scholarly journals mRNA loading into ATP-responsive polyplex micelles with optimal density of phenylboronate ester crosslinking to balance robustness in the biological milieu and intracellular translational efficiency

2021 ◽  
Vol 330 ◽  
pp. 317-328
Author(s):  
Naoto Yoshinaga ◽  
Satoshi Uchida ◽  
Anjaneyulu Dirisala ◽  
Mitsuru Naito ◽  
Kensuke Osada ◽  
...  
2005 ◽  
Vol 1 (1) ◽  
pp. 21-24
Author(s):  
Hamid Reza Samadi

In exploration geophysics the main and initial aim is to determine density of under-research goals which have certain density difference with the host rock. Therefore, we state a method in this paper to determine the density of bouguer plate, the so-called variogram method based on fractal geometry. This method is based on minimizing surface roughness of bouguer anomaly. The fractal dimension of surface has been used as surface roughness of bouguer anomaly. Using this method, the optimal density of Charak area insouth of Hormozgan province can be determined which is 2/7 g/cfor the under-research area. This determined density has been used to correct and investigate its results about the isostasy of the studied area and results well-coincided with the geology of the area and dug exploratory holes in the text area


2019 ◽  
Vol 26 (8) ◽  
pp. 1351-1365 ◽  
Author(s):  
Zhentao Huang ◽  
Qingxin Yao ◽  
Simin Wei ◽  
Jiali Chen ◽  
Yuan Gao

Precision medicine is in an urgent need for public healthcare. Among the past several decades, the flourishing development in nanotechnology significantly advances the realization of precision nanomedicine. Comparing to well-documented nanoparticlebased strategy, in this review, we focus on the strategy using enzyme instructed selfassembly (EISA) in biological milieu for theranostics purpose. In principle, the design of small molecules for EISA requires two aspects: (1) the substrate of enzyme of interest; and (2) self-assembly potency after enzymatic conversion. This strategy has shown its irreplaceable advantages in nanomedicne, specifically for cancer treatments and Vaccine Adjuvants. Interestingly, all the reported examples rely on only one kind of enzymehydrolase. Therefore, we envision that the application of EISA strategy just begins and will lead to a new paradigm in nanomedicine.


Author(s):  
Jacek Jemielity ◽  
Janusz Stępiński ◽  
Joanna Zuberek ◽  
Ewa Grudzien ◽  
Magdalena Lewdorowicz ◽  
...  

Gels ◽  
2021 ◽  
Vol 7 (1) ◽  
pp. 20
Author(s):  
Matan Mussel ◽  
Peter J. Basser ◽  
Ferenc Horkay

Incremental changes in ionic composition, solvent quality, and temperature can lead to reversible and abrupt structural changes in many synthetic and biopolymer systems. In the biological milieu, this nonlinear response is believed to play an important functional role in various biological systems, including DNA condensation, cell secretion, water flow in xylem of plants, cell resting potential, and formation of membraneless organelles. While these systems are markedly different from one another, a physicochemical framework that treats them as polyelectrolytes, provides a means to interpret experimental results and make in silico predictions. This article summarizes experimental results made on ion-induced volume phase transition in a polyelectrolyte model gel (sodium polyacrylate) and observations on the above-mentioned biological systems indicating the existence of a steep response.


Atmosphere ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 959
Author(s):  
Shengkai Pan ◽  
Xiaokai Feng ◽  
Daniel Pass ◽  
Rachel A. Adams ◽  
Yusong Wang ◽  
...  

Adverse health outcomes caused by ambient particulate matter (PM) pollution occur in a progressive process, with neutrophils eliciting inflammation or pathogenesis. We investigated the toxico-transcriptomic mechanisms of PM in real-life settings by comparing healthy residents living in Beijing and Chengde, the opposing ends of a well-recognised air pollution (AP) corridor in China. Beijing recruits (BRs) uniquely expressed ~12,000 alternative splicing (AS)-derived transcripts, largely elevating the proportion of transcripts significantly correlated with PM concentration. BRs expressed PM-associated isoforms (PMAIs) of PFKFB3 and LDHA, encoding enzymes responsible for stimulating and maintaining glycolysis. PMAIs of PFKFB3 featured different COOH-terminals, targeting PFKFB3 to different sub-cellular functional compartments and stimulating glycolysis. PMAIs of LDHA have longer 3′UTRs relative to those expressed in Chengde recruits (CRs), allowing glycolysis maintenance by enhancing LDHA mRNA stability and translational efficiency. PMAIs were directly regulated by different HIF-1A and HIF-1B isoforms. BRs expressed more non-functional Fas isoforms, and a resultant reduction of intact Fas proportion is expected to inhibit the transmission of apoptotic signals and prolong neutrophil lifespan. BRs expressed both membrane-bound and soluble IL-6R isoforms instead of only one in CRs. The presence of both IL-6R isoforms suggested a higher migration capacity of neutrophils in BRs. PMAIs of HIF-1A and PFKFB3 were downregulated in Chronic Obstructive Pulmonary Disease patients compared with BRs, implying HIF-1 mediated defective glycolysis may mediate neutrophil dysfunction. PMAIs could explain large variances of different phenotypes, highlighting their potential application as biomarkers and therapeutic targets in PM-induced diseases, which remain poorly elucidated.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kyle A. Cottrell ◽  
Ryan C. Chiou ◽  
Jason D. Weber

AbstractTumor cells require nominal increases in protein synthesis in order to maintain high proliferation rates. As such, tumor cells must acquire enhanced ribosome production. How the numerous mutations in tumor cells ultimately achieve this aberrant production is largely unknown. The gene encoding ARF is the most commonly deleted gene in human cancer. ARF plays a significant role in regulating ribosomal RNA synthesis and processing, ribosome export into the cytoplasm, and global protein synthesis. Utilizing ribosome profiling, we show that ARF is a major suppressor of 5′-terminal oligopyrimidine mRNA translation. Genes with increased translational efficiency following loss of ARF include many ribosomal proteins and translation factors. Knockout of p53 largely phenocopies ARF loss, with increased protein synthesis and expression of 5′-TOP encoded proteins. The 5′-TOP regulators eIF4G1 and LARP1 are upregulated in Arf- and p53-null cells.


Author(s):  
Davide Arella ◽  
Maddalena Dilucca ◽  
Andrea Giansanti

AbstractIn each genome, synonymous codons are used with different frequencies; this general phenomenon is known as codon usage bias. It has been previously recognised that codon usage bias could affect the cellular fitness and might be associated with the ecology of microbial organisms. In this exploratory study, we investigated the relationship between codon usage bias, lifestyles (thermophiles vs. mesophiles; pathogenic vs. non-pathogenic; halophilic vs. non-halophilic; aerobic vs. anaerobic and facultative) and habitats (aquatic, terrestrial, host-associated, specialised, multiple) of 615 microbial organisms (544 bacteria and 71 archaea). Principal component analysis revealed that species with given phenotypic traits and living in similar environmental conditions have similar codon preferences, as represented by the relative synonymous codon usage (RSCU) index, and similar spectra of tRNA availability, as gauged by the tRNA gene copy number (tGCN). Moreover, by measuring the average tRNA adaptation index (tAI) for each genome, an index that can be associated with translational efficiency, we observed that organisms able to live in multiple habitats, including facultative organisms, mesophiles and pathogenic bacteria, are characterised by a reduced translational efficiency, consistently with their need to adapt to different environments. Our results show that synonymous codon choices might be under strong translational selection, which modulates the choice of the codons to differently match tRNA availability, depending on the organism’s lifestyle needs. To our knowledge, this is the first large-scale study that examines the role of codon bias and translational efficiency in the adaptation of microbial organisms to the environment in which they live.


Genetics ◽  
1998 ◽  
Vol 149 (1) ◽  
pp. 37-44 ◽  
Author(s):  
Xuhua Xia

Abstract The optimization of the translational machinery in cells requires the mutual adaptation of codon usage and tRNA concentration, and the adaptation of tRNA concentration to amino acid usage. Two predictions were derived based on a simple deterministic model of translation which assumes that elongation of the peptide chain is rate-limiting. The highest translational efficiency is achieved when the codon recognized by the most abundant tRNA reaches the maximum frequency. For each codon family, the tRNA concentration is optimally adapted to codon usage when the concentration of different tRNA species matches the square-root of the frequency of their corresponding synonymous codons. When tRNA concentration and codon usage are well adapted to each other, the optimal content of all tRNA species carrying the same amino acid should match the square-root of the frequency of the amino acid. These predictions are examined against empirical data from Escherichia coli, Salmonella typhimurium, and Saccharomyces cerevisiae.


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