Synonymous codon substitutions modulate transcription and translation of a divergent upstream gene by modulating antisense RNA production.

Synonymous codons were originally viewed as interchangeable, with no phenotypic consequences. However, substantial evidence has now demonstrated that synonymous substitutions can perturb a variety of gene expression and protein homeostasis mechanisms, including translational efficiency, translational fidelity, and cotranslational folding of the encoded protein. To date, most studies of synonymous codon-derived perturbations have focused on effects within a single gene.

CHARMING: Harmonizing synonymous codon usage to replicate a desired codon usage pattern.

There is a growing appreciation that synonymous codon usage, although historically regarded as phenotypically silent, can instead alter a wide range of mechanisms related to functional protein production, a term we use here to describe the net effect of transcription (mRNA synthesis), mRNA half-life, translation (protein synthesis) and the probability of a protein folding correctly to its active, functional structure. In particular, recent discoveries have highlighted the important role that sub-optimal codons can play in modifying co-translational protein folding. These results have drawn increased attention to the patterns of synonymous codon usage within coding sequences, particularly in light of the discovery that these patterns can be conserved across evolution for homologous proteins.

Network analysis of synonymous codon usage.

Motivation: Most amino acids are encoded by multiple synonymous codons, some of which are used more rarely than others. Analyses of positions of such rare codons in protein sequences revealed that rare codons can impact co-translational protein folding and that positions of some rare codons are evolutionarily conserved. Analyses of their positions in protein 3-dimensional structures, which are richer in biochemical information than sequences alone, might further explain the role of rare codons in protein folding.

Analysis of computational codon usage models and their association with translationally slow codons.

Improved computational modeling of protein translation rates, including better prediction of where translational slowdowns along an mRNA sequence may occur, is critical for understanding co-translational folding. Because codons within a synonymous codon group are translated at different rates, many computational translation models rely on analyzing synonymous codons. Some models rely on genome-wide codon usage bias (CUB), believing that globally rare and common codons are the most informative of slow and fast translation, respectively.

A New Look at Codon Usage and Protein Expression.

%MinMax, a model of intra-gene translational elongation rate, relies on codon usage frequencies. Historically, %MinMax has used tables that measure codon usage bias for all genes in an organism, such as those found at HIVE-CUT. In this paper, we provide evidence that codon usage bias based on all genes is insufficient to accurately measure absolute translation rate.

%MinMax: A versatile tool for calculating and comparing synonymous codon usage and its impact on protein folding.

Most amino acids can be encoded by more than one synonymous codon, but these are rarely used with equal frequency. In many coding sequences the usage patterns of rare versus common synonymous codons is nonrandom and under selection. Moreover, synonymous substitutions that alter these patterns can have a substantial impact on the folding efficiency of the encoded protein.

High-frequency percussive ventilation for intercontinental aeromedical evacuation.

High-frequency percussive ventilation (HFPV) has been used for the management of patients with smoke inhalation injury for more than 20 years and is considered a standard of care at many burn centers. Because the ventilator is powered by air and oxygen rather than electricity, prehospital use has been limited by large-volume medical gas requirements. Since 2003, Operations Iraqi Freedom and Enduring Freedom have created a need for long-range aeromedical transfer of service members with severe burn and inhalation injuries.

An emergency medical bag set for long-range aeromedical transportation.

The global war on terror has created the need for urgent long-range aeromedical transport of severely wounded service members over distances of several thousand miles from Afghanistan or Iraq to the United States. This need is met by specialized medical transport teams such as US Air Force Critical Care Air Transport Teams (CCATT) or by the US Army Burn Flight Team (BFT). Both teams travel with multiple bags or cases of emergency equipment, which are comprehensive but cumbersome.

Automated 3-D echocardiography analysis compared with manual delineations and SPECT MUGA.

A major barrier for using 3-D echocardiography for quantitative analysis of heart function in routine clinical practice is the absence of accurate and robust segmentation and tracking methods necessary to make the analysis automatic. In this paper, we present an automated three-dimensional (3-D) echocardiographic acquisition and image-processing methodology for assessment of left ventricular (LV) function. We combine global image information provided by a novel multiscale fuzzy-clustering segmentation algorithm, with local boundaries obtained with phase-based acoustic feature detection.