mRNA vaccine quality analysis using RNA sequencing.

The success of mRNA vaccines has been realised, in part, by advances in manufacturing that enabled billions of doses to be produced at sufficient quality and safety. However, mRNA vaccines must be rigorously analysed to measure their integrity and detect contaminants that reduce their effectiveness and induce side-effects. Currently, mRNA vaccines and therapies are analysed using a range of time-consuming and costly methods.

Biostimulation of Bacteria in Liquid Culture for Identification of New Antimicrobial Compounds.

We hypothesized that environmental microbiomes contain a wide range of bacteria that produce yet uncharacterized antimicrobial compounds (AMCs) that can potentially be used to control pathogens. Over 600 bacterial strains were isolated from soil and food compost samples, and 68 biocontrol bacteria with antimicrobial activity were chosen for further studies based on inhibition assays against a wide range of food and plant pathogens. For further characterization of the bioactive compounds, a new method was established that used living pathogens in a liquid culture to stimulate bacteria to produce high amounts of AMCs in bacterial supernatants.

Suppression of Mediator Subunit-Encoding Confers Broad Resistance Against DNA and RNA Viruses While Is Required for Virus Defense.

Mediator subunits play key roles in numerous physiological pathways and developmental processes in plants. Mediator subunits, MED18 and MED25, have previously been shown to modulate disease resistance against fungal and bacterial pathogens through their role in jasmonic acid (JA) signaling. In this study, mutant plants of the two Mediator subunits, and , were tested against three ssRNA viruses and one dsDNA virus belonging to four different families: (TuMV), (CaMV), (AltMV), and (CMV).

Chiral cognisance: a road to safer and more effective medicinal products.

A quarter of all synthetic medicinal drugs contain a mixture of equal proportions of two molecules that have the same chemical constitution but differ in the spatial arrangement of their constituent atoms such that each is a mirror-image of the other, like the right and left hand. Biologically, receptors which are stereospecific react with only one of the two components of the mixture to produce the desired therapeutic effect, while the other is inactive or may interact with different receptors to cause undesirable, even toxic, effects. Development of syntheses that produce a preponderance of the required form, and efficient separation of mixtures, will result in safer and more effective medicinal products.

Nonchiral, homochiral and composite chiral drugs.

Chirality and the implicit stereoselectivity in pharmacodynamics and pharmacokinetics, in particular of racemic therapeutics, are interesting from both scientific and applied points of view. There is much literature on the subject, including a series of papers on chirality in TiPS in 1986 (Vol. 7, pp.

Racemic therapeutics--ethical and regulatory aspects.

Racemic therapeutics are fixed ratio mixtures of stereoisomers to be regarded biologically as different compounds. Usually only one of the isomers fully contributes to the therapeutics action, and the other is often classifiable as "isomeric ballast". Due to differences in turnover and pharmacokinetics, the proportion of enantiomers (1:1 in the racemate) continuously changes in plasma.

Receptors and dormant receptors--messengers and opportunistic ligands.

On the basis of the question what came first, the messenger or its specific receptor, the relation between the receptor concept and the messenger concept is discussed. Special attention is paid to opportunistic ligands that serve as messenger molecules and to dormant receptors, receptor-like proteins of unknown function. It is concluded that there is no receptor without a messenger and no messenger without a receptor.

Stereoselectivity in pharmacodynamics and pharmacokinetics.

Stereoisomers of bioactive products, particularly drugs and pesticides, usually differ greatly in their biological properties. Usually only one of the enantiomers, the eutomer, is largely responsible for the therapeutic action. The distomer, the "isomeric ballast", must be considered an impurity which often contributes to, or is even the main cause of, the undesired actions of the racemate.

Implications of the neglect of stereochemistry in pharmacokinetics and clinical pharmacology.

An outline is given of the implications of stereoselectivity in biological action and the use of racemic fixed-ratio combinations in pharmacology and pharmacotherapeutics. Pitfalls of the neglect of stereochemistry, such as generation of senseless pharmacokinetic data, are exemplified and emphasized.

Simultaneous assay of muscarinic and beta-adrenergic receptors using a double isotope technique.

Muscarinic receptor and beta-adrenergic receptor binding were measured simultaneously in a membrane fraction of bovine tracheal smooth muscle using [3H]-L-quinuclidinyl benzilate and [125I]-(-) iodocyanopindolol. The binding characteristics, affinity and receptor density, obtained in the double receptor assay and in the control experiments were the same within experimental error. Moreover, there appears to be neither a significant influence of an excess of d,1-propranolol on [3H]-L-quinuclidinyl benzilate binding nor a significant influence of an excess of 1-quinuclidinyl benzilate on [125I]-(-)iodocyanopindolol binding.