Mutations in the RNA exosome component gene EXOSC3 cause pontocerebellar hypoplasia and spinal motor neuron degeneration

RNA exosomes are multi-subunit complexes conserved throughout evolution and are emerging as the major cellular machinery for processing, surveillance and turnover of a diverse spectrum of coding and noncoding RNA substrates essential for viability. By exome sequencing, we discovered recessive mutations in EXOSC3 (encoding exosome component 3) in four siblings with infantile spinal motor neuron disease, cerebellar atrophy, progressive microcephaly and profound global developmental delay, consistent with pontocerebellar hypoplasia type 1 (PCH1; MIM 607596). We identified mutations in EXOSC3 in an additional 8 of 12 families with PCH1. Morpholino knockdown of exosc3 in zebrafish embryos caused embryonic maldevelopment, resulting in small brain size and poor motility, reminiscent of human clinical features, and these defects were largely rescued by co-injection with wild-type but not mutant exosc3 mRNA. These findings represent the first example of an RNA exosome core component gene that is responsible for a human disease and further implicate dysregulation of RNA processing in cerebellar and spinal motor neuron maldevelopment and degeneration.     

The cytotoxicity of eosinophil cationic protein/ribonuclease 3 on eukaryotic cell lines takes place through its aggregation on the cell membrane

Human eosinophil cationic protein (ECP)/ ribonuclease 3 (RNase 3) is a protein secreted from the secondary granules of activated eosinophils. Specific properties of ECP contribute to its cytotoxic activities associated with defense mechanisms. In this work the ECP cytotoxic activity on eukaryotic cell lines is analyzed. The ECP effects begin with its binding and aggregation to the cell surface, altering the cell membrane permeability and modifying the cell ionic equilibrium. No internalization of the protein is observed. These signals induce cell-specific morphological and biochemical changes such as chromatin condensation, reversion of membrane asymmetry, reactive oxygen species production and activation of caspase-3-like activity and, eventually, cell death. However, the ribonuclease activity component of ECP is not involved in this process as no RNA degradation is observed. In summary, the cytotoxic effect of ECP is attained through a mechanism different from that of other cytotoxic RNases and may be related with the ECP accumulation associated with the inflammatory processes, in which eosinophils are present. Received 26 October 2007; accepted 23 November 2007     

Dealing with Distances and Transformations for Fuzzy C-Means Clustering of Compositional Data

Clustering techniques are based upon a dissimilarity or distance measure between objects and clusters. This paper focuses on the simplex space, whose elements??compositions??are subject to non-negativity and constant-sum constraints. Any data analysis involving compositions should fulfill two main principles: scale invariance and subcompositional coherence. Among fuzzy clustering methods, the FCM algorithm is broadly applied in a variety of fields, but it is not well-behaved when dealing with compositions. Here, the adequacy of different dissimilarities in the simplex, together with the behavior of the common log-ratio transformations, is discussed in the basis of compositional principles. As a result, a well-founded strategy for FCM clustering of compositions is suggested. Theoretical findings are accompanied by numerical evidence, and a detailed account of our proposal is provided. Finally, a case study is illustrated using a nutritional data set known in the clustering literature.     

Cycloheximide-induced ultrastructural changes in the adrenal cortex of the rat

Zusammenfassung Cycloheximid als allgemeiner Inhibitor der Proteinsynthese verursacht submikroskopische Veränderungen in der Nebennierenrinde der Ratte. Kompaktes Material und konzentrische Membranstrukturen im Zytoplasma von Zellen der Zona fasciculata finden sich um Mitochondrien und Lipidtropfen.     

Influence des stimulations auditives sur le comportement sexuel du taureau

Summary In a preliminary series of experiments, it was noted that dairy bulls who refused to mount the cow for a long time, could be induced to mount it again when acoustically stimulated by specific calls of cows emitted by a magnetophone. In these conditions, the reaction time of the bulls was also shorter, while ejaculated quantities did not differ from those obtained before the experiments. It is suggested that this rather simple procedure could be helpful when the use of bulls as teasers raises difficulties.     

What's new in chitinase research?

This review article deals with recent developments in molecular and physiological aspects of chitinases from plants, fungi, bacteria, insects and fishes.