Biology subjects

Xu, P.

Publications and source records attributed to Xu, P..

262 records · Page 15Linked to original sources

bioRxiv2018

Identification and Quantification of Paclitaxel and its Metabolites in Human Meconium from Newborns with Gestational Chemotherapeutic Exposure

ObjectiveCancer diagnosis during pregnancy occurs in 1 out of 1000 pregnancies with common malignancies including breast and hematological cancers. Fetal exposure to currently utilized agents is poorly described. We directly assessed fetal exposure by screening meconium from 23 newborns whose mothers had undergone treatment for cancer during pregnancy.\n\nStudy DesignMeconium was collected from newborns whose mothers were diagnosed with cancer during pregnancy and underwent chemotherapy in the second or third trimester as part of the Cancer and Pregnancy Registry. We conducted screening of 23 meconium samples for chemotherapeutics and known metabolites of chemotherapeutics by liquid chromatography-high resolution mass spectrometry (LC-HRMS). Putative identification of paclitaxel and/or its metabolites was made in 8 screened samples. In positively screened samples, we quantified paclitaxel, 3-p-hydroxypaclitaxel, and 6-hydroxypaclitaxel by stable isotope dilution-LC-HRMS.\n\nResultsMean levels of paclitaxel were 399.9 pg/mg in meconium samples from newborn born to mothers that underwent chemotherapy during pregnancy. 3-p-hydroxypaclitaxel and 6-hydroxypaclitaxel mean levels were 105.2 and 113.4 pg/mg meconium, respectively.\n\nConclusionIntact paclitaxel, and at least two of its major metabolites were detected in meconium, providing unambiguous confirmation of human fetal exposure. Variability in meconium levels between individuals may indicate a potential for reducing fetal exposure based on timing, dosing, and individual characteristics. This preliminary study may provide an efficient approach for examining the effects of cancer diagnosis during pregnancy on other outcomes by providing a measure of direct fetal exposure.

pharmacology and toxicology↗

bioRxiv2018

Open-pFind enables precise, comprehensive and rapid peptide identification in shotgun proteomics

Shotgun proteomics has grown rapidly in recent decades, but a large fraction of tandem mass spectrometry (MS/MS) data in shotgun proteomics are not successfully identified. We have developed a novel database search algorithm, Open-pFind, to efficiently identify peptides even in an ultra-large search space which takes into account unexpected modifications, amino acid mutations, semi- or non-specific digestion and co-eluting peptides. Tested on two metabolically labeled MS/MS datasets, Open-pFind reported 50.5-117.0% more peptide-spectrum matches (PSMs) than the seven other advanced algorithms. More importantly, the Open-pFind results were more credible judged by the verification experiments using stable isotopic labeling. Tested on four additional large-scale datasets, 70-85% of the spectra were confidently identified, and high-quality spectra were nearly completely interpreted by Open-pFind. Further, Open-pFind was over 40 times faster than the other three open search algorithms and 2-3 times faster than three restricted search algorithms. Re-analysis of an entire human proteome dataset consisting of [~]25 million spectra using Open-pFind identified a total of 14,064 proteins encoded by 12,723 genes by requiring at least two uniquely identified peptides. In this search results, Open-pFind also excelled in an independent test for false positives based on the presence or absence of olfactory receptors. Thus, a practical use of the open search strategy has been realized by Open-pFind for the truly global-scale proteomics experiments of today and in the future.

bioinformatics↗

bioRxiv2018

Artefactual formation of pyruvate from in-source conversion of lactate

RationaleLactate and pyruvate are high abundance products of glucose metabolism. Analysis of both molecules as part metabolomics studies in cellular metabolism and physiology have been aided by advances in liquid chromatography-mass spectrometry (LC-MS).\n\nMethodsWe used ion pairing-chromatography and negative ion mode ESI on an QExactive HF to perform stable isotope assisted metabolomics profiling of lactate and pyruvate metabolism.\n\nResultsUsing an LC-MS method for polar metabolite analysis we discovered an artefactual formation of pyruvate from in-source fragmentation of lactate. Surprisingly, this in-source fragmentation has not been previously described, thus we report this identification to warn other investigators. This artefact was detected by baseline chromatographic resolution of lactate and pyruvate by LC with confirmation of this artefact by stable isotope labeling of lactate and pyruvate.\n\nConclusionsThese findings have immediate implications for metabolomics studies by LC-MS and direct infusion MS, especially in negative ion mode, whereby users should resolve lactate from pyruvate or robustly quantify the potential formation of pyruvate from higher abundance lactate in their assays.

biochemistry↗

bioRxiv2018

Peripheral, intrareceptor inhibition in mosquito olfaction

How chemical signals are integrated at the peripheral sensory system of insects is still an enigma. Here we show that when coexpressed with Orco in Xenopus oocytes, an odorant receptor from the southern house mosquito, CquiOR32, generated inward (regular) currents when challenged with cyclohexanone and methyl salicylate, whereas eucalyptol and fenchone elicited inhibitory (upward) currents. Responses of CquiOR32-CquiOrco-expressing oocytes to odorants were reduced in a dose-dependent fashion by coapplication of inhibitors. This intrareceptor inhibition was also manifested in vivo in fruit flies expressing the mosquito receptor CquiOR32, as well in neurons on the antennae of the southern house mosquito. Likewise, an orthologue from the yellow fever mosquito, AaegOR71, showed intrareceptor inhibition in the Xenopus oocyte recording system and corresponding inhibition in antennal neurons. Intrareceptor inhibition was also manifested in mosquito behavior. Blood-seeking females were repelled by methyl salicylate, but repellence was significantly reduced when methyl salicylate was coapplied with eucalyptol.\n\nOne Sentence SummaryIntrareceptor inhibition was observed in mosquito odorant receptors expressed in heterologous systems, in vivo, and manifested in behavioral responses.

neuroscience↗

bioRxiv2017

A Genetic Pathway Composed of EDT1/HDG11, ERECTA, and E2Fa Loci Regulates Water Use Efficiency by Modulating Stomatal Density

Improvement of crop drought resistance and water use efficiency (WUE) has been a major endeavor in agriculture. ERECTA is the first identified major effector of water use efficiency. However, the underlying molecular mechanism is not well understood. Here, we report a genetic pathway, composed of EDT1/HDG11, ERECTA, and E2Fa loci, which regulates water use efficiency by modulating stomatal density. The HD-START transcription factor EDT1/HDG11 transcriptionally activates ERECTA expression by binding to an HD cis-element in the ERECTA promoter. ERECTA in turn relies on E2Fa to control the expression of cell-cycle related genes and the transition from mitosis to endocycle, which leads to increased nuclear DNA content in leaf cells, and therefore increased cell size and decreased stomatal density. The decreased stomatal density improves plant WUE. Our study demonstrates the EDT1/HDG11-ERECTA-E2Fa genetic pathway that reduces stomatal density by increasing cell size, providing a new avenue to improve WUE of crops.

plant biology↗

bioRxiv2017

Sulforaphane modulates microRNA expression in colon cancer cells to implicate the regulation of oncogenes CDC25A, HMGA2 and MYC

Colorectal cancer is an increasingly important cause of morbidity and mortality, whose incidence is associated with dietary and lifestyle factors, particularly inversely so with the consumption of cruciferous vegetables. These vegetables contain glucosinolates, from the breakdown of which are derived isothiocyanates, such as sulforaphane. Sulforaphane is well-characterised for wide-ranging tumour-suppressive and chemoprotective activities in vitro, yet deeper elucidation of its biological interactions would aid in better realising its potential in chemoprevention and/or chemotherapy. There is evidence to suggest that sulforaphane modulates microRNA expression in the colon, thus implying the potential for microRNA modulation to play a role in the anti-cancer effects of sulforaphane. Therefore, the effects of sulforaphane on microRNA expression profiles in the colonic adenocarcinoma Caco-2 and non-cancerous colonic CCD-841 cell lines were investigated by small RNA cloning and deep sequencing, followed by Northern Blot validation experiments. Sulforaphane upregulated let-7f-5p and let-7g-5p expression at 24 h in Caco-2 cells, but not in CCD-841. Such treatment also downregulated miR-29b-3p in Caco-2. Dual luciferase assays with a let-7f-5p mimic and inhibitor confirmed the binding of the miRNA to predicted binding sites in the mRNA transcript 3-UTRs of cell division cycle 25A (CDC25A), high-mobility group AT-hook-2 (HMGA2) and MYC. Therefore, we hypothesize that let-7f-5p translationally represses CDC25A, HMGA2 and MYC, thereby playing a role in the tumour-suppressive effects of sulforaphane. The apparent selectivity of let-7f-5p induction towards tumour cells would be therapeutically desirable if applicable in vivo. MiR-29b-3p is predicted to target a number of tumour-suppressing genes, further investigation of which could be informative regarding the potential of sulforaphane to suppress tumour progression.

cancer biology↗

bioRxiv2017

Ingredients in Victoria’s Secret Bombshell and Ivanka Trump eaux de parfums that repel mosquitoes

Insect repellents are widely used to fend off nuisance mosquitoes and, more importantly, to reduce or eliminate mosquito bites in areas where viruses and other vector-borne diseases are circulating. Synthesized more than six decades ago, DEET is the most widely used insect repellent. Plant-derived compounds are used in a plethora of commercial formulations and natural recipes to repel mosquitoes. They are also used as fragrances. We analysed Bombshell(R) to identify the constituent(s) eliciting a previously reported \"off-label\" repellence activity. The two major fragrance ingredients in Bombshell, i.e., methyl dihydrojasmonate and lilial, demonstrated strong repellence against the southern house mosquito, Culex quinquefasciatus, in laboratory assays. Both compounds activated a previously identified DEET-sensitive odorant receptor, CquiOR136. These compounds were also major constituents of Ivanka Trump eau de parfum. The methyl dihydrojasmonate content was higher in the Ivanka Trump perfume than in Bombshell, the reverse being true for lilial. Both Bombshell and Ivanka Trump eaux de parfums retained activity for as long as 6 hours in laboratory assays. Although wearing these perfumes may repel nuisance mosquitoes, their use as \"off-label\" repellents against infected mosquitoes is not recommended. A panel of 104 students (18-23 years old) conducted a blind test to compare the two eaux de parfums and showed a preference for Bombshell over Ivanka Trumps brand, particularly among women.

physiology↗

bioRxiv2017

Evaluation of Topramezone on Zebrafish Retinoid Signaling

Topramezone is a highly selective herbicide developed for broadleaf and grass weeds control in corn. In this study, the effects of topramezone on zebrafish, especially in retinoid signaling were investigated. Zebrafish embryos were treated with topramezone from 4 hours post-fertilization (hpf) to 144 hpf. Exposed to topramezone significantly reduced the retinal and retinoic levels compared to controls. The transcriptional expression levels of retinol dehydrogenase (rdh1), retinoic acid receptor subunit (raraa), retinal dehydrogenase (raldh2), retinol binding protein (rbp1a), and cellular retinoic acid binding protein (crabp1a and crabp2a) were significantly decreased. Our results suggested that topramezone significantly impaired zebrafish retinoid signaling during a short time exposure. However, treatment with topramezone significantly increased the mRNA expression levels of zfblue, zfrho, zfgr1, zfuv, and zfred. Our data demonstrated that topramezone treatment could interrupt retinoid signaling and further affect zebrafish eye development.

molecular biology↗

bioRxiv2017

COPI Mediates Recycling Of An Exocytic SNARE From Endosomes By Recognition Of A Ubiquitin Sorting Signal

ABSTRACTThe COPI coat forms transport vesicles from the Golgi complex and plays a poorly defined role in endocytic trafficking. Here we show that COPI mediates delivery of a budding yeast SNARE (Snc1) from early endosomes to the Golgi complex through recognition of a polyubiquitin sorting signal. Snc1 is a v-SNARE that drives fusion of exocytic vesicles with the plasma membrane, and then recycles through early endosomes back to the Golgi for reuse. Removal of ubiquitin from Snc1, or deletion of a {beta}-COP subunit propeller domain that binds K63-linked polyubiquitin, causes aberrant accumulation of Snc1 in early endosomes. Moreover, replacement of the {beta}-COP propeller domain with unrelated ubiquitin-binding domains restores Snc1 recycling. These results indicate that ubiquitination, a modification well known to target membrane proteins to the lysosome or vacuole for degradation, can also function as recycling signal to sort a SNARE into COPI vesicles at early endosomes for Golgi delivery.

cell biology↗

bioRxiv2017

Genome-Wide Analysis of Facial Regionalization in Zebrafish

Patterning of the facial skeleton involves the precise deployment of thousands of genes in distinct regions of the pharyngeal arches. Despite the significance for craniofacial development, how genetic programs drive this regionalization remains incompletely understood. Here we use combinatorial labeling of zebrafish cranial neural crest-derived cells (CNCCs) to define global gene expression along the dorsoventral axis of the developing arches. Intersection of region-specific transcriptomes with expression changes in response to signaling perturbations demonstrates complex roles for Endothelin1 (Edn1) signaling in the intermediate joint-forming region yet a surprisingly minor role in ventral-most regions. Analysis of co-variance across multiple sequencing experiments further reveals clusters of coregulated genes, with in situ hybridization confirming the domain-specific expression of novel genes. We then performed mutational analysis of a number of these genes, which uncovered antagonistic functions of two new Edn1 targets, follistatin a (fsta) and emx2, in regulating cartilaginous joints in the hyoid arch. Our unbiased discovery and functional analysis of genes with regional expression in zebrafish arch CNCCs reveals complex regulation by Ednl and points to novel candidates for craniofacial disorders.\n\nSummary StatementUsing zebrafish to purify distinct groups of embryonic cells, Askary et al. have created a detailed map of how thousands of genes are deployed to shape the developing face.

developmental biology↗