/chemistry , Magnetics , Models, Theoretical , Quantum Theory , Anisotropy , Models, MolecularABSTRACT
We show that a crystal of mesoscopic Fe(8) single-molecule magnets is an experimental realization of the quantum Ising model in a transverse field, with dipolar interactions. Quantum annealing has enabled us to explore the quantum and classical phase transitions between the paramagnetic and ferromagnetic phases, at thermodynamical equilibrium. The phase diagram and critical exponents that we obtain agree with expectations for the mean-field universality class.
Subject(s)
Iron/chemistry , Magnetics , Quantum Theory , Neutron DiffractionABSTRACT
Left-right asymmetrical brain function underlies much of human cognition, behavior and emotion. Abnormalities of cerebral asymmetry are associated with schizophrenia and other neuropsychiatric disorders. The molecular, developmental and evolutionary origins of human brain asymmetry are unknown. We found significant association of a haplotype upstream of the gene LRRTM1 (Leucine-rich repeat transmembrane neuronal 1) with a quantitative measure of human handedness in a set of dyslexic siblings, when the haplotype was inherited paternally (P=0.00002). While we were unable to find this effect in an epidemiological set of twin-based sibships, we did find that the same haplotype is overtransmitted paternally to individuals with schizophrenia/schizoaffective disorder in a study of 1002 affected families (P=0.0014). We then found direct confirmatory evidence that LRRTM1 is an imprinted gene in humans that shows a variable pattern of maternal downregulation. We also showed that LRRTM1 is expressed during the development of specific forebrain structures, and thus could influence neuronal differentiation and connectivity. This is the first potential genetic influence on human handedness to be identified, and the first putative genetic effect on variability in human brain asymmetry. LRRTM1 is a candidate gene for involvement in several common neurodevelopmental disorders, and may have played a role in human cognitive and behavioral evolution.
Subject(s)
Chromosomes, Human, Pair 2 , Functional Laterality/genetics , Genetic Predisposition to Disease , Membrane Proteins/genetics , Schizophrenia/genetics , Animals , Brain/metabolism , Brain/pathology , Cell Line, Transformed , Family Health , Female , Gene Expression Regulation, Developmental/physiology , Genotype , Humans , In Situ Hybridization/methods , Karyotyping , Male , Membrane Proteins/metabolism , Mice , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Schizophrenia/pathology , Subcellular Fractions/metabolism , Subcellular Fractions/pathology , Subcellular Fractions/ultrastructureABSTRACT
Genomic imprinting, the phenomenon in which alleles of genes are expressed differentially depending on their parental origins, has important consequences for mammalian development, and disturbance of normal imprinting leads to abnormal embryogenesis and some inherited diseases and is also associated with various cancers. In the context of screening for novel imprinted genes on human chromosome 19q13.4 with mouse A9 hybrids, we identified a maternal allele-specific methylated CpG island in exon 1 of paternally expressed imprinted gene 3 (PEG3), a gene that exhibits paternal allele-specific expression. Because PEG3 expression is downregulated in some gliomas and glioma cell lines, despite high-level expression in normal brain tissues, we investigated whether the loss of PEG3 expression is related to epigenetic modifications involving DNA methylation. We found monoallelic expression of PEG3 in all normal brain tissues examined and five of nine glioma cell lines that had both unmethylated and methylated alleles; the remaining four glioma cell lines exhibited gain of imprinting with hypermethylated alleles. In addition, treatment of glioma cell lines with the DNA demethylating agent 5-aza-2'-deoxycytidine reversed the silencing of PEG3 biallelically. In this article, we report that the epigenetic silencing of PEG3 expression in glioma cell lines depends on aberrant DNA methylation of an exonic CpG island, suggesting that PEG3 contributes to glioma carcinogenesis in certain cases.
Subject(s)
Brain Neoplasms/genetics , Gene Silencing , Glioma/genetics , Protein Kinases , Proteins/genetics , Transcription Factors , Animals , Brain/metabolism , Chromosomes, Human, Pair 19/genetics , DNA Methylation , DNA Primers/chemistry , Female , Fibroblasts/metabolism , Gene Expression , Genomic Imprinting , Humans , Kruppel-Like Transcription Factors , Male , Mice , Polymerase Chain Reaction , Proteins/metabolism , Species Specificity , Tumor Cells, CulturedABSTRACT
As an in vitro assay system for the identification of human imprinted genes, a library of human/mouse A9 monochromosomal hybrids containing a single, intact bsr-tagged human chromosome of known parental origin, derived from normal human fibroblasts, has been previously generated by microcell-mediated chromosome transfer (MMCT). To supplement this assay system, we constructed additional 700 A9 monochromosomal hybrids, using a pSTneo or pPGKneo selection marker. To validate the A9 hybrids, we screened them with chromosome-specific polymorphic markers, and identified the hybrids containing either human chromosome 6, 7, 14, 18, or 21 of known parental origin. Matching paternal and maternal chromosome pairs of A9 hybrids were identified for chromosomes 6, 7, 14, and 18. The paternal-specific expression of ZAC (zinc finger protein, which regulates apoptosis and cell cycle arrest) and HYMAI (hydatidiform mole-associated and imprinted transcript), and the maternal-specific methylation of a CpG island within an imprinted domain on human chromosome 6q24, were maintained in A9 hybrids. For an example, we profiled the expression of expressed sequence tags (ESTs) and the methylation of CpG islands in the 300-kb imprinted domain around 6q24, which may be associated with cancers and transient neonatal diabetes mellitus (TNDM). Thus, the 700 A9 hybrids should be useful for various aspects of imprinting studies.
Subject(s)
Chromosomes, Human, Pair 6/genetics , Genomic Imprinting , Hybrid Cells , Animals , Base Sequence , CpG Islands , DNA Methylation , DNA Primers/genetics , Expressed Sequence Tags , Female , Genetic Techniques , Humans , In Situ Hybridization, Fluorescence , Infant, Newborn , Male , MiceSubject(s)
Exons/genetics , Genes, Tumor Suppressor/genetics , Polymorphism, Genetic , Proteins/genetics , Serine/genetics , Tuberous Sclerosis/genetics , Humans , Mutagenesis, Insertional/genetics , Repetitive Sequences, Amino Acid/genetics , Tuberous Sclerosis Complex 1 Protein , Tumor Suppressor ProteinsABSTRACT
Asymmetric distribution of maternal mRNAs has not been well documented in zebrafish. Recently, we have shown that dazl mRNA is localized at the vegetal pole. Here we report a novel zebrafish gene, bruno-like (brul), which provides another example of vegetal mRNA localization. brul encodes an Elav-type RNA-binding protein that belongs to the Bruno-like family that includes mammalian CUG-BP, Xenopus EDEN-BP, and Drosophila Bruno. At 24 hpf, brul mRNA was abundant in lens fiber cells. At the onset of embryogenesis, maternal brul mRNA was detected at the vegetal pole, and it then migrated rapidly toward the blastoderm through yolk cytoplasmic streams. During oogenesis, brul mRNA became localized at the vegetal cortex at stage II, later than dazl mRNA. We found that anchoring of brul mRNA was dependent on microfilaments.
Subject(s)
Drosophila Proteins , RNA-Binding Proteins/genetics , Xenopus Proteins , Zebrafish Proteins , Zebrafish/genetics , Amino Acid Sequence , Animals , CELF1 Protein , Gene Expression , Humans , Molecular Sequence Data , RNA, Messenger , Zebrafish/embryologyABSTRACT
Members of the DAZ gene family encode RNA-binding proteins and have been shown to play a pivotal role in gametogenesis. In Xenopus, a DAZ-like gene encodes an RNA component of the germ plasm. We have identified a zebrafish DAZ homologue, zDazl. zDazl mRNA was expressed in gonads of both sexes. In ovary, it was localized in the cortex of oocytes. At the onset of embryogenesis, maternal zDazl mRNA was detected at the vegetal pole. It migrated toward blastomeres through cytoplasmic streams as early embryogenesis proceeded. This is the first report showing maternal mRNA localization at the vegetal pole in fish and the existence of mRNA streams in the yolk cytoplasm.
Subject(s)
RNA, Messenger/metabolism , RNA-Binding Proteins/genetics , Zebrafish/embryology , Animals , Blotting, Northern , Deleted in Azoospermia 1 Protein , Female , Gene Library , In Situ Hybridization , Male , Models, Genetic , Molecular Sequence Data , Ovary/metabolism , RNA-Binding Proteins/analysis , RNA-Binding Proteins/metabolism , Sequence Homology, Amino Acid , Testis/metabolism , Tissue DistributionABSTRACT
A new method to evaluate the retinal adhesive force, which was defined as the force needed to achieve adhesive failure per unit length, in the in vivo rabbit eye was tested. A small dome-shaped retinal detachment (bleb) was made in the posterior pole by injecting balanced salt solution into the subretinal space. A separate measuring micropipette with a tip diameter of 5 microns was inserted into the subretinal space. The subretinal pressure was measured directly with the resistance servonulling method as the solution was injected repeatedly into the subretinal space. According to Laplace's law, the retinal adhesive force per unit length in normal Dutch rabbits was calculated to be (1.8 +/- 0.2) X 10(2) dyn/cm (n = 87). This value was about five times larger than that reported previously with in vitro peeling methods. The new method will resolve several problems encountered in the previous methods and will allow for the measurement of the retinal adhesive force more physiologically and precisely.