Increased S-nitrosylation and proteasomal degradation of caspase-3 during infection contribute to the persistence of adherent invasive escherichia coli (AIEC) in immune cells

Adherent invasive Escherichia coli (AIEC) have been implicated as a causative agent of Crohn's disease (CD) due to their isolation from the intestines of CD sufferers and their ability to persist in macrophages inducing granulomas. The rapid intracellular multiplication of AIEC sets it apart from other enteric pathogens such as Salmonella Typhimurium which after limited replication induce programmed cell death (PCD). Understanding the response of infected cells to the increased AIEC bacterial load and associated metabolic stress may offer insights into AIEC pathogenesis and its association with CD. Here we show that AIEC persistence within macrophages and dendritic cells is facilitated by increased proteasomal degradation of caspase-3. In addition S-nitrosylation of pro- and active forms of caspase-3, which can inhibit the enzymes activity, is increased in AIEC infected macrophages. This S-nitrosylated caspase-3 was seen to accumulate upon inhibition of the proteasome indicating an additional role for S-nitrosylation in inducing caspase-3 degradation in a manner independent of ubiquitination. In addition to the autophagic genetic defects that are linked to CD, this delay in apoptosis mediated in AIEC infected cells through increased degradation of caspase-3, may be an essential factor in its prolonged persistence in CD patients

Explaining the dynamics of the ultra-relativistic third Van Allen radiation belt

Since the discovery of the Van Allen radiation belts over 50 years ago, an explanation for their complete dynamics has remained elusive. Especially challenging is understanding the recently discovered ultra-relativistic third electron radiation belt. Current theory asserts that loss in the heart of the outer belt, essential to the formation of the third belt, must be controlled by high-frequency plasma wave–particle scattering into the atmosphere, via whistler mode chorus, plasmaspheric hiss, or electromagnetic ion cyclotron waves. However, this has failed to accurately reproduce the third belt. Using a data driven, time-dependent specification of ultra-low-frequency (ULF) waves we show for the first time how the third radiation belt is established as a simple, elegant consequence of storm-time extremely fast outward ULF wave transport. High-frequency wave–particle scattering loss into the atmosphere is not needed in this case. When rapid ULF wave transport coupled to a dynamic boundary is accurately specified, the sensitive dynamics controlling the enigmatic ultra-relativistic third radiation belt are naturally explaine

The Synthesis, Self-Assembly and Self-Organisation of Polysilane Block Copolymers

Block copolymers containing polysilane blocks are unique in that the polysilane components possess electro-active properties and are readily photodegradable. This review will discuss and assess the two major approaches to the synthesis of polysilane block copolymers via pre-formed polymer chain coupling and living polymerisation techniques. The self-organisation of polysilane block copolymers and the morphologies adopted in thin films are reviewed. Amphiphilic polysilane-containing block copolymers self-assemble in solvents selective for one block and a number of examples are highlighted. The versatility of these materials is highlighted by recent significant applications including the preparation of hollow crosslinked micellar aggregates in aqueous solutions and in patterned thin film generation subsequently employed as templates for the growth of cell cultures and CaCO (3.