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SCON—a Short Conditional intrON for conditional knockout with one-step zygote injection
Wu Szu-Hsien Sam,Lee Heetak,Szép-Bakonyi Réka,Colozza Gabriele,Boese Ayse,Gert Krista R.,Hallay Natalia,Lee Ji-Hyun,Kim Jihoon,Zhu Yi,Linssen Margot M.,Pilat-Carotta Sandra,Hohenstein Peter,Theussl Ha 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-
The generation of conditional alleles using CRISPR technology is still challenging. Here, we introduce a Short Conditional intrON (SCON, 189 bp) that enables the rapid generation of conditional alleles via one-step zygote injection. In this study, a total of 13 SCON mouse lines were successfully generated by 2 different laboratories. SCON has conditional intronic functions in various vertebrate species, and its target insertion is as simple as CRISPR/Cas9-mediated gene tagging.
Linkage Disequilibrium Estimation of Chinese Beef Simmental Cattle Using High-density SNP Panels
Zhu, M.,Zhu, B.,Wang, Y.H.,Wu, Y.,Xu, L.,Guo, L.P.,Yuan, Z.R.,Zhang, L.P.,Gao, X.,Gao, H.J.,Xu, S.Z.,Li, J.Y. Asian Australasian Association of Animal Productio 2013 Animal Bioscience Vol.26 No.6
Linkage disequilibrium (LD) plays an important role in genomic selection and mapping quantitative trait loci (QTL). In this study, the pattern of LD and effective population size ($N_e$) were investigated in Chinese beef Simmental cattle. A total of 640 bulls were genotyped with IlluminaBovinSNP50BeadChip and IlluminaBovinHDBeadChip. We estimated LD for each autosomal chromosome at the distance between two random SNPs of <0 to 25 kb, 25 to 50 kb, 50 to 100 kb, 100 to 500 kb, 0.5 to 1 Mb, 1 to 5 Mb and 5 to 10 Mb. The mean values of $r^2$ were 0.30, 0.16 and 0.08, when the separation between SNPs ranged from 0 to 25 kb to 50 to 100 kb and then to 0.5 to 1 Mb, respectively. The LD estimates decreased as the distance increased in SNP pairs, and increased with the increase of minor allelic frequency (MAF) and with the decrease of sample sizes. Estimates of effective population size for Chinese beef Simmental cattle decreased in the past generations and $N_e$ was 73 at five generations ago.
Quanxin Zhu,R. Raja,S. Senthilraj,R. Samidurai 제어·로봇·시스템학회 2017 International Journal of Control, Automation, and Vol.15 No.5
This paper focuses on the stability analysis for neutral systems with discrete and distributed constanttime-delays. Lyapunov-Krasovskii functionals (LKFs) are constructed by non uniformly dividing the whole delayinterval into multiple segments and choosing proper functionals with different weighting matrices coressponding todifferent segments in the LKFs. By employing these LKFs, some new delay-derivative-dependent stability criteriaare established for the neutral system in the delay partition approach. By utilizing the delay partition approach, theobtained stability criteria are stated in terms of linear matrix inequalities. Finally, some numerical examples areprovided to illustrate the effectiveness of the proposed approach less conservative than the existing ones.
An Isolated Microlens Observed from <i>K2</i> , <i>Spitzer</i> , and Earth
Zhu, Wei,Udalski, A.,Huang, C. X.,Novati, S. Calchi,Sumi, T.,Poleski, R.,Skowron, J.,Mró,z, P.,Szymań,ski, M. K.,Soszyń,ski, I.,Pietrukowicz, P.,Kozłowski, S.,Ulaczyk, K.,Pawlak, M.,Be American Astronomical Society 2017 ASTROPHYSICAL JOURNAL LETTERS - Vol.849 No.2
Zhu, Xi,Xu, Yingjie,Solis, Luisa M.,Tao, Wei,Wang, Liangzhe,Behrens, Carmen,Xu, Xiaoyang,Zhao, Lili,Liu, Danny,Wu, Jun,Zhang, Ning,Wistuba, Ignacio I.,Farokhzad, Omid C.,Zetter, Bruce R.,Shi, Jinjun National Academy of Sciences 2015 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.112 No.25
<P><B>Significance</B></P><P>This study developed a new generation lipid–polymer hybrid nanoparticle platform for effective systemic delivery of small interfering RNA (siRNA) to tumors, which represents a challenging hurdle for the widespread application of RNA interference (RNAi) in cancer research and therapy. With promising in vivo features such as long blood circulation, high tumor accumulation, and effective gene silencing, the hybrid siRNA nanoparticles were successfully used to reveal and validate a putative therapeutic target, Prohibitin1 (PHB1), in non-small cell lung cancer treatment. In vivo antitumor efficacy results and human tissue microarray analysis further suggested the feasibility of utilizing PHB1 siRNA nanoparticles as a novel therapeutic agent. This hybrid RNAi nanoparticle platform may serve as a valuable tool for validating potential cancer targets and developing new cancer therapies.</P><P>RNA interference (RNAi) represents a promising strategy for identification and validation of putative therapeutic targets and for treatment of a myriad of important human diseases including cancer. However, the effective systemic in vivo delivery of small interfering RNA (siRNA) to tumors remains a formidable challenge. Using a robust self-assembly strategy, we develop a unique nanoparticle (NP) platform composed of a solid polymer/cationic lipid hybrid core and a lipid-poly(ethylene glycol) (lipid-PEG) shell for systemic siRNA delivery. The new generation lipid–polymer hybrid NPs are small and uniform, and can efficiently encapsulate siRNA and control its sustained release. They exhibit long blood circulation (<I>t</I><SUB>1/2</SUB> ∼8 h), high tumor accumulation, effective gene silencing, and negligible in vivo side effects. With this RNAi NP, we delineate and validate the therapeutic role of Prohibitin1 (PHB1), a target protein that has not been systemically evaluated in vivo due to the lack of specific and effective inhibitors, in treating non-small cell lung cancer (NSCLC) as evidenced by the drastic inhibition of tumor growth upon PHB1 silencing. Human tissue microarray analysis also reveals that high PHB1 tumor expression is associated with poorer overall survival in patients with NSCLC, further suggesting PHB1 as a therapeutic target. We expect this long-circulating RNAi NP platform to be of high interest for validating potential cancer targets in vivo and for the development of new cancer therapies.</P>