eIF5A Promotes Translation Elongation, Polysome Disassembly and Stress Granule Assembly

Stress granules (SGs) are cytoplasmic foci at which untranslated mRNAs accumulate in cells exposed to environmental stress. We have identified ornithine decarboxylase (ODC), an enzyme required for polyamine synthesis, and eIF5A, a polyamine (hypusine)-modified translation factor, as proteins required for arsenite-induced SG assembly. Knockdown of deoxyhypusine synthase (DHS) or treatment with a deoxyhypusine synthase inhibitor (GC7) prevents hypusine modification of eIF5A as well as arsenite-induced polysome disassembly and stress granule assembly. Time-course analysis reveals that this is due to a slowing of stress-induced ribosome run-off in cells lacking hypusine-eIF5A. Whereas eIF5A only marginally affects protein synthesis under normal conditions, it is required for the rapid onset of stress-induced translational repression. Our results reveal that hypusine-eIF5A-facilitated translation elongation promotes arsenite-induced polysome disassembly and stress granule assembly in cells subjected to adverse environmental conditions

Functional magnetic resonance imaging (fMRI) of attention processes in presumed obligate carriers of schizophrenia: preliminary findings

<p>Abstract</p> <p>Background</p> <p>Presumed obligate carriers (POCs) are the first-degree relatives of people with schizophrenia who, although do not exhibit the disorder, are in direct lineage of it. Thus, this subpopulation of first-degree relatives could provide very important information with regard to the investigation of endophenotypes for schizophrenia that could clarify the often contradictory findings in schizophrenia high-risk populations. To date, despite the extant literature on schizophrenia endophenotypes, we are only aware of one other study that examined the neural mechanisms that underlie cognitive abnormalities in this group. The aim of this study was to investigate whether a more homogeneous group of relatives, such as POCs, have neural abnormalities that may be related to schizophrenia.</p> <p>Methods</p> <p>We used functional magnetic resonance imaging (fMRI) to collect blood oxygenated level dependent (BOLD) response data in six POCs and eight unrelated healthy controls while performing under conditions of sustained, selective and divided attention.</p> <p>Results</p> <p>The POCs indicated alterations in a widely distributed network of regions involved in attention processes, such as the prefrontal and temporal (including the parahippocampal gyrus) cortices, in addition to the anterior cingulate gyrus. More specifically, a general reduction in BOLD response was found in these areas compared to the healthy participants during attention processes.</p> <p>Conclusion</p> <p>These preliminary findings of decreased activity in POCs indicate that this more homogeneous population of unaffected relatives share similar neural abnormalities with people with schizophrenia, suggesting that reduced BOLD activity in the attention network may be an intermediate marker for schizophrenia.</p