Mutations in mRNA export mediator GLE1 result in a fetal motoneuron disease

The most severe forms of motoneuron disease manifest in utero are characterized by marked atrophy of spinal cord motoneurons and fetal immobility. Here, we report that the defective gene underlying lethal motoneuron syndrome LCCS1 is the mRNA export mediator GLE1. Our finding of mutated GLE1 exposes a common pathway connecting the genes implicated in LCCS1, LCCS2 and LCCS3 and elucidates mRNA processing as a critical molecular mechanism in motoneuron development and maturation.     

Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6 cause limb-girdle muscular dystrophy

Limb-girdle muscular dystrophy type 1D (LGMD1D) was linked to chromosome 7q36 over a decade ago, but its genetic cause has remained elusive. Here we studied nine LGMD-affected families from Finland, the United States and Italy and identified four dominant missense mutations leading to p.Phe93Leu or p.Phe89Ile changes in the ubiquitously expressed co-chaperone DNAJB6. Functional testing in vivo showed that the mutations have a dominant toxic effect mediated specifically by the cytoplasmic isoform of DNAJB6. In vitro studies demonstrated that the mutations increase the half-life of DNAJB6, extending this effect to the wild-type protein, and reduce its protective anti-aggregation effect. Further, we show that DNAJB6 interacts with members of the CASA complex, including the myofibrillar myopathy-causing protein BAG3. Our data identify the genetic cause of LGMD1D, suggest that its pathogenesis is mediated by defective chaperone function and highlight how mutations in a ubiquitously expressed gene can exert effects in a tissue-, isoform- and cellular compartment-specific manner.     

Textural changes in metallurgical coke prepared with polyethylene

The effect of high-density polyethylene (HDPE) on the textural features of experimental coke was investigated using polarized-light optical microscopy and wavelet-based image analysis. Metallurgical coke samples were prepared in a laboratory-scale furnace with 2.5%, 5.0%, 7.5%, 10.0%, and 12.5% HDPE by mass, and one sample was prepared by 100% coal. The amounts and distribution of textures (isotropic, mosaic and banded) and pores were obtained. The calculations reveal that the addition of HDPE results in a decrease of mosaic texture and an increase of isotropic texture. Ethylene formed from the decomposition of HDPE is considered as a probable reason for the texture modifications. The approach used in this study can be applied to indirect evaluation for the reactivity and strength of coke.