Stem cell quest

Chronic Myeloid Leukaemia has been a valuable model system for experimental haematologists for many years. Virtually all patients (>95 %) have the same genetic change which has driven the development of the first targeted therapies, tyrosine kinase inhibitors (TKIs). Since the introduction of TKIs in 2000 it has become clear that this approach has significantly improved the outcome for these patients. Nevertheless drug resistance inevitably develops and it is clear that the disease is controlled rather than eradicated. The recent publication by Herrmann et al. has defined a sub-population of leukaemic stem cells which are responsible for propagating the disease. CD26 now provides a new specific target for the malignant stem cells and offers the possibility of true curative therapy.     

An ustilaginomycetous yeast,Pseudozyma graminicola sp. nov., isolated from the leaves of pasture plants

Two strains belonging to a novel anamorphic species, Pseudozyma graminicola, were isolated from the leaves of herbaceous plants in the Moscow region (Russia). This species was genetically distinct from all known Pseudozyma species, based on sequence divergence in the D1/D2 domains of the large subunit rDNA and the ITS region. It is related phylogenetically to species of the genus Sporisorium (Ustilaginaceae, Ustilaginales). Physiological characteristics distinguishing this novel species from the other species of the genus Pseudozyma are presented.     

Evidence that the Piromyces gene family encoding endo-l,4-mannanases arose through gene duplication

Abstract The sequences of two Piromyces cDNAs ( manB and manC ) encoding functional mannanases, defined as mannanase B (MANB) and mannanase C (MANC), revealed that both the cDNAs, and the encoded enzymes, exhibited extensive sequence identity with each other and with a previously described Piromyces mannanase. MANB and MANC, which belong to glycosyl hydrolase family 26, hydrolyse several forms of mannan but do not attack the other major plant structural polysaccharides. The data presented in this paper indicate that the Piromyces gene family encoding mannanases arose through gene duplication.     

Adrenomyeloneuropathy: increased accumulation of very long chain fatty acid in cultured skeletal muscle

Skeletal muscle cultures from a patient with the rare disease adrenomyeloneuropathy (AMN), challenged by the addition of an extra amount of docosanoic or hexacosanoic acid to the usual growth medium, accumulated much more of these fatty acids into several lipid classes than did control patient cultures. Triglycerides were particularly affected. These experiments are the first demonstrating an enhanced capacity of AMN cultured tissue to accumulate medium-derived fatty acids into cellular lipid. Cultured human skeletal muscle represents a new model system for evaluating the metabolic defect which results in the pathological accumulation of very-long-chain fatty-acids in AMN patients.     

Molecular dynamics study of thrombin capture by aptamers TBA26 and TBA29 coupled to a DNA origami

The fabrication of DNA origamis is one of the very few possibilities to create nanostructures with precise atomistic-tailored geometries in a variety of shapes. In addition, these origamis can be functionalized or be impregnated with specialised aptamers in order to convert them into nanosensors or to tune them with pre-specified properties simply by impregnating single-stranded DNA or RNA chains (aptamers) via the precise features of DNA pairing. We performed molecular dynamics simulations to determine the relative energetics associated with the capture of thrombin by two aptamers TBA26 and TBA29 attached to a rectangular DNA origami. The molecular simulations provided detailed structural information of aptamer–enzyme interactions which are crucial for the efficient design of aptamer-based biosensors. In addition, the simulations showed a remarkable selectivity of the biosensor assembly for thrombin. The detection, capture, and sensing of enzymes is of great significance in biomedicine. In particular, the detection of thrombin is a major task in cardiovascular diagnostics and therapeutics. On the other hand, our simulations can be extended to detect biotoxins or any other chemical or biological agent by simply choosing proper aptamers. Finally, the problems due to the large number of atoms involved as well as the quality of the approximations are also discussed.     

Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant-dependent manner

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