Biliary atresia (BA) is a rapidly progressive and destructive fibrotic disorder of unknown etiology affecting the extrahepatic biliary tree of neonates. Epidemiological studies suggest that an environmental factor, such as a virus or toxin, is the cause of the disease, although none have been definitively established. Several naturally occurring outbreaks of BA in Australian livestock have been associated with the ingestion of unusual plants by pregnant animals during drought conditions. We used a biliary secretion assay in zebrafish to isolate a previously undescribed isoflavonoid, biliatresone, from Dysphania species implicated in a recent BA outbreak. This compound caused selective destruction of the extrahepatic, but not intrahepatic, biliary system of larval zebrafish. A mutation that enhanced biliatresone toxicity mapped to a region of the zebrafish genome that has conserved synteny with an established human BA susceptibility locus. The toxin also caused loss of cilia in neonatal mouse extrahepatic cholangiocytes in culture and disrupted cell polarity and monolayer integrity in cholangiocyte spheroids. Together, these findings provide direct evidence that BA could be initiated by perinatal exposure to an environmental toxin.
We present four experiments concerned with children's responses to, and judgments of, ambiguous verbal messages. We demonstrated that 5-to 7-year-olds were more likely to respond differently to ambiguous and unambiguous messages if they were prevented from pointing at the potential referents. We also found that (a) the improvement in differential responding was not accompanied by an improvement in verbal judgments of message quality; and (b) the differential responses were closely related to judgments of certainty and uncertainty about the interpretation of the message. We concluded that children who did not know that verbal messages could be ambiguous could nevertheless respond differently to ambiguous and unambiguous messages by attending to their own certainty or uncertainty about the interpretation of those messages. They were more likely to do that when they were prevented from pointing at the potential referents.
The paper is in six sections. In the first, we summarize interpretations of the results of laboratory investigations in which children give or receive information about a particular object or event in the real world. In these studies there is assumed to be a match between the speaker' intended meaning (an internal representation) and the intended referent in the outside world, and it appears that 5–6‐year‐old children are often oblivious to the importance of a one‐to‐one relationship between meaning/referent and message. In the second section we offer a description to account for this: young children may treat the meaning of a message as being the intended outcome rather than the speaker' internal representation, and treat the message within its social context as being unproblematic, rather than as a clue from which it may or may not be possible to infer the intended meaning. In the third section we argue that experience of explicitly educational settings may be responsible for their achieving a conception of messages as being clues to internal representations, clues which may be inadequate. However, in the fourth section we show that there is little direct evidence concerning children' conceptions of meaning as internal representation. In the fifth section we show that children of this age appear to be able to handle relationships between internal representations and the real world when these are a straightforward match or mismatch, but they may not be able to do so in more complex cases such as those involving a slight mismatch. They may have equivalent difficulties with relationships between verbal messages and the internal representations which these express. In the final section we raise possible research issues for the future.
We identified a reactive natural toxin, biliatresone, from Dysphania glomulifera and D. littoralis collected in Australia that produces extrahepatic biliary atresia in a zebrafish model. Three additional isoflavonoids, including the known isoflavone betavulgarin, were also isolated. Biliatresone is in the very rare 1,2-diaryl-2-propenone class of isoflavonoids. The α-methylene of the 1,2-diaryl-2-propenone of biliatresone spontaneously reacts via Michael addition in the formation of water and methanol adducts. The lethal dose of biliatresone in a zebrafish assay was 1 μg/mL, while the lethal dose of synthetic 1,2-diaryl-2-propen-1-one was 5 μg/mL, suggesting 1,2-diaryl-2-propenone as the toxic Michael acceptor.
The aims of this study were to evaluate the performance of a new medium, desferrioxamine oxacillin tellurite egg-yolk mannitol salt agar (DOTEMSA) in detecting methicillin-resistant Staphylococcus aureus (MRSA) and then to compare this medium against the Public Health Laboratory Service (PHLS) recommendation of mannitol salt agar (Oxoid) with oxacillin (OMSA) and Baird-Parker medium with cipro¯oxacin (BPC) for the isolation of MRSA. The individual selective agents contained in DOTEMSA were tested against isolates of coagulase-negative staphylococci (CNS) and the medium with all constituents was challenged with various bacteria. Routine screening specimens were plated out on OMSA, BPC and DOTEMSA and the plates were incubated and examined at 24 and 48 h. Tellurite, desferrioxamine and oxacillin each inhibited the majority of CNS isolates; only three (of 103) grew in the presence of all three agents. Sixty-two of 63 isolates of MRSA grew on DOTEMSA and 59 produced lipase. Most other bacteria were inhibited. In all, 184 MRSA isolates were isolated from 540 screening specimens. The sensitivity of OMSA, BPC and DOTEMSA was 42%, 81% and 51% at 24 h, and 60%, 89% and 89% at 48 h. At 48 h, the combination of BPC and DOTEMSA detected 99% of MRSA isolates. Seventy, 49 and one non-MRSA isolates needed investigation for each of the three media respectively. A proposed strategy for MRSA screening would use BPC and DOTEMSA, examining BPC at 24 h and both media at 48 h. Provisional reports could then be issued at 24 h on the basis of rapid agglutination tests to con®rm isolates as S. aureus from BPC and at 48 h on the basis of typical colonies from DOTEMSA.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.