In the version of this caption initially published, the cover artwork was credited to Erin Dewalt, based on imagery from the author, rather than stating that it was created by Michael B. Battles and the design was by Erin Dewalt. The error has been corrected in the HTML and PDF versions of the caption. ERRATUM In the version of this article initially published, the genus name 'Mycoplasma' was incorrectly used in place of the correct 'Mycobacterium'. The error has been corrected in the HTML and PDF versions of the article. ERRATUM npg

Juvenile oysters Crassostrea gigas cultured in the Bay of Morlaix (France) have suffered unexplained summer mortalities for over a decade. In the present study, we tested the hypothesis that a bacterial pathogen could be responsible for this phenomenon. A first attempt failed to isolate a bacterial pathogen from moribund or weak oysters. Only non-pathogenic, probably opportunistic, bacteria were isolated. As an alternative approach, we focused on oysters presenting reduced stressresponse capacities (determined by circulating noradrenaline measurements), a characteristic of juvenile oysters entering an early phase of the disease. Cultures of bacterial isolates on TCBS plates revealed that a Vibrio strain was present in diseased oysters and scarce or absent in healthy oysters. Experimental infections indicated that this Vibrio can cause mortalities of juvenile oysters when injected at concentrations ranging from 10 4 to 10 8 CFU oyster -1. Similarly to the summer mortality disease, the Vibrio isolate caused higher mortalities at higher temperatures; apparently, it could not be transmitted horizontally, it did not affect adult oysters and it induced stress-response dysfunctions in juvenile oysters. Phenotypic and genotypic characterizations identified the pathogen as Vibrio splendidus. Taken together, the present results satisfy Koch's postulate and suggest that this bacterial strain is probably responsible for the juvenile oyster summer mortalities in the Bay of Morlaix. KEY WORDS: Crassostrea gigas · Summer mortality · Juveniles · Vibrio splendidus · Stress · Noradrenaline Resale or republication not permitted without written consent of the publisherDis Aquat Org 46: [139][140][141][142][143][144][145] 2001 tality rates decreased within 24 to 48 h . A similar approach gave similar results when applied to Crassostrea virginica to elucidate the etiology of the JOD (Boettcher et al. 1999, Elston 1999b). In addition, previous studies indicated that 2 to 3 wk before mortalities occur, juvenile oysters showed signs of neuroendocrine system dysfunction. Indeed, the stress-induced noradrenaline (NA) responses were reduced in these oysters . In the present study, juvenile oysters presenting this early sign were selected to test the hypothesis that a bacterial pathogen was responsible for the juvenile oyster summer mortalities observed in the Bay of Morlaix. MATERIALS AND METHODSOysters. Twenty batches (n ≥ 500 organisms per batch) of juvenile Crassostrea gigas oysters originating from different hatchery or oyster farm stocks were placed on an experimental field site in the Bay of Morlaix between May and September 1999. They consisted of 2 reference batches, 1 wild-caught batch (named Batch B) and 1 hatchery produced batch (named Batch V), which experienced low mortality (< 5%), and of 18 other wild-caught or hatchery produced batches which experienced 10 to 65% mortality (including Batch RRB, which suffered 63.75% mortality). Juvenile oysters belonging to batches exhibiting > 45% mortality were termed 'natura...

Unraveling the therapeutic potential of human embryonic stem cells (hESC) requires tools to modify their genome. We have engineered the PiggyBac transposable element to create an efficient system for gene delivery in hESCs. This redesigned system, named "ePiggyBac," can deliver up to 18 Kb inserts, and transgene expression is observed in almost 90% of hES cells. ePiggyBac transposons can also carry insulators, inducible expression cassettes, and short hairpin RNAs for gain- and loss-of-function approaches. In hES cells, ePiggyBac's efficiency is superior to that of viral vectors and previously described transposons, including other PiggyBac-based systems. In addition, ePiggyBac transgenes can be removed from the hESC genome without leaving any mutation. We used this system to direct hESC differentiation toward a neuronal phenotype. We then removed the transposons to obtain transgene-free neuronal precursors and neurons. The ability to create fully reversible genetic modifications represents an important step toward clinical applications of hESCs.

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Huntington's disease is caused by expanded CAG repeats in HTT, conferring toxic gain of function on mutant HTT (mHTT) protein. Reducing mHTT amounts is postulated as a strategy for therapeutic intervention. We conducted genome-wide RNA interference screens for genes modifying mHTT abundance and identified 13 hits. We tested 10 in vivo in a Drosophila melanogaster Huntington's disease model, and 6 exhibited activity consistent with the in vitro screening results. Among these, negative regulator of ubiquitin-like protein 1 (NUB1) overexpression lowered mHTT in neuronal models and rescued mHTT-induced death. NUB1 reduces mHTT amounts by enhancing polyubiquitination and proteasomal degradation of mHTT protein. The process requires CUL3 and the ubiquitin-like protein NEDD8 necessary for CUL3 activation. As a potential approach to modulating NUB1 for treatment, interferon-β lowered mHTT and rescued neuronal toxicity through induction of NUB1. Thus, we have identified genes modifying endogenous mHTT using high-throughput screening and demonstrate NUB1 as an exemplar entry point for therapeutic intervention of Huntington's disease.