Wen J

References (15)

Title : Xanthophyll esterases in association with fibrillins control the stable storage of carotenoids in yellow flowers of rapeseed (Brassica juncea) - Li_2023_New.Phytol__
Author(s) : Li R , Zeng Q , Zhang X , Jing J , Ge X , Zhao L , Yi B , Tu J , Fu T , Wen J , Shen J
Ref : New Phytol , : , 2023
Abstract : Biosynthesis, stabilization, and storage of carotenoids are vital processes in plants that collectively contribute to the vibrant colors observed in flowers and fruits. Despite its importance, the carotenoid storage pathway remains poorly understood and lacks thorough characterization. We identified two homologous genes, BjA02.PC1 and BjB04.PC2, belonging to the esterase/lipase/thioesterase (ELT) family of acyltransferases. We showed that BjPCs in association with fibrillin gene BjFBN1b control the stable storage of carotenoids in yellow flowers of Brassica juncea. Through genetic, high-resolution mass spectrometry and transmission electron microscopy analyses, we demonstrated that both BjA02.PC1 and BjB04.PC2 can promote the accumulation of esterified xanthophylls, facilitating the formation of carotenoid-enriched plastoglobules (PGs) and ultimately producing yellow pigments in flowers. The elimination of BjPCs led to the redirection of metabolic flux from xanthophyll ester biosynthesis to lipid biosynthesis, resulting in white flowers for B. juncea. Moreover, we genetically verified the function of two fibrillin genes, BjA01.FBN1b and BjB05.FBN1b, in mediating PG formation and demonstrated that xanthophyll esters must be deposited in PGs for stable storage. These findings identified a previously unknown carotenoid storage pathway that is regulated by BjPCs and BjFBN1b, while offering unique opportunities for improving the stability, deposition, and bioavailability of carotenoids.
ESTHER : Li_2023_New.Phytol__
PubMedSearch : Li_2023_New.Phytol__
PubMedID: 37194444

Title : Inhibition mechanism of fisetin on acetylcholinesterase and its synergistic effect with galantamine - Shi_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_305_123452
Author(s) : Shi W , Han W , Liao Y , Wen J , Zhang G
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 305 :123452 , 2023
Abstract : The search for acetylcholinesterase (AChE) inhibitors produced by natural sources is of great significance for the prevention and therapy of Alzheimer's disease and has been widely concerned. In this study, fisetin, a flavonoid compound of plant origin, displayed a mixed inhibition mode on AChE (IC(50) = 8.88 +/- 0.14 microM). Fluorescence spectra analysis revealed that fisetin statically quenched AChE fluorescence, and the ground state complex was formed by hydrogen bonds and hydrophobic interactions. Circular dichroism assays showed that fisetin induced AChE structure loosened with a decrease in alpha-helix structure (from 20.6 % to 19.5 %). Computer simulation exhibited that fisetin bound to both the peripheral anionic site (PAS) and the catalytic active site (CAS) and increased the stability of the AChE. Interestingly, the combination of fisetin and galantamine enhanced the binding affinity between AChE and galantamine and induced AChE structure further loosened, while the inhibition mode was still the mixed type. The heatmap analysis indicated that galantamine (0.2 microM) combined with fisetin (2.25 microM) had a significant synergy on AChE inhibition, probably because fisetin binding at the PAS-AChE induced conformation changes of the gorge and CAS, which enhanced galantamine binding affinity with CAS, and a further loose structure of AChE was induced by the mixture, so finally the interaction between the substrate and AChE was strongly affected. This work may offer a theoretical reference for the functional research of fisetin as a potential AChE inhibitor and an enhanced supplement for galantamine.
ESTHER : Shi_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_305_123452
PubMedSearch : Shi_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_305_123452
PubMedID: 37769468

Title : Iron Single-Atom Catalysts Boost Photoelectrochemical Detection by Integrating Interfacial Oxygen Reduction and Enzyme-Mimicking Activity - Qin_2022_ACS.Nano__
Author(s) : Qin Y , Wen J , Wang X , Jiao L , Wei X , Wang H , Li J , Liu M , Zheng L , Hu L , Gu W , Zhu C
Ref : ACS Nano , : , 2022
Abstract : The investigations on the generation, separation, and interfacial-redox-reaction processes of the photoinduced carriers are of paramount importance for realizing efficient photoelectrochemical (PEC) detection. However, the sluggish interfacial reactions of the photogenerated carriers, combined with the need for appropriate photoactive layers for sensing, remain challenges for the construction of advanced PEC platforms. Here, as a proof of concept, well-defined Fe single-atom catalysts (Fe SACs) were integrated on the surface of semiconductors, which amplified the PEC signals via boosting oxygen reduction reaction. Besides, Fe SACs were evidenced with efficient peroxidase-like activity, which depresses the PEC signals through the Fe SACs-mediated enzymatic precipitation reaction. Harnessing the oxygen reduction property and peroxidase-like activity of Fe SACs, a robust PEC sensing platform was successfully constructed for the sensitive detection of acetylcholinesterase activity and organophosphorus pesticides, providing guidelines for the employment of SACs for sensitive PEC analysis.
ESTHER : Qin_2022_ACS.Nano__
PubMedSearch : Qin_2022_ACS.Nano__
PubMedID: 35147022

Title : The Novel Monoacylglycerol Lipase Inhibitor MJN110 Suppresses Neuroinflammation, Normalizes Synaptic Composition and Improves Behavioral Performance in the Repetitive Traumatic Brain Injury Mouse Model - Selvaraj_2021_Cells_10_3454
Author(s) : Selvaraj P , Tanaka M , Wen J , Zhang Y
Ref : Cells , 10 : , 2021
Abstract : Modulation of the endocannabinoid system has emerged as an effective approach for the treatment of many neurodegenerative and neuropsychological diseases. However, the underlying mechanisms are still uncertain. Using a repetitive mild traumatic brain injury (mTBI) mouse model, we found that there was an impairment in locomotor function and working memory within two weeks post-injury, and that treatment with MJN110, a novel inhibitor of the principal 2-arachidononyl glycerol (2-AG) hydrolytic enzyme monoacylglycerol lipase dose-dependently ameliorated those behavioral changes. Spatial learning and memory deficits examined by Morris water maze between three and four weeks post-TBI were also reversed in the drug treated animals. Administration of MJN110 selectively elevated the levels of 2-AG and reduced the production of arachidonic acid (AA) and prostaglandin E(2) (PGE(2)) in the TBI mouse brain. The increased production of proinflammatory cytokines, accumulation of astrocytes and microglia in the TBI mouse ipsilateral cerebral cortex and hippocampus were significantly reduced by MJN110 treatment. Neuronal cell death was also attenuated in the drug treated animals. MJN110 treatment normalized the expression of the NMDA receptor subunits NR2A and NR2B, the AMPA receptor subunits GluR1 and GluR2, and the GABA(A) receptor subunits alpha1, beta2,3 and gamma2, which were all reduced at 1, 2 and 4 weeks post-injury. The reduced inflammatory response and restored glutamate and GABA receptor expression likely contribute to the improved motor function, learning and memory in the MJN110 treated animals. The therapeutic effects of MJN110 were partially mediated by activation of CB1 and CB2 cannabinoid receptors and were eliminated when it was co-administered with DO34, a novel inhibitor of the 2-AG biosynthetic enzymes. Our results suggest that augmentation of the endogenous levels of 2-AG can be therapeutically useful in the treatment of TBI by suppressing neuroinflammation and maintaining the balance between excitatory and inhibitory neurotransmission.
ESTHER : Selvaraj_2021_Cells_10_3454
PubMedSearch : Selvaraj_2021_Cells_10_3454
PubMedID: 34943962

Title : Expression Profiling of Plant Cell Wall-Degrading Enzyme Genes in Eucryptorrhynchus scrobiculatus Midgut - Gao_2020_Front.Physiol_11_1111
Author(s) : Gao P , Liu Z , Wen J
Ref : Front Physiol , 11 :1111 , 2020
Abstract : In China, the wood-boring weevil Eucryptorrhynchus scrobiculatus damages and eventually kills the tree of heaven Ailanthus altissima. To feed and digest the cell wall of A. altissima, E. scrobiculatus requires plant cell wall-degrading enzymes (PCWDEs). In the present study, we used next-generation sequencing to analyze the midgut transcriptome of E. scrobiculatus. Using three midgut transcriptomes, we assembled 21,491 unigenes from 167,714,100 clean reads. We identified 25 putative PCWDEs, including 11 cellulases and 14 pectinases. We constructed phylogenetic trees with a maximum likelihood algorithm to elucidate the relationships between sequences of the PCWDE protein families and speculate the functions of the PCWDE genes in E. scrobiculatus. The expression patterns of 17 enzymes in the midgut transcriptome were analyzed in various tissues by quantitative real-time PCR (RT-qPCR). The relative expression levels of 12 genes in the midgut and two genes in the proboscis were significantly higher than those in the other tissues. The proboscis and midgut are the digestive organs of insects, and the high expression level indirectly indicates that these genes are related to digestion. The present study has enabled us to understand the types and numbers of the PCWDEs of E. scrobiculatus and will be helpful for research regarding other weevils' PCWDEs in the future.
ESTHER : Gao_2020_Front.Physiol_11_1111
PubMedSearch : Gao_2020_Front.Physiol_11_1111
PubMedID: 33013475

Title : A novel ABHD12 nonsense variant in Usher syndrome type 3 family with genotype-phenotype spectrum review - Li_2019_Gene_704_113
Author(s) : Li T , Feng Y , Liu Y , He C , Liu J , Chen H , Deng Y , Li M , Li W , Song J , Niu Z , Sang S , Wen J , Men M , Chen X , Li J , Liu X , Ling J
Ref : Gene , 704 :113 , 2019
Abstract : Usher syndrome (USH) is a clinically common autosomal recessive disorder characterized by retinitis pigmentosa (RP) and sensorineural hearing loss with or without vestibular dysfunction. In this study, we identified a Hunan family of Chinese descent with two affected members clinically diagnosed with Usher syndrome type 3 (USH3) displaying hearing, visual acuity, and olfactory decline. Whole-exome sequencing (WES) identified a nonsense variant in ABHD12 gene that was confirmed to be segregated in this family by Sanger sequencing and exhibited a recessive inheritance pattern. In this family, two patients carried homozygous variant in the ABHD12 (NM_015600: c.249C>G). Mutation of ABHD12, an enzyme that hydrolyzes an endocannabinoid lipid transmitter, caused incomplete PHARC syndrome, as demonstrated in previous reports. Therefore, we also conducted a summary based on variants in ABHD12 in PHARC patients, and in PHARC patients showing that there was no obvious correlation between the genotype and phenotype. We believe that this should be considered during the differential diagnosis of USH. Our findings predicted the potential function of this gene in the development of hearing and vision loss, particularly with regard to impaired signal transmission, and identified a novel nonsense variant to expand the variant spectrum in ABHD12.
ESTHER : Li_2019_Gene_704_113
PubMedSearch : Li_2019_Gene_704_113
PubMedID: 30974196
Gene_locus related to this paper: human-ABHD12

Title : STAT3-induced upregulation of lncRNA ABHD11-AS1 promotes tumour progression in papillary thyroid carcinoma by regulating miR-1301-3p\/STAT3 axis and PI3K\/AKT signalling pathway - Wen_2019_Cell.Prolif_52_e12569
Author(s) : Wen J , Wang H , Dong T , Gan P , Fang H , Wu S , Li J , Zhang Y , Du R , Zhu Q
Ref : Cell Prolif , 52 :e12569 , 2019
Abstract : OBJECTIVES: Emerging evidences indicated the importance of long non-coding RNAs (lncRNAs) in the tumorigenesis and deterioration of malignant tumours. To our knowledge, the study about lncRNAs in papillary thyroid carcinoma (PTC) is still inadequate. ABHD11-AS1 was highly expressed in the PTC samples of The Cancer Genome Atlas database. This study focused on the biological function and mechanism of lncRNA ABHD11-AS1 in PTC. MATERIALS AND METHODS: qRT-PCR analysis was used to examine the expression of ABHD11-AS1 in PTC tissues and cell lines. The prognostic significance of ABHD11-AS1 for the patients with PTC was analysed with Kaplan-Meier analysis. The effects of ABHD11-AS1 knockdown on the cell proliferation and metastasis were evaluated by in vitro functional assays and in vivo experiments. The molecular mechanism which contributed to the oncogenic role of ABHD11-AS1 in PTC was explored by conducting mechanism experiments. Rescue assays were carried out for final demonstration. RESULTS: High expression of ABHD11-AS1 predicted poor prognosis for patients with PTC and promoted cell proliferation and metastasis in vitro and in vivo. ABHD11-AS1 was activated by the transcription factor STAT3. ABHD11-AS1 positively regulated PI3K/AKT signalling pathway. ABHD11-AS1 acted as a competitive endogenous (ce) RNA to upregulate STAT3 by sponging miR-1301-3p. CONCLUSIONS: STAT3-induced lncRNA ABHD11-AS1 promoted PTC progression by regulating PI3K/AKT signalling pathway and miR-1301-3p/STAT3 axis.
ESTHER : Wen_2019_Cell.Prolif_52_e12569
PubMedSearch : Wen_2019_Cell.Prolif_52_e12569
PubMedID: 30657221
Gene_locus related to this paper: human-ABHD11

Title : Possible mechanism of Vitis vinifera L. flavones on neurotransmitters, synaptic transmission and related learning and memory in Alzheimer model rats - Ma_2018_Lipids.Health.Dis_17_152
Author(s) : Ma L , Xiao H , Wen J , Liu Z , He Y , Yuan F
Ref : Lipids Health Dis , 17 :152 , 2018
Abstract : BACKGROUND: This study explored the possible mechanism of flavones from Vitis vinifera L. (VTF) on neurotransmitters, synaptic transmission and related learning and memory in rats with Alzheimer disease (AD). METHODS: The researchers injected amyloid-beta(25-35) into the hippocampus to establish AD model rats. The Sprague-Dawley (SD) rats were divided into a control group, a donepezil group, an AD model group, a VTF low-dose group, a VTF medium-dose group and a VTF high-dose group. The researchers detected the activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) according to kit instructions. The protein expression of brain-derived neurotrophic factor (BDNF), synaptotagmin-1 (SYT1) and cyclic adenosine monophosphate response element binding protein (CREB) in the rats' hippocampi was detected by immunohistochemistry and Western blot, and the gene expression of cAMP-regulated enhancer (CRE) was detected by real-time quantitative polymerase chain reaction (PCR). RESULTS: VTF may enhance the protein expression of p-CREB, BDNF and SYT1 in rat hippocampi, depending on dose. The messenger RNA (mRNA) level of CREB was significantly higher in the VTF high-dose group than in the model group, which was consistent with the results of Western blotting. VTF may reduce the activity of AChE and increase that of ChAT in rat hippocampi. Finally, VTF effectively improved the learning and memory abilities of AD rats. CONCLUSIONS: VTF can promote synaptic plasticity and indirectly affect the expression of cholinergic neurotransmitters, which may be one mechanism of VTF protection in AD rats.
ESTHER : Ma_2018_Lipids.Health.Dis_17_152
PubMedSearch : Ma_2018_Lipids.Health.Dis_17_152
PubMedID: 29973282

Title : Recovery of respiratory function and autonomic diaphragm movement following unilateral recurrent laryngeal nerve to phrenic nerve anastomosis in rabbits - Wen_2018_J.Neurosurg.Spine__1
Author(s) : Wen J , Han Y , Guo S , Yang M , Li L , Sun G , Wang J , Hu F , Liang J , Wei L , Zhou Q , Zhang W , Tan J
Ref : Journal of Neurosurgery Spine , :1 , 2018
Abstract : OBJECTIVE Respiratory dysfunction is the leading cause of mortality following upper cervical spinal cord injury (SCI). The authors' previous study suggested that vagus nerve (VN) and phrenic nerve (PN) anastomosis could partially improve respiratory function in rabbits that had been subjected to PN transection. As a branch of the VN and a motor fiber-dominated nerve, the recurrent laryngeal nerve (RLN) seems a better choice to anastomose with the PN for respiratory function restoration after upper cervical SCI. This study was designed to determine whether RLN-PN anastomosis could restore the respiratory function after upper cervical SCI in rabbits. METHODS Twelve male New Zealand rabbits were randomly divided into 3 groups: 1) sham group (no injury), 2) transection group (right RLN and PN were transected), and 3) bridge group (transected right RLN and PN were immediately anastomosed). Spontaneous discharges of the RLN and PN were compared using a bio-signal collection system. RLN and PN cross sections were stained for acetylcholinesterase (AChE), and the numbers of motor fibers were compared. Three months after the initial surgical procedures, the movement of the diaphragm was assessed using a digital subtraction angiography (DSA) system, and discharges from the right diaphragm muscle were recorded. Toluidine blue staining, electron microscopy, and staining for AChE were used to assess whether motor fibers from the RLN regenerated into the PN, and sections of diaphragm were examined after AChE staining to assess the motor endplates. RESULTS Both the RLN and PN exhibited highly rhythmic discharges, synchronized with respiration, and most fibers in the RLN and PN were found to be motor fibers. Numerous myelinated fibers were observed in anastomosed PN using toluidine blue staining and electron microscopy. Staining for AChE showed that those regenerated fibers had typical characteristics of motor fibers, and motor endplates with typical morphological characteristics were observed in the diaphragm. Reestablished rhythmic contraction of the hemidiaphragm was directly observed using the DSA system, and rhythmic spontaneous discharge was recorded from the reinnervated hemidiaphragm using the bio-signal collection system. CONCLUSIONS Motor fibers from the RLN could regenerate into the PN after end-to-end anastomosis and reinnervate the denervated hemidiaphragm in rabbits. Those regenerated motor fibers restored rhythmic and autonomic movement of the paralyzed diaphragm. These results suggest that the RLN is an optimal donor nerve to anastomose with the PN in order to reestablish the autonomic movement of paralyzed diaphragms after high-level SCI.
ESTHER : Wen_2018_J.Neurosurg.Spine__1
PubMedSearch : Wen_2018_J.Neurosurg.Spine__1
PubMedID: 29979142

Title : WWL70 protects against chronic constriction injury-induced neuropathic pain in mice by cannabinoid receptor-independent mechanisms - Wen_2018_J.Neuroinflammation_15_9
Author(s) : Wen J , Jones M , Tanaka M , Selvaraj P , Symes AJ , Cox B , Zhang Y
Ref : J Neuroinflammation , 15 :9 , 2018
Abstract : BACKGROUND: Targeting the endocannabinoid system has emerged as an effective strategy for the treatment of inflammatory and neurological diseases. Unlike the inhibition of the principal 2-arachidonyl glycerol (2-AG) hydrolytic enzyme monoacylglycerol lipase (MAGL), which leads to 2-AG overload and cannabinoid receptor desensitization, selective inhibition of the minor 2-AG hydrolytic enzyme alpha, beta-hydrolase domain 6 (ABHD6) can provide therapeutic benefits without producing cannabimimetic side effects. We have shown that inhibition of ABHD6 significantly reduces neuroinflammation and exerts neuroprotection in animal models of traumatic brain injury and multiple sclerosis. However, the role of ABHD6 inhibition on neuropathic pain has not been explored. METHODS: Neuropathic pain was induced by chronic constriction injury (CCI) of the mouse sciatic nerve and examined by Hargreaves and Von Frey tests. Activation of inflammatory cells and the production of cytokines and chemokines in the spinal cord dorsal horn, dorsal root ganglion (DRG), and sciatic nerve were assessed by qRT-PCR, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry. The levels of 2-AG and arachidonic acid (AA) in sciatic nerve were quantified by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). RESULTS: Treatment with the selective ABHD6 inhibitor WWL70 significantly alleviated CCI-induced thermal hyperalgesia and mechanical allodynia. Microglia activation, macrophage infiltration, and the production of nociceptive mediators were reduced in the ipsilateral lumbar spinal cord dorsal horn, DRG, and sciatic nerve of WWL70-treated animals. The diminished cytokine and chemokine production is likely due to the inhibitory effect of WWL70 on NF-kappaB phosphorylation. Surprisingly, the anti-nociceptive and anti-inflammatory effects of WWL70 were not reversed by addition of the cannabinoid receptor antagonists. Treatment with WWL70 did not alter the levels of 2-AG, AA, and the phosphorylation of cytosolic phospholipase A2 (cPLA2), but significantly reduced the production of prostaglandin E2 (PGE2) and the expression of cyclooxygenase-2 (COX-2) and prostaglandin E synthase-2 (PGES2) in the injured sciatic nerve. CONCLUSIONS: This study reveals a novel mechanism for the antinociceptive effect of the 2-AG catabolic enzyme ABHD6 inhibitor WWL70. Understanding the interaction between endocannabinoid and eicosanoid pathways might provide a new avenue for the treatment of inflammatory and neuropathic pain.
ESTHER : Wen_2018_J.Neuroinflammation_15_9
PubMedSearch : Wen_2018_J.Neuroinflammation_15_9
PubMedID: 29310667

Title : WWL70 attenuates PGE2 production derived from 2-arachidonoylglycerol in microglia by ABHD6-independent mechanism - Tanaka_2017_J.Neuroinflammation_14_7
Author(s) : Tanaka M , Moran S , Wen J , Affram K , Chen T , Symes AJ , Zhang Y
Ref : J Neuroinflammation , 14 :7 , 2017
Abstract : BACKGROUND: alpha/beta-Hydrolase domain 6 (ABHD6) is one of the major enzymes for endocannabinoid 2-arachidonoylglycerol (2-AG) hydrolysis in microglia cells. Our recent studies have shown that a selective ABHD6 inhibitor WWL70 has anti-inflammatory and neuroprotective effects in animal models of traumatic brain injury and multiple sclerosis. However, the role of ABHD6 in the neuroinflammatory response and the mechanisms by which WWL70 suppresses inflammation has not yet been elucidated in reactive microglia.
METHODS: The hydrolytic activity and the levels of 2-AG in BV2 cells were measured by radioactivity assay and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The expression of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) synthases in microglia treated with lipopolysaccharide (LPS) with/without WWL70 was determined by western blot and quantitative RT-PCR. The conversion of 2-AG to PGE2 or PGE2-glyceryl ester (PGE2-G) was assessed by enzyme-linked immunoassay (EIA) or LC-MS/MS. The involvement of ABHD6 in PGE2 production was assessed using pharmacological inhibitors and small interfering RNA (siRNA). The effect of WWL70 on PGE2 biosynthesis activity in the microsome fraction from BV2 cells and experimental autoimmune encephalopathy (EAE) mouse brain was also examined.
RESULTS: We found that WWL70 suppressed PGE2 production in LPS-activated microglia via cannabinoid receptor-independent mechanisms, although intracellular levels of 2-AG were elevated by WWL70 treatment. This reduction was not attributable to WWL70 inhibition of ABHD6, given the fact that downregulation of ABHD6 by siRNA or use of KT182, an alternative ABHD6 inhibitor failed to suppress PGE2 production. WWL70 attenuated the expression of COX-2 and PGES-1/2 leading to the downregulation of the biosynthetic pathways of PGE2 and PGE2-G. Moreover, PGE2 production from arachidonic acid was reduced in the microsome fraction, indicating that WWL70 also targets PGE2 biosynthetic enzymes, which are likely to contribute to the therapeutic mechanisms of WWL70 in the EAE mouse model.
CONCLUSIONS: WWL70 is an anti-inflammatory therapeutic agent capable of inhibiting PGE2 and PGE2-G production, primarily due to its reduction of COX-2 and microsomal PGES-1/2 expression and their PGE2 biosynthesis activity in microglia cells, as well as in the EAE mouse brain.
ESTHER : Tanaka_2017_J.Neuroinflammation_14_7
PubMedSearch : Tanaka_2017_J.Neuroinflammation_14_7
PubMedID: 28086912

Title : Strigolactones contribute to shoot elongation and to the formation of leaf margin serrations in Medicago truncatula R108 - Lauressergues_2015_J.Exp.Bot_66_1237
Author(s) : Lauressergues D , Andre O , Peng J , Wen J , Chen R , Ratet P , Tadege M , Mysore KS , Rochange SF
Ref : J Exp Bot , 66 :1237 , 2015
Abstract : Strigolactones were recently identified as a new class of plant hormones involved in the control of shoot branching. The characterization of strigolactone mutants in several species has progressively revealed their contribution to several other aspects of development in roots and shoots. In this article, we characterize strigolactone-deficient and strigolactone-insensitive mutants of the model legume Medicago truncatula for aerial developmental traits. The most striking mutant phenotype observed was compact shoot architecture. In contrast with what was reported in other species, this could not be attributed to enhanced shoot branching, but was instead due to reduced shoot elongation. Another notable feature was the modified leaf shape in strigolactone mutants: serrations at the leaf margin were smaller in the mutants than in wild-type plants. This phenotype could be rescued in a dose-dependent manner by exogenous strigolactone treatments of strigolactone-deficient mutants, but not of strigolactone-insensitive mutants. Treatment with the auxin transport inhibitor N-1-naphthylphtalamic acid resulted in smooth leaf margins, opposite to the effect of strigolactone treatment. The contribution of strigolactones to the formation of leaf serrations in M. truncatula R108 line represents a novel function of these hormones, which has not been revealed by the analysis of strigolactone mutants in other species.
ESTHER : Lauressergues_2015_J.Exp.Bot_66_1237
PubMedSearch : Lauressergues_2015_J.Exp.Bot_66_1237
PubMedID: 25472976

Title : Activation of CB2 receptor is required for the therapeutic effect of ABHD6 inhibition in experimental autoimmune encephalomyelitis - Wen_2015_Neuropharmacol_99_196
Author(s) : Wen J , Ribeiro R , Tanaka M , Zhang Y
Ref : Neuropharmacology , 99 :196 , 2015
Abstract : Alpha/beta-hydrolase domain 6 (ABHD6) is a novel 2-arachidonoylglycerol (2-AG) hydrolytic enzyme, that can fine-tune the endocannabinoid signaling in the central nervous system. Recently we and others have demonstrated the protective effect of ABHD6 inhibition in the animal models of traumatic brain injury and epileptic seizures. In this study, we investigated the role of targeting ABHD6 in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Post-symptom treatment with an ABHD6 inhibitor WWL70 increased the brain levels of 2-AG and ameliorated the clinical signs of EAE, T cells infiltration, microglia activation and the expression of activated leukocyte cell adhesion molecules. The production of iNOS, COX-2, TNF-alpha and IL-1beta and the phosphorylation of NF-kappaB were also significantly reduced by WWL70 treatment. The neuroprotective effect of WWL70 was demonstrated by increased survival of mature oligodendrocytes, reduced demyelination and axonal loss in WWL70 treated EAE mouse spinal cord. The therapeutic effect of WWL70 on EAE was absent by co-administration of CB2 receptor antagonist, but not CB1 receptor antagonist. Consistently, WWL70 did not afford any protection in CB2 receptor knockout mice after EAE induction. Given the increased expression of ABHD6 in microglia/macrophages, but not in T cells, we speculated that inhibition of ABHD6 might enhance 2-AG signaling particularly in microglia/macrophages to exert anti-inflammatory effects via activation of CB2 receptors. These results suggest that inhibition of ABHD6 might be used as an ideal strategy for the treatment of MS and other neurodegenerative diseases.
ESTHER : Wen_2015_Neuropharmacol_99_196
PubMedSearch : Wen_2015_Neuropharmacol_99_196
PubMedID: 26189763

Title : Dried blood spot analysis of donepezil in support of a GLP 3-month dose-range finding study in rats - Meier-Davis_2012_Int.J.Toxicol_31_337
Author(s) : Meier-Davis SR , Meng M , Yuan W , Diehl L , Arjmand FM , Lucke RM , Huang B , Wen J , Shudo J , Nagata T
Ref : Int J Toxicol , 31 :337 , 2012
Abstract : Donepezil hydrochloride is a reversible acetyl cholinesterase inhibitor approved for Alzheimer disease treatment. As an alternate therapy, a donepezil hydrochloride transdermal patch is in development. Recommended nonclinical safety studies include a 3-month Good Laboratory Practice (GLP) dose-range finding (DRF) study prior to conducting the 2-year dermal carcinogenicity study in rats. Demonstration of systemic exposure is necessary to interpret the in vivo data. Previous nonclinical reports supporting oral dosing have utilized liquid chromatography tandem mass spectrometry (LC/MS/MS) to quantify donepezil concentrations in plasma. Smaller species with limited blood volumes do not allow serial sampling to derive the full pharmacokinetic profile from a single animal. Therefore, the option of another analytical method requiring decreased sample volumes is desirable as it would decrease the required number of animals while obtaining the complete profile. The dried blood spot (DBS) technique allows drug level measurement from a few microliters; however, the method is still not widely utilized in GLP studies. Because donepezil plasma levels are known by the oral route, DBS was used to bridge the previous oral data and to support a 13-week GLP DRF study for repeated topical application in rats, comparing oral administration with 4 topical formulations. The DBS method was validated and demonstrated robustness and reproducibility for application to the DRF study. The assay results were comparable to a previously reported plasma LC/MS/MS assay-derived pharmacokinetic profile and provided justification for selection of the topical formulation and dose levels for the subsequent dermal carcinogenicity study.
ESTHER : Meier-Davis_2012_Int.J.Toxicol_31_337
PubMedSearch : Meier-Davis_2012_Int.J.Toxicol_31_337
PubMedID: 22705881

Title : A high-resolution map of human evolutionary constraint using 29 mammals - Lindblad-Toh_2011_Nature_478_476
Author(s) : Lindblad-Toh K , Garber M , Zuk O , Lin MF , Parker BJ , Washietl S , Kheradpour P , Ernst J , Jordan G , Mauceli E , Ward LD , Lowe CB , Holloway AK , Clamp M , Gnerre S , Alfoldi J , Beal K , Chang J , Clawson H , Cuff J , Di Palma F , Fitzgerald S , Flicek P , Guttman M , Hubisz MJ , Jaffe DB , Jungreis I , Kent WJ , Kostka D , Lara M , Martins AL , Massingham T , Moltke I , Raney BJ , Rasmussen MD , Robinson J , Stark A , Vilella AJ , Wen J , Xie X , Zody MC , Baldwin J , Bloom T , Chin CW , Heiman D , Nicol R , Nusbaum C , Young S , Wilkinson J , Worley KC , Kovar CL , Muzny DM , Gibbs RA , Cree A , Dihn HH , Fowler G , Jhangiani S , Joshi V , Lee S , Lewis LR , Nazareth LV , Okwuonu G , Santibanez J , Warren WC , Mardis ER , Weinstock GM , Wilson RK , Delehaunty K , Dooling D , Fronik C , Fulton L , Fulton B , Graves T , Minx P , Sodergren E , Birney E , Margulies EH , Herrero J , Green ED , Haussler D , Siepel A , Goldman N , Pollard KS , Pedersen JS , Lander ES , Kellis M
Ref : Nature , 478 :476 , 2011
Abstract : The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering approximately 4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for approximately 60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.
ESTHER : Lindblad-Toh_2011_Nature_478_476
PubMedSearch : Lindblad-Toh_2011_Nature_478_476
PubMedID: 21993624
Gene_locus related to this paper: cavpo-1plip , cavpo-2plrp , cavpo-h0v1b7 , cavpo-h0v5v8 , cavpo-h0vj36 , cavpo-lipli , rabit-1hlip , rabit-1plip , rabit-g1t6x7 , rabit-LIPH , myolu-l7n1c2 , myolu-g1pqd9 , cavpo-h0uyz6 , cavpo-h0vi56 , rabit-g1tbj4 , myolu-g1p5c0 , rabit-g1sds3 , rabit-g1sye0 , cavpo-h0v0r2 , cavpo-h0v7s5 , rabit-g1sp43 , myolu-g1p4p3 , cavpo-h0vw09 , rabit-g1ssu3 , myolu-g1pds0 , rabit-g1sic4 , cavpo-h0v2c4 , myolu-g1pg61 , myolu-g1pnb1 , myolu-g1pu06 , myolu-g1qa15 , myolu-g1qfu0 , rabit-g1sn99 , rabit-g1snq9 , rabit-g1sns7 , rabit-g1tuu8 , rabit-g1tzq7 , cavpo-h0v2i2 , cavpo-h0v2j0 , cavpo-h0vsf5 , cavpo-a0a286x8d3 , cavpo-a0a286xbr3 , cavpo-a0a286y0i8 , cavpo-a0a286y4p3 , myolu-g1q2n9 , cavpo-h0v1p4 , myolu-g1pan8 , myolu-g1paq0 , myolu-g1par4 , myolu-g1prn3 , myolu-g1q3i0 , myolu-g1q463 , myolu-g1pat6 , myolu-g1q859 , rabit-g1sul9 , rabit-g1sun0 , rabit-g1sup0 , myolu-l7n125 , myolu-g1pan2 , rabit-g1sxd0 , cavpo-h0v8j4 , rabit-d5fit0 , rabit-g1tkr5 , myolu-g1nty6 , myolu-g1p1p3 , cavpo-h0vdd5 , myolu-g1pdp2 , rabit-g1tmm5 , cavpo-h0vhq3 , myolu-g1nth4 , cavpo-h0vqx6 , rabit-g1tqr7 , myolu-g1p1e9 , cavpo-h0v8y6 , rabit-g1skt3 , myolu-g1nzg3 , cavpo-h0v5z0 , rabit-g1sgz5 , myolu-g1pkg5 , rabit-g1tmw5 , rabit-g1t134 , cavpo-a0a286x9v5 , myolu-g1qc57 , myolu-g1q061 , rabit-g1tnp4 , rabit-g1tyf7 , cavpo-h0w2w1 , rabit-g1ta36 , cavpo-h0w342 , myolu-g1q4e3 , rabit-g1sqa1 , cavpo-h0uxk7 , myolu-g1p353 , cavpo-h0vpm0 , rabit-a0a5f9cru6 , cavpo-a0a286xtc0