The involvement of tau in nucleolar transcription and the stress response

Tau is known for its pathological role in neurodegenerative diseases, including Alzheimer’s disease (AD) and other tauopathies. Tau is found in many subcellular compartments such as the cytosol and the nucleus. Although its normal role in microtubule binding is well established, its nuclear role is still unclear. Here, we reveal that tau localises to the nucleolus in undifferentiated and differentiated neuroblastoma cells (SHSY5Y), where it associates with TIP5, a key player in heterochromatin stability and ribosomal DNA (rDNA) transcriptional repression. Immunogold labelling on human brain sample confirms the physiological relevance of this finding by showing tau within the nucleolus colocalises with TIP5. Depletion of tau results in an increase in rDNA transcription with an associated decrease in heterochromatin and DNA methylation, suggesting that under normal conditions tau is involved in silencing of the rDNA. Cellular stress induced by glutamate causes nucleolar stress associated with the redistribution of nucleolar non-phosphorylated tau, in a similar manner to fibrillarin, and nuclear upsurge of phosphorylated tau (Thr231) which doesn’t colocalise with fibrillarin or nucleolar tau. This suggests that stress may impact on different nuclear tau species. In addition to involvement in rDNA transcription, nucleolar non-phosphorylated tau also undergoes stress-induced redistribution similar to many nucleolar protein

An ethnobotanical study of medicinal plants used by local people in the lowlands of Konta Special Woreda, southern nations, nationalities and peoples regional state, Ethiopia

<p>Abstract</p> <p>Background</p> <p>Research was carried out in Konta Special Woreda (District); it is a remote area with lack of infrastructure like road to make any research activities in the area. Therefore, this research was conducted to investigate medicinal plants of the Konta people and to document the local knowledge before environmental and cultural changes deplete the resources.</p> <p>Methods</p> <p>The information was collected between October 2006 and February 2007. Interview-based field study constituted the main data collection method in which the gathering, preparation, use, previous and current status and cultivation practices were systematically investigated. The abundance, taxonomic diversity and distribution of medicinal plants were studied using ecological approach.</p> <p>Results</p> <p>A total of 120 species, grouped within 100 genera and 47 families that are used in traditional medical practices were identified and studied. The Fabaceae and Lamiaceae were the most commonly reported medicinal plants with 16 (13.3%) and 14 (12%) species, respectively. 25.4% of the total medicinal plants are collected from homegardens and the rest (74.6%) are collected from wild habitats. Of the total number of medicinal plants, 108 species (90%) were used to treat human ailments, 6 (5%) for livestock diseases and the remaining 6 (5%) were used to treat both human and livestock health problems. The major threats to medicinal plants reported include harvesting medicinal plants for firewood (24.8%) followed by fire (22.3%) and construction (19%). Of the four plant communities identified in the wild, more medicinal plant species (34) were found in community type-4 (<it>Hyparrhenia cymbaria</it>-<it>Erythrina abyssinica </it>community), which accounted for 61.8%.</p> <p>Conclusion</p> <p>Konta Special Woreda is an important area for medicinal plants and associated local knowledge; the natural vegetation being the most important reservoir for the majority of the medicinal plants. Environmental and cultural changes are in the process of threatening the resources and this signals the need for serious efforts to create public awareness so that measures are taken to conserve the medicinal plants in the natural ecosystems and other suitable environments.</p

The CDR1 and other regions of immunoglobulin light chains are hot spots for amyloid aggregation

Immunoglobulin light chain-derived (AL) amyloidosis is a debilitating disease without known cure. Almost nothing is known about the structural factors driving the amyloidogenesis of the light chains. This study aimed to identify the fibrillogenic hotspots of the model protein 6aJL2 and in pursuing this goal, two complementary approaches were applied. One of them was based on several web-based computational tools optimized to predict fibrillogenic/aggregation-prone sequences based on different structural and biophysical properties of the polypeptide chain. Then, the predictions were confirmed with an ad-hoc synthetic peptide library. In the second approach, 6aJL2 protein was proteolyzed with trypsin, and the products incubated in aggregation-promoting conditions. Then, the aggregation-prone fragments were identified by combining standard proteomic methods, and the results validated with a set of synthetic peptides with the sequence of the tryptic fragments. Both strategies coincided to identify a fibrillogenic hotspot located at the CDR1 and β-strand C of the protein, which was confirmed by scanning proline mutagenesis analysis. However, only the proteolysis-based strategy revealed additional fibrillogenic hotspots in two other regions of the protein. It was shown that a fibrillogenic hotspot associated to the CDR1 is also encoded by several κ and λ germline variable domain gene segments. Some parts of this study have been included in the chapter “The Structural Determinants of the Immunoglobulin Light Chain Amyloid Aggregation”, published in Physical Biology of Proteins and Peptides, Springer 2015 (ISBN 978-3-319-21687-4)