Functional rescue of dystrophin deficiency in mice caused by frameshift mutations using Campylobacter jejuni Cas9

Duchenne muscular dystrophy (DMD) is a fatal, X-linked muscle wasting disease caused by mutations in the DMD gene. In 51% of DMD cases, a reading frame is disrupted because of deletion of several exons. Here, we show that CjCas9 derived from Campylobacter jejuni can be used as a gene editing tool to correct an out-of-frame Dmd exon in Dmd knockout mice. Herein, we used Cas9 derived from S. pyogenes to generate Dmd knockout (KO) mice with a frameshift mutation in Dmd gene. Then, we expressed CjCas9, its single-guide RNA, and the eGFP gene in the tibialis anterior muscle of the Dmd KO mice using an all-in-one adeno-associated virus (AAV) vector. CjCas9 cleaved the target site in the Dmd gene efficiently in vivo and induced small insertions or deletions at the target site. This treatment resulted in conversion of the disrupted Dmd reading frame from out-of-frame to in-frame, leading to the expression of dystrophin in the sarcolemma. Importantly, muscle strength was enhanced in the CjCas9-treated muscles, without off-target mutations, indicating high efficiency and specificity of CjCas9. This work suggests that in vivo DMD frame correction, mediated by CjCas9 has great potential for the treatment of DMD and other neuromuscular diseases

The exporting and subcontracting decisions of Viet Nam\u27s small- and medium-sized enterprises

The exporting and subcontracting decisions of a panel of Vietnamese private small- and medium-sized enterprises is investigated. We find that among subcontractors, subcontracting is a supplementary rather than primary activity; the propensity to export increases with managers\u27 or owners\u27 knowledge of customs law; and, there is some evidence that subcontractors are more likely to have made product improvements while exporters are more likely to have adopted new processes or technologies. Our study provides useful insights into SME exporting and subcontracting strategies made more relevant by the expected reductions in trade costs associated with the World Trade Organization\u27s Trade Facilitation Agreement

Application of finite element code to characterize mechanical properties of complex microstructured materials

A technique to solve the periodic homogenization problem is described systematically in this work. The method is to solve the cell problems by imposing eigenstrains in terms of a thermal or a piezoelectric strain to the representative volume element (RVE). Homogenized coefficients are then calculated from stress solutions of those cell problems. As a dual approach, an imposed stress field can also be applied to solve the cell problems. Numerical examples of characterization mechanical properties of complicated microstructure materials are examined. The obtained results show good agreements with the published data. Comparisons show that the technique in this study can be effectively used to characterize the mechanical properties of complex microstructured materials

A heparin-mimicking polymer conjugate stabilizes basic fibroblast growth factor.

Basic fibroblast growth factor (bFGF) is a protein that plays a crucial role in diverse cellular functions, from wound healing to bone regeneration. However, a major obstacle to the widespread application of bFGF is its inherent instability during storage and delivery. Here, we describe the stabilization of bFGF by covalent conjugation with a heparin-mimicking polymer, a copolymer consisting of styrene sulfonate units and methyl methacrylate units bearing poly(ethylene glycol) side chains. The bFGF conjugate of this polymer retained bioactivity after synthesis and was stable to a variety of environmentally and therapeutically relevant stressors--such as heat, mild and harsh acidic conditions, storage and proteolytic degradation--unlike native bFGF. Following the application of stress, the conjugate was also significantly more active than the control conjugate system in which the styrene sulfonate units were omitted from the polymer structure. This research has important implications for the clinical use of bFGF and for the stabilization of heparin-binding growth factors in general

Innovative in silico approaches to address avian flu using grid technology

The recent years have seen the emergence of diseases which have spread very quickly all around the world either through human travels like SARS or animal migration like avian flu. Among the biggest challenges raised by infectious emerging diseases, one is related to the constant mutation of the viruses which turns them into continuously moving targets for drug and vaccine discovery. Another challenge is related to the early detection and surveillance of the diseases as new cases can appear just anywhere due to the globalization of exchanges and the circulation of people and animals around the earth, as recently demonstrated by the avian flu epidemics. For 3 years now, a collaboration of teams in Europe and Asia has been exploring some innovative in silico approaches to better tackle avian flu taking advantage of the very large computing resources available on international grid infrastructures. Grids were used to study the impact of mutations on the effectiveness of existing drugs against H5N1 and to find potentially new leads active on mutated strains. Grids allow also the integration of distributed data in a completely secured way. The paper presents how we are currently exploring how to integrate the existing data sources towards a global surveillance network for molecular epidemiology.Comment: 7 pages, submitted to Infectious Disorders - Drug Target

Chemical-Rheological Evaluation of the Short-Term and Long-Term Effectiveness of Binder Rejuvenators

Many previous studies have investigated how rejuvenators affect/alter mechanical/chemical characteristics of aged binders. However, it has not been actively examined how the rejuvenated binders will perform for the next round of service after the rejuvenation was made. A better understanding of the short-term and long-term effect of rejuvenating agents in RAP blended asphalt mixtures is necessary to achieve more appropriate selection and use of rejuvenating agents

SOCIAL-EMOTIONAL SKILLS IN STUDENTS’ LEARNING IN CAN THO UNIVERSITY, VIETNAM

Based on an overview of domestic and foreign research related to the research field of the topic; the research of the topic has determined the urgency of the topic, research objectives, research objects and scope, research hypotheses, research tasks, and methods. The research on the topic has systematized the theoretical basis for the concept and manifestation of social-emotional skills in student learning: generalizing the picture of the current situation of recognizing the importance of social-emotional skills in student learning, the level of assessment of the manifestation and educational measures of social-emotional skills in learning, and finding out the factors that affect social emotions in student learning such as from the external environment, at school, family and external social relationships. Factors from the internal environment are the self-awareness of each student. From the current situation of the problem, the study has proposed educational measures for 504 students from 8 schools and colleges in Can Tho University (CTU), Vietnam. Some measures were to educate social-emotional skills for students through soft skills topics, teach soft skills to students through extracurricular activities, and soft skills education for students through integrated teaching.  Article visualizations

Mapping of Two High Mobility Group Protein Genes for Growth and Composition traits in Pig

Using information from the human genome two new candidate genes for growth and composition traits were studied. The porcine high mobility group isoforms protein [HMGI(Y) and HMGIC] genes were chosen based on their presumed role in fat cell growth and differentiation. The HMGI(Y) gene was assigned to pig chromosome 7 by both linkage and physical mapping methods. This assignment agrees with other comparative mapping studies as the human HMGI(Y) gene maps to human chromosome 6p21, which is known to share a homology with pig chromosome 7. Interestingly, the pig HMGIC gene was assigned to the pig chromosome 1 by both methods. The localization of these candidate genes in the pig genome could improve the power of analyses for quantitative traits associated with growth and meat quality traits