371 research outputs found

    Calculation of impurity radiation from Non-Corona-Equilibrium Plasmas

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    Sorption of Plutonium on a Biotite Mineral

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    It is necessary to obtain the data of some parameters concerning migration behavior of radionuclides in underground water for the safety assessment of radioactive waste disposal. Sorption and desorption experiments were carried out by using tracer amount of plutonium on biotite in a granitic rock. In this study, pH dependence of distribution coefficients of plutonium on a biotite mineral were measured. The following results are obtained; (1) The biotite has the pH buffer capacity at around pH 5. (2) Plutonium sorption rate was fast around pH 6 but slow at lower pH than 5. (3) The 95 percent of plutonium was sorbed on biotite at around pH 5. (4) The 10 to 30 percent of sorbed plutonium in biotite was desorbed with 1N KCl, the 50 to 60 percent with 1N HN0_3. (5) The rest of plutonium sorbed in biotite could not be desorbed even with 1N HN0_3. (6) The neutral plutonyl hydroxide could be an important species sorbed on the biotite.sorptionplutoniumbiotit

    Cryo-EM structures and binding of mouse and human ACE2 to SARS-CoV-2 variants of concern indicate that mutations enabling immune escape could expand host range.

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    Investigation of potential hosts of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is crucial to understanding future risks of spillover and spillback. SARS-CoV-2 has been reported to be transmitted from humans to various animals after requiring relatively few mutations. There is significant interest in describing how the virus interacts with mice as they are well adapted to human environments, are used widely as infection models and can be infected. Structural and binding data of the mouse ACE2 receptor with the Spike protein of newly identified SARS-CoV-2 variants are needed to better understand the impact of immune system evading mutations present in variants of concern (VOC). Previous studies have developed mouse-adapted variants and identified residues critical for binding to heterologous ACE2 receptors. Here we report the cryo-EM structures of mouse ACE2 bound to trimeric Spike ectodomains of four different VOC: Beta, Omicron BA.1, Omicron BA.2.12.1 and Omicron BA.4/5. These variants represent the oldest to the newest variants known to bind the mouse ACE2 receptor. Our high-resolution structural data complemented with bio-layer interferometry (BLI) binding assays reveal a requirement for a combination of mutations in the Spike protein that enable binding to the mouse ACE2 receptor

    Chiral patterns arising from electrostatic growth models

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    Recently, unusual and strikingly beautiful seahorse-like growth patterns have been observed under conditions of quasi-two-dimensional growth. These `S'-shaped patterns strongly break two-dimensional inversion symmetry; however such broken symmetry occurs only at the level of overall morphology, as the clusters are formed from achiral molecules with an achiral unit cell. Here we describe a mechanism which gives rise to chiral growth morphologies without invoking microscopic chirality. This mechanism involves trapped electrostatic charge on the growing cluster, and the enhancement of growth in regions of large electric field. We illustrate the mechanism with a tree growth model, with a continuum model for the motion of the one-dimensional boundary, and with microscopic Monte Carlo simulations. Our most dramatic results are found using the continuum model, which strongly exhibits spontaneous chiral symmetry breaking, and in particular finned `S' shapes like those seen in the experiments.Comment: RevTeX, 12 pages, 9 figure

    The Prosensory Function of Sox2 in the Chicken Inner Ear Relies on the Direct Regulation of Atoh1

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    The proneural gene Atoh1 is crucial for the development of inner ear hair cells and it requires the function of the transcription factor Sox2 through yet unknown mechanisms. In the present work, we used the chicken embryo and HEK293T cells to explore the regulation of Atoh1 by Sox2. The results show that hair cells derive from Sox2-positive otic progenitors and that Sox2 directly activates Atoh1 through a transcriptional activator function that requires the integrity of Sox2 DNA binding domain. Atoh1 activation depends on Sox transcription factor binding sites (SoxTFBS) present in the Atoh1 3′ enhancer where Sox2 directly binds, as shown by site directed mutagenesis and chromatin immunoprecipitation (ChIP). In the inner ear, Atoh1 enhancer activity is detected in the neurosensory domain and it depends on Sox2. Dominant negative competition (Sox2HMG-Engrailed) and mutation of the SoxTFBS abolish the reporter activity in vivo. Moreover, ChIP assay in isolated otic vesicles shows that Sox2 is bound to the Atoh1 enhancer in vivo. However, besides activating Atoh1, Sox2 also promotes the expression of Atoh1 negative regulators and the temporal profile of Atoh1 activation by Sox2 is transient suggesting that Sox2 triggers an incoherent feed-forward loop. These results provide a mechanism for the prosensory function of Sox2 in the inner ear. We suggest that sensory competence is established early in otic development through the activation of Atoh1 by Sox2, however, hair cell differentiation is prevented until later stages by the parallel activation of negative regulators of Atoh1 function

    Identification and Replication of Three Novel Myopia Common Susceptibility Gene Loci on Chromosome 3q26 using Linkage and Linkage Disequilibrium Mapping

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    Refractive error is a highly heritable quantitative trait responsible for considerable morbidity. Following an initial genome-wide linkage study using microsatellite markers, we confirmed evidence for linkage to chromosome 3q26 and then conducted fine-scale association mapping using high-resolution linkage disequilibrium unit (LDU) maps. We used a preliminary discovery marker set across the 30-Mb region with an average SNP density of 1 SNP/15 kb (Map 1). Map 1 was divided into 51 LDU windows and additional SNPs were genotyped for six regions (Map 2) that showed preliminary evidence of multi-marker association using composite likelihood. A total of 575 cases and controls selected from the tails of the trait distribution were genotyped for the discovery sample. Malecot model estimates indicate three loci with putative common functional variants centred on MFN1 (180,566 kb; 95% confidence interval 180,505–180, 655 kb), approximately 156 kb upstream from alternate-splicing SOX2OT (182,595 kb; 95% CI 182,533–182,688 kb) and PSARL (184,386 kb; 95% CI 184,356–184,411 kb), with the loci showing modest to strong evidence of association for the Map 2 discovery samples (p<10−7, p<10−10, and p = 0.01, respectively). Using an unselected independent sample of 1,430 individuals, results replicated for the MFN1 (p = 0.006), SOX2OT (p = 0.0002), and PSARL (p = 0.0005) gene regions. MFN1 and PSARL both interact with OPA1 to regulate mitochondrial fusion and the inhibition of mitochondrial-led apoptosis, respectively. That two mitochondrial regulatory processes in the retina are implicated in the aetiology of myopia is surprising and is likely to provide novel insight into the molecular genetic basis of common myopia

    Nucleic Acids Res

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    The non-coding RNA 7SK is the scaffold for a small nuclear ribonucleoprotein (7SKsnRNP) which regulates the function of the positive transcription elongation factor P-TEFb in the control of RNA polymerase II elongation in metazoans. The La-related protein LARP7 is a component of the 7SKsnRNP required for stability and function of the RNA. To address the function of LARP7 we determined the crystal structure of its La module, which binds a stretch of uridines at the 3'-end of 7SK. The structure shows that the penultimate uridine is tethered by the two domains, the La-motif and the RNA-recognition motif (RRM1), and reveals that the RRM1 is significantly smaller and more exposed than in the La protein. Sequence analysis suggests that this impacts interaction with 7SK. Binding assays, footprinting and small-angle scattering experiments show that a second RRM domain located at the C-terminus binds the apical loop of the 3' hairpin of 7SK, while the N-terminal domains bind at its foot. Our results suggest that LARP7 uses both its N- and C-terminal domains to stabilize 7SK in a closed structure, which forms by joining conserved sequences at the 5'-end with the foot of the 3' hairpin and has thus functional implications
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