7 research outputs found

    Efficient and precise CRISPR/Cas9-mediated MECP2 modifications in human-induced pluripotent stem cells

    Get PDF
    Patients with Rett syndrome (RTT) have severe mental and physical disabilities. The majority of RTT patients carry a heterozygous mutation in methyl-CpG binding protein 2 (MECP2), an X-linked gene encoding an epigenetic factor crucial for normal nerve cell function. No curative therapy for RTT syndrome exists, and cellular mechanisms are incompletely understood. Here, we developed a CRISPR/Cas9-mediated system that targets and corrects the disease relevant regions of the MECP2 exon 4 coding sequence. We achieved homologous recombination (HR) efficiencies of 20% to 30% in human cell lines and iPSCs. Furthermore, we successfully introduced a MECP2(R270X) mutation into the MECP2 gene in human induced pluripotent stem cells (iPSCs). Consequently, using CRISPR/Cas9, we were able to repair such mutations with high efficiency in human mutant iPSCs. In summary, we provide a new strategy for MECP2 gene targeting that can be potentially translated into gene therapy or for iPSCs-based disease modeling of RTT syndrome

    Ortho-Lithium/Magnesium Carboxylate-Driven Aromatic Nucleophilic Substitution Reactions on Unprotected Naphthoic Acids

    Get PDF
    Substitution of an ortho-fluoro or methoxy group in 1- and 2-naphthoic acids furnishing substituted naphthoic acids occurs in good to excellent yields upon reaction with alkyl/vinyl/aryl organolithium and Grignard reagents, in the absence of a metal catalyst without the need to protect the carboxyl (CO2H) group. This novel nucleophilic aromatic substitution is presumed to proceed via a precoordination of the organometallic with the substrate, followed by an addition/elimination

    Occurrence of Taenia species in pigs in slaughterhouses in Phu Tho province, northern Vietnam

    No full text
    Pigs act as the intermediate hosts of the zoonotic tapewormsTaenia soliumandTaenia asiatica, as well as of the non-zoonoticTaenia hydatigena.In Vietnam, human taeniasis and cysticercosis have been reported throughout the country; however, data on porcine cysticercosis are scarce. Our study aimed to estimate the prevalence ofTaeniaspp. in slaughtered pigs in two districts in Phu Tho, a mountainous province in northern Vietnam from where neurocysticercosis patients commonly originate. The carcasses of 399 pigs from 51 small-scale abattoirs were checked for cysticerci, while tongue, liver, masseter muscles, diaphragm and heart were sliced and examined. Retrieved cysticerci underwent polymerase chain reaction-restriction fragment length polymorphism and sequencing for species confirmation. Blood was also collected to detect antibodies by lentil lectin-purified glycoprotein enzyme-linked immunoelectrotransfer blot (LLGP-EITB) and recombinant T24H antigen (rT24H)-EITB and circulating antigens by B158/B60 Ag-ELISA. In two pigs,T. asiaticacysticerci were found, confirming the presence of the parasite in pigs in Vietnam at a low prevalence (0.5%; 95% exact confidence interval (CI): 0-1.19%). Cysticerci ofT. soliumwere found in none of the pigs, although one serum sample was positive for antibodies in both LLGP-EITB and rT24H-EITB. Furthermore, a high prevalence ofT. hydatigenacysticercosis was observed (18.0%; 95% Wilson score CI: 14.6-22.1%). In more than half of theT. hydatigena-positive pigs, circulating antigens were detected by Ag-ELISA, confirming that this test cannot be used to diagnoseT. soliumcysticercosis in this region. Finally,Spirometra erinaceieuropaeiwas found in one pig liver. It is the first record of this zoonotic cestode species in pigs in Vietnam. Overall, the findings confirmed the complex epidemiology ofTaeniaspp. in pigs in Vietnam

    Psychogeography and (In)Sanity: Walking London, New York, and Dubai with Will Self

    Get PDF
    Hartner M. Psychogeography and (In)Sanity: Walking London, New York, and Dubai with Will Self. In: Gurr JM, Raussert W, eds. Cityscapes in the Americas and Beyond. Representations of Urban Complexity in Literature and Film. Inter-American Studies: Culture - Societies - History. Vol 4. 1st ed. Trier: WVT: Wissenschaftlicher Verlag Trier; 2011: 145-156

    Large expert-curated database for benchmarking document similarity detection in biomedical literature search

    No full text
    Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical science. © The Author(s) 2019. Published by Oxford University Press
    corecore