Generation of NSE-MerCreMer Transgenic Mice with Tamoxifen Inducible Cre Activity in Neurons

To establish a genetic tool for conditional deletion or expression of gene in neurons in a temporally controlled manner, we generated a transgenic mouse (NSE-MerCreMer), which expressed a tamoxifen inducible type of Cre recombinase specifically in neurons. The tamoxifen inducible Cre recombinase (MerCreMer) is a fusion protein containing Cre recombinase with two modified estrogen receptor ligand binding domains at both ends, and is driven by the neural-specific rat neural specific enolase (NSE) promoter. A total of two transgenic lines were established, and expression of MerCreMer in neurons of the central and enteric nervous systems was confirmed. Transcript of MerCreMer was detected in several non-neural tissues such as heart, liver, and kidney in these lines. In the background of the Cre reporter mouse strain Rosa26R, Cre recombinase activity was inducible in neurons of adult NSE-MerCreMer mice treated with tamoxifen by intragastric gavage, but not in those fed with corn oil only. We conclude that NSE-MerCreMer lines will be useful for studying gene functions in neurons for the conditions that Cre-mediated recombination resulting in embryonic lethality, which precludes investigation of gene functions in neurons through later stages of development and in adult

Liquid biopsies come of age: towards implementation of circulating tumour DNA

Improvements in genomic and molecular methods are expanding the range of potential applications for circulating tumour DNA (ctDNA), both in a research setting and as a ‘liquid biopsy’ for cancer management. Proof-of-principle studies have demonstrated the translational potential of ctDNA for prognostication, molecular profiling and monitoring. The field is now in an exciting transitional period in which ctDNA analysis is beginning to be applied clinically, although there is still much to learn about the biology of cell-free DNA. This is an opportune time to appraise potential approaches to ctDNA analysis, and to consider their applications in personalized oncology and in cancer research.We would like to acknowledge the support of The University of Cambridge, Cancer Research UK (grant numbers A11906, A20240, A15601) (to N.R., J.D.B.), the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement n. 337905 (to N.R.), the Cambridge Experimental Cancer Medicine Centre, and Hutchison Whampoa Limited (to N.R.), AstraZeneca (to R.B., S.P.), the Cambridge Experimental Cancer Medicine Centre (ECMC) (to R.B., S.P.), and NIHR Biomedical Research Centre (BRC) (to R.B., S.P.). J.G.C. acknowledges clinical fellowship support from SEOM

Psychiatric care for a person with MELAS syndrome: A case report

10.1002/ccr3.4146Clinical Case Reports95e04146

The double-stranded RNA-binding protein PACT functions as a cellular activator of RIG-I to facilitate innate antiviral response

RIG-I, a virus sensor that triggers innate antiviral response, is a DExD/H box RNA helicase bearing structural similarity with Dicer, an RNase III-type nuclease that mediates RNA interference. Dicer requires double-stranded RNA-binding protein partners, such as PACT, for optimal activity. Here we show that PACT physically binds to the C-terminal repression domain of RIG-I and potently stimulates RIG-I-induced type I interferon production. PACT potentiates the activation of RIG-I by poly(I:C) of intermediate length. PACT also cooperates with RIG-I to sustain the activation of antiviral defense. Depletion of PACT substantially attenuates viral induction of interferons. The activation of RIG-I by PACT does not require double-stranded RNA-dependent protein kinase or Dicer, but is mediated by a direct interaction that leads to stimulation of its ATPase activity. Our findings reveal PACT as an important component in initiating and sustaining the RIG-I-dependent antiviral response. © 2011 Elsevier Inc.link_to_OA_fulltex

Accretionary tectonics of the Western Kunlun Orogen, China: A Paleozoic-Early Mesozoic, long-lived active continental margin with implications for the growth of Southern Eurasia

Our new SHRIMP U-Pb zircon ages from the Western Kunlun Orogen allow us to constrain the history of an active continental margin developed on the southern boundary of the Tarim block from the Ordovician to the Triassic. A 492 ± 7-Ma dacite from Yixieke extrusive rocks that contain 220 ± 5-Ma reheated zircons is interpreted as an intraoceanic arc complex that accreted to the Tarim block. The Yirba granodiorite has a continental arc geochemical signature, a 471 ± 5-Ma U-Pb crystallization age, and 491 ± 3-Ma inherited zircons. It formed during the first, early Paleozoic stage of an active continental margin arc that was juxtaposed to the south against the Kudi high-grade gneiss complex, the Buziwan ophiolite, and the Yixieke volcanic and sedimentary rocks. Zircons from a paragneiss in the Kudi gneiss complex range in age from 398 ± 12 to 1345 ± 31 Ma; the oldest reflect protolith ages of a gneissic continental block (incorporated into the trench), and the youngest may represent the age of a refoliated high-grade fabric created during accretion. The Buziwan ophiolite occupies a thrust sheet tectonically overlying the Kudi gneiss complex. A leuco-gabbro pegmatite, with a zircon age of 403 ± 7 Ma and ca. 490-Ma inherited zircons, and the North Kudi granite, with a zircon age of 408 ± 7 Ma, were emplaced during the second mid-Paleozoic stage of the active continental margin. The Akarz subduction-related granite that has a 214 ± 1-Ma zircon crystallization age formed during the final, early Mesozoic stage of the active margin. The long-lasting active continental margin in the western Kunlun forms a key, well-documented section of the Andean-type margin that extends from the Caucasus to the Qinling. © 2005 by The University of Chicago. All rights reserved.link_to_subscribed_fulltex

Survey of the chemical defence potential of diatoms: Screening of fifty one species for alphabetagammadelta-unsaturated aldehydes

In recent years a negative influence of diatom-derived α,β,γ,δ-unsaturated aldehydes (PUA) on the reproductive success of copepods and invertebrates has been suggested. Since adverse chemical properties of diatoms would question the traditional view of the marine food web, this defense mechanism has been investigated in detail, but the PUA-release by test organisms has only been determined in a few cases. The observed effects were nevertheless frequently discussed from a general point of view often leading to contradictory conclusions. We have examined the PUA-production of 50 diatom species (71 isolates) in order to provide a basis for the interpretation of laboratory and field results on the influence of diatom food on the reproductive success of their consumers. PUA-production is species and strain dependent. Thirty-six percent of the investigated species (38% of the cultivated isolates) release α,β,γ,δ-unsaturated aldehydes upon cell disruption in concentrations from 0.01 to 9.8 fmol per cell. Thalassiosira rotula and Thalassiosira pacifica, major spring-bloom forming diatoms isolated from Roscoff (Bretagne, English Channel, France) and Puget Sound (Washington, USA) were among the PUA-producing strains