Pan L

References (21)

Title : Perilipin1 deficiency prompts lipolysis in lipid droplets and aggravates the pathogenesis of persistent immune activation in Drosophila - Wang_2023_J.Innate.Immun__
Author(s) : Wang L , Lin J , Yang K , Wang W , Lv Y , Zeng X , Zhao Y , Yu J , Pan L
Ref : J Innate Immun , : , 2023
Abstract : Lipid droplets (LDs) are highly dynamic intracellular organelles, which are involved in lots of biological processes. However, the dynamic morphogenesis and functions of intracellular LDs during persistent innate immune responses remain obscure. In this study, we induce long-term systemic immune activation in Drosophila through genetic manipulation. Then, the dynamic pattern of LDs is traced in the Drosophila fat body. We find that deficiency of Plin1, a key regulator of LDs' reconfiguration, blocks LDs minimization at the initial stage of immune hyperactivation but enhances LDs breakdown at the later stage of sustained immune activation via recruiting the lipase Brummer (Bmm, homologous to human ATGL). The high wasting in LDs shortens the lifespan of flies with high-energy-cost immune hyperactivation. Therefore, these results suggest a critical function of LDs during long-term immune activation and provide a potential treatment for the resolution of persistent inflammation.
ESTHER : Wang_2023_J.Innate.Immun__
PubMedSearch : Wang_2023_J.Innate.Immun__
PubMedID: 37742619

Title : Alzheimer's disease as an autoimmune disorder of innate immunity endogenously modulated by tryptophan metabolites - Meier-Stephenson_2022_Alzheimers.Dement.(N.Y)_8_e12283
Author(s) : Meier-Stephenson FS , Meier-Stephenson VC , Carter MD , Meek AR , Wang Y , Pan L , Chen Q , Jacobo S , Wu F , Lu E , Simms GA , Fisher L , McGrath AJ , Fermo V , Barden CJ , Clair HDS , Galloway TN , Yadav A , Campagna-Slater V , Hadden M , Reed M , Taylor M , Kelly B , Diez-Cecilia E , Kolaj I , Santos C , Liyanage I , Sweeting B , Stafford P , Boudreau R , Reid GA , Noyce RS , Stevens L , Staniszewski A , Zhang H , Murty M , Lemaire P , Chardonnet S , Richardson CD , Gabelica V , DePauw E , Brown R , Darvesh S , Arancio O , Weaver DF
Ref : Alzheimers Dement (N Y) , 8 :e12283 , 2022
Abstract : INTRODUCTION: Alzheimer's disease (AD) is characterized by neurotoxic immuno-inflammation concomitant with cytotoxic oligomerization of amyloid beta (Abeta) and tau, culminating in concurrent, interdependent immunopathic and proteopathic pathogeneses. METHODS: We performed a comprehensive series of in silico, in vitro, and in vivo studies explicitly evaluating the atomistic-molecular mechanisms of cytokine-mediated and Abeta-mediated neurotoxicities in AD. Next, 471 new chemical entities were designed and synthesized to probe the pathways identified by these molecular mechanism studies and to provide prototypic starting points in the development of small-molecule therapeutics for AD. RESULTS: In response to various stimuli (e.g., infection, trauma, ischemia, air pollution, depression), Abeta is released as an early responder immunopeptide triggering an innate immunity cascade in which Abeta exhibits both immunomodulatory and antimicrobial properties (whether bacteria are present, or not), resulting in a misdirected attack upon "self" neurons, arising from analogous electronegative surface topologies between neurons and bacteria, and rendering them similarly susceptible to membrane-penetrating attack by antimicrobial peptides (AMPs) such as Abeta. After this self-attack, the resulting necrotic (but not apoptotic) neuronal breakdown products diffuse to adjacent neurons eliciting further release of Abeta, leading to a chronic self-perpetuating autoimmune cycle. AD thus emerges as a brain-centric autoimmune disorder of innate immunity. Based upon the hypothesis that autoimmune processes are susceptible to endogenous regulatory processes, a subsequent comprehensive screening program of 1137 small molecules normally present in human brain identified tryptophan metabolism as a regulator of brain innate immunity and a source of potential endogenous anti-AD molecules capable of chemical modification into multi-site therapeutic modulators targeting AD's complex immunopathic-proteopathic pathogenesis. DISCUSSION: Conceptualizing AD as an autoimmune disease, identifying endogenous regulators of this autoimmunity, and designing small molecule drug-like analogues of these endogenous regulators represents a novel therapeutic approach for AD.
ESTHER : Meier-Stephenson_2022_Alzheimers.Dement.(N.Y)_8_e12283
PubMedSearch : Meier-Stephenson_2022_Alzheimers.Dement.(N.Y)_8_e12283
PubMedID: 35415204

Title : Wheat Embryo Globulin Nutrients Ameliorate D-galactose and Aluminum Chloride-Induced Cognitive Impairment in Rats - Zheng_2021_Brain.Res__147672
Author(s) : Zheng SN , Pan L , Liao AM , Hou YC , Yu GH , Li XX , Yuan YJ , Dong YQ , Zhang ZS , Tian CZ , Liu ZL , Lin WJ , Hui M , Cao J , Huang JH
Ref : Brain Research , :147672 , 2021
Abstract : Wheat embryo globulin nutrient (WEGN), with wheat embryo globulin (WEG) as the main functional component, is a nutritional combination that specifically targets memory impairment. In this study, we explored the protective role of WEGN on Alzheimer's disease (AD)-triggered cognitive impairment, neuronal injury, oxidative stress, and acetylcholine system disorder. Specifically, we established an AD model via administration of D-galactose (D-gal) and Aluminum chloride (AlCl(3)) for 70 days, then on the 36th day, administered animals in the donepezil and WEGN (300, 600, and 900 mg/kg) groups with drugs by gavage for 35 days. Learning and memory ability of the treated rats was tested using the Morris water maze (MWM) and novel object recognition (NOR) test, while pathological changes and neuronal death in their hippocampus CA1 were detected via HE staining and Nissl staining. Moreover, we determined antioxidant enzymes by measuring levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) in serum, cortex, and hippocampus, whereas changes in the acetylcholine system were determined by evaluating choline acetyltransferase (ChAT), and acetylcholinesterase (AChE) activities, as well as choline acetylcholine (Ach) content. Results revealed that rats in the WEGN group exhibited significantly lower escape latency, as well as a significantly higher number of targeted crossings and longer residence times in the target quadrant, relative to those in the model group. Notably, rats in the WEGN group spent more time exploring new objects and exhibited lower damage to their hippocampus neuron, had improved learning and memory activity, as well as reversed histological alterations, relative to those in the model group. Meanwhile, biochemical examinations revealed that rats in the WEGN group had significantly lower MDA levels and AChE activities, but significantly higher GSH, SOD, and ChAT activities, as well as Ach content, relative to those in the model group. Overall, these findings indicate that WEGN exerts protective effects on cognitive impairment, neuronal damage, oxidative stress, and choline function in AD rats treated by D-gal/AlCl(3).
ESTHER : Zheng_2021_Brain.Res__147672
PubMedSearch : Zheng_2021_Brain.Res__147672
PubMedID: 34606748

Title : Ensemble machine learning to evaluate the in vivo acute oral toxicity and in vitro human acetylcholinesterase inhibitory activity of organophosphates - Wang_2021_Arch.Toxicol__
Author(s) : Wang L , Ding J , Shi P , Fu L , Pan L , Tian J , Cao D , Jiang H , Ding X
Ref : Archives of Toxicology , : , 2021
Abstract : Organophosphates (OPs) are hazardous chemicals widely used in industry and agriculture. Distribution of their residues in nature causes serious risks to humans, animals, and plants. To reduce hazards from OPs, quantitative structure-activity relationship (QSAR) models for predicting their acute oral toxicity in rats and mice and inhibition constants concerning human acetylcholinesterase were developed according to the bioactivity data of 456 unique OPs. Based on robust, two-dimensional molecular descriptors and quantum chemical descriptors, which accurately reflect OP electronic structures and reactivities, the influences of eight machine-learning algorithms on the prediction performance of the QSAR models were explored, and consensus QSAR models were constructed. Several strict model validation indices and the results of applicability domain evaluations show that the established consensus QSAR models exhibit good robustness, practical prediction abilities, and wide application scopes. Poor correlation was observed between acute oral toxicity at the mammalian level and the inhibition constants at the molecular level, indicating that the acute toxicity of OPs cannot be evaluated only by the experimental data of enzyme inhibitory activity, their toxicokinetic characteristics must also be considered. The constructed QSAR models described herein provide rapid, theoretical assessment of the bioactivity of unstudied or unknown OPs, as well as guidance for making decisions regarding their regulation.
ESTHER : Wang_2021_Arch.Toxicol__
PubMedSearch : Wang_2021_Arch.Toxicol__
PubMedID: 33934188

Title : Recombinant expression and surface display of a zearalenone lactonohydrolase from Trichoderma aggressivum in Escherichia coli - Chen_2021_Protein.Expr.Purif_187_105933
Author(s) : Chen S , Pan L , Liu S , Li X , Wang B
Ref : Protein Expr Purif , 187 :105933 , 2021
Abstract : Zearalenone (ZEN), one of the most dangerous mycotoxins, causes enormous economic losses in the food and feed industries. To solve the problem of ZEN pollution, ZEN detoxifying enzymes are in emergent need. In this study, a zearalenone lactonohydrolase from Trichoderma aggressivum, denoted as ZHD-P, was heterologously expressed and characterized. The intracellular ZHD-P from E. coli BL21(DE3) exhibited high activity for ZEN degradation (191.94 U/mg), with the optimal temperature and pH of 45 degreesC and 7.5-9.0, respectively. With excellent temperature stability, the intracellular ZHD-P retained 100% activity when it was incubated at 25-40 degreesC for 1 h. Furthermore, we firstly constructed an E. coli cell surface display system for ZHD-P. The surface-displayed ZHD-P exhibited high activity against ZEN and showed optimal activity at 40 degreesC and pH 9.0. With superior pH stability, the surface-displayed ZHD-P retained 80% activity when it was incubated at pH 5.0-11.0 for 12 h. Interestingly, the metal ions tolerance of the surface-displayed ZHD-P was better than the intracellular form. Additionally, the surface-displayed ZHD-P could be reused four times with the residual enzyme activity of more than 50%. The biotoxicity assessment using P. phosphoreum T3 indicated that ZEN could be degraded into hypotoxic products by the intracellular or surface-displayed ZHD-P. ZHD-P could be feasible for ZEN detoxification.
ESTHER : Chen_2021_Protein.Expr.Purif_187_105933
PubMedSearch : Chen_2021_Protein.Expr.Purif_187_105933
PubMedID: 34273541

Title : Crystal structure of fungal tannase from Aspergillus niger - Dong_2021_Acta.Crystallogr.D.Struct.Biol_77_267
Author(s) : Dong L , McKinstry WJ , Pan L , Newman J , Ren B
Ref : Acta Crystallographica D Struct Biol , 77 :267 , 2021
Abstract : Tannases are serine esterases that were first discovered in fungi more than one and half centuries ago. They catalyze the hydrolysis of the gallolyl ester bonds in gallotannins to release gallic acid, which is an important intermediate in the chemical and pharmaceutical industries. Since their discovery, fungal tannases have found wide industrial applications, although there is scarce knowledge about these enzymes at the molecular level, including their catalytic and substrate-binding sites. While this lack of knowledge hinders engineering efforts to modify the enzymes, many tannases have been isolated from various fungal strains in a search for the desired enzymatic properties. Here, the first crystal structure of a fungal tannase, that from Aspergillus niger, is reported. The enzyme possesses a typical alpha/beta-hydrolase-fold domain with a large inserted cap domain, which together form a bowl-shaped hemispherical shape with a surface concavity surrounded by N-linked glycans. Gallic acid is bound at the junction of the two domains within the concavity by forming two hydrogen-bonding networks with neighbouring residues. One is formed around the carboxyl group of the gallic acid and involves residues from the hydrolase-fold domain, including those from the catalytic triad, which consists of Ser206, His485 and Asp439. The other is formed around the three hydroxyl groups of the compound, with the involvement of residues mainly from the cap domain, including Gln238, Gln239, His242 and Ser441. Gallic acid is bound in a sandwich-like mode by forming a hydrophobic contact with Ile442. All of these residues are found to be highly conserved among fungal and yeast tannases.
ESTHER : Dong_2021_Acta.Crystallogr.D.Struct.Biol_77_267
PubMedSearch : Dong_2021_Acta.Crystallogr.D.Struct.Biol_77_267
PubMedID: 33559614
Gene_locus related to this paper: aspnc-a2qir3

Title : An integrated approach using chemical ecological risk assessment and multi-integrated biomarker indexes approach to assess pollution: A case study of Ruditapes philippinarum in four bays on the Shandong Peninsula in China - Sun_2021_Environ.Res__111793
Author(s) : Sun J , Ma Y , Qin H , Li Z , Pan L
Ref : Environ Research , :111793 , 2021
Abstract : Considering the ecological risks of polycyclic aromatic hydrocarbons (PAHs) to the marine environment, it is urgent to find scientific and effective monitoring methods. In this study, an integrated approach combining chemical ecological risk assessment and multi-integrated biomarker indexes approach was used to assess the marine environment. Samples included seawater, sediments, and clam Ruditapes philippinarum were collected from four bays on the Shandong Peninsula, China in the four seasons of 2019. The concentrations, composition, potential sources, and ecological risk of PAHs were investigated in seawater and sediments. Risk quotient (RQ) and sediment quality guidelines (SQGs) were calculated to assess the ecological risks of PAHs in seawater and sediment, respectively. And then, clam Ruditapes philippinarum's multi-level biological response, including its ethoxyresorufin-O-deethylase (EROD), glutathione S-transferase (GST), superoxide dismutase (SOD), lipid peroxidation (LPO), and acetylcholinesterase (AChE) were investigated in-depth, by which multi-integrated biomarker indexes approach were calculated to evaluate marine environmental quality. Taken together, the results showed that the concentration of PAHs was in good agreement with the response of biomarkers, and the usefulness of the combined use of chemical ecological risk assessment and integrated biomarker indexes to assess PAHs pollution was verified.
ESTHER : Sun_2021_Environ.Res__111793
PubMedSearch : Sun_2021_Environ.Res__111793
PubMedID: 34339694

Title : Biomonitoring of polycyclic aromatic hydrocarbons (PAHs) from Manila clam Ruditapes philippinarum in Laizhou, Rushan and Jiaozhou, bays of China, and investigation of its relationship with human carcinogenic risk - Sun_2020_Mar.Pollut.Bull_160_111556
Author(s) : Sun J , Pan L , Cao Y , Li Z
Ref : Mar Pollut Bull , 160 :111556 , 2020
Abstract : This study examined the marine environment and seafood safety using chemical monitoring and multiple biomarkers. Samples were collected from three bays on the Shandong Peninsula in China, Laizhou, Rushan and Jiaozhou, in March, May, August, and October of 2018 and 2019. The polycyclic aromatic hydrocarbon (PAH) concentrations in sediments and tissue samples from the clam Ruditapes philippinarum and multiple biomarkers were measured. All the sampling sites were found to be medium-PAH-contaminated areas (100-1000 ng/g d.w.). According to the correlation analysis, ethoxyresorufin-o-deethylase (EROD) and superoxide dismutase (SOD) activity in the clam's digestive gland were sensitive to PAHs (p < .05), but the incremental lifetime cancer risk (ILCR) was lower than the priority risk level (10(-4)) at most sampling sites. EROD, SOD and acetylcholinesterase activity exhibited significant correlations with the ILCR values (p < .01), suggesting that they may serve as good indicators for assessing safe seafood consumption levels for human beings.
ESTHER : Sun_2020_Mar.Pollut.Bull_160_111556
PubMedSearch : Sun_2020_Mar.Pollut.Bull_160_111556
PubMedID: 32836194

Title : Small Molecule Natural Products and Alzheimer's Disease - Wu_2019_Curr.Top.Med.Chem_19_187
Author(s) : Wu X , Cai H , Pan L , Cui G , Qin F , Li Y , Cai Z
Ref : Curr Top Med Chem , 19 :187 , 2019
Abstract : Alzheimer's disease (AD) is a progressive and deadly neurodegenerative disease that is characterized by memory loss, cognitive impairment and dementia. Several hypotheses have been proposed for the pathogenesis based on the pathological changes in the brain of AD patients during the last few decades. Unfortunately, there is no effective agents/therapies to prevent or control AD at present. Currently, only a few drugs, which function as acetylcholinesterase (AChE) inhibitors or N-methyl-Daspartate (NMDA) receptor antagonists, are available to alleviate symptoms. Since many small molecule natural products have shown their functions as agonists or antagonists of receptors, as well as inhibitors of enzymes and proteins in the brain during the development of central nervous system (CNS) drugs, it is likely that natural products will play an important role in anti-AD drug development. We review recent papers on using small molecule natural products as drug candidates for the treatment of AD. These natural products possess antioxidant, anti-inflammatory, anticholinesterase, anti-amyloidogenic and neuroprotective activities. Moreover, bioactive natural products intended to be used for preventing AD, reducing the symptoms of AD and the new targets for treatment of AD are summarized.
ESTHER : Wu_2019_Curr.Top.Med.Chem_19_187
PubMedSearch : Wu_2019_Curr.Top.Med.Chem_19_187
PubMedID: 30714527

Title : High level expression and characterization of tannase tan7 using Aspergillus niger SH-2 with low-background endogenous secretory proteins as the host - Liu_2018_Protein.Expr.Purif_144_71
Author(s) : Liu F , Wang B , Ye Y , Pan L
Ref : Protein Expr Purif , 144 :71 , 2018
Abstract : Tannin acyl hydrolase (tannase, EC3.1.1.20) catalyzes the hydrolysis of hydrolyzable tannins. It is used in the manufacture of instant tea and in the production of gallic acid. In this study, we reported that the overexpression, purification and characterization of an Aspergillus niger tannase. The tannase gene was cloned from A. niger SH-2 and expressed in the A. niger strain Bdel4 which is low-background of secreted proteins. The recombinant tannase was purified by desalting, followed by gel filtration for characterization. The tannase activity achieved 111.5 U/mL at 168 h, and the purity of the enzyme in the broth supernatant was estimated to be over 70%. The optimum temperature and pH of the recombinant tannase was -40 degreesC and 7.0, respectively. The tannase activity was inhibited by Mg(2+), Ca(2+), Cu(2+), Ba(2+), Ni(2+) and EDTA, and was enhanced by Mn(2+) and Co(2+). Since A. niger is a GRAS microorganism, the recombinant tannase could be purification-free due to its high purity. The results of this study suggested that this recombinant strain could be subjected to large-scale production of A. niger tannase.
ESTHER : Liu_2018_Protein.Expr.Purif_144_71
PubMedSearch : Liu_2018_Protein.Expr.Purif_144_71
PubMedID: 29162409
Gene_locus related to this paper: aspnc-a2qir3

Title : Antifeedant Activity of Ginkgo biloba Secondary Metabolites against Hyphantria cunea Larvae: Mechanisms and Applications - Pan_2016_PLoS.One_11_e0155682
Author(s) : Pan L , Ren L , Chen F , Feng Y , Luo Y
Ref : PLoS ONE , 11 :e0155682 , 2016
Abstract : Ginkgo biloba is a typical relic plant that rarely suffers from pest hazards. This study analyzed the pattern of G. biloba pest hazards in Beijing; tested the antifeedant activity of G. biloba extracts, including ginkgo flavonoids, ginkgolide, and bilobalide, against Hyphantria cunea larvae; determined the activities of glutathione transferase (GSTs), acetylcholinesterase (AChE), carboxylesterase (CarE) and mixed-functional oxidase (MFO), in larvae after feeding on these G. biloba secondary metabolites; and screened for effective botanical antifeedants in the field. In this study, no indicators of insect infestation were found for any of the examined leaves of G. biloba; all tested secondary metabolites showed significant antifeedant activity and affected the activity of the four larval detoxifying enzymes. Ginkgolide had the highest antifeedant activity and the most significant effect on the detoxifying enzymes (P<0.05). Spraying leaves with G. biloba extracts or ginkgolide both significantly repelled H. cunea larvae in the field (P<0.05), although the former is more economical and practical. This study investigated the antifeedant activity of G. biloba secondary metabolites against H. cunea larvae, and the results provide new insights into the mechanism of G. biloba pest resistance. This study also developed new applications of G. biloba secondary metabolites for effective pest control.
ESTHER : Pan_2016_PLoS.One_11_e0155682
PubMedSearch : Pan_2016_PLoS.One_11_e0155682
PubMedID: 27214257

Title : Genome sequence of the date palm Phoenix dactylifera L - Al-Mssallem_2013_Nat.Commun_4_2274
Author(s) : Al-Mssallem IS , Hu S , Zhang X , Lin Q , Liu W , Tan J , Yu X , Liu J , Pan L , Zhang T , Yin Y , Xin C , Wu H , Zhang G , Ba Abdullah MM , Huang D , Fang Y , Alnakhli YO , Jia S , Yin A , Alhuzimi EM , Alsaihati BA , Al-Owayyed SA , Zhao D , Zhang S , Al-Otaibi NA , Sun G , Majrashi MA , Li F , Tala , Wang J , Yun Q , Alnassar NA , Wang L , Yang M , Al-Jelaify RF , Liu K , Gao S , Chen K , Alkhaldi SR , Liu G , Zhang M , Guo H , Yu J
Ref : Nat Commun , 4 :2274 , 2013
Abstract : Date palm (Phoenix dactylifera L.) is a cultivated woody plant species with agricultural and economic importance. Here we report a genome assembly for an elite variety (Khalas), which is 605.4 Mb in size and covers >90% of the genome (~671 Mb) and >96% of its genes (~41,660 genes). Genomic sequence analysis demonstrates that P. dactylifera experienced a clear genome-wide duplication after either ancient whole genome duplications or massive segmental duplications. Genetic diversity analysis indicates that its stress resistance and sugar metabolism-related genes tend to be enriched in the chromosomal regions where the density of single-nucleotide polymorphisms is relatively low. Using transcriptomic data, we also illustrate the date palm's unique sugar metabolism that underlies fruit development and ripening. Our large-scale genomic and transcriptomic data pave the way for further genomic studies not only on P. dactylifera but also other Arecaceae plants.
ESTHER : Al-Mssallem_2013_Nat.Commun_4_2274
PubMedSearch : Al-Mssallem_2013_Nat.Commun_4_2274
PubMedID: 23917264
Gene_locus related to this paper: phodc-a0a2h3y3d5 , phodc-a0a2h3z529 , phodc-a0a2h3y147 , phodc-a0a2h3xrz4 , phodc-a0a3q0ic37 , phodc-a0a2h3yxf0 , phodc-a0a2h3zh01 , phodc-a0a3q0hs32

Title : Genome sequences of wild and domestic bactrian camels - Jirimutu_2012_Nat.Commun_3_1202
Author(s) : Jirimutu , Wang Z , Ding G , Chen G , Sun Y , Sun Z , Zhang H , Wang L , Hasi S , Zhang Y , Li J , Shi Y , Xu Z , He C , Yu S , Li S , Zhang W , Batmunkh M , Ts B , Narenbatu , Unierhu , Bat-Ireedui S , Gao H , Baysgalan B , Li Q , Jia Z , Turigenbayila , Subudenggerile , Narenmanduhu , Wang J , Pan L , Chen Y , Ganerdene Y , Dabxilt , Erdemt , Altansha , Altansukh , Liu T , Cao M , Aruuntsever , Bayart , Hosblig , He F , Zha-ti A , Zheng G , Qiu F , Zhao L , Zhao W , Liu B , Li C , Tang X , Guo C , Liu W , Ming L , Temuulen , Cui A , Li Y , Gao J , Wurentaodi , Niu S , Sun T , Zhai Z , Zhang M , Chen C , Baldan T , Bayaer T , Meng H
Ref : Nat Commun , 3 :1202 , 2012
Abstract : Bactrian camels serve as an important means of transportation in the cold desert regions of China and Mongolia. Here we present a 2.01 Gb draft genome sequence from both a wild and a domestic bactrian camel. We estimate the camel genome to be 2.38 Gb, containing 20,821 protein-coding genes. Our phylogenomics analysis reveals that camels shared common ancestors with other even-toed ungulates about 55-60 million years ago. Rapidly evolving genes in the camel lineage are significantly enriched in metabolic pathways, and these changes may underlie the insulin resistance typically observed in these animals. We estimate the genome-wide heterozygosity rates in both wild and domestic camels to be 1.0 x 10(-3). However, genomic regions with significantly lower heterozygosity are found in the domestic camel, and olfactory receptors are enriched in these regions. Our comparative genomics analyses may also shed light on the genetic basis of the camel's remarkable salt tolerance and unusual immune system.
ESTHER : Jirimutu_2012_Nat.Commun_3_1202
PubMedSearch : Jirimutu_2012_Nat.Commun_3_1202
PubMedID: 23149746
Gene_locus related to this paper: 9ceta-s9yik4 , 9ceta-s9yb99 , 9ceta-s9x0n3 , 9ceta-s9xqa3 , 9ceta-s9xi02 , camfr-s9wiw9 , camfr-s9x3r3 , camfr-s9xce1 , camfr-s9xcr2 , camfr-s9yuz0 , camfr-s9xlc8 , camfr-s9w5f6 , camfr-s9xmm4

Title : Complete genome sequence of Bacillus amyloliquefaciens XH7, which exhibits production of purine nucleosides - Yang_2011_J.Bacteriol_193_5593
Author(s) : Yang H , Liao Y , Wang B , Lin Y , Pan L
Ref : Journal of Bacteriology , 193 :5593 , 2011
Abstract : Here, we report the complete annotated genome sequence of Bacillus amyloliquefaciens XH7, which is used to produce purine nucleosides in industry. The genome sequence will allow for the characterization of the molecular mechanisms underlying its beneficial properties.
ESTHER : Yang_2011_J.Bacteriol_193_5593
PubMedSearch : Yang_2011_J.Bacteriol_193_5593
PubMedID: 21914895
Gene_locus related to this paper: baca2-a7z811 , bacas-e1ur92

Title : Genome sequence of Escherichia coli XH140A, which produces L-threonine - Yang_2011_J.Bacteriol_193_6090
Author(s) : Yang H , Liao Y , Wang B , Lin Y , Pan L
Ref : Journal of Bacteriology , 193 :6090 , 2011
Abstract : Here we report the draft annotated genome sequence of Escherichia coli XH140A, which is used to produce l-threonine in industry. The genome sequence will allow the characterization of the molecular mechanisms underlying its beneficial properties.
ESTHER : Yang_2011_J.Bacteriol_193_6090
PubMedSearch : Yang_2011_J.Bacteriol_193_6090
PubMedID: 21994923
Gene_locus related to this paper: ecoli-ybff , ecoli-ycfp , ecoli-yqia , ecoli-YfhR

Title : Thiostrepton biosynthesis: prototype for a new family of bacteriocins - Kelly_2009_J.Am.Chem.Soc_131_4327
Author(s) : Kelly WL , Pan L , Li C
Ref : Journal of the American Chemical Society , 131 :4327 , 2009
Abstract : Thiopeptide antibiotics are a group of highly modified peptide metabolites. The defining scaffold for the thiopeptides is a macrocycle containing a dehydropiperidine or pyridine ring, dehydrated amino acids, and multiple thiazole or oxazole rings. Some members of the thiopeptides, such as thiostrepton, also contain either a quinaldic acid or indolic acid substituent derived from tryptophan. Although the amino acid precursors of these metabolites are well-established, the biogenesis of these complex peptides has remained elusive. Whole-genome scanning of Streptomyces laurentii permitted identification of a thiostrepton prepeptide, TsrA, and involvement of TsrA in thiostrepton biosynthesis was confirmed by mutagenesis. A gene cluster responsible for thiostrepton biosynthesis is reported, and the encoded gene products are discussed. The disruption of a gene encoding an amidotransferase, tsrT, led to the loss of thiostrepton production and the detection of a new metabolite, contributing further support to the identification of the tsr cluster. The tsr locus also appears to possess the gene products needed to convert tryptophan to the quinaldic acid moiety, and an aminotransferase was found to catalyze an early step in this pathway. This work establishes that the thiopeptides are a type of bacteriocin, a family of genetically encoded antimicrobial peptides, and are subjected to extensive posttranslational modification during maturation of the prepeptide.
ESTHER : Kelly_2009_J.Am.Chem.Soc_131_4327
PubMedSearch : Kelly_2009_J.Am.Chem.Soc_131_4327
PubMedID: 19265401
Gene_locus related to this paper: strlu-c0jry1 , strlu-c0l0l7

Title : Preclinical characterization of A-582941: a novel alpha7 neuronal nicotinic receptor agonist with broad spectrum cognition-enhancing properties - Tietje_2008_CNS.Neurosci.Ther_14_65
Author(s) : Tietje KR , Anderson DJ , Bitner RS , Blomme EA , Brackemeyer PJ , Briggs CA , Browman KE , Bury D , Curzon P , Drescher KU , Frost JM , Fryer RM , Fox GB , Gronlien JH , Hakerud M , Gubbins EJ , Halm S , Harris R , Helfrich RJ , Kohlhaas KL , Law D , Malysz J , Marsh KC , Martin RL , Meyer MD , Molesky AL , Nikkel AL , Otte S , Pan L , Puttfarcken PS , Radek RJ , Robb HM , Spies E , Thorin-Hagene K , Waring JF , Ween H , Xu H , Gopalakrishnan M , Bunnelle WH
Ref : CNS Neurosci Ther , 14 :65 , 2008
Abstract : Among the diverse sets of nicotinic acetylcholine receptors (nAChRs), the alpha7 subtype is highly expressed in the hippocampus and cortex and is thought to play important roles in a variety of cognitive processes. In this review, we describe the properties of a novel biaryl diamine alpha7 nAChR agonist, A-582941. A-582941 was found to exhibit high-affinity binding and partial agonism at alpha7 nAChRs, with acceptable pharmacokinetic properties and excellent distribution to the central nervous system (CNS). In vitro and in vivo studies indicated that A-582941 activates signaling pathways known to be involved in cognitive function such as ERK1/2 and CREB phosphorylation. A-582941 enhanced cognitive performance in behavioral models that capture domains of working memory, short-term recognition memory, memory consolidation, and sensory gating deficit. A-582941 exhibited a benign secondary pharmacodynamic and tolerability profile as assessed in a battery of assays of cardiovascular, gastrointestinal, and CNS function. The studies summarized in this review collectively provide preclinical validation that alpha7 nAChR agonism offers a mechanism with potential to improve cognitive deficits associated with various neurodegenerative and psychiatric disorders.
ESTHER : Tietje_2008_CNS.Neurosci.Ther_14_65
PubMedSearch : Tietje_2008_CNS.Neurosci.Ther_14_65
PubMedID: 18482100

Title : Lipolysis and the integrated physiology of lipid energy metabolism - Wang_2008_Mol.Genet.Metab_95_117
Author(s) : Wang S , Soni KG , Semache M , Casavant S , Fortier M , Pan L , Mitchell GA
Ref : Mol Genet Metab , 95 :117 , 2008
Abstract : Fat cell lipolysis, the cleavage of triglycerides and release of fatty acids and glycerol, evolved to enable survival during prolonged food deprivation but is paradoxically increased in obesity, in which a surfeit of all energy metabolites is found. Essential, previously-unsuspected components have been discovered in the lipolytic machinery, at the protective interface of the lipid droplet surface and in the signaling pathways that control lipolysis. At least two adipocyte lipases are important for controlling lipolysis, hormone-sensitive lipase (HSL) and adipocyte triglyceride lipase (ATGL). Perilipin (PLIN) and possibly other proteins of the lipid droplet surface are master regulators of lipolysis, protecting or exposing the triglyceride core of the droplet to lipases. The prototypes for hormonal lipolytic control are beta adrenergic stimulation and suppression by insulin, both of which affect cyclic AMP levels and hence the protein kinase A-mediated phosphorylation of HSL and PLIN. Newly-recognized mediators of lipolysis include atrial natriuretic peptide, cyclic GMP, the ketone body 3-hydroxybutyrate, AMP kinase and mitogen-activated kinases. Lipolysis must be interpreted in its physiological context since similar rates of basal or stimulated lipolysis occur under different conditions and by different mechanisms. Age, sex, anatomical site, genotype and species differences are each important variables. Manipulation of lipolysis has therapeutic potential in several inborn errors and in the metabolic syndrome that frequently complicates obesity.
ESTHER : Wang_2008_Mol.Genet.Metab_95_117
PubMedSearch : Wang_2008_Mol.Genet.Metab_95_117
PubMedID: 18762440

Title : Design, synthesis and evaluation of isaindigotone derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors - Pan_2008_Bioorg.Med.Chem.Lett_18_3790
Author(s) : Pan L , Tan JH , Hou JQ , Huang SL , Gu LQ , Huang ZS
Ref : Bioorganic & Medicinal Chemistry Lett , 18 :3790 , 2008
Abstract : A series of isaindigotone derivatives 5a-d and 6a-d were designed, synthesized and evaluated as acetylcholinesterase and butyrylcholinesterase inhibitors. Results showed that the novel class of isaindigotone derivatives could inhibit both cholinesterases and the selectivity of AChE over BuChE inhibition was related to the aromatic, the species and length of the alkyl amino side chain of compounds. The structure-activity relationships were discussed and their multiple binding modes were further clarified in the molecular docking studies.
ESTHER : Pan_2008_Bioorg.Med.Chem.Lett_18_3790
PubMedSearch : Pan_2008_Bioorg.Med.Chem.Lett_18_3790
PubMedID: 18524585

Title : Infertility and testicular defects in hormone-sensitive lipase-deficient mice - Chung_2001_Endocrinology_142_4272
Author(s) : Chung S , Wang SP , Pan L , Mitchell G , Trasler J , Hermo L
Ref : Endocrinology , 142 :4272 , 2001
Abstract : The 84-kDa hormone-sensitive lipase (gene designation Lipe; EC 3.1.1.3) is a cholesterol esterase and triglyceride hydrolase that functions in the release of fatty acids from adipocytes. The role of hormone-sensitive lipase in other tissues such as the testis, where a specific 120-kDa testis-specific isoform is expressed, is unknown. To study this, we examined the fertility and testicular histology of gene-targeted hormone-sensitive lipase-deficient mice. Homozygous hormone-sensitive lipase-deficient male mice are infertile and have decreased testis weights; female homozygotes are fertile. Testicular abnormalities, detected at the light and electron microscopic levels, included the presence of multinucleated round and elongating spermatids, vacuolization of the seminiferous epithelium, asynchronization of the spermatogenic cycle, sloughing of postmeiotic germ cells from the seminiferous epithelium into the lumen, and a marked reduction in the numbers of late spermatids. Extensive nuclear head deformation was noted in late spermatids as well as the sharing of a common acrosome in multinucleated cells. In some multinucleated cells, nuclei were separated from their acrosomes, with the acrosomes remaining attached to areas of ectoplasmic specializations, suggesting defects in intercellular cytoplasmic bridge integrity. Although the lumen of the epididymis was essentially devoid of spermatozoa and filled instead with spherical degenerating cells, the epididymal epithelial cells appeared normal. The few late spermatids present in the epididymis were abnormal. There was no morphological evidence, as judged by the absence of lipid droplets of triacylglycerol or cholesteryl ester accumulation in the testis. Together, the data suggest that hormone-sensitive lipase deficiency results in abnormalities in spermiogenesis that are incompatible with normal fertility. We speculate that a metabolite downstream from the hormone-sensitive lipase reaction may be essential for membrane stabilization and integrity in the seminiferous epithelium and, in particular, may play an important role in the maintenance of intercellular cytoplasmic bridges between postmeiotic germ cells.
ESTHER : Chung_2001_Endocrinology_142_4272
PubMedSearch : Chung_2001_Endocrinology_142_4272
PubMedID: 11564684
Gene_locus related to this paper: mouse-hslip

Title : The adipose tissue phenotype of hormone-sensitive lipase deficiency in mice - Wang_2001_Obes.Res_9_119
Author(s) : Wang SP , Laurin N , Himms-Hagen J , Rudnicki MA , Levy E , Robert MF , Pan L , Oligny L , Mitchell GA
Ref : Obes Res , 9 :119 , 2001
Abstract : OBJECTIVE: To directly ascertain the physiological roles in adipocytes of hormone-sensitive lipase (HSL; E.C. 3.1.1.3), a multifunctional hydrolase that can mediate triacylglycerol cleavage in adipocytes. RESEARCH METHODS AND PROCEDURES: We performed constitutive gene targeting of the mouse HSL gene (Lipe), subsequently studied the adipose tissue phenotype clinically and histologically, and measured lipolysis in isolated adipocytes. RESULTS: Homozygous HSL-/- mice have no detectable HSL peptide or cholesteryl esterase activity in adipose tissue, and heterozygous mice have intermediate levels with respect to wild-type and deficient littermates. HSL-deficient mice have normal body weight but reduced abdominal fat mass compared with normal littermates. Histologically, both white and brown adipose tissues in HSL-/- mice show marked heterogeneity in cell size, with markedly enlarged adipocytes juxtaposed to cells of normal morphology. In isolated HSL-/- adipocytes, lipolysis is not significantly increased by beta3-adrenergic stimulation, but under basal conditions in the absence of added catecholamines, the lipolytic rate of isolated HSL-/- adipocytes is at least as high as that of cells from normal controls. Cold tolerance during a 48-hour period at 4 degrees C was similar in HSL-/- mice and controls. Overnight fasting was well-tolerated clinically by HSL-/- mice, but after fasting, liver triglyceride content was significantly lower in HSL-/- mice compared with wild-type controls. CONCLUSIONS: In isolated fat cells, the lipolytic rate after beta-adrenergic stimulation is mainly dependent on HSL. However, the observation of a normal rate of lipolysis in unstimulated HSL-/- adipocytes suggests that HSL-independent lipolytic pathway(s) exist in fat. Physiologically, HSL deficiency in mice has a modest effect under normal fed conditions and is compatible with normal maintenance of core body temperature during cold stress. However, the lipolytic response to overnight fasting is subnormal.
ESTHER : Wang_2001_Obes.Res_9_119
PubMedSearch : Wang_2001_Obes.Res_9_119
PubMedID: 11316346
Gene_locus related to this paper: mouse-hslip