TY  - JOUR
A1  - Patterson, Jenelle A.
A1  - He, Hai
A1  - Folz, Jacob S.
A1  - Li, Qiang
A1  - Wilson, Mark A.
A1  - Fiehn, Oliver
A1  - Bruner, Steven D.
A1  - Bar-Even, Arren
A1  - Hanson, Andrew D.
T1  - Thioproline formation as a driver of formaldehyde toxicity in Escherichia coli
JF  - Biochemical Journal
N2  - Formaldehyde (HCHO) is a reactive carbonyl compound that formylates and cross-links proteins, DNA, and small molecules. It is of specific concern as a toxic intermediate in the design of engineered pathways involving methanol oxidation or formate reduction. The interest in engineering these pathways is not, however, matched by engineering-relevant information on precisely why HCHO is toxic or on what damage-control mechanisms cells deploy to manage HCHO toxicity. The only well-defined mechanism for managing HCHO toxicity is formaldehyde dehydrogenase-mediated oxidation to formate, which is counterproductive if HCHO is a desired pathway intermediate. We therefore sought alternative HCHO damage-control mechanisms via comparative genomic analysis. This analysis associated homologs of the Escherichia coli pepP gene with HCHO-related one-carbon metabolism. Furthermore, deleting pepP increased the sensitivity of E. coli to supplied HCHO but not other carbonyl compounds. PepP is a proline aminopeptidase that cleaves peptides of the general formula X-Pro-Y, yielding X + Pro-Y. HCHO is known to react spontaneously with cysteine to form the close proline analog thioproline (thiazolidine-4-carboxylate), which is incorporated into proteins and hence into proteolytic peptides. We therefore hypothesized that certain thioproline-containing peptides are toxic and that PepP cleaves these aberrant peptides. Supporting this hypothesis, PepP cleaved the model peptide Ala-thioproline-Ala as efficiently as Ala-Pro-Ala in vitro and in vivo, and deleting pepP increased sensitivity to supplied thioproline. Our data thus (i) provide biochemical genetic evidence that thioproline formation contributes substantially to HCHO toxicity and (ii) make PepP a candidate damage-control enzyme for engineered pathways having HCHO as an intermediate.
KW  - formaldehyde
KW  - thiazolidine-4-carboxylic acid
KW  - thioproline
KW  - Xaa-Pro aminopeptidase
Y1  - 2020
U6  - https://doi.org/10.1042/BCJ20200198
SN  - 1470-8728
SN  - 0006-2936
VL  - 477
IS  - 9
SP  - 1745
EP  - 1757
PB  - Portland Press
CY  - London
ER  - 
TY  - JOUR
A1  - Jäger, Lena Ann
A1  - Chen, Zhong
A1  - Li, Qiang
A1  - Lin, Chien-Jer Charles
A1  - Vasishth, Shravan
T1  - The subject-relative advantage in Chinese: Evidence for expectation-based processing
JF  - Journal of memory and language
N2  - Chinese relative clauses are an important test case for pitting the predictions of expectation-based accounts against those of memory-based theories. The memory-based accounts predict that object relatives are easier to process than subject relatives because, in object relatives, the distance between the relative clause verb and the head noun is shorter. By contrast, expectation-based accounts such as surprisal predict that the less frequent object relative should be harder to process. In previous studies on Chinese relative clause comprehension, local ambiguities may have rendered a comparison between relative clause types uninterpretable. We designed experimental materials in which no local ambiguities confound the comparison. We ran two experiments (self-paced reading and eye-tracking) to compare reading difficulty in subject and object relatives which were placed either in subject or object modifying position. The evidence from our studies is consistent with the predictions of expectation-based accounts but not with those of memory-based theories. (C) 2014 Elsevier Inc. All rights reserved.
KW  - Sentence processing
KW  - Relative clause
KW  - Structural expectation
KW  - Working-memory
KW  - Surprisal
KW  - Chinese
Y1  - 2015
U6  - https://doi.org/10.1016/j.jml.2014.10.005
SN  - 0749-596X
SN  - 1096-0821
VL  - 79
SP  - 97
EP  - 120
PB  - Elsevier
CY  - San Diego
ER  - 
TY  - JOUR
A1  - Vasishth, Shravan
A1  - Chen, Zhong
A1  - Li, Qiang
A1  - Guo, Gueilan
T1  - Processing chinese relative clauses - evidence for the subject-relative advantage
JF  - PLoS one
N2  - A general fact about language is that subject relative clauses are easier to process than object relative clauses. Recently, several self-paced reading studies have presented surprising evidence that object relatives in Chinese are easier to process than subject relatives. We carried out three self-paced reading experiments that attempted to replicate these results. Two of our three studies found a subject-relative preference, and the third study found an object-relative advantage. Using a random effects bayesian meta-analysis of fifteen studies (including our own), we show that the overall current evidence for the subject-relative advantage is quite strong (approximate posterior probability of a subject-relative advantage given the data: 78-80%). We argue that retrieval/integration based accounts would have difficulty explaining all three experimental results. These findings are important because they narrow the theoretical space by limiting the role of an important class of explanation-retrieval/integration cost-at least for relative clause processing in Chinese.
Y1  - 2013
U6  - https://doi.org/10.1371/journal.pone.0077006
SN  - 1932-6203
VL  - 8
IS  - 10
PB  - PLoS
CY  - San Fransisco
ER  -