Chinchinstway!

Summaries of B.C. Library Conference 2012 sessions: Business Research: Buried Treasures & Secret Strategies, Working together towards common goals: new directions and developments in information services for Indigenous peoples in BC, World Digital Library: A Free, Multilingual Collection of Cultural Treasures, and Location, Location, Co-location

The RNA-binding protein FUS/TLS undergoes calcium-mediated nuclear egress during excitotoxic stress and is required for GRIA2 mRNA processing

Excitotoxic levels of glutamate represent a physiological stress that is strongly linked to amyotrophic lateral sclerosis (ALS) and other neurological disorders. Emerging evidence indicates a role for neurodegenerative disease-linked RNA-binding proteins (RBPs) in the cellular stress response. However, the relationships between excitotoxicity, RBP function, and disease have not been explored. Here, using primary cortical and motor neurons, we found that excitotoxicity induced the translocation of select ALS-linked RBPs from the nucleus to the cytoplasm within neurons. RBPs affected by excitotoxicity included TAR DNA-binding protein 43 (TDP-43) and, most robustly, fused in sarcoma/translocated in liposarcoma (FUS/TLS). We noted that FUS is translocated through a calcium-dependent mechanism and that its translocation coincides with striking alterations in nucleocytoplasmic transport. Further, glutamate-induced up-regulation of glutamate ionotropic receptor AMPA type subunit 2 (GRIA2) in neurons depended on FUS expression, consistent with a functional role for FUS in excitotoxic stress. These findings reveal molecular links among prominent factors in neurodegenerative diseases, namely excitotoxicity, disease-associated RBPs, and nucleocytoplasmic transport

Amyotrophic lateral sclerosis-linked FUS/TLS alters stress granule assembly and dynamics

BACKGROUND: Amyotrophic lateral sclerosis (ALS)-linked fused in sarcoma/translocated in liposarcoma (FUS/TLS or FUS) is concentrated within cytoplasmic stress granules under conditions of induced stress. Since only the mutants, but not the endogenous wild-type FUS, are associated with stress granules under most of the stress conditions reported to date, the relationship between FUS and stress granules represents a mutant-specific phenotype and thus may be of significance in mutant-induced pathogenesis. While the association of mutant-FUS with stress granules is well established, the effect of the mutant protein on stress granules has not been examined. Here we investigated the effect of mutant-FUS on stress granule formation and dynamics under conditions of oxidative stress. RESULTS: We found that expression of mutant-FUS delays the assembly of stress granules. However, once stress granules containing mutant-FUS are formed, they are more dynamic, larger and more abundant compared to stress granules lacking FUS. Once stress is removed, stress granules disassemble more rapidly in cells expressing mutant-FUS. These effects directly correlate with the degree of mutant-FUS cytoplasmic localization, which is induced by mutations in the nuclear localization signal of the protein. We also determine that the RGG domains within FUS play a key role in its association to stress granules. While there has been speculation that arginine methylation within these RGG domains modulates the incorporation of FUS into stress granules, our results demonstrate that this post-translational modification is not involved. CONCLUSIONS: Our results indicate that mutant-FUS alters the dynamic properties of stress granules, which is consistent with a gain-of-toxic mechanism for mutant-FUS in stress granule assembly and cellular stress response

Analysis of the Genetic Components of the cAMP-CRP Global Regulatory System in the Bacterial Predator, Bdellovibrio bacteriovorus.

Bdellovibrio bacteriovorus is a genus of Gram-negative bacteria that preys on other bacteria. These bacteria have an unusual life cycle consisting of two stages: a motile attack phase and an intraperiplasmic growth phase. Little is known of the genetic and biochemical mechanisms responsible for this developmental switch. The intracellular regulator cAMP and its receptor protein CRP (catabolite regulatory protein) may play a role in such a genetic switch. Both the cya (adenylate cyclase) and crp (CRP) genes have previously been isolated from our Bdellovibrio genomic library by functional complementation of relevant E. coli mutants. In analyzing phenotypes of Bdellovibrio cosmids in E. coli mutants, it was found that the cosmid carrying the putative Bdellovibrio crp gene appeared to also carry another cya gene. Restriction enzyme and gel electrophoresis analysis of the cosmid containing the cya gene (pMJW100) and the crp gene (pMJW101) showed no overlapping segments, arguing for a possible second cya gene in Bdellovibrio . Yet cAMP assays (using ELISA analysis) demonstrated that pMJW101 did not in fact carry a functional cya gene. This argued that the crp gene of Bdellovibrio is able to activate carbohydrate catabolic gene promoters in the absence of cAMP, which does not occur in E.coli . As Bdellovibrio does not use exogenous carbohydrates for growth or energy in either of its developmental stages, these results are consistent. Further analysis of the cya and crp genes of Bdellovibrio may shed light on gene regulation in this unusual predatory bacterium

Comparative strategies for managing linguistic repertoires: Examining situational code choice among adolescent speakers in a micro-community in Austria.

Geographically diverse approaches to the Dialect-Standard continuum in German raise the issue of how speakers manage these repertoires. Sociolinguistic precedents indicate that factors such as age, social status, gender, network ties, and education are reflected in linguistic choices; by examining a small, relatively homogeneous group, this study focuses on the impact of just a few of these factors. The role of educational institutions in propagating Standard coupled with social and linguistic development in adolescence suggested study of a school class. Fifteen students at the Bundeshandelsakademie Lustenau , located in the German-Austrian-Swiss Dreilandereck in Vorarlberg, Austria, participated in this peer-group study of situational code-choice. Data from two interviews are set against the backdrop of ethnographic observations and recordings of these students (1990--1993). Formal individual interviews were expected to yield the greatest proportion of Standard. Subsequent peer-pair interviews were expected to yield a lower proportion of Standard use due to peer presence and greater familiarity with the interviewer. Standardness/Dialectness were determined on the basis of seven phonological features selected for their frequency, distinguishability, and salience. Aggregate results clearly showed a higher proportion of Standard features in the first interviews than in the second. Aggregate results show females using more Dialect features than males in both interview types. This finding does not follow expectations, based on the literature, of female preference for Standard, and goes against the usage pattern observed among adults in the community. Aspirations and the corresponding (lack of) need for active Standard language use in the future appear to coincide largely with (future) gender roles and may account for these unusual results. The increased use of Dialect in formal situations also conforms to an ideological shift that attributes greater value to Dialects in Europe generally and in the German-speaking area specifically; the females may be leading this trend (as is often the case) in their community. Hypotheses about early adopters and innovators raise difficulties, which are fully discussed.Ph.D.German literatureLanguage, Literature and LinguisticsLinguisticsModern languageUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/131849/2/9938399.pd

Midbody accumulation through evasion of autophagy contributes to cellular reprogramming and tumorigenicity

The midbody is a singular organelle formed between daughter cells during cytokinesis and required for their final separation. Midbodies persist in cells long after division as midbody derivatives (MB(d)s), but their fate is unclear. Here we show that MB(d)s are inherited asymmetrically by the daughter cell with the older centrosome. They selectively accumulate in stem cells, induced pluripotent stem cells and potential cancer \u27stem cells\u27 in vivo and in vitro. MB(d) loss accompanies stem-cell differentiation, and involves autophagic degradation mediated by binding of the autophagic receptor NBR1 to the midbody protein CEP55. Differentiating cells and normal dividing cells do not accumulate MB(d)s and possess high autophagic activity. Stem cells and cancer cells accumulate MB(d)s by evading autophagosome encapsulation and exhibit low autophagic activity. MB(d) enrichment enhances reprogramming to induced pluripotent stem cells and increases the in vitro tumorigenicity of cancer cells. These results indicate unexpected roles for MB(d)s in stem cells and cancer \u27stem cells\u27