Repeated slip along a major decoupling horizon between crustal-scale nappesof the Central Western Carpathians documented in the Ochtinà tectonicmélange

International audienceThe Ochtiná Unit is situated in the ENE-WSW-trending contact zone between two crustal-scale nappes, the upper Gemer Unit and the lower Vepor Unit, in the Central Western Carpathians, Slovakia. The Ochtiná Unit consists mainly of Carboniferous phyllitic schists and sandstones enclosing lenses of diverse lithological nature and contrasting metamorphic history. Peak PT conditions obtained by means of phase equilibrium modelling from lenses of amphibolite and chloritoid schist in this unit indicate 500-600 °C and 4-6.5 kbar and 500-520 °C and 9-11 kbar, respectively. These PT conditions contrast not only with the greenschist-facies metamorphism of dominant phyllite but also with each other documenting two distinct metamorphic field gradients related to Variscan and Alpine metamorphic events. Geochemical data reveal an affinity of the amphibolite lenses to similar Variscan rocks in the basement of the upper Gemer Unit and of the chloritoid schist to similar Alpine rocks in the cover of the lower Vepor Unit. Such heterogeneous lithological and metamorphic record is consistent with a block-in-matrix rock arrangement and the Ochtiná Unit is interpreted as deep seated tectonic mélange. The mélange evolved via repeated slip along the rheologically weak sediments of the Ochtiná Unit during the building and collapse of the Eo-Alpine orogenic wedge of the Central Western Carpathians. Deformation record indicates that the mélange separates two distinct structural domains marked by a decoupled behaviour, i.e. the orogenic suprastructure represented by the Gemer Unit and the infrastructure represented by the Vepor Unit. With this respect, the Ochtiná Unit represents an unusual example of a suprastructure-infrastructure transition zone with its position being controlled by the mechanical weakness of this sedimentary horizon and not by the temperature-dependent rheological transition

Hydrogenation via a low energy mechanochemical approach: The MgB2 case

This work aims at investigating the effect that the energy transferred during particle collisions in a milling process entails on solid-gas reactions. For this purpose, the synthesis of Mg(BH4)2 from MgB2 in a pressurized hydrogen atmosphere was chosen as a model reaction. MgB2 was milled under a broad set of milling parameters (i.e. milling times and rotation regimes) and the obtained product thoroughly characterized. By proving the partial formation of Mg(BH4)2, the results of this investigation indicate that the energy transferred to the powder bed by the powder particles during milling is not negligible, in particular when the milling process is protracted for a long period

Rapid dissemination of Francisella tularensis and the effect of route of infection

<p>Abstract</p> <p>Background</p> <p><it>Francisella tularensis </it>subsp. <it>tularensis </it>is classified as a Category A bioweapon that is capable of establishing a lethal infection in humans upon inhalation of very few organisms. However, the virulence mechanisms of this organism are not well characterized. <it>Francisella tularensis </it>subsp. <it>novicida</it>, which is an equally virulent subspecies in mice, was used in concert with a microPET scanner to better understand its temporal dissemination in vivo upon intranasal infection and how such dissemination compares with other routes of infection. Adult mice were inoculated intranasally with <it>F. tularensis </it>subsp. <it>novicida </it>radiolabeled with ⁶⁴Cu and imaged by microPET at 0.25, 2 and 20 hours post-infection.</p> <p>Results</p> <p>⁶⁴Cu labeled <it>F. tularensis </it>subsp. <it>novicida </it>administered intranasally or intratracheally were visualized in the respiratory tract and stomach at 0.25 hours post infection. By 20 hours, there was significant tropism to the lung compared with other tissues. In contrast, the images of radiolabeled <it>F. tularensis </it>subsp. <it>novicida </it>when administered intragastrically, intradermally, intraperitoneally and intravenouslly were more generally limited to the gastrointestinal system, site of inoculation, liver and spleen respectively. MicroPET images correlated with the biodistribution of isotope and bacterial burdens in analyzed tissues.</p> <p>Conclusion</p> <p>Our findings suggest that Francisella has a differential tissue tropism depending on the route of entry and that the virulence of Francisella by the pulmonary route is associated with a rapid bacteremia and an early preferential tropism to the lung. In addition, the use of the microPET device allowed us to identify the cecum as a novel site of colonization of <it>Francisella tularensis </it>subsp. <it>novicida </it>in mice.</p

m6A RNA methylation of major satellite repeat transcripts facilitates chromatin association and RNA:DNA hybrid formation in mouse heterochromatin

Heterochromatin has essential functions in maintaining chromosome structure, in protecting genome integrity and in stabilizing gene expression programs. Heterochromatin is often nucleated by underlying DNA repeat sequences, such as major satellite repeats (MSR) and long interspersed nuclear elements (LINE). In order to establish heterochromatin, MSR and LINE elements need to be transcriptionally competent and generate non-coding repeat RNA that remain chromatin associated. We explored whether these heterochromatic RNA, similar to DNA and histones, may be methylated, particularly for 5-methylcytosine (5mC) or methyl-6-adenosine (m6A). Our analysis in mouse ES cells identifies only background level of 5mC but significant enrichment for m6A on heterochromatic RNA. Moreover, MSR transcripts are a novel target for m6A RNA modification, and their m6A RNA enrichment is decreased in ES cells that are mutant for Mettl3 or Mettl14, which encode components of a central RNA methyltransferase complex. Importantly, MSR transcripts that are partially deficient in m6A RNA methylation display impaired chromatin association and have a reduced potential to form RNA:DNA hybrids. We propose that m6A modification of MSR RNA will enhance the functions of MSR repeat transcripts to stabilize mouse heterochromatin

Changing POU dimerization preferences converts Oct6 into a pluripotency inducer

� 2016 The Authors. Published under the terms of the CC BY 4.0 license The transcription factor Oct4 is a core component of molecular cocktails inducing pluripotent stem cells (iPSCs), while other members of the POU family cannot replace Oct4 with comparable efficiency. Rather, group III POU factors such as Oct6 induce neural lineages. Here, we sought to identify molecular features determining the differential DNA-binding and reprogramming activity of Oct4 and Oct6. In enhancers of pluripotency genes, Oct4 cooperates with Sox2 on heterodimeric SoxOct elements. By re-analyzing ChIP-Seq data and performing dimerization assays, we found that Oct6 homodimerizes on palindromic OctOct more cooperatively and more stably than Oct4. Using structural and biochemical analyses, we identified a single amino acid directing binding to the respective DNA elements. A change in this amino acid decreases the ability of Oct4 to generate iPSCs, while the reverse mutation in Oct6 does not augment its reprogramming activity. Yet, with two additional amino acid exchanges, Oct6 acquires the ability to generate iPSCs and maintain pluripotency. Together, we demonstrate that cell type-specific POU factor function is determined by select residues that affect DNA-dependent dimerization.Link_to_subscribed_fulltex

Switched-current filter structure for synthesizing arbitrary characteristics based on follow-the-leader feedback configuration

This document is the Accepted Manuscript version of the following article: Wenshan Zhao, Yigang He, and Yichuang Sun, ‘Switched-current filter structure for synthesizing arbitrary characteristics based on follow-the-leader feedback configuration’, Analog Integrated Circuits and Signal Processing, (2015), Vol. 82 (2): 479-486. The version of record is available online at doi: 10.1007/s10470-014-0477-8 © Springer Science+Business Media New York 2015Peer reviewedFinal Accepted Versio

Large Exchange Bias, High Dielectric Constant, and Outstanding Ionic Conductivity in a Single Phase Spin Glass

The multigram synthesis of K [Fe S ] starting from K S and FeS is presented, and its electronic and magnetic properties are investigated. The title compound obtains a defect variant of the K[Fe Se ] structure type. Dielectric and impedance measurements indicate a dielectric constant of 1120 at 1 kHz and an outstanding ionic conductivity of 24.37 mS cm at 295 K, which is in the range of the highest reported value for potential solid state electrolytes for potassium ion batteries. The Seebeck coeffcient of the n type conductor amounts to amp; 8722;60 amp; 956;V K at 973 K. The mismatch of the measured electrical resistivity and the predicted metal like band structure by periodic quantum chemical calculations indicates Mott insulating behavior. Magnetometry demonstrates temperature dependent, large exchange biasfields of 35 mT, as a consequence of the coexistence of spin glass and antiferromagnetic orderings due to the iron vacancies in the lattice. In addition, the decreasing training effects of 34 in the exchange bias are identified at temperatures lower than 20 K. These results demonstrate the critical role of iron vacancies in tuning the electronic and magnetic properties and a multifunctional material from abundant and accessible element

Kinetic properties and small-molecule inhibition of human myosin-6.

Myosin-6 is an actin-based motor protein that moves its cargo towards the minus-end of actin filaments. Mutations in the gene encoding the myosin-6 heavy chain and changes in the cellular abundance of the protein have been linked to hypertrophic cardiomyopathy, neurodegenerative diseases, and cancer. Here, we present a detailed kinetic characterization of the human myosin-6 motor domain, describe the effect of 2,4,6-triiodophenol on the interaction of myosin-6 with F-actin and nucleotides, and show how addition of the drug reduces the number of myosin-6-dependent vesicle fusion events at the plasma membrane during constitutive secretion

Expression patterns of protein C inhibitor in mouse development

Proteolysis of extracellular matrix is an important requirement for embryonic development and is instrumental in processes such as morphogenesis, angiogenesis, and cell migration. Efficient remodeling requires controlled spatio-temporal expression of both the proteases and their inhibitors. Protein C inhibitor (PCI) effectively blocks a range of serine proteases, and recently has been suggested to play a role in cell differentiation and angiogenesis. In this study, we mapped the expression pattern of PCI throughout mouse development using in situ hybridization and immunohistochemistry. We detected a wide-spread, yet distinct expression pattern with prominent PCI levels in skin including vibrissae, and in fore- and hindgut. Further sites of PCI expression were choroid plexus of brain ventricles, heart, skeletal muscles, urogenital tract, and cartilages. A strong and stage-dependent PCI expression was observed in the developing lung. In the pseudoglandular stage, PCI expression was present in distal branching tubules whereas proximal tubules did not express PCI. Later in development, in the saccular stage, PCI expression was restricted to distal bronchioli whereas sacculi did not express PCI. PCI expression declined in postnatal stages and was not detected in adult lungs. In general, embryonic PCI expression indicates multifunctional roles of PCI during mouse development. The expression pattern of PCI during lung development suggests its possible involvement in lung morphogenesis and angiogenesis

Expression-Dependent Folding of Interphase Chromatin

Multiple studies suggest that chromatin looping might play a crucial role in organizing eukaryotic genomes. To investigate the interplay between the conformation of interphase chromatin and its transcriptional activity, we include information from gene expression profiles into a polymer model for chromatin that incorporates genomic loops. By relating loop formation to transcriptional activity, we are able to generate chromosome conformations whose structural and topological properties are consistent with experimental data. The model particularly allows to reproduce the conformational variations that are known to occur between highly and lowly expressed chromatin regions. As previously observed in experiments, lowly expressed regions of the simulated polymers are much more compact. Due to the changes in loop formation, the distributions of chromatin loops are also expression-dependent and exhibit a steeper decay in highly active regions. As a results of entropic interaction between differently looped parts of the chromosome, we observe topological alterations leading to a preferential positioning of highly transcribed loci closer to the surface of the chromosome territory. Considering the diffusional behavior of the chromatin fibre, the simulations furthermore show that the higher the expression level of specific parts of the chromatin fibre is, the more dynamic they are. The results exhibit that variations of loop formation along the chromatin fibre, and the entropic changes that come along with it, do not only influence the structural parameters on the local scale, but also effect the global chromosome conformation and topology