A new polycythaemia vera-associated SOCS3 SH2 mutant (SOCS3(F136L)) cannot regulate erythropoietin responses

Recently several different JAK2 exon12 mutations have been identified in V617F negative polycythaemia vera (PV) or idiopathic erythrocytosis (IE) patients. The patients present with erythrocytosis, ligand-independent cell growth and low serum erythropoietin (EPO) levels. Within this group, a deletion of amino acids 542-543 (N542-E543del) of JAK2 is most prevalent. We have previously shown that in the presence of JAK2(V617F), suppressor of cytokine signalling 3 (SOCS3) is unable to negatively regulate EPO signalling and proliferation of V617F-expressing cells. Here we report a PV patient heterozygous for the somatic JAK2(N542-E543del) mutation and a previously unreported germline mutation within the SH2 domain of SOCS3 (F136L). Interestingly, the SOCS3(F136L) mutation was detected in a Japanese myeloproliferative disorder patient cohort at double the frequency of healthy controls. Cells expressing SOCS3(F136L) had markedly elevated EPO-induced proliferation and extended EPO-induced JAK2 phosphorylation. Additionally, compared to wild-type SOCS3, mutant SOCS3 had an extended half-life in the presence of JAK2 and JAK2(N542-E543del). Our findings suggest that this loss-of-function SOCS3 mutation may have contributed to disease onset by causing deregulated JAK2 signalling in the presence of a constitutively active JAK2(N542-E543del) mutant.

Effect of rudder angle on propeller wash velocities at a seabed

This paper deals with an experimental investigation into the velocity distribution downstream of a propeller, operating at bollard pull conditions and in the presence of a mobile sediment bed. Previous investigations either ignored the effect of a rudder in the wash or considered only its influence on an unconfined jet. The velocity profiles within the jet produced by a rotating propeller with a rudder present were measured at a mobile bed and compared to currently available predictive equations. The velocity distribution profiles in the jet, influenced by bed proximity, were found not to comply with current predictive methods. The velocity distributions measured within the jet were found to be complex and non-symmetrical. To provide a basic velocity predictive tool, a neural network analysis toolbox within Matlab was utilised and trained using the experimental data.

Crystal polymorphism in 1-butyl-3-methylimidazolium halides: supporting ionic liquid formation by inhibition of crystallization

Crystallization of 1-butyl-3-methylimidazolium chloride from mixed ionic liquid or ionic liquid-aromatic solution, and from the melt yields different crystalline polymorphs, the first direct evidence for inhibition of crystallization in ionic liquids by polymorphism.