scholarly journals 897. A Class I FIV Integrase Mutant Reveals Short-Term Gene Expression from Unintegrated Lentiviral Vector DNA in Non-Dividing Cells

2002 ◽  
Vol 5 (5) ◽  
pp. S292-S293
1999 ◽  
Vol 73 (7) ◽  
pp. 6141-6146 ◽  
Author(s):  
Airi Harui ◽  
Shinobu Suzuki ◽  
Stefan Kochanek ◽  
Kohnosuke Mitani

ABSTRACT One of the limitations of adenovirus vectors is the lack of machinery necessary for their integration into host chromosomes, resulting in short-term gene expression in dividing cells. We analyzed frequencies of integration and persistence of gene expression from integrated adenovirus vectors. Both E1-substituted and helper-dependent adenovirus vectors achieved similar integration efficiencies of ∼10−3 to 10−5 per cell, with the helper-dependent vector showing slightly higher efficiencies. In stable cell pools, gene expression of the integrated vector persisted for at least 50 cell divisions without selection. However, some stable cell clones showed changes in gene expression, which were accompanied by structural changes in the integrated vector DNA.


Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1288
Author(s):  
Wendy Dong ◽  
Boris Kantor

CRISPR/Cas technology has revolutionized the fields of the genome- and epigenome-editing by supplying unparalleled control over genomic sequences and expression. Lentiviral vector (LV) systems are one of the main delivery vehicles for the CRISPR/Cas systems due to (i) its ability to carry bulky and complex transgenes and (ii) sustain robust and long-term expression in a broad range of dividing and non-dividing cells in vitro and in vivo. It is thus reasonable that substantial effort has been allocated towards the development of the improved and optimized LV systems for effective and accurate gene-to-cell transfer of CRISPR/Cas tools. The main effort on that end has been put towards the improvement and optimization of the vector’s expression, development of integrase-deficient lentiviral vector (IDLV), aiming to minimize the risk of oncogenicity, toxicity, and pathogenicity, and enhancing manufacturing protocols for clinical applications required large-scale production. In this review, we will devote attention to (i) the basic biology of lentiviruses, and (ii) recent advances in the development of safer and more efficient CRISPR/Cas vector systems towards their use in preclinical and clinical applications. In addition, we will discuss in detail the recent progress in the repurposing of CRISPR/Cas systems related to base-editing and prime-editing applications.


2021 ◽  
Vol 21 (4) ◽  
pp. 1-28
Author(s):  
Song Deng ◽  
Fulin Chen ◽  
Xia Dong ◽  
Guangwei Gao ◽  
Xindong Wu

Load forecasting in short term is very important to economic dispatch and safety assessment of power system. Although existing load forecasting in short-term algorithms have reached required forecast accuracy, most of the forecasting models are black boxes and cannot be constructed to display mathematical models. At the same time, because of the abnormal load caused by the failure of the load data collection device, time synchronization, and malicious tampering, the accuracy of the existing load forecasting models is greatly reduced. To address these problems, this article proposes a Short-Term Load Forecasting algorithm by using Improved Gene Expression Programming and Abnormal Load Recognition (STLF-IGEP_ALR). First, the Recognition algorithm of Abnormal Load based on Probability Distribution and Cross Validation is proposed. By analyzing the probability distribution of rows and columns in load data, and using the probability distribution of rows and columns for cross-validation, misjudgment of normal load in abnormal load data can be better solved. Second, by designing strategies for adaptive generation of population parameters, individual evolution of populations and dynamic adjustment of genetic operation probability, an Improved Gene Expression Programming based on Evolutionary Parameter Optimization is proposed. Finally, the experimental results on two real load datasets and one open load dataset show that compared with the existing abnormal data detection algorithms, the algorithm proposed in this article have higher advantages in missing detection rate, false detection rate and precision rate, and STLF-IGEP_ALR is superior to other short-term load forecasting algorithms in terms of the convergence speed, MAE, MAPE, RSME, and R 2 .


2008 ◽  
Vol 32 (2) ◽  
pp. 219-228 ◽  
Author(s):  
Adeel Safdar ◽  
Nicholas J. Yardley ◽  
Rodney Snow ◽  
Simon Melov ◽  
Mark A. Tarnopolsky

Creatine monohydrate (CrM) supplementation has been shown to increase fat-free mass and muscle power output possibly via cell swelling. Little is known about the cellular response to CrM. We investigated the effect of short-term CrM supplementation on global and targeted mRNA expression and protein content in human skeletal muscle. In a randomized, placebo-controlled, crossover, double-blind design, 12 young, healthy, nonobese men were supplemented with either a placebo (PL) or CrM (loading phase, 20 g/day × 3 days; maintenance phase, 5 g/day × 7 days) for 10 days. Following a 28-day washout period, subjects were put on the alternate supplementation for 10 days. Muscle biopsies of the vastus lateralis were obtained and were assessed for mRNA expression (cDNA microarrays + real-time PCR) and protein content (Kinetworks KPKS 1.0 Protein Kinase screen). CrM supplementation significantly increased fat-free mass, total body water, and body weight of the participants ( P < 0.05). Also, CrM supplementation significantly upregulated (1.3- to 5.0-fold) the mRNA content of genes and protein content of kinases involved in osmosensing and signal transduction, cytoskeleton remodeling, protein and glycogen synthesis regulation, satellite cell proliferation and differentiation, DNA replication and repair, RNA transcription control, and cell survival. We are the first to report this large-scale gene expression in the skeletal muscle with short-term CrM supplementation, a response that suggests changes in cellular osmolarity.


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