A Novel Signaling Pathway Mediated by the Nuclear Targeting of C-Terminal Fragments of Mammalian Patched 1

Background: Patched 1 (Ptc1) is a polytopic receptor protein that is essential for growth and differentiation. Its extracellular domains accept its ligand, Sonic Hedgehog, while the function of its C-terminal intracellular domain is largely obscure. Principal Findings: In this study, we stably expressed human Ptc1 protein in HeLa cells and found that it is subjected to proteolytic cleavage at the C-terminus, resulting in the generation of soluble C-terminal fragments. These fragments accumulated in the nucleus, while the N-terminal region of Ptc1 remained in the cytoplasmic membrane fractions. Using an anti-Ptc1 C-terminal domain antibody, we provide conclusive evidence that C-terminal fragments of endogenous Ptc1 accumulate in the nucleus of C3H10T1/2 cells. Similar nuclear accumulation of endogenous C-terminal fragments was observed not only in C3H10T1/2 cells but also in mouse embryonic primary cells. Importantly, the C-terminal fragments of Ptc1 modulate transcriptional activity of Gli1. Conclusions: Although Ptc1 protein was originally thought to be restricted to cell membrane fractions, our findings sugges

The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Microbial diversity in waters, sediments and microbial mats evaluated using fatty acid-based methods

The review summarises recent advances towards a greater comprehensive assessment of microbial diversity in aquatic environments using the fatty acid methyl esters and phospholipid fatty acids approaches. These methods are commonly used in microbial ecology because they do not require the culturing of micro-organisms, are quantitative and reproducible and provide valuable information regarding the structure of entire microbial communities. Because some fatty acids are associated with taxonomic and functional groups of micro-organisms, they allow particular groups of micro-organisms to be distinguished. The integration of fatty acid-based methods with stable isotopes, RNA and DNA analyses enhances our knowledge of the role of micro-organisms in global nutrient cycles, functional activity and phylogenetic lineages within microbial communities. Additionally, the analysis of fatty acid profiles enables the shifts in the microbial diversity in pristine and contaminated environments to be monitored. The main objective of this review is to present the use of lipid-based approaches for the characterisation of microbial communities in water columns, sediments and biomats

The quest for a globally comprehensible Russula language

Since 2007, the quality of Russula descriptions has improved and the use of molecular support for species delimitation and the number of published new species has increased. However, the description style is not consistent and has regional or author-specific patterns. Most recent publications still favour descriptions of spores compared to hymenium and pileipellis elements, and usually only the spore size is provided with statistical support. This study proposes standards for descriptions of the microscopic structure of Russula species (Russulaceae, Agaricomycetes). We present the description template, the template measurements table, the specific terminology and the essential chemical reagents. The proposed standards were tested by mycologists from 11 countries who met at the Russula Microscopy Workshop in Slovakia. Descriptions of 26 species from 9 countries and four continents were prepared, among them R. amarissima, R. castanopsidis, R. seperina and R. subtilis are re-described and 15 species are introduced as new: R. abietiphila, R. amerorecondita, R. aurantioflava, R. echidna, R. flavobrunnescens, R. fluvialis, R. fortunae, R. garyensis, R. gemmata, R. laevis, R. madrensis, R. olivaceohimalayensis, R. purpureogracilis, R. sancti-pauli and R. wielangtae. Seven descriptions for candidate new species are provided without a formal name assignment. Pairwise comparison of species described in this study with available similar descriptions of related species suggests that microscopic characters from all parts of the basidiomata can be equally important for species recognition and they deserve the same treatment including number of measurements and statistics. The majority of recent studies does not recognise differences between the pileus margin and centre, but more than one-third of the species described in this study show distinct differences between the pileus areas, emphasizing the importance to specify the origin of pileipellis observations. This study proved that there is frequently insufficient difference in the ITS barcode between closely related species and that it is necessary to use more genetic markers combined with ecological and geographical data