Adult T-cell progenitors retain myeloid potential

During haematopoiesis, pluripotent haematopoietic stem cells are sequentially restricted to give rise to a variety of lineage-committed progenitors. The classical model of haematopoiesis postulates that, in the first step of differentiation, the stem cell generates common myelo-erythroid progenitors and common lymphoid progenitors (CLPs). However, our previous studies in fetal mice showed that myeloid potential persists even as the lineage branches segregate towards T and B cells. We therefore proposed the 'myeloid-based' model of haematopoiesis, in which the stem cell initially generates common myelo-erythroid progenitors and common myelo-lymphoid progenitors. T-cell and B-cell progenitors subsequently arise from common myelo-lymphoid progenitors through myeloid-T and myeloid-B stages, respectively. However, it has been unclear whether this myeloid-based model is also valid for adult haematopoiesis. Here we provide clonal evidence that the early cell populations in the adult thymus contain progenitors that have lost the potential to generate B cells but retain substantial macrophage potential as well as T-cell, natural killer (NK)-cell and dendritic-cell potential. We also show that such T-cell progenitors can give rise to macrophages in the thymic environment in vivo. Our findings argue against the classical dichotomy model in which T cells are derived from CLPs; instead, they support the validity of the myeloid-based model for both adult and fetal haematopoiesis.     

The diterpenoid alkaloid noroxoaconitine is a Mapkap kinase 5 (MK5/PRAK) inhibitor

The mitogen-activated protein kinase-activated protein kinase MK5 is ubiquitously expressed in vertebrates and is implicated in cell proliferation, cytoskeletal remodeling, and anxiety behavior. This makes MK5 an attractive drug target. We tested several diterpenoid alkaloids for their ability to suppress MK5 kinase activity. We identified noroxoaconitine as an ATP competitor that inhibited the catalytic activity of MK5 in vitro (IC₅₀ = 37.5 μM; K _i = 0.675 μM) and prevented PKA-induced nuclear export of MK5, a process that depends on kinase active MK5. MK5 is closely related to MK2 and MK3, and noroxoaconitine inhibited MK3- and MK5- but not MK2-mediated phosphorylation of the common substrate Hsp27. Molecular docking of noroxoaconitine into the ATP binding sites indicated that noroxoaconitine binds more strongly to MK5 than to MK3. Noroxoaconitine and derivatives may help in elucidating the precise biological functions of MK5 and may prove to have therapeutic values.     

Assessment of deterioration in RHA-concrete due to magnesium sulphate attack

The assessment of magnesium sulphate attack on concretes containing rice husk ash (RHA, 20wt% of the cementitious materials) with various average particle sizes was investigated. The total cementitious materials were 390 kg and the water-to-binder ratio (W/B) was 0.53 for all mixtures. Specimens were initially cured in water for 7 d and then immersed in the 3wt% magnesium sulphate solution for up to 111 d of exposure. The specimens were subjected to drying-wetting cycles to accelerate sulphate attack. In addition to the visual monitoring of the specimens, the concrete specimens were subsequently tested for compressive strength, dynamic modulus of elasticity, and length and mass changes. The results show that the specimens exposed to sulphate attack exhibit higher strength and dynamic modulus than those kept in water. The length change is negligible and can be attributed to the normal swelling of concrete. On the other hand, concretes suffers mass loss and surface spalling and softening; the fine RHA-concrete results in a better resistance. For the accelerated sulphate attack method used in this study, mass change and visual monitoring are recommended for assessing the deterioration degree and the effectiveness of supplementary cementitious materials to resist sulphate attack.