Codon-optimization in gene therapy: promises, prospects and challenges.

Codon optimization has evolved to enhance protein expression efficiency by exploiting the genetic code's redundancy, allowing for multiple codon options for a single amino acid. Initially observed in , optimal codon usage correlates with high gene expression, which has propelled applications expanding from basic research to biopharmaceuticals and vaccine development. The method is especially valuable for adjusting immune responses in gene therapies and has the potenial to create tissue-specific therapies.

Remembering foods and foes: emerging principles of transcriptional memory.

Transcriptional memory is characterized by a primed cellular state, induced by an external stimulus that results in an altered expression of primed genes upon re-exposure to the inducing signal. Intriguingly, the primed state is heritably maintained across somatic cell divisions even after the initial stimulus and target gene transcription cease. This phenomenon is widely observed across various organisms and appears to enable cells to retain a memory of external signals, thereby adapting to environmental changes.

Cap-Independent Circular mRNA Translation Efficiency.

Recently, the mRNA platform has become the method of choice in vaccine development to find new ways to fight infectious diseases. However, this approach has shortcomings, namely that mRNA vaccines require special storage conditions, which makes them less accessible. This instability is due to the fact that the five-prime and three-prime ends of the mRNA are a substrate for the ubiquitous exoribonucleases.

The Sperm Protein Spaca6 is Essential for Fertilization in Zebrafish.

Fertilization is a key process in all sexually reproducing species, yet the molecular mechanisms that underlie this event remain unclear. To date, only a few proteins have been shown to be essential for sperm-egg binding and fusion in mice, and only some are conserved across vertebrates. One of these conserved, testis-expressed factors is SPACA6, yet its function has not been investigated outside of mammals.

A structural view of the dissociation of Escherichia coli tryptophanase.

Tryptophanase (Trpase) is a pyridoxal 5'-phosphate (PLP)-dependent homotetrameric enzyme which catalyzes the degradation of L-tryptophan. Trpase is also known for its cold lability, which is a reversible loss of activity at low temperature (2°C) that is associated with the dissociation of the tetramer. Escherichia coli Trpase dissociates into dimers, while Proteus vulgaris Trpase dissociates into monomers.

Structures of Escherichia coli tryptophanase in holo and 'semi-holo' forms.

Two crystal forms of Escherichia coli tryptophanase (tryptophan indole-lyase, Trpase) were obtained under the same crystallization conditions. Both forms belonged to the same space group P43212 but had slightly different unit-cell parameters. The holo crystal form, with pyridoxal phosphate (PLP) bound to Lys270 of both polypeptide chains in the asymmetric unit, diffracted to 2.

Gender and birth trauma in full-term infants.

Objective: To investigate the association between gender and birth trauma in full-term infants.

Methods: A retrospective, cohort, case-control study was conducted. All singleton full-term neonates born in 1986-2009 and diagnosed with birth trauma (ICD9-CM codes 767.

Conformational changes and loose packing promote E. coli Tryptophanase cold lability.

Background: Oligomeric enzymes can undergo a reversible loss of activity at low temperatures. One such enzyme is tryptophanase (Trpase) from Escherichia coli. Trpase is a pyridoxal phosphate (PLP)-dependent tetrameric enzyme with a Mw of 210 kD.

Formation and characterization of ordered bicontinuous microemulsions.

Ordered bicontinuous microstructures formed in a fully water-dilutable, pseudoternary unique nonionic microemulsion were obtained and characterized. The concentrate contained a mixture of triacetin/d-alpha-tocopherol acetate/ethanol/Tween 60. Upon dilution, the concentrate was transformed from a reversed micellar system to oil-in-water microemulsion droplets.

Characterization of the nonionic microemulsions by EPR. I. Effect of solubilized drug on nanostructure.

The effect of the solubilized model drug, carbamazepine, on the internal structure of fully dilutable nonionic microemulsions was examined for the first time using electron paramagnetic resonance (EPR). Systems containing different surfactant to oil ratios, at two different pH values (4.6 and 8.

Characterization of nonionic microemulsions by EPR. Part II. The effect of competitive solubilization of cholesterol and phytosterols on the nanostructure.

One of the theories for the reduction of cholesterol (CH) in the blood stream by the consumption of phytosterols (PS) states that these two types of sterols compete for solubilization within the dietary mixed micelles (DMM). In this study, a fully dilutable nonionic microemulsion system was used as a model to explain a possible competitive solubilization mechanism of CH and PS molecules using an electron paramagnetic resonance (EPR) technique that reveals relevant intramicellar properties. The effect of the solubilized sterols on the structural changes occurring in the vicinity of the surfactant head groups or closer to the oil phase was examined by controlling the pH of the environment, which influences the probe locus between the surfactant molecules.

Viability and permeability across Caco-2 cells of CBZ solubilized in fully dilutable microemulsions.

The purpose of this study was to evaluate the viability and permeability of carbamazepine (CBZ) solubilized in fully dilutable non-ionic microemulsions across Caco-2 cells used as a model for intestinal epithelium. Maximum solubilization capacity (SC) of CBZ was determined within water-in-oil (W/O), bicontinuous and oil-in-water (O/W) structures formed upon dilution. The effect of the nature of the oil phase, surfactant type, and the ratio between the oil phase and surfactant on the quantity of solubilized CBZ, droplets size, the viability of the cells and drug permeability was elucidated.

Congenital heart disease: correlation with fluctuations in cosmophysical activity, 1995-2005.

Background: Environmental physical activity is known to be associated with many factors of human homeostasis, such as fetal development, birth number, and some genetic abnormalities. This study sought to investigate possible temporal links between the occurrence of congenital heart disease and solar, geomagnetic, and cosmic ray activities.

Patients And Methods: The study sample include 79,085 infants born live at a tertiary medical center in central Israel from 1995 to 2005, of whom 1739 were diagnosed with congenital heart disease, including 309 with patent ductus arteriosus (PDA).

Crystallization of carbamazepine pseudopolymorphs from nonionic microemulsions.

Crystallization of carbamazepine (CBZ), an antiepileptic drug, precipitated from confined spaces of nonionic microemulsions was investigated. The study was aimed to correlate the structure of the microemulsion [water-in-oil (W/O), bicontinuous, and oil-in-water (O/W)] with the crystalline structure and morphology of solid CBZ. The precipitated CBZ was studied by DSC, TGA, powder XRD, single-crystal XRD, SEM, and optical microscopy.

Improved solubilization of carbamazepine and structural transitions in nonionic microemulsions upon aqueous phase dilution.

Solubilization capacity and structural transformations in nonionic microemulsions characterized by a large continuous isotropic region forming dilutable self-assembled nanodroplets containing solubilized carbamazepine, were studied along dilution lines 73 and 82 (70 and 80 wt% surfactant and 30 and 20 wt% of oil phase, respectively). The preparations were based on pharma-grade ingredients, water, R-(+)-limonene, ethanol, propylene glycol, and Tween 60. Solubilization capacity (SC) of the drug was dependent on the microstructure of the microemulsion and on the surfactant-to-oil phase weight ratio.

The structure of apo tryptophanase from Escherichia coli reveals a wide-open conformation.

The crystal structure of apo tryptophanase from Escherichia coli (space group F222, unit-cell parameters a = 118.4, b = 120.1, c = 171.

Microemulsions as transdermal drug delivery vehicles.

Microemulsions are clear, stable, isotropic mixtures of oil, water, and surfactant, frequently in combination with a cosurfactant. Microemulsions have been intensively studied during the last decades by many scientists and technologists because of their great potential in many food and pharmaceutical applications. The use of microemulsions is advantageous not only due to the facile and low cost preparation, but also because of the improved bioavailability.

Crystallization and preliminary X-ray analysis of the apo form of Escherichia coli tryptophanase.

Tryptophanase from Escherichia coli is a pyridoxal phosphate-dependent homotetrametic enzyme with a subunit weight of 52 kDa. It has been crystallized in the apo form by the hanging-drop vapour-diffusion method using polyethylene glycol 400 as a precipitant and magnesium chloride as an additive. The crystals belong to the orthorhombic space group F222, with unit-cell parameters a = 118.