Li K

References (53)

Title : DPP8\/9 inhibition attenuates the TGF-beta1-induced excessive deposition of extracellular matrix (ECM) in human mesangial cells via Smad and Akt signaling pathway - Li_2024_Toxicol.Lett__
Author(s) : Li K , Zhang Y , Zhao W , Wang R , Li Y , Wei L , Wang L , Chen X , Chen Z , Liu P , Nie N , Tian X , Fu R
Ref : Toxicol Lett , : , 2024
Abstract : The pathogenesis of glomerular diseases is strongly influenced by abnormal extracellular matrix (ECM) deposition in mesangial cells. Dipeptidyl peptidase IV (DPPIV) enzyme family contains DPP8 and DPP9 involved in multiple diseases. However, the pathogenic roles of DPP8 and DPP9 in mesangial cells ECM deposition remain unclear. In this study, we observed that DPP8 and DPP9 were significantly increased in glomerular mesangial cells and podocytes in CKD patients compared with healthy individuals, and DPP9 levels were higher in the urine of IgAN patients than in control urine. Therefore, we further explored the mechanism of DPP8 and DPP9 in mesangial cells and revealed a significant increase in the expression of DPP8 and DPP9 in human mesangial cells (HMCs) following TGF-beta1 stimulation. Silencing DPP8 and DPP9 by siRNAs alleviated the expression of ECM-related proteins including collagen , collagen , fibronectin, MMP2, in TGF-beta1-treated HMCs. Furthermore, DPP8 siRNA and DPP9 siRNA inhibited TGF-beta1-induced phosphorylation of Smad2 and Smad3, as well as the phosphorylation of Akt in HMCs. The findings suggested the inhibition of DPP8/9 may alleviate HMCs ECM deposition induced by TGF-beta1 via suppressing TGF-beta1/Smad and AKT signaling pathway.
ESTHER : Li_2024_Toxicol.Lett__
PubMedSearch : Li_2024_Toxicol.Lett__
PubMedID: 38458339

Title : The reactivation kinetic analysis, molecular docking, and dynamics of oximes against three V-type nerve agents inhibited four human cholinesterases - Li_2024_Chem.Biol.Interact__111061
Author(s) : Li K , Liu Y , Li Q , Guo L , Xie J
Ref : Chemico-Biological Interactions , :111061 , 2024
Abstract : Nerve agents pose significant threats to civilian and military populations. The reactivation of acetylcholinesterase (AChE) is critical in treating acute poisoning, but there is still lacking broad-spectrum reactivators, which presents a big challenge. Therefore, insights gained from the reactivation kinetic analysis and molecular docking are essential for understanding the behavior of reactivators towards intoxicated AChE. In this research, we present a systematic determination of the reactivation kinetics of three V agents-inhibited four human ChEs [(AChE and butyrylcholinesterase (BChE)) from either native or recombinant resources, namely, red blood cell (RBC) AChE, rhAChE, hBChE, rhBChE) reactivated by five standard oximes. We unveiled the effect of native and recombinant ChEs on the reactivation kinetics of V agents ex vitro, where the reactivation kinetics characteristic of Vs-inhibited BChE was reported for the first time. In terms of the inhibition type, all of the five oxime reactivators exhibited noncompetitive inhibition. The inhibition potency of these reactivators would not lead to the difference in the reactivation kinetics between native and recombinant ChE. Despite the significant differences between the native and recombinant ChEs observed in the inhibition, aging, and spontaneous reactivation kinetics, the reactivation kinetics of V agent-inhibited ChEs by oximes were less differentiated, which were supported by the ligand docking results. We also found differences in the reactivation efficiency between five reactivators and the phosphorylated enzyme, and molecular dynamic simulations can further explain from the perspectives of conformational stability, hydrogen bonding, binding free energies, and amino acid contributions. By Poisson-Boltzmann surface area (MM-PBSA) calculations, the total binding free energy trends aligned well with the experimental k(r2) values.
ESTHER : Li_2024_Chem.Biol.Interact__111061
PubMedSearch : Li_2024_Chem.Biol.Interact__111061
PubMedID: 38763347

Title : Frequencies of insecticide resistance mutations detected by the amplicon sequencing in Plutella xylostella (Lepidoptera: Plutellidae) and Spodoptera exigua (Lepidoptera: Noctuidae) from China - Liu_2024_J.Econ.Entomol__
Author(s) : Liu Z , Ma H , Li K , Liu J , Zhu H , Zhou Y , Man Y , Zhou X
Ref : J Econ Entomol , : , 2024
Abstract : The globally prevalent pests, Diamondback moth, Plutella xylostella (Lepidoptera: Plutellidae) and Beet armyworm, Spodoptera exigua (Lepidoptera: Noctuidae), pose significant threats to cruciferous vegetables. They have rapidly developed resistance to a wide range of insecticides, leading to significant yield losses and increased control expenses. In this study, we have established an efficient approach utilizing amplicon sequencing to detect the frequency of 15 target resistance mutant sites in 6 molecular targets, acetylcholinesterase 1 (ACE1), chitin synthase 1 (CHS1), the gamma-aminobutyric acid receptor (GABAR), glutamate-gated chloride channel (GluCl), voltage-gated sodium channels (NaV), and ryanodine receptor (RyR) in P. xylostella and the frequency of 11 mutations in 5 molecular targets (except GluCl) in S. exigua in China. Our findings indicate that P. xylostella exhibits remarkably high frequency (over 88.67%) in pyrethroid resistance-related mutations T929I and L1014F of NaV. In S. exigua, the frequencies of L659F mutation were ranging from 41.92% to 74.89%. In addition, the organophosphorus resistance-related mutations A298S and G324A of ACE1 were detected at frequencies ranging from 34.29% to 75.66%, and these 2 mutations occurred simultaneously (from 29.22% to 65.79%) in P. xylostella. An interannual variation in mutation frequency from 2019 to 2021 was found for P. xylostella in HNCS. The frequency of A298S and G324A mutations steadily increased while the frequency of G4946E and I4790M mutations continuously decreased. These results unveil a worrisome scenario of multiple resistance sites in these 2 pests in China and provide valuable insights for the practical application of pesticides in the field.
ESTHER : Liu_2024_J.Econ.Entomol__
PubMedSearch : Liu_2024_J.Econ.Entomol__
PubMedID: 38748551

Title : ANGPTL3 is a novel HDL component that regulates HDL function - Yang_2024_J.Transl.Med_22_263
Author(s) : Yang L , Wang Y , Xu Y , Li K , Yin R , Zhang L , Wang D , Wei L , Lang J , Cheng Y , Wang L , Ke J , Zhao D
Ref : J Transl Med , 22 :263 , 2024
Abstract : BACKGROUND: Angiopoietin-like protein 3 (ANGPTL3) is secreted by hepatocytes and inhibits lipoprotein lipase and endothelial lipase activity. Previous studies reported the correlation between plasma ANGPTL3 levels and high-density lipoprotein (HDL). Recently ANGPTL3 was found to preferentially bind to HDL in healthy human circulation. Here, we examined whether ANGPTL3, as a component of HDL, modulates HDL function and affects HDL other components in human and mice with non-diabetes or type 2 diabetes mellitus. METHODS: HDL was isolated from the plasma of female non-diabetic subjects and type-2 diabetic mellitus (T2DM) patients. Immunoprecipitation, western blot, and ELISA assays were used to examine ANGPTL3 levels in HDL. Db/m and db/db mice, AAV virus mediated ANGPTL3 overexpression and knockdown models and ANGPTL3 knockout mice were used. The cholesterol efflux capacity induced by HDL was analyzed in macrophages preloaded with fluorescent cholesterol. The anti-inflammation capacity of HDL was assessed using flow cytometry to measure VCAM-1 and ICAM-1 expression levels in TNF-alpha-stimulated endothelial cells pretreated with HDL. RESULTS: ANGPTL3 was found to bind to HDL and be a component of HDL in both non-diabetic subjects and T2DM patients. Flag-ANGPTL3 was found in the HDL of transgenic mice overexpressing Flag-ANGPTL3. ANGPLT3 of HDL was positively associated with cholesterol efflux in female non-diabetic controls (r = 0.4102, p = 0.0117) but not in female T2DM patients (r = - 0.1725, p = 0.3224). Lower ANGPTL3 levels of HDL were found in diabetic (db/db) mice compared to control (db/m) mice and were associated with reduced cholesterol efflux and inhibition of VCAM-1 and ICAM-1 expression in endothelial cells (p < 0.05 for all). Following AAV-mediated ANGPTL3 cDNA transfer in db/db mice, ANGPTL3 levels were found to be increased in HDL, and corresponded to increased cholesterol efflux and decreased ICAM-1 expression. In contrast, knockdown of ANGPTL3 levels in HDL by AAV-mediated shRNA transfer led to a reduction in HDL function (p < 0.05 for both). Plasma total cholesterol, total triglycerides, HDL-c, protein components of HDL and the cholesterol efflux function of HDL were lower in ANGPTL3-/- mice than ANGPTL3+/+ mice, suggesting that ANGPTL3 in HDL may regulate HDL function by disrupting the balance of protein components in HDL. CONCLUSION: ANGPTL3 was identified as a component of HDL in humans and mice. ANGPTL3 of HDL regulated cholesterol efflux and the anti-inflammatory functions of HDL in T2DM mice. Both the protein components of HDL and cholesterol efflux capacity of HDL were decreased in ANGPTL3-/- mice. Our findings suggest that ANGPTL3 in HDL may regulate HDL function by disrupting the balance of protein components in HDL. Our study contributes to a more comprehensive understanding of the role of ANGPTL3 in lipid metabolism.
ESTHER : Yang_2024_J.Transl.Med_22_263
PubMedSearch : Yang_2024_J.Transl.Med_22_263
PubMedID: 38462608

Title : Establishment of transgenic fluorescent mice for labeling synapses and screening synaptogenic adhesion molecules - Yang_2024_Elife_13_
Author(s) : Yang L , Zhang J , Liu S , Zhang Y , Wang L , Wang X , Wang S , Li K , Wei M , Zhang C
Ref : Elife , 13 : , 2024
Abstract : Synapse is the fundamental structure for neurons to transmit information between cells. The proper synapse formation is crucial for developing neural circuits and cognitive functions of the brain. The aberrant synapse formation has been proved to cause many neurological disorders, including autism spectrum disorders and intellectual disability. Synaptic cell adhesion molecules (CAMs) are thought to play a major role in achieving mechanistic cell-cell recognition and initiating synapse formation via trans-synaptic interactions. Due to the diversity of synapses in different brain areas, circuits and neurons, although many synaptic CAMs, such as Neurexins (NRXNs), Neuroligins (NLGNs), Synaptic cell adhesion molecules (SynCAMs), Leucine-rich-repeat transmembrane neuronal proteins (LRRTMs) and SLIT and NTRK-like protein (SLITRKs) have been identified as synaptogenic molecules, how these molecules determine specific synapse formation and whether other molecules driving synapse formation remain undiscovered are unclear. Here, to providing a tool for synapse labeling and synaptic CAMs screening by artificial synapse formation (ASF) assay, we generated synaptotagmin-1-tdTomato (Syt1-tdTomato) transgenic mice by inserting the tdTomato-fused synaptotagmin-1 coding sequence into the genome of C57BL/6J mice. In the brain of Syt1-tdTomato transgenic mice, the tdTomato-fused synaptotagmin-1 (SYT1-tdTomato) signals were widely observed in different areas and overlapped with synapsin-1, a widely-used synaptic marker. In olfactory bulb, the SYT1-tdTomato signals are highly enriched in glomerulus. In the cultured hippocampal neurons, the SYT1-tdTomato signals showed colocalization with several synaptic markers. Compared to the wild-type (WT) mouse neurons, cultured hippocampal neurons from Syt1-tdTomato transgenic mice presented normal synaptic neurotransmission. In ASF assays, neurons from Syt1-tdTomato transgenic mice could form synaptic connections with HEK293T cells expressing NLGN2, LRRTM2, and SLITRK2 without immunostaining. Therefore, our work suggested that the Syt1-tdTomato transgenic mice with the ability to label synapses by tdTomato, and it will be a convenient tool for screening synaptogenic molecules.
ESTHER : Yang_2024_Elife_13_
PubMedSearch : Yang_2024_Elife_13_
PubMedID: 38450720

Title : Genome-wide identification and expression analysis of the cotton patatin-related phospholipase A genes and response to stress tolerance - Wei_2023_Planta_257_49
Author(s) : Wei Y , Chong Z , Lu C , Li K , Liang C , Meng Z , Wang Y , Guo S , He L , Zhang R
Ref : Planta , 257 :49 , 2023
Abstract : Patatin-related phospholipase A genes were involved in the response of Gossypium hirsutum to drought and salt tolerance. pPLA (patatin-related phospholipase A) is a key enzyme that catalyzes the initial step of lipid hydrolysis, which is involved in biological processes, such as drought, salt stress, and freezing injury. However, a comprehensive analysis of the pPLA gene family in cotton, especially the role of pPLA in the response to drought and salt tolerance, has not been reported so far. A total of 33 pPLA genes were identified in this study using a genome-wide search approach, and phylogenetic analysis classified these genes into three groups. These genes are unevenly distributed on the 26 chromosomes of cotton, and most of them contain a few introns. The results of the collinear analysis showed that G. hirsutum contained 1-5 copies of each pPLA gene found in G. arboreum and G. raimondii. The subcellular localization analysis of Gh_D08G061200 showed that the protein was localized in the nucleus. In addition, analysis of published upland cotton transcriptome data revealed that six GhPLA genes were expressed in various tissues and organs. Two genes (Gh_A04G142100.1 and Gh_D04G181000.1) were highly expressed in all tissues under normal conditions, showing the expression characteristics of housekeeping genes. Under different drought and salt tolerance stresses, we detected four genes with different expression levels. This study helps to clarify the role of pPLA in the response to drought and salt tolerance.
ESTHER : Wei_2023_Planta_257_49
PubMedSearch : Wei_2023_Planta_257_49
PubMedID: 36752875

Title : Design of a near-infrared fluoro-photoacoustic probe for rapid imaging of carboxylesterase in liver injury - Chen_2023_Chem.Commun.(Camb)_59_10520
Author(s) : Chen H , Li K , Yuan L , Zhang XB
Ref : Chem Commun (Camb) , 59 :10520 , 2023
Abstract : Carboxylesterase (CE) is crucial in metabolizing ester-containing biomolecules and is particularly significant in liver metabolic diseases. Herein, we present the first activatable NIRF/PA dual-mode imaging probe QHD-CE for detection of CE in vitro and in vivo. QHD-CE displays excellent sensitivity and selectivity for CE with a high reaction efficiency (-90 min). By utilizing QHD-CE, the dynamic changes of CE in drug-induced liver injury and diabetic mice models were monitored.
ESTHER : Chen_2023_Chem.Commun.(Camb)_59_10520
PubMedSearch : Chen_2023_Chem.Commun.(Camb)_59_10520
PubMedID: 37644758

Title : The East Asian-specific LPL p.Ala288Thr (c.862G > A) missense variant exerts a mild effect on protein function - Hu_2023_Lipids.Health.Dis_22_119
Author(s) : Hu Y , Zhang G , Yang Q , Pu N , Li K , Li B , Cooper DN , Tong Z , Li W , Chen JM
Ref : Lipids Health Dis , 22 :119 , 2023
Abstract : BACKGROUND: Lipoprotein lipase (LPL) is the key enzyme responsible for the hydrolysis of triglycerides. Loss-of-function variants in the LPL gene are associated with hypertriglyceridemia (HTG) and HTG-related diseases. Unlike nonsense, frameshift and canonical GT-AG splice site variants, a pathogenic role for clinically identified LPL missense variants should generally be confirmed by functional analysis. Herein, we describe the clinical and functional analysis of a rare LPL missense variant. METHODS: Chinese patients with HTG-associated acute pancreatitis (HTG-AP) were screened for rare nonsense, frameshift, missense or canonical GT-AG splice site variants in LPL and four other lipid metabolism-related genes (APOC2, APOA5, GPIHBP1 and LMF1) by Sanger sequencing. The functional consequences of the LPL missense variant of interest were characterized by in vitro expression in HEK-293T and COS-7 cells followed by Western blot and LPL activity assays. RESULTS: Five unrelated HTG-AP patients were found to be heterozygous for a rare East Asian-specific LPL missense variant, c.862G > A (p.Ala288Thr). All five patients were adult males, and all were overweight and had a long history of alcohol consumption. Transfection of LPL wild-type and c.862G > A expression vectors into two cell lines followed by Western blot analysis served to exclude the possibility that the p.Ala288Thr missense variant either impaired protein synthesis or increased protein degradation. Contrary to a previous functional study that claimed that p.Ala288Thr had a severe impact on LPL function (reportedly having 36% normal activity), our experiments consistently demonstrated that the variant had a comparatively mild effect on LPL functional activity, which was mediated through its impact upon LPL protein secretion (~ 20% reduced secretion compared to wild-type). CONCLUSIONS: In this study, we identified the East Asian-specific LPL c.862G > A (p.Ala288Thr) missense variant in five unrelated HTG-AP patients. We demonstrated that this variant exerted only a relatively mild effect on LPL function in two cell lines. Heterozygosity for this LPL variant may have combined with alcohol consumption to trigger HTG-AP in these patients.
ESTHER : Hu_2023_Lipids.Health.Dis_22_119
PubMedSearch : Hu_2023_Lipids.Health.Dis_22_119
PubMedID: 37550668
Gene_locus related to this paper: human-LPL

Title : The kinetic and molecular docking analysis of interactions between three V-type nerve agents and four human cholinesterases - Li_2023_Chem.Biol.Interact_372_110369
Author(s) : Li K , Liu Y , Li Q , Guo L , Xie J
Ref : Chemico-Biological Interactions , 372 :110369 , 2023
Abstract : G and V-type nerve agents represent the most toxic chemical warfare agents. Their primary toxicity was the consequence of the covalent inhibition of the pivotal acetylcholinesterase (AChE), which induces overstimulation of cholinergic receptors and overaccumulation of cholines, eventually leading to death by respiratory arrest. The inhibitory and reactivation kinetics of cholinesterase (ChE) are essential for the toxicology and countermeasures of nerve agents. Medical defensive research on V-type nerve agents (V agents) has been mainly reported on VX and VR. Here we demonstrated the first systematical kinetic analysis between the type of ChE [native or recombinant human AChE and butyrylcholinesterase (BChE)] and three V agents, including VX, VR, and Vs, another isomer of VX, and highlighted the effects of native and recombinant ChE differences. The spontaneous reactivation and aging kinetics data of Vs-inhibited BChEs were firstly reported here. The results showed that AChE was more easily inhibited by three V agent compared to BChE, regardless of whether it is native or recombinant. The increased inhibitory potency order on AChE was VX, Vs, then VR, and on BChE was VX, then Vs and VR. The difference between native and recombinant ChE could influence the inhibition, aging, and spontaneous reactivation kinetics of three V agents, whether AChE or BChE, which was systematically revealed for the first time. For inhibition kinetics, the k(i) of three V agents for recombinant AChE was significantly higher than native AChE, and the stronger the inhibitory potency of V agents, the more pronounced difference in k(i). In terms of aging and spontaneous reactivation kinetics, recombinant ChE was found to be more prone to spontaneous reactivation, but more resistant to aging compared to native ChE, particularly for AChE. The performed covalent molecular docking results partially explained the effects of differences between native and recombinant ChE on enzyme kinetics from the perspective of binding energy and conformation.
ESTHER : Li_2023_Chem.Biol.Interact_372_110369
PubMedSearch : Li_2023_Chem.Biol.Interact_372_110369
PubMedID: 36708975

Title : IL-13 induced inflammation increases DPP4 abundance but does not enhance MERS-CoV replication in airway epithelia - Li_2023_J.Infect.Dis__
Author(s) : Li K , Bartlett JA , Wohlford-Lenane CL , Xue B , Thurman AL , Gallagher TM , Pezzulo AA , McCray PB
Ref : J Infect Dis , : , 2023
Abstract : BACKGROUND: Chronic pulmonary conditions such as asthma and COPD increase the risk of morbidity and mortality during infection with the Middle East respiratory syndrome coronavirus (MERS-CoV). We hypothesized that individuals with such comorbidities are more susceptible to MERS-CoV infection due to increased expression of its receptor, dipeptidyl peptidase 4 (DPP4). METHODS: We modeled chronic airway disease by treating primary human airway epithelia with the Th2 cytokine IL-13, examining how this impacted DPP4 protein levels along with MERS-CoV entry and replication. RESULTS: IL-13 exposure for 3 days led to increased DPP4 protein abundance, while a 21-day treatment increased DPP4 levels and caused goblet cell metaplasia. Surprisingly, despite this increase in receptor availability, MERS-CoV entry and replication were not significantly impacted by IL-13 treatment. CONCLUSIONS: Our results suggest that increased DPP4 abundance is likely not the primary mechanism leading to increased MERS severity in the setting of Th2 inflammation. Transcriptional profiling analysis highlighted the complexity of IL-13 induced changes in airway epithelia, including altered expression of genes involved in innate immunity, antiviral responses, and maintenance of the extracellular mucus barrier. These data suggest that additional factors likely interact with DPP4 abundance to determine MERS-CoV infection outcomes.
ESTHER : Li_2023_J.Infect.Dis__
PubMedSearch : Li_2023_J.Infect.Dis__
PubMedID: 37698016

Title : Immobilization of Rhizomucor miehei lipase on magnetic multiwalled carbon nanotubes towards the synthesis of structured lipids rich in sn-2 palmitic acid and sn-1,3 oleic acid (OPO) for infant formula use - Ghide_2022_Food.Chem_390_133171
Author(s) : Ghide MK , Li K , Wang J , Abdulmalek SA , Yan Y
Ref : Food Chem , 390 :133171 , 2022
Abstract : Nowadays, breast milk is considered as the ideal food for infants owing to the most common oleic acid-palmitic acid-oleic acid (OA-PA-OA) fatty acid distribution of the human milk fat (HMF). This study reports the synthesis of 1,3-dioleoyl-2-palmotoylglycerol (OPO)-rich human milk fat substitutes in a two-step enzymatic acidolysis reaction with Rhizomucor miehei lipase (RML) immobilized on magnetic multi-walled carbon nanotubes(mMWCNTs). The immobilized RML (RML-mMWCNTs) showed better thermal and pH stability, convenient recovery and reusability than the free soluble form. Under optimized reaction conditions (1:8 tripalmitin (PPP)/OA, 10%wt. enzyme, 50 degreesC, 5 h), PA content at the sn-2 position and OA incorporation at the sn-1,3 positions reached 93.46% and 59.54%, respectively. Comparison tests have also showed that RML-mMWCNTs has better catalytic activity and reusability than the commercial lipase Lipozyme RM IM. The results suggest that RML-mMWCNTs is a promising biocatalyst for the synthesis of OPO-rich TAGs with potential use in infant formulas.
ESTHER : Ghide_2022_Food.Chem_390_133171
PubMedSearch : Ghide_2022_Food.Chem_390_133171
PubMedID: 35551020

Title : Biodegradation of Fumonisins by the Consecutive Action of a Fusion Enzyme - Li_2022_Toxins.(Basel)_14_
Author(s) : Li K , Yu S , Yu D , Lin H , Liu N , Wu A
Ref : Toxins (Basel) , 14 : , 2022
Abstract : Fumonisins (FBs) are toxic mycotoxins that commonly exist in food and feed. FBs can induce many aspects of toxicity, leading to adverse effects on human and animal health; therefore, investigating methods to reduce fumonisin contamination is necessary. In our study, we generated a recombinant fusion enzyme called FUMDI by linking the carboxylesterase gene (fumD) and the aminotransferase gene (fumI) by overlapping polymerase chain reaction (PCR). The fusion enzyme FUMDI was successfully, secretively expressed in the host Pichia pastoris (P. pastoris) GS115, and its expression was optimized. Our results demonstrated that the fusion enzyme FUMDI had high biodegradation activity of fumonisin B1 (FB1) and other common FBs, such as fumonisin B2 (FB2) and fumonisin B3 (FB3), and almost completely degraded 5 microg/mL of each toxin within 24 h. We also found that FUMDI enzyme and its reaction products had no negative effect on cell viability and did not induce cell apoptosis, oxidative stress, or endoplasmic reticulum (ER) stress in a human gastric epithelial cell line (GES-1). The results indicated that these FBs degradation products cannot have adverse effects in a cell model. In conclusion, a safe and efficient fumonisin-degrading enzyme was discovered, which could be a new a technical method for hazard control of FBs in the future.
ESTHER : Li_2022_Toxins.(Basel)_14_
PubMedSearch : Li_2022_Toxins.(Basel)_14_
PubMedID: 35448875
Gene_locus related to this paper: sphmc-FumD

Title : Adeno-associated virus-mediated in vivo suppression of expression of EPHX2 gene modulates the activity of paraventricular nucleus neurons in spontaneously hypertensive rats - Zhu_2022_Biochem.Biophys.Res.Commun_606_121
Author(s) : Zhu X , Li K , Gao Y
Ref : Biochemical & Biophysical Research Communications , 606 :121 , 2022
Abstract : BACKGROUND: Hypertension can be attributed to increased sympathetic activities. Presympathetic neurons in the paraventricular nucleus (PVN) of the hypothalamus are capable of modulating sympathetic outflow, thus contributing to the pathogenesis of neurogenic hypertension. Epoxyeicosatrienoic acids (EETs) were reported to have anti-hypertensive effects, which could be degraded by soluble epoxide hydrolase (sEH), encoded by EPHX2. However, the potential effect of EETs on PVN neuron activity and the underlying molecular mechanism are largely unknown. METHODS: Knockdown of EPHX2 in spontaneously hypertensive rats (SHRs) was achieved by tail-intravenous injection of AAV plasmid containing shRNA targeting EPHX2. Whole-cell patch clamp was used to record action potentials of PVN neurons. An LC-MS/MS System was employed to determine 14,15-EET levels in rat cerebrospinal fluid. qPCR and western blotting were applied to examine the expression level of EPHX2 in various tissues. ELISA and immunofluorescence staining were applied to examine the levels of ATP, D-serine and glial fibrillary acidic protein (GFAP) in isolated astrocytes. RESULTS: The expression level of EPHX2 was higher, while the level of 14,15-EET was lower in SHRs than normotensive Wistar-Kyoto rats (WKY) rats. The spike firing frequency of PNV neurons in SHRs was higher than in WKY rats at a given stimulus current, which could be reduced by either EPHX2 downregulation or 14,15-EET administration. In isolated hypothalamic astrocytes, the elevated intracellular ATP or D-serine induced by Angiotensin II (Ang II) treatment could be rescued by 14,15-EET addition or 14,15-EET combing serine racemase (SR) downregulation by siRNA, respectively. Furthermore, 14,15-EET treatment reduced the Ang II-induced elevation of GFAP immunofluorescence. CONCLUSIONS: The elevation of EET levels by EPHX2 downregulation reduced presympathetic neuronal activity in the PVN of SHRs, leading to a reduced sympathetic outflow in hypertension rats. The ATP/SR/D-serine pathway of astrocytes is involved in EET-mediated neuroprotection.
ESTHER : Zhu_2022_Biochem.Biophys.Res.Commun_606_121
PubMedSearch : Zhu_2022_Biochem.Biophys.Res.Commun_606_121
PubMedID: 35344709

Title : Identification of Host Molecules Involved in the Proliferation of Nucleopolyhedrovirus in Bombyx mori - Xu_2022_J.Agric.Food.Chem__
Author(s) : Xu J , Xie X , Ma Q , Zhang L , Li Y , Chen Y , Li K , Xiao Y , Tettamanti G , Xu H , Tian L
Ref : Journal of Agricultural and Food Chemistry , : , 2022
Abstract : The Bombyx mori nucleopolyhedrovirus (BmNPV), a foodborne infectious virus, is the pathogen causing nuclear polyhedrosis and high lethality in the silkworm. In this study, we characterized the molecules involved in BmNPV-silkworm interaction by RNA sequencing of the fat body isolated from the virus-susceptible strain P50. Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation showed that the upregulated differentially expressed genes (DEGs) were mainly involved in translation, signal transduction, folding, sorting, and degradation, as well as transport and catabolism, while the downregulated DEGs were predominantly enriched in the metabolism of carbohydrates, amino acids, and lipids at 72 h post BmNPV infection. Knockout of the upregulated somatomedin-B and thrombospondin type-1 domain-containing protein, probable allantoicase, trifunctional purine biosynthetic protein adenosine-3, and Psl and pyoverdine operon regulator inhibited the proliferation of BmNPV, while knockout of the downregulated clip domain serine protease 3 and carboxylesterase clade H, member 1 promoted it. The molecules herein identified provide a foundation for developing strategies and designing drugs against BmNPV.
ESTHER : Xu_2022_J.Agric.Food.Chem__
PubMedSearch : Xu_2022_J.Agric.Food.Chem__
PubMedID: 36321811

Title : Assessing Dietary Pesticide Intake and Potential Health Effects: The Application of Global Metabolomics Analysis - Cheng_2022_J.Agric.Food.Chem__
Author(s) : Cheng Q , Liu QQ , Li K , Chang CH , Lu CA
Ref : Journal of Agricultural and Food Chemistry , : , 2022
Abstract : Scientific information is not yet available to provide insight into how individual metabolome might be affected by the presence of pesticides in regular diets. This study aimed to evaluate the perturbation of metabolomic pathways in children who switched their diets from conventional foods to mostly organic foods for five consecutive days. We selected 46 child-matched spot urine samples with distinct differences of urinary pesticide metabolite levels between the conventional and organic eating days and then analyzed those urine samples on three analytical platforms to perform global metabolomics analysis. We found statistically significant perturbations of metabolic pathways relevant to inflammation, oxidative stress, and the demands of xenobiotic detoxification when children switched their conventional diets to mostly organic foods. The outcomes of this study allow us to extend the current understanding beyond organophosphate pesticides' acute toxicity of cholinesterase inhibition to the perturbation of metabolic pathways at dietary intake levels.
ESTHER : Cheng_2022_J.Agric.Food.Chem__
PubMedSearch : Cheng_2022_J.Agric.Food.Chem__
PubMedID: 35320672

Title : Profibrotic mechanisms of DPP8 and DPP9 highly expressed in the proximal renal tubule epithelial cells - Zhang_2021_Pharmacol.Res_169_105630
Author(s) : Zhang Y , Li K , Li Y , Zhao W , Wang L , Chen Z , Ma X , Yao T , Wang J , Dong W , Li X , Tian X , Fu R
Ref : Pharmacol Res , 169 :105630 , 2021
Abstract : BACKGROUND: DPP8 and DPP9 have been demonstrated to play important roles in multiple diseases. Evidence for increased gene expression of DPP8 and DPP9 in tubulointerstitium was found to be associated with the decline of kidney function in chronic kidney disease (CKD) patients, which was observed in the Nephroseq human database. To examine the role of DPP8 and DPP9 in the tubulointerstitial injury, we determined the efficacy of DPP8 and DPP9 on epithelial-to-mesenchymal transition (EMT) and tubulointerstitial fibrosis (TIF) as well as the underlying mechanisms. METHODS: We conducted the immunofluorescence of DPP8 and DPP9 in kidney biopsy specimens of CKD patients, established unilateral ureteral obstruction (UUO) animal model, treated with TC-E5007 (a specific inhibitor of both DPP8 and DPP9) or Saxagliptin (positive control) or saline, and HK-2 cells model. RESULTS: We observed the significantly increased expression of DPP8 and DPP9 in the renal proximal tubule epithelial cells of CKD patients compared to the healthy control subjects. DPP8/DPP9 inhibitor TC-E5007 could significantly attenuate the EMT and extracellular matrix (ECM) synthesis in UUO mice, all these effects were mediated via interfering with the TGF-beta1/Smad signaling. TC-E5007 treatment also presented reduced renal inflammation and improved renal function in the UUO mice compared to the placebo-treated UUO group. Furthermore, the siRNA for DPP8 and DPP9, and TC-E5007 treatment decreased EMT- and ECM-related proteins in TGF-beta1-treated HK-2 cells respectively, which could be reversed significantly by transduction with lentivirus-DPP8 and lentivirus-DPP9. CONCLUSION: These data obtained provide evidence that the DPP8 and DPP9 could be potential therapeutic targets against TIF.
ESTHER : Zhang_2021_Pharmacol.Res_169_105630
PubMedSearch : Zhang_2021_Pharmacol.Res_169_105630
PubMedID: 33932609
Gene_locus related to this paper: human-DPP8 , human-DPP9

Title : Supplemental Choline Modulates Growth Performance and Gut Inflammation by Altering the Gut Microbiota and Lipid Metabolism in Weaned Piglets - Qiu_2021_J.Nutr_151_20
Author(s) : Qiu Y , Liu S , Hou L , Li K , Wang L , Gao K , Yang X , Jiang Z
Ref : J Nutr , 151 :20 , 2021
Abstract : BACKGROUND: Whether dietary choline and bile acids affect lipid use via gut microbiota is unclear. OBJECTIVES: This study aimed to investigate the effect of choline and bile acids on growth performance, lipid use, intestinal immunology, gut microbiota, and bacterial metabolites in weaned piglets. METHODS: A total of 128 weaned piglets [Duroc x (Landrace x Yorkshire), 21-d-old, 8.21 +/- 0.20 kg body weight (BW)] were randomly allocated to 4 treatments (8 replicate pens per treatment, each pen containing 2 males and 2 females; n = 32 per treatment) for 28 d. Piglets were fed a control diet (CON) or the CON diet supplemented with 597 mg choline/kg (C), 500 mg bile acids/kg (BA) or both (C + BA) in a 2 x 2 factorial design. Growth performance, intestinal function, gut microbiota, and metabolites were determined. RESULTS: Compared with diets without choline, choline supplementation increased BW gain (6.13%), average daily gain (9.45%), gain per feed (8.18%), jejunal lipase activity (60.2%), and duodenal IL10 gene expression (51%), and decreased the mRNA abundance of duodenal TNFA (TNFalpha) (40.7%) and jejunal toll-like receptor 4 (32.9%) (P < 0.05); additionally, choline increased colonic butyrate (29.1%) and the abundance of Lactobacillus (42.3%), while decreasing the bile acid profile (55.8% to 57.6%) and the abundance of Parabacteroides (75.8%), Bacteroides (80.7%), and unidentified-Ruminococcaceae (32.5%) (P >= 0.05). Compared with diets without BA, BA supplementation decreased the mRNA abundance of colonic TNFA (37.4%), NF-kappaB p65 (42.4%), and myeloid differentiation factor 88 (42.5%) (P >= 0.01); BA also increased colonic butyrate (20.9%) and the abundance of Lactobacillus (39.7%) and Faecalibacterium (71.6%) and decreased that of Parabacteroides (67.7%) (P < 0.05). CONCLUSIONS: Choline supplementation improved growth performance and prevented gut inflammation in weaned piglets by altering gut microbiota and lipid metabolism. BA supplementation suppressed intestinal inflammation with no effect on growth performance, which was associated with changed gut microbiota and metabolites.
ESTHER : Qiu_2021_J.Nutr_151_20
PubMedSearch : Qiu_2021_J.Nutr_151_20
PubMedID: 33245135

Title : Capsulation of AuNCs with AIE Effect into Metal-Organic Framework for the Marriage of a Fluorescence and Colorimetric Biosensor to Detect Organophosphorus Pesticides - Cai_2021_Anal.Chem__
Author(s) : Cai Y , Zhu H , Zhou W , Qiu Z , Chen C , Qileng A , Li K , Liu Y
Ref : Analytical Chemistry , : , 2021
Abstract : Organophosphorus pesticides (OPs) can inhibit the activity of acetylcholinesterase (AChE) to induce neurological diseases. It is significant to exploit a rapid and sensitive strategy to monitor OPs. Here, a metal-organic framework (MOF) acted as a carrier to encapsulate AuNCs, which can limit the molecular motion of AuNCs, trigger the aggregation-induced emission (AIE) effect, and exhibit a strong fluorescence with a fluorescence lifetime and quantum yield of 6.83 micros and 4.63%, respectively. Then, the marriage of fluorescence and colorimetric signals was realized on the basis of the dual function of the enzymolysis product from AChE and choline oxidase (CHO) on AuNCs@ZIF-8. First, it can decompose ZIF-8 to weaken the restraint on AuNCs, and thus the fluorescence receded. Second, it can be used as a substrate for the peroxidase mimics of the released AuNCs to oxidize 3,3',5,5'-tetramethylbenzidine (TMB) and a visible blue appeared. Thus, on the basis of the inhibition of AChE activity by OPs, a fluorescence-colorimetric dual-signal biosensor was established. In addition, colorimetric paper strips were exploited to realize a visual semiquantitative detection, and a smartphone APP was developed to make the visualization results more precise and realize real-time supervision of pesticide contamination.
ESTHER : Cai_2021_Anal.Chem__
PubMedSearch : Cai_2021_Anal.Chem__
PubMedID: 33957044

Title : Heterozygous lipoprotein lipase knockout mice exhibit impaired hematopoietic stem\/progenitor cell compartment - Shi_2021_Animal.Model.Exp.Med_4_418
Author(s) : Shi G , Li X , Li K , Huang Y , Lei X , Bai L , Qin C
Ref : Animal Model Exp Med , 4 :418 , 2021
Abstract : BACKGROUND: Hematopoietic stem cells (HSC) maintain the hematopoietic system homeostasis through self-renewal and multilineage differentiation potential. HSC are regulated by the microenvironment, cytokine signaling, and transcription factors. Recent results have shown that lipid pathways play a key role in the regulation of HSC quiescence, proliferation, and division. However, the mechanism by which lipid metabolism regulates HSC proliferation and differentiation remains to be clarified. Lipoprotein lipase (LPL) is an essential enzyme in the anabolism and catabolism of very low-density lipoprotein, chylomicrons, and triglyceride-rich lipoproteins. METHODS: The percentage of hematopoietic stem/progenitor cells and immune cells were determined by fluorescence-activated cell sorting (FACS). The function and the mechanism of HSCs were analyzed by cell colony forming assay and qPCR analysis. The changes in LPL(+/-) HSC microenvironment were detected by transplantation assays using red fluorescent protein (RFP) transgenic mice. RESULTS: To explore the function of LPL in HSC regulation, heterozygous LPL-knockout mice (LPL(+/-)) were established and analyzed by FACS. LPL(+/-) mice displayed decreased hematopoietic stem/progenitor cell compartments. In vitro single-cell clonogenic assays and cell-cycle assays using FACS promoted the cell cycle and increased proliferation ability. qPCR analysis showed the expression of p57(KIP2) and p21(WAF1/CIP1) in LPL(+/-) mice was upregulated. CONCLUSIONS: LPL(+/-) mice exhibited HSC compartment impairment due to promotion of HSC proliferation, without any effects on the bone marrow (BM) microenvironment.
ESTHER : Shi_2021_Animal.Model.Exp.Med_4_418
PubMedSearch : Shi_2021_Animal.Model.Exp.Med_4_418
PubMedID: 34977493

Title : Tacrine accelerates spatial long-term memory via improving impaired neural oscillations and modulating GAD isomers including neuro-receptors in the hippocampus of APP\/PS1 AD mice - Kumari_2020_Brain.Res.Bull__
Author(s) : Kumari E , Li K , Yang Z , Zhang T
Ref : Brain Research Bulletin , : , 2020
Abstract : Tacrine (Amino tetrahydroacridine hydrochloride hydrate) is a non-competitive and reversible inhibitor of acetylcholine esterase, and butylcholinesterase. Alzheimer's disease (AD) shows multiple types of pathological pathway in which cholinergic neuron deficiency is 95 % popular and the oldest pathological mechanism. However, the effect of tacrine on the hippocampal dependent memory is not yet known. In this study, we did verify that tacrine induced recovery of the specific pattern associated memory along with long-term memory through the improvement in the pattern of neural oscillation from deficits condition in the hippocampus of 6th month old AD mice. Our results showed that tacrine improved the performance of Morris water maze related spatial cognitive functions, and enhanced LTP in AD-TAC mice. Furthermore, our results implied that tacrine strongly improve the patterns of neural oscillations, and hippocampal synaptic plasticity in the 6th month old APP-PS1 double transgenic AD-TAC mice via changing the theta and alpha power spectra including with the improvement in theta, alpha and gamma synchronization. Moreover, tacrine generated the improvement in the theta cross spectra, theta-gamma phase-phase synchronization and theta-gamma phase-amplitude coupling. Besides, the data represented that tacrine accelerated the expression of NR2B, SYP and GAD65 while it caused deceleration on the expression of GAD67 neurotransmitter and Abeta. Thus, our results infer that tacrine works as a strong causative agent for improving the specific pattern-associated spatial long-term memory in the AD mice without showing any side effect.
ESTHER : Kumari_2020_Brain.Res.Bull__
PubMedSearch : Kumari_2020_Brain.Res.Bull__
PubMedID: 32473192

Title : IRREGULAR POLLEN EXINE2 Encodes a GDSL Lipase Essential for Male Fertility in Maize - Huo_2020_Plant.Physiol_184_1438
Author(s) : Huo Y , Pei Y , Tian Y , Zhang Z , Li K , Liu J , Xiao S , Chen H
Ref : Plant Physiol , 184 :1438 , 2020
Abstract : Anther cuticle and pollen exine are two physical barriers protecting plant reproductive cells against environmental stresses; defects in either often cause male sterility. Here, we report the characterization of a male-sterile mutant irregular pollen exine2 (ipe2) of maize (Zea mays), which displays shrunken anthers and no starch accumulation in mature pollen grains. We cloned the causal gene IPE2 and confirmed its role in male fertility in maize with a set of complementary experiments. IPE2 is specifically expressed in maize developing anthers during stages 8 to 9 and encodes an endoplasmic-reticulum-localized GDSL lipase. Dysfunction of IPE2 resulted in delayed degeneration of tapetum and middle layer, leading to defective formation of anther cuticle and pollen exine, and complete male sterility. Aliphatic metabolism was greatly altered, with the contents of lipid constituents, especially C16/C18 fatty acids and their derivatives, significantly reduced in ipe2 developing anthers. Our study elucidates GDSL function in anther and pollen development and provides a promising genetic resource for breeding hybrid maize.
ESTHER : Huo_2020_Plant.Physiol_184_1438
PubMedSearch : Huo_2020_Plant.Physiol_184_1438
PubMedID: 32913046

Title : Toxicity Assessment of 4 Azo Dyes in Zebrafish Embryos - Jiang_2020_Int.J.Toxicol__1091581819898396
Author(s) : Jiang LL , Li K , Yan DL , Yang MF , Ma L , Xie LZ
Ref : Int J Toxicol , :1091581819898396 , 2020
Abstract : Azo dyes are used widely as color additives in food, drugs, and cosmetics; hence, there is an increasing concern about their safety and possible health hazards. In the present study, we chose 4 azo dyes tartrazine, Sunset Yellow, amaranth, and Allura red and evaluated their developmental toxicity on zebrafish embryos. At concentration levels of 5 to 50 mM, we found that azo dyes can induce hatching difficulty and developmental abnormalities such as cardiac edema, decreased heart rate, yolk sac edema, and spinal defects including spinal curvature and tail distortion. Exposure to 100 mM of each azo dye was completely embryolethal. The median lethal concentration (LC50), median effective concentration (EC50), and teratogenic index (TI) were calculated for each azo dye at 72 hours postfertilization. For tartrazine, the LC50 was 47.10 mM and EC50 value was at 42.66 mM with TI ratio of 1.10. For Sunset Yellow, the LC50 was 38.93 mM and EC50 value was at 29.81 mM with TI ratio of 1.31. For amaranth, the LC50 was 39.86 mM and EC50 value was at 31.94 mM with TI ratio of 1.25. For Allura red, the LC50 was 47.42 mM and EC50 value was 40.05 mM with TI ratio of 1.18. This study reports the developmental toxicity of azo dyes in zebrafish embryos at concentrations higher than the expected human exposures from consuming food and drugs containing azo dyes.
ESTHER : Jiang_2020_Int.J.Toxicol__1091581819898396
PubMedSearch : Jiang_2020_Int.J.Toxicol__1091581819898396
PubMedID: 31933405

Title : Enhanced anti-amnestic effect of donepezil by Ginkgo biloba extract (EGb 761) via further improvement in pro-cholinergic and antioxidative activities - Zhao_2020_J.Ethnopharmacol__113711
Author(s) : Zhao J , Li K , Wang Y , Li D , Wang Q , Xie S , Wang J , Zuo Z
Ref : J Ethnopharmacol , :113711 , 2020
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: EGb 761 is a standardized dry extract of Ginkgo biloba L. leaves traditionally used by Eastern Asia and has been associated with beneficial effects on neurodegeneration disorders, including Alzheimer's disease. AIM OF THE STUDY: Since beneficial interactions between EGb 761 and donepezil have been observed in previous clinical studies, the current study was proposed aiming to further explore related mechanisms from both pharmacokinetics and pharmacodynamics aspects. MATERIALS AND METHODS: Pharmacodynamic interactions were studied in scopolamine-induced cognitive impairment rats received two-weeks treatment of vehicle, EGb 761 and/or donepezil by the Morris water maze test and ex vivo evaluation of biomarkers of cholinergic transmission and oxidative stress in rat brain. In the meantime, pharmacokinetic profiles of donepezil and bilobalide were obtained and compared among all treatment groups. In addition, impact of the bioavailable EGb 761 components on donepezil brain penetration was evaluated with the hCMEC/D3 cell monolayer model. RESULTS: Scopolamine-induced rats with co-treatment of EGb 761 and donepezil had significantly improved cognitive function in the Morris water maze test with increased brain levels of superoxide dismutase and decreased brain levels of acetylcholinesterase and malondialdehyde than that with treatment of only EGb 761 or donepezil. Despite such beneficial pharmacodynamics outcomes, the two-week co-treatment of EGb 761 and donepezil did not alter the plasma pharmacokinetics and brain uptake of donepezil or bilobalide, which was further verified in the hCMEC/D3 monolayer model. CONCLUSION: Co-administration of EGb 761 and donepezil exerted better anti-amnestic effect via further enhanced pro-cholinergic and antioxidative effects of EGb 761 or donepezil in scopolamine-induced cognitive impairment rat without alteration in their systemic/brain exposure.
ESTHER : Zhao_2020_J.Ethnopharmacol__113711
PubMedSearch : Zhao_2020_J.Ethnopharmacol__113711
PubMedID: 33352242

Title : The Chromosome-Based Rubber Tree Genome Provides New Insights into Spurge Genome Evolution and Rubber Biosynthesis - Liu_2020_Mol.Plant_13_336
Author(s) : Liu J , Shi C , Shi CC , Li W , Zhang QJ , Zhang Y , Li K , Lu HF , Zhu ST , Xiao ZY , Nan H , Yue Y , Zhu XG , Wu Y , Hong XN , Fan GY , Tong Y , Zhang D , Mao CL , Liu YL , Hao SJ , Liu WQ , Lv MQ , Zhang HB , Liu Y , Hu-Tang GR , Wang JP , Wang JH , Sun YH , Ni SB , Chen WB , Zhang XC , Jiao YN , Eichler EE , Li GH , Liu X , Gao LZ
Ref : Mol Plant , 13 :336 , 2020
Abstract : The rubber tree, Hevea brasiliensis, produces natural rubber that serves as an essential industrial raw material. Here, we present a high-quality reference genome for a rubber tree cultivar GT1 using single-molecule real-time sequencing (SMRT) and Hi-C technologies to anchor the -1.47-Gb genome assembly into 18 pseudochromosomes. The chromosome-based genome analysis enabled us to establish a model of spurge chromosome evolution, since the common paleopolyploid event occurred before the split of Hevea and Manihot. We show recent and rapid bursts of the three Hevea-specific LTR-retrotransposon families during the last 10 million years, leading to the massive expansion by -65.88% (-970 Mbp) of the whole rubber tree genome since the divergence from Manihot. We identify large-scale expansion of genes associated with whole rubber biosynthesis processes, such as basal metabolic processes, ethylene biosynthesis, and the activation of polysaccharide and glycoprotein lectin, which are important properties for latex production. A map of genomic variation between the cultivated and wild rubber trees was obtained, which contains -15.7 million high-quality single-nucleotide polymorphisms. We identified hundreds of candidate domestication genes with drastically lowered genomic diversity in the cultivated but not wild rubber trees despite a relatively short domestication history of rubber tree, some of which are involved in rubber biosynthesis. This genome assembly represents key resources for future rubber tree research and breeding, providing novel targets for improving plant biotic and abiotic tolerance and rubber production.
ESTHER : Liu_2020_Mol.Plant_13_336
PubMedSearch : Liu_2020_Mol.Plant_13_336
PubMedID: 31838037
Gene_locus related to this paper: hevbr-a0a6a6mdr9

Title : Development of a Mouse-Adapted MERS Coronavirus - Li_2020_Methods.Mol.Biol_2099_161
Author(s) : Li K , McCray PB, Jr.
Ref : Methods Mol Biol , 2099 :161 , 2020
Abstract : First identified in 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel virus that can cause acute respiratory distress syndrome (ARDS), multiorgan failure, and death, with a case fatality rate of ~35%. An animal model that supports MERS-CoV infection and causes severe lung disease is useful to study pathogenesis and evaluate therapies and vaccines. The murine dipeptidyl peptidase 4 (Dpp4) protein is not a functional receptor for MERS-CoV; thus, mice are resistant to MERS-CoV infection. We generated human DPP4 knock-in (hDPP4 KI) mice by replacing exons 10-12 at the mouse Dpp4 locus with exons 10-12 from the human DPP4 gene. The resultant human DPP4 KI mice are permissive to MERS-CoV (HCoV-EMC/2012 strain) infection but develop no disease. To generate a mouse model with associated morbidity and mortality from respiratory disease, we serially passaged HCoV-EMC/2012 strain in the lungs of young hDPP4 KI mice. After 30 in vivo passages, an adapted virus clone was isolated and designated MERSMA6.1.2. This virus clone produced significantly higher titers than the parental clone in the lungs of hDPP4 KI mice and caused diffuse lung injury and a fatal respiratory infection. In this chapter, we will describe in detail the procedures used to mouse adapt MERS-CoV by serial passage of the virus in lungs. We also describe the methods used to isolate virus clones and characterize virus infection.
ESTHER : Li_2020_Methods.Mol.Biol_2099_161
PubMedSearch : Li_2020_Methods.Mol.Biol_2099_161
PubMedID: 31883095

Title : Lipopeptide Epimers and a Phthalide Glycerol Ether with AChE Inhibitory Activities from the Marine-Derived Fungus Cochliobolus Lunatus SCSIO41401 - Dai_2020_Mar.Drugs_18_
Author(s) : Dai Y , Li K , She J , Zeng Y , Wang H , Liao S , Lin X , Yang B , Wang J , Tao H , Dai H , Zhou X , Liu Y
Ref : Mar Drugs , 18 : , 2020
Abstract : A pair of novel lipopeptide epimers, sinulariapeptides A (1) and B (2), and a new phthalide glycerol ether (3) were isolated from the marine algal-associated fungus Cochliobolus lunatus SCSIO41401, together with three known chromanone derivates (4-6). The structures of the new compounds, including the absolute configurations, were determined by comprehensive spectroscopic methods, experimental and calculated electronic circular dichroism (ECD), and Mo(2) (OAc)(4)-induced ECD methods. The new compounds 1-3 showed moderate inhibitory activity against acetylcholinesterase (AChE), with IC(50) values of 1.3-2.5 M, and an in silico molecular docking study was also performed.
ESTHER : Dai_2020_Mar.Drugs_18_
PubMedSearch : Dai_2020_Mar.Drugs_18_
PubMedID: 33143384

Title : Two transcription factors cooperatively regulate DHN melanin biosynthesis and development in Pestalotiopsis fici - Zhang_2019_Mol.Microbiol_112_649
Author(s) : Zhang P , Zhou S , Wang G , An Z , Liu X , Li K , Yin WB
Ref : Molecular Microbiology , 112 :649 , 2019
Abstract : Fungal 1,8-dihydroxynaphthalene (DHN) melanin plays important roles in UV protection, oxidative stress and pathogenesis. However, knowledge of the regulatory mechanisms of its biosynthesis is limited. Previous studies showed two transcription factors, PfmaF and PfmaH, located in the DHN melanin biosynthetic gene cluster (Pfma) in Pestalotiopsis fici. In this study, deletion of PfmaH resulted in loss of melanin and affected conidia cell wall integrity. Specifically, PfmaH directly regulates the expression of scytalone dehydratase, which catalyzes the transition of scytalone to T(3) HN. However, PfmaF disruption using CRISPR/Cas9 system affected neither DHN melanin distribution nor conidia cell wall integrity in P. fici. Unexpectedly, overexpression of PfmaF leads to heavy pigment accumulation in P. fici hyphae. Transcriptome and qRT-PCR analyses provide insight into the roles of PfmaF and PfmaH in DHN melanin regulation. PfmaH, as a pathway specific regulator, mainly regulates melanin biosynthesis that contributes to cell wall development. Furthermore, PfmaF functions as a broad regulator to stimulate PfmaH expression in melanin production, secondary metabolism as well as fungal development.
ESTHER : Zhang_2019_Mol.Microbiol_112_649
PubMedSearch : Zhang_2019_Mol.Microbiol_112_649
PubMedID: 31116900
Gene_locus related to this paper: pesfw-pfmab , pesfw-pfmae

Title : Rational Design of a Long-Wavelength Fluorescent Probe for Highly Selective Sensing of Carboxylesterase 1 in Living Systems - Tian_2019_Anal.Chem_91_5638
Author(s) : Tian Z , Ding L , Li K , Song Y , Dou T , Hou J , Tian X , Feng L , Ge G , Cui J
Ref : Analytical Chemistry , 91 :5638 , 2019
Abstract : Rational design of practical probes with excellent specificity and improved optical properties for a particular enzyme is always a big challenge. Herein, a practical and highly specific fluorescent probe for carboxylesterase 1 (CES1) was rationally designed using meso-carboxyl-BODIPY as the basic fluorophore based on the substrate preference and catalytic properties of CES1. Following molecular docking-based virtual screening combined with reaction phenotyping-based experimental screening, we found that MMB (probe 7) exhibited the optimal combination of sensitivity and specificity toward human CES1 in contrast to other ester derivatives. Under physiological conditions, MMB could be readily hydrolyzed by CES1 and release MCB; such biotransformation brought great changes in the electronic properties at the meso position of the fluorophore and triggered a dramatic increase in fluorescence emission around 595 nm. Moreover, MMB was cell membrane permeable and was successfully applied to monitor the real activities of CES1 in various biological samples including living cells, tissue slices, organs, and zebrafish. In summary, this study showed a good example for constructing specific fluorescent probe(s) for a target enzyme and also provided a practical and sensitive tool for real-time sensing of CES1 activities in complicated biological samples. All these findings would strongly facilitate high-throughput screening of CES1 modulators and the studies on CES1-associated physiological and pathological processes.
ESTHER : Tian_2019_Anal.Chem_91_5638
PubMedSearch : Tian_2019_Anal.Chem_91_5638
PubMedID: 30968686

Title : Diagnosis of Hirschsprung's Disease by Immunostaining Rectal Suction Biopsies for Calretinin, S100 Protein and Protein Gene Product 9.5 - Chi_2019_J.Vis.Exp__
Author(s) : Chi S , Fang M , Li K , Yang L , Tang ST
Ref : J Vis Exp , : , 2019
Abstract : Hirschsprung's disease (HD) is a congenital intestinal disease that is clinically manifested as an inability to pass meconium in infants or as long-term constipation in children. Rectal suction biopsy (RSB) to determine the absence of ganglion cells and neural hypertrophy is the most accurate test for the diagnosis of HD at present. Traditional hematoxylin-eosin staining lacks sensitivity and specificity. Acetylcholinesterase staining cannot be widely used due to its complex process. Our novel protocol of immunostaining for calretinin, S100 protein, and protein gene product 9.5 (PGP9.5), which we conducted on RSBs, exhibits high sensitivity and specificity rates of 96.49% (95% confidence interval, 0.88-0.99) and 100% (95% confidence interval, 0.97-1.00), respectively. The HD-affected segments often present as the absence of the expression of calretinin, S100 protein, and PGP9.5, which are markers of neural hypertrophy in the submucosal tissue. This protocol describes the detailed operating process of this new diagnostic method.
ESTHER : Chi_2019_J.Vis.Exp__
PubMedSearch : Chi_2019_J.Vis.Exp__
PubMedID: 31081806

Title : Tacrine modulates Kv2.1 channel gene expression and cell proliferation - Hu_2019_Int.J.Neurosci__1
Author(s) : Hu XM , Ren S , Li K , Li XT
Ref : International Journal of Neuroscience , :1 , 2019
Abstract : Besides as a cholinesterase (ChE) inhibitor, tacrine is able to act on multiple targets such as nicotinic receptors (nAChRs) and voltage-gated K(+) (Kv) channels. Kv2.1, a Kv channel subunit underlying delayed rectifier currents with slow kinetics of inactivation, is highly expressed in the mammalian brain, especially in the hippocampus. Nevertheless, limited data are available concerning the relationship between tacrine and Kv2.1 channels. In the present study, incubation with tacrine induced a significant reduction of the mRNA level of Kv2.1 channels heterologously expressed in HEK293 cells. The decline of corresponding currents carried by Kv2.1 was also detected by whole-cell recording. Moreover, the proliferation rates of HEK293 cells with Kv2.1 channel were substantially enhanced after treatment with this chemical for 24 h. Similar results were also detected after exposure to tacrine in N2A cells with native expression of Kv2.1 channels. These lines of evidence indicate that application of tacrine downregulates the expression of Kv2.1 channels and increase cell proliferation. The effect of tacrine on Kv2.1 channels may provide an alternative explanation for its neuroprotective action.
ESTHER : Hu_2019_Int.J.Neurosci__1
PubMedSearch : Hu_2019_Int.J.Neurosci__1
PubMedID: 31847645

Title : Therapeutic efficacy and safety of umbilical cord mesenchymal stem cell transplantation for liver cirrhosis in Chinese population: A meta-analysis - Sang_2018_Clin.Res.Hepatol.Gastroenterol_42_193
Author(s) : Sang W , Lv B , Li K , Lu Y
Ref : Clin Res Hepatol Gastroenterol , 42 :193 , 2018
Abstract : BACKGROUND AND OBJECTIVE: Mesenchymal stem cells transfusion has been considered as a promising option for liver cirrhosis (LC). The aim of this study was to systematically evaluate the efficacy and safety of umbilical cord mesenchymal stem cells (UMSC) combined with traditional supportive therapy (TST) for the treatment of patients with LC. METHODS: Data was extracted from clinical trials published on Web of Science, PubMed, EMBASE, Cochrane Library, Wanfang and CNKI database. The evaluated outcome measurements included liver function, coagulation function, liver fibrosis indexes, clinical symptoms, quality of life (QOL) and adverse events. RESULTS: A total of 14 trials including 717 LC patients met our selection criteria were involved. The liver function of LC patients was significantly improved after combined therapy (UMSC plus TST), indicated by decreased total bilirubin, alanine aminotransferase and prothrombin time, and increased serum albumin, cholinesterase and prothrombin activity. The QOL of patients was also improved after UMSC therapy. Compared with TST alone, the combined therapy showed better treatment effect based on measurements of hyaluronic acid (OR=-143.20, CI=-181.58 to -104.82, P<0.00001), laminin (OR=-50.65, CI=-53.70 to -47.61, P<0.00001), type III procollagen (OR=-8.68, CI=-9.00 to -8.36, P<0.00001), type IV collagen (OR=-105.79, CI=-132.44 to -79.14, P<0.00001) and plasma prolidase (OR=-876.54, CI=-911.89 to -840.56, P<0.00001). Moreover, the patients' clinical symptoms including fatigue (4th, P=0.003; 8th, P=0.01), appetite (4th, P<0.0001; 8th, P=0.06), ascites (4th, P=0.03; 8th, P=0.17), and abdominal distension (4th, P=0.0008; 8th, P=0.64) were also improved in patients treated by combined therapy without adverse events observed. CONCLUSION: UMSC and TST combined therapy for LC patients improved their liver function, clinical symptoms and QOL without severe adverse events, therefore is safe and effective in LC therapy.
ESTHER : Sang_2018_Clin.Res.Hepatol.Gastroenterol_42_193
PubMedSearch : Sang_2018_Clin.Res.Hepatol.Gastroenterol_42_193
PubMedID: 29223366

Title : Hydrolysis Activity of Pyloric Cecal Enterocytes of Brown Trout (Salmo trutta) toward Monoacylglycerol and Lysophosphatidylcholine - Li_2018_Lipids_53_615
Author(s) : Li K , Egelandsdal B , Olsen RE
Ref : Lipids , 53 :615 , 2018
Abstract : Some lipid digestion pathways in fish deviate from those in mammals, and many differences may also be species dependent. This report describes a pathway for monoacylglycerol (MAG) and lysophospholipid absorption by intestinal enterocytes in brown trout that may be of significance in salmonids. When culturing primary cells in a medium containing 1- and 2-MAG, we observed a massive hydrolysis of unesterified fatty acids. The hydrolysis activity was retained in the medium even after the removal of the cells. To further characterize these activities, both extracellular and isolated membrane proteins were tested for lipase activity toward triacylglycerol (TAG), diacylglycerol (DAG), MAG, phosphatidylcholine (PtdCho), and lysoPtdCho. In both cases, the main hydrolyzing activity was toward MAG followed by lysoPtdCho with very little activity toward DAG, TAG, or PtdCho. The extracellular and membrane proteins were partially purified by fast protein liquid chromatography and identified by proteomics (liquid chromatography-tandem mass spectrometry) focusing on lipase/hydrolase enzymes. In the membrane protein fraction, the data suggested that MAG was produced as an intermediate in the hydrolysis of lysoPtdCho by either lysophospholipase C or lysophospholipase D activity. Both abhydrolase-domain-containing protein 6 and abhydrolase-domain-containing protein 12 were identified in the membrane protein and they could be responsible for the hydrolysis of MAG. In the culture medium, low-peptide matches were found for ABHD6 and phospholipases and further studies are needed. In summary, trout enterocytes are capable of hydrolyzing MAG and lysoPtdCho. The enzymes are both extracellular and membrane bound. The pathways may be of significance during lipid absorption in fish lacking a 1,3 specific pancreatic lipase.
ESTHER : Li_2018_Lipids_53_615
PubMedSearch : Li_2018_Lipids_53_615
PubMedID: 30198578

Title : A novel chlorpyrifos hydrolase CPD from Paracoccus sp. TRP: Molecular cloning, characterization and catalytic mechanism - Fan_2018_Electron.J.Biotechnol_31_10
Author(s) : Fan S , Li K , Yan Y , Wang J , Qiao C , Yang T , Jia Y , Zhao B
Ref : Electronic Journal of Biotechnology , 31 :10 , 2018
Abstract : Background: Biodegradation is a reliable approach for efficiently eliminating persistent pollutants such as chlorpyrifos. Despite many bacteria or fungi isolated from contaminated environment and capable of degrading chlorpyrifos, limited enzymes responsible for its degradation have been identified, let alone the catalytic mechanism of the enzymes. Results: In present study, the gene cpd encoding a chlorpyrifos hydrolase was cloned by analysis of genomic sequence of Paracoccus sp. TRP. Phylogenetic analysis and BLAST indicated that CPD was a novel member of organophosphate hydrolases. The purified CPD enzyme, with conserved catalytic triad (Ser155-Asp251-His281) and motif Gly-Asp-Ser-Ala-Gly, was significantly inhibited by PMSF, a serine modifier. Molecular docking between CPD and chlorpyrifos showed that Ser155 was adjacent to chlorpyrifos, which indicated that Ser155 may be the active amino acid involved in chlorpyrifos degradation. This speculation was confirmed by site-directed mutagenesis of Ser155Ala accounting for the decreased activity of CPD towards chlorpyrifos. According to the key role of Ser155 in chlorpyrifos degradation and molecular docking conformation, the nucleophilic catalytic mechanism for chlorpyrifos degradation by CPD was proposed. Conclusion: The novel enzyme CPD was capable of hydrolyze chlorpyrifos and Ser155 played key role during degradation of chlorpyrifos.
ESTHER : Fan_2018_Electron.J.Biotechnol_31_10
PubMedSearch : Fan_2018_Electron.J.Biotechnol_31_10
Gene_locus related to this paper: 9rhob-a0a1x7ll67

Title : IMA Genome-F 9: Draft genome sequence of Annulohypoxylon stygium, Aspergillus mulundensis, Berkeleyomyces basicola (syn. Thielaviopsis basicola), Ceratocystis smalleyi, two Cercospora beticola strains, Coleophoma cylindrospora, Fusarium fracticaudum, Phialophora cf. hyalina, and Morchella septimelata - Wingfield_2018_IMA.Fungus_9_199
Author(s) : Wingfield BD , Bills GF , Dong Y , Huang W , Nel WJ , Swalarsk-Parry BS , Vaghefi N , Wilken PM , An Z , de Beer ZW , De Vos L , Chen L , Duong TA , Gao Y , Hammerbacher A , Kikkert JR , Li Y , Li H , Li K , Li Q , Liu X , Ma X , Naidoo K , Pethybridge SJ , Sun J , Steenkamp ET , van der Nest MA , van Wyk S , Wingfield MJ , Xiong C , Yue Q , Zhang X
Ref : IMA Fungus , 9 :199 , 2018
Abstract : Draft genomes of the species Annulohypoxylon stygium, Aspergillus mulundensis, Berkeleyomyces basicola (syn. Thielaviopsis basicola), Ceratocystis smalleyi, two Cercospora beticola strains, Coleophoma cylindrospora, Fusarium fracticaudum, Phialophora cf. hyalina and Morchella septimelata are presented. Both mating types (MAT1-1 and MAT1-2) of Cercospora beticola are included. Two strains of Coleophoma cylindrospora that produce sulfated homotyrosine echinocandin variants, FR209602, FR220897 and FR220899 are presented. The sequencing of Aspergillus mulundensis, Coleophoma cylindrospora and Phialophora cf. hyalina has enabled mapping of the gene clusters encoding the chemical diversity from the echinocandin pathways, providing data that reveals the complexity of secondary metabolism in these different species. Overall these genomes provide a valuable resource for understanding the molecular processes underlying pathogenicity (in some cases), biology and toxin production of these economically important fungi.
ESTHER : Wingfield_2018_IMA.Fungus_9_199
PubMedSearch : Wingfield_2018_IMA.Fungus_9_199
PubMedID: 30018880
Gene_locus related to this paper: 9helo-a0a370tge3 , 9helo-a0a3d8spg6 , 9euro-a0a3d8t2t6 , 9euro-a0a3d8t644 , 9helo-a0a370te58 , 9helo-a0a370tt42 , 9helo-a0a370u2s4 , 9helo-a0a3d8s0y2 , 9helo-a0a3d8stp9 , 9helo-a0a370u370 , 9euro-a0a3d8rk78 , 9helo-a0a370tat5 , 9helo-a0a3d8qpi0

Title : The Aegilops tauschii genome reveals multiple impacts of transposons - Zhao_2017_Nat.Plants_3_946
Author(s) : Zhao G , Zou C , Li K , Wang K , Li T , Gao L , Zhang X , Wang H , Yang Z , Liu X , Jiang W , Mao L , Kong X , Jiao Y , Jia J
Ref : Nat Plants , 3 :946 , 2017
Abstract : Wheat is an important global crop with an extremely large and complex genome that contains more transposable elements (TEs) than any other known crop species. Here, we generated a chromosome-scale, high-quality reference genome of Aegilops tauschii, the donor of the wheat D genome, in which 92.5% sequences have been anchored to chromosomes. Using this assembly, we accurately characterized genic loci, gene expression, pseudogenes, methylation, recombination ratios, microRNAs and especially TEs on chromosomes. In addition to the discovery of a wave of very recent gene duplications, we detected that TEs occurred in about half of the genes, and found that such genes are expressed at lower levels than those without TEs, presumably because of their elevated methylation levels. We mapped all wheat molecular markers and constructed a high-resolution integrated genetic map corresponding to genome sequences, thereby placing previously detected agronomically important genes/quantitative trait loci (QTLs) on the Ae. tauschii genome for the first time.
ESTHER : Zhao_2017_Nat.Plants_3_946
PubMedSearch : Zhao_2017_Nat.Plants_3_946
PubMedID: 29158546
Gene_locus related to this paper: horvv-m0utz9 , wheat-a0a3b6c2m6 , wheat-a0a3b5zwb6 , wheat-a0a3b6bzs8 , wheat-a0a1d5zte7 , wheat-a0a1d5uwn5

Title : Depletion of juvenile hormone esterase extends larval growth in Bombyx mori - Zhang_2017_Insect.Biochem.Mol.Biol_81_72
Author(s) : Zhang Z , Liu X , Shiotsuki T , Wang Z , Xu X , Huang Y , Li M , Li K , Tan A
Ref : Insect Biochemistry & Molecular Biology , 81 :72 , 2017
Abstract : Two major hormones, juvenile hormone (JH) and 20-hydroxyecdysone (20E), regulate insect growth and development according to their precisely coordinated titres, which are controlled by both biosynthesis and degradation pathways. Juvenile hormone esterase (JHE) is the primary JH-specific degradation enzyme that plays a key role in regulating JH titers, along with JH epoxide hydrolase (JHEH) and JH diol kinase (JHDK). In the current study, a loss-of-function analysis of JHE in the silkworm, Bombyx mori, was performed by targeted gene disruption using the transgenic CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/RNA-guided Cas9 nucleases) system. Depletion of B. mori JHE (BmJHE) resulted in the extension of larval stages, especially the penultimate and ultimate larval stages, without deleterious effects to silkworm physiology. The expression of JHEH and JHDK was upregulated in mutant animals, indicating the existence of complementary routes in the JH metabolism pathway in which inactivation of one enzyme will activate other enzymes. RNA-Seq analysis of mutant animals revealed that genes involved in protein processing in the endoplasmic reticulum and in amino acid metabolism were affected by BmJHE depletion. Depletion of JHE and subsequent delayed JH metabolism activated genes in the TOR pathway, which are ultimately responsible for extending larval growth. The transgenic Cas9 system used in the current study provides a promising approach for analysing the actions of JH, especially in nondrosophilid insects. Furthermore, prolonging larval stages produced larger larvae and cocoons, which is greatly beneficial to silk production.
ESTHER : Zhang_2017_Insect.Biochem.Mol.Biol_81_72
PubMedSearch : Zhang_2017_Insect.Biochem.Mol.Biol_81_72
PubMedID: 28057597

Title : The tetraspanin CD9 facilitates MERS-coronavirus entry by scaffolding host cell receptors and proteases - Earnest_2017_PLoS.Pathog_13_e1006546
Author(s) : Earnest JT , Hantak MP , Li K , McCray PB, Jr. , Perlman S , Gallagher T
Ref : PLoS Pathog , 13 :e1006546 , 2017
Abstract : Infection by enveloped coronaviruses (CoVs) initiates with viral spike (S) proteins binding to cellular receptors, and is followed by proteolytic cleavage of receptor-bound S proteins, which prompts S protein-mediated virus-cell membrane fusion. Infection therefore requires close proximity of receptors and proteases. We considered whether tetraspanins, scaffolding proteins known to facilitate CoV infections, hold receptors and proteases together on cell membranes. Using knockout cell lines, we found that the tetraspanin CD9, but not the tetraspanin CD81, formed cell-surface complexes of dipeptidyl peptidase 4 (DPP4), the MERS-CoV receptor, and the type II transmembrane serine protease (TTSP) member TMPRSS2, a CoV-activating protease. This CD9-facilitated condensation of receptors and proteases allowed MERS-CoV pseudoviruses to enter cells rapidly and efficiently. Without CD9, MERS-CoV viruses were not activated by TTSPs, and they trafficked into endosomes to be cleaved much later and less efficiently by cathepsins. Thus, we identified DPP4:CD9:TTSP as the protein complexes necessary for early, efficient MERS-CoV entry. To evaluate the importance of these complexes in an in vivo CoV infection model, we used recombinant Adenovirus 5 (rAd5) vectors to express human DPP4 in mouse lungs, thereby sensitizing the animals to MERS-CoV infection. When the rAd5-hDPP4 vectors co-expressed small RNAs silencing Cd9 or Tmprss2, the animals were significantly less susceptible, indicating that CD9 and TMPRSS2 facilitated robust in vivo MERS-CoV infection of mouse lungs. Furthermore, the S proteins of virulent mouse-adapted MERS-CoVs acquired a CD9-dependent cell entry character, suggesting that CD9 is a selective agent in the evolution of CoV virulence.
ESTHER : Earnest_2017_PLoS.Pathog_13_e1006546
PubMedSearch : Earnest_2017_PLoS.Pathog_13_e1006546
PubMedID: 28759649

Title : Inhibitory effects of cholinesterase inhibitor donepezil on the Kv1.5 potassium channel - Li_2017_Sci.Rep_7_41509
Author(s) : Li K , Cheng N , Li XT
Ref : Sci Rep , 7 :41509 , 2017
Abstract : Kv1.5 channels carry ultra-rapid delayed rectifier K+ currents in excitable cells, including neurons and cardiac myocytes. In the current study, the effects of cholinesterase inhibitor donepezil on cloned Kv1.5 channels expressed in HEK29 cells were explored using whole-cell recording technique. Exposure to donepezil resulted in a rapid and reversible block of Kv1.5 currents, with an IC50 value of 72.5 muM. The mutant R476V significantly reduced the binding affinity of donepezil to Kv1.5 channels, showing the target site in the outer mouth region. Donepezil produced a significant delay in the duration of activation and deactivation, and mutant R476V potentiated these effects without altering activation curves. In response to slowed deactivation time course, a typical crossover of Kv1.5 tail currents was clearly evident after bath application of donepezil. In addition, both this chemical and mutant R476V accelerated current decay during channel inactivation in a voltage-dependent way, but barely changed the inactivation and recovery curves. The presence of donepezil exhibited the use-dependent block of Kv1.5 currents in response to a series of depolarizing pulses. Our data indicate that donepezil can directly block Kv1.5 channels in its open and closed states.
ESTHER : Li_2017_Sci.Rep_7_41509
PubMedSearch : Li_2017_Sci.Rep_7_41509
PubMedID: 28198801

Title : Mouse-adapted MERS coronavirus causes lethal lung disease in human DPP4 knockin mice - Li_2017_Proc.Natl.Acad.Sci.U.S.A_114_E3119
Author(s) : Li K , Wohlford-Lenane CL , Channappanavar R , Park JE , Earnest JT , Bair TB , Bates AM , Brogden KA , Flaherty HA , Gallagher T , Meyerholz DK , Perlman S , McCray PB, Jr.
Ref : Proc Natl Acad Sci U S A , 114 :E3119 , 2017
Abstract : The Middle East respiratory syndrome (MERS) emerged in Saudi Arabia in 2012, caused by a zoonotically transmitted coronavirus (CoV). Over 1,900 cases have been reported to date, with approximately 36% fatality rate. Lack of autopsies from MERS cases has hindered understanding of MERS-CoV pathogenesis. A small animal model that develops progressive pulmonary manifestations when infected with MERS-CoV would advance the field. As mice are restricted to infection at the level of DPP4, the MERS-CoV receptor, we generated mice with humanized exons 10-12 of the mouse Dpp4 locus. Upon inoculation with MERS-CoV, human DPP4 knockin (KI) mice supported virus replication in the lungs, but developed no illness. After 30 serial passages through the lungs of KI mice, a mouse-adapted virus emerged (MERSMA) that grew in lungs to over 100 times higher titers than the starting virus. A plaque-purified MERSMA clone caused weight loss and fatal infection. Virus antigen was observed in airway epithelia, pneumocytes, and macrophages. Pathologic findings included diffuse alveolar damage with pulmonary edema and hyaline membrane formation associated with accumulation of activated inflammatory monocyte-macrophages and neutrophils in the lungs. Relative to the parental MERS-CoV, MERSMA viruses contained 13-22 mutations, including several within the spike (S) glycoprotein gene. S-protein mutations sensitized viruses to entry-activating serine proteases and conferred more rapid entry kinetics. Recombinant MERSMA bearing mutant S proteins were more virulent than the parental virus in hDPP4 KI mice. The hDPP4 KI mouse and the MERSMA provide tools to investigate disease causes and develop new therapies.
ESTHER : Li_2017_Proc.Natl.Acad.Sci.U.S.A_114_E3119
PubMedSearch : Li_2017_Proc.Natl.Acad.Sci.U.S.A_114_E3119
PubMedID: 28348219

Title : Calretinin, S100 and protein gene product 9.5 immunostaining of rectal suction biopsies in the diagnosis of Hirschsprung' disease - Jiang_2016_Am.J.Transl.Res_8_3159
Author(s) : Jiang M , Li K , Li S , Yang L , Yang D , Zhang X , Fang M , Cao G , Wang Y , Chen W , Tang S
Ref : Am J Transl Res , 8 :3159 , 2016
Abstract : Evaluation of rectal suction biopsies for the ganglion cells and neural hypertrophy is the basic modality for the diagnosis of Hirschsprung's disease (HD). However, the traditional hematoxylin and eosin staining coupled with acetylcholinesterase histochemistry remain challenging, especially in newborns. Thus we conducted a prospective study to evaluate the usefulness of calretinin combined with S100 and protein gene product 9.5 (PGP9.5) immunostaining of rectal suction biopsies for the diagnosis of HD. A total of 195 patients were enrolled in our study. Of the 195 patients 69% had ganglion cells on the initial diagnostic protocol. Sixty cases were devoid of ganglion cells, and of these, 90% and 91% showed submucosal neural hypertrophy on S-100 staining and PGP9.5 staining, respectively. Eighty-one patients underwent a colonic resection, and of these, 59 had confirmed aganglionic segment, the other 22 patients were diagnosed as intestinal neuronal dysplasia type B (n=13) and isolated hypoganglionosis (n=9). Of the rest 114 patients, 51 cases underwent a full-thickness biopsy, and HD was excluded; sixty-three patients were thoroughly followed-up with no evidence of HD. We encountered two false-negatives and they were proved to be short segment HD after the surgery. The sensitivity and specificity rates of our diagnostic protocol was 96.49% (95% CI, 0.88-0.99) and 100% (95% CI, 0.97-1.00), respectively, excluding 5 patients with inconclusive results. Our findings demonstrated that calretinin coupled with S100 and PGP9.5 immunostaining on suction rectal biopsies is sensitive and specific for diagnosing HD.
ESTHER : Jiang_2016_Am.J.Transl.Res_8_3159
PubMedSearch : Jiang_2016_Am.J.Transl.Res_8_3159
PubMedID: 27508037

Title : Structure of Human GIVD Cytosolic Phospholipase A2 Reveals Insights into Substrate Recognition - Wang_2016_J.Mol.Biol_428_2769
Author(s) : Wang H , Klein MG , Snell G , Lane W , Zou H , Levin I , Li K , Sang BC
Ref : Journal of Molecular Biology , 428 :2769 , 2016
Abstract : Cytosolic phospholipases A2 (cPLA2s) consist of a family of calcium-sensitive enzymes that function to generate lipid second messengers through hydrolysis of membrane-associated glycerophospholipids. The GIVD cPLA2 (cPLA2delta) is a potential drug target for developing a selective therapeutic agent for the treatment of psoriasis. Here, we present two X-ray structures of human cPLA2delta, capturing an apo state, and in complex with a substrate-like inhibitor. Comparison of the apo and inhibitor-bound structures reveals conformational changes in a flexible cap that allows the substrate to access the relatively buried active site, providing new insight into the mechanism for substrate recognition. The cPLA2delta structure reveals an unexpected second C2 domain that was previously unrecognized from sequence alignments, placing cPLA2delta into the class of membrane-associated proteins that contain a tandem pair of C2 domains. Furthermore, our structures elucidate novel inter-domain interactions and define three potential calcium-binding sites that are likely important for regulation and activation of enzymatic activity. These findings provide novel insights into the molecular mechanisms governing cPLA2's function in signal transduction.
ESTHER : Wang_2016_J.Mol.Biol_428_2769
PubMedSearch : Wang_2016_J.Mol.Biol_428_2769
PubMedID: 27220631

Title : Middle East Respiratory Syndrome Coronavirus Causes Multiple Organ Damage and Lethal Disease in Mice Transgenic for Human Dipeptidyl Peptidase 4 - Li_2016_J.Infect.Dis_213_712
Author(s) : Li K , Wohlford-Lenane C , Perlman S , Zhao J , Jewell AK , Reznikov LR , Gibson-Corley KN , Meyerholz DK , McCray PB, Jr.
Ref : J Infect Dis , 213 :712 , 2016
Abstract : Middle East respiratory syndrome coronavirus (MERS-CoV) causes life-threatening disease. Dipeptidyl peptidase 4 (DPP4) is the receptor for cell binding and entry. There is a need for small-animal models of MERS, but mice are not susceptible to MERS because murine dpp4 does not serve as a receptor. We developed transgenic mice expressing human DPP4 (hDPP4) under the control of the surfactant protein C promoter or cytokeratin 18 promoter that are susceptible to infection with MERS-CoV. Notably, mice expressing hDPP4 with the cytokeratin 18 promoter developed progressive, uniformly fatal disease following intranasal inoculation. High virus titers were present in lung and brain tissues 2 and 6 days after infection, respectively. MERS-CoV-infected lungs revealed mononuclear cell infiltration, alveolar edema, and microvascular thrombosis, with airways generally unaffected. Brain disease was observed, with the greatest involvement noted in the thalamus and brain stem. Animals immunized with a vaccine candidate were uniformly protected from lethal infection. These new mouse models of MERS-CoV should be useful for investigation of early disease mechanisms and therapeutic interventions.
ESTHER : Li_2016_J.Infect.Dis_213_712
PubMedSearch : Li_2016_J.Infect.Dis_213_712
PubMedID: 26486634

Title : Rapid generation of a mouse model for Middle East respiratory syndrome - Zhao_2014_Proc.Natl.Acad.Sci.U.S.A_111_4970
Author(s) : Zhao J , Li K , Wohlford-Lenane C , Agnihothram SS , Fett C , Gale MJ, Jr. , Baric RS , Enjuanes L , Gallagher T , McCray PB, Jr. , Perlman S
Ref : Proc Natl Acad Sci U S A , 111 :4970 , 2014
Abstract : In this era of continued emergence of zoonotic virus infections, the rapid development of rodent models represents a critical barrier to public health preparedness, including the testing of antivirus therapy and vaccines. The Middle East respiratory syndrome coronavirus (MERS-CoV) was recently identified as the causative agent of a severe pneumonia. Given the ability of coronavirus to rapidly adapt to new hosts, a major public health concern is that MERS-CoV will further adapt to replication in humans, triggering a pandemic. No small-animal model for this infection is currently available, but studies suggest that virus entry factors can confer virus susceptibility. Here, we show that mice were sensitized to MERS-CoV infection by prior transduction with adenoviral vectors expressing the human host-cell receptor dipeptidyl peptidase 4. Mice developed a pneumonia characterized by extensive inflammatory-cell infiltration with virus clearance occurring 6-8 d after infection. Clinical disease and histopathological changes were more severe in the absence of type-I IFN signaling whereas the T-cell response was required for virus clearance. Using these mice, we demonstrated the efficacy of a therapeutic intervention (poly I:C) and a potential vaccine [Venezuelan equine encephalitis replicon particles expressing MERS-CoV spike protein]. We also found little protective cross-reactivity between MERS-CoV and the severe acute respiratory syndrome-CoV. Our results demonstrate that this system will be useful for MERS-CoV studies and for the rapid development of relevant animal models for emerging respiratory viral infections.
ESTHER : Zhao_2014_Proc.Natl.Acad.Sci.U.S.A_111_4970
PubMedSearch : Zhao_2014_Proc.Natl.Acad.Sci.U.S.A_111_4970
PubMedID: 24599590

Title : GPCRDB: an information system for G protein-coupled receptors - Isberg_2014_Nucleic.Acids.Res_42_D422
Author(s) : Isberg V , Vroling B , Van der Kant R , Li K , Vriend G , Gloriam D
Ref : Nucleic Acids Research , 42 :D422 , 2014
Abstract : For the past 20 years, the GPCRDB (G protein-coupled receptors database; has been a 'one-stop shop' for G protein-coupled receptor (GPCR)-related data. The GPCRDB contains experimental data on sequences, ligand-binding constants, mutations and oligomers, as well as many different types of computationally derived data, such as multiple sequence alignments and homology models. The GPCRDB also provides visualization and analysis tools, plus a number of query systems. In the latest GPCRDB release, all multiple sequence alignments, and >65,000 homology models, have been significantly improved, thanks to a recent flurry of GPCR X-ray structure data. Tools were introduced to browse X-ray structures, compare binding sites, profile similar receptors and generate amino acid conservation statistics. Snake plots and helix box diagrams can now be custom coloured (e.g. by chemical properties or mutation data) and saved as figures. A series of sequence alignment visualization tools has been added, and sequence alignments can now be created for subsets of sequences and sequence positions, and alignment statistics can be produced for any of these subsets.
ESTHER : Isberg_2014_Nucleic.Acids.Res_42_D422
PubMedSearch : Isberg_2014_Nucleic.Acids.Res_42_D422
PubMedID: 24304901

Title : Comparative genomics and transcriptomics analyses reveal divergent lifestyle features of nematode endoparasitic fungus Hirsutella minnesotensis - Lai_2014_Genome.Biol.Evol_6_3077
Author(s) : Lai Y , Liu K , Zhang X , Li K , Wang N , Shu C , Wu Y , Wang C , Bushley KE , Xiang M , Liu X
Ref : Genome Biol Evol , 6 :3077 , 2014
Abstract : Hirsutella minnesotensis [Ophiocordycipitaceae (Hypocreales, Ascomycota)] is a dominant endoparasitic fungus by using conidia that adhere to and penetrate the secondary stage juveniles of soybean cyst nematode. Its genome was de novo sequenced and compared with five entomopathogenic fungi in the Hypocreales and three nematode-trapping fungi in the Orbiliales (Ascomycota). The genome of H. minnesotensis is 51.4 Mb and encodes 12,702 genes enriched with transposable elements up to 32%. Phylogenomic analysis revealed that H. minnesotensis was diverged from entomopathogenic fungi in Hypocreales. Genome of H. minnesotensis is similar to those of entomopathogenic fungi to have fewer genes encoding lectins for adhesion and glycoside hydrolases for cellulose degradation, but is different from those of nematode-trapping fungi to possess more genes for protein degradation, signal transduction, and secondary metabolism. Those results indicate that H. minnesotensis has evolved different mechanism for nematode endoparasitism compared with nematode-trapping fungi. Transcriptomics analyses for the time-scale parasitism revealed the upregulations of lectins, secreted proteases and the genes for biosynthesis of secondary metabolites that could be putatively involved in host surface adhesion, cuticle degradation, and host manipulation. Genome and transcriptome analyses provided comprehensive understanding of the evolution and lifestyle of nematode endoparasitism.
ESTHER : Lai_2014_Genome.Biol.Evol_6_3077
PubMedSearch : Lai_2014_Genome.Biol.Evol_6_3077
PubMedID: 25359922
Gene_locus related to this paper: 9hypo-a0a0f7zjg7 , 9hypo-a0a0f7zm48 , 9hypo-a0a0f7zrk5 , 9hypo-a0a0f7ztt4 , 9hypo-a0a0f7ztz3 , 9hypo-a0a0f7zun4 , 9hypo-a0a0f7zus6 , 9hypo-a0a0f7zx75 , 9hypo-a0a0f7zy63 , 9hypo-a0a0f8a122 , 9hypo-a0a0f8a341 , 9hypo-a0a0f8a483 , 9hypo-a0a0f8a644 , 9hypo-a0a0f8a655 , 9hypo-a0a0f8a6k2 , 9hypo-a0a0f7zgk0 , 9hypo-a0a0f7zy10 , 9hypo-a0a0f7zmp5

Title : Retinotopic maps in the pulvinar of bush baby (otolemur garnettii) - Li_2013_J.Comp.Neurol_521_3432
Author(s) : Li K , Patel J , Purushothaman G , Marion RT , Casagrande VA
Ref : Journal of Comparative Neurology , 521 :3432 , 2013
Abstract : Despite its anatomical prominence, the function of the primate pulvinar is poorly understood. A few electrophysiological studies in simian primates have investigated the functional organization of pulvinar by examining visuotopic maps. Multiple visuotopic maps have been found for all studied simians, with differences in organization reported between New and Old World simians. Given that prosimians are considered closer to the common ancestors of New and Old World primates, we investigated the visuotopic organization of pulvinar in the prosimian bush baby (Otolemur garnettii). Single-electrode extracellular recording was used to find the retinotopic maps in the lateral (PL) and inferior (PI) pulvinar. Based on recordings across cases, a 3D model of the map was constructed. From sections stained for Nissl bodies, myelin, acetylcholinesterase, calbindin, or cytochrome oxidase, we identified three PI chemoarchitectonic subdivisions, lateral central (PIcl), medial central (PIcm), and medial (PIm) inferior pulvinar. Two major retinotopic maps were identified that cover PL and PIcl, the dorsal one in dorsal PL and the ventral one in PIcl and ventral PL. Both maps represent central vision at the posterior end of the border between the maps, the upper visual field in the lateral half and the lower visual field in the medial half. They share many features with the maps reported for the pulvinar of simians, including the location in pulvinar and the representation of the upper-lower and central-peripheral visual field axes. The second-order representation in the lateral map and a laminar organization are likely features specific to Old World simians. J. Comp. Neurol. 521:3432-3450, 2013. (c) 2013 Wiley Periodicals, Inc.
ESTHER : Li_2013_J.Comp.Neurol_521_3432
PubMedSearch : Li_2013_J.Comp.Neurol_521_3432
PubMedID: 23640865

Title : The genome and transcriptome of Haemonchus contortus, a key model parasite for drug and vaccine discovery - Laing_2013_Genome.Biol_14_R88
Author(s) : Laing R , Kikuchi T , Martinelli A , Tsai IJ , Beech RN , Redman E , Holroyd N , Bartley DJ , Beasley H , Britton C , Curran D , Devaney E , Gilabert A , Hunt M , Jackson F , Johnston SL , Kryukov I , Li K , Morrison AA , Reid AJ , Sargison N , Saunders GI , Wasmuth JD , Wolstenholme A , Berriman M , Gilleard JS , Cotton JA
Ref : Genome Biol , 14 :R88 , 2013
Abstract : BACKGROUND: The small ruminant parasite Haemonchus contortus is the most widely used parasitic nematode in drug discovery, vaccine development and anthelmintic resistance research. Its remarkable propensity to develop resistance threatens the viability of the sheep industry in many regions of the world and provides a cautionary example of the effect of mass drug administration to control parasitic nematodes. Its phylogenetic position makes it particularly well placed for comparison with the free-living nematode Caenorhabditis elegans and the most economically important parasites of livestock and humans.
RESULTS: Here we report the detailed analysis of a draft genome assembly and extensive transcriptomic dataset for H. contortus. This represents the first genome to be published for a strongylid nematode and the most extensive transcriptomic dataset for any parasitic nematode reported to date. We show a general pattern of conservation of genome structure and gene content between H. contortus and C. elegans, but also a dramatic expansion of important parasite gene families. We identify genes involved in parasite-specific pathways such as blood feeding, neurological function, and drug metabolism. In particular, we describe complete gene repertoires for known drug target families, providing the most comprehensive understanding yet of the action of several important anthelmintics. Also, we identify a set of genes enriched in the parasitic stages of the lifecycle and the parasite gut that provide a rich source of vaccine and drug target candidates.
CONCLUSIONS: The H. contortus genome and transcriptome provide an essential platform for postgenomic research in this and other important strongylid parasites.
ESTHER : Laing_2013_Genome.Biol_14_R88
PubMedSearch : Laing_2013_Genome.Biol_14_R88
PubMedID: 23985316
Gene_locus related to this paper: haeco-u6nsf0 , haeco-u6psa2 , haeco-u6pu58

Title : Molecular cloning and characterization of a newly isolated pyrethroid-degrading esterase gene from a genomic library of Ochrobactrum anthropi YZ-1 - Ruan_2013_PLoS.One_8_e77329
Author(s) : Ruan Z , Zhai Y , Song J , Shi Y , Li K , Zhao B , Yan Y
Ref : PLoS ONE , 8 :e77329 , 2013
Abstract : A novel pyrethroid-degrading esterase gene pytY was isolated from the genomic library of Ochrobactrum anthropi YZ-1. It possesses an open reading frame (ORF) of 897 bp. Blast search showed that its deduced amino acid sequence shares moderate identities (30% to 46%) with most homologous esterases. Phylogenetic analysis revealed that PytY is a member of the esterase VI family. pytY showed very low sequence similarity compared with reported pyrethroid-degrading genes. PytY was expressed, purified, and characterized. Enzyme assay revealed that PytY is a broad-spectrum degrading enzyme that can degrade various pyrethroids. It is a new pyrethroid-degrading gene and enriches genetic resource. Kinetic constants of Km and Vmax were 2.34 mmol.L(-1) and 56.33 nmol min(-1), respectively, with lambda-cyhalothrin as substrate. PytY displayed good degrading ability and stability over a broad range of temperature and pH. The optimal temperature and pH were of 35 degrees C and 7.5. No cofactors were required for enzyme activity. The results highlighted the potential use of PytY in the elimination of pyrethroid residuals from contaminated environments.
ESTHER : Ruan_2013_PLoS.One_8_e77329
PubMedSearch : Ruan_2013_PLoS.One_8_e77329
PubMedID: 24155944
Gene_locus related to this paper: 9rhiz-c4wm13

Title : Molecular cloning, purification and biochemical characterization of a novel pyrethroid-hydrolyzing carboxylesterase gene from Ochrobactrum anthropi YZ-1 - Zhai_2012_J.Hazard.Mater_221-222_206
Author(s) : Zhai Y , Li K , Song J , Shi Y , Yan Y
Ref : J Hazard Mater , 221-222 :206 , 2012
Abstract : Strain YZ-1 was isolated from activated sludge and identified as Ochrobactrum anthropi. This strain was capable of degrading pyrethroids pesticides, suggesting the presence of degrading enzymes. In the present study, a novel esterase gene pytZ was cloned from the genomic library of YZ-1 successfully. The pytZ contained an open reading frame of 606bp encoding a pyrethroid-hydrolyzing carboxylesterase. Deduced amino acid sequence showed moderate identities (39-59%) with most homologous carboxylesterase, except a putative carboxylesterase from O. anthropi ATCC 49188 with the highest identity of 85%. Phylogenetic analysis revealed that PytZ belonged to esterase VI family. The gene pytZ showed no any sequence similarity with reported pyrethroid-hydrolyzing genes and was a new pyrethroid-degrading gene. PytZ was expressed in Escherichia coli BL21 (DE3) and purified using Ni-NTA Fast Start. PytZ was able to degrade various pyrethroids. The optimal temperature and pH were 35 degrees C and 7.5. This enzyme was very stable over a wide range of temperature and pH. No cofactors were required for enzyme activity. Broad substrate specificity, high enzyme activity, and the favorable stability make the PytZ a potential candidate for the detoxification of pyrethroid residues in biotechnological application.
ESTHER : Zhai_2012_J.Hazard.Mater_221-222_206
PubMedSearch : Zhai_2012_J.Hazard.Mater_221-222_206
PubMedID: 22579404
Gene_locus related to this paper: 9hyph-h2esq9

Title : Integrated transcriptional and proteomic analysis with in vitro biochemical assay reveal the important role of CYP3A46 in T-2 toxin hydroxylation in porcine primary hepatocytes - Wang_2011_Mol.Cell.Proteomics_10_M111 008748
Author(s) : Wang J , Jiang J , Zhang H , Cai H , Li C , Li K , Liu J , Guo X , Zou G , Wang D , Deng Y , Dai J
Ref : Mol Cell Proteomics , 10 :M111 008748 , 2011
Abstract : Both T-2 toxin and its metabolites are highly potent mycotoxins that can cause severe human and animal diseases upon exposure. Understanding the toxic mechanism and biotransformation process of T-2 toxin at a cellular level is essential for the development of counter-measures. We investigated the effect of T-2 toxin in porcine primary hepatocytes using porcine genome array and two-dimensional difference gel electrophoresis with matrix-assisted laser desorption/ionization tandem time of flight mass spectrometry. Integrated transcriptional and proteomic analysis demonstrated that T-2 toxin adversely affected porcine hepatocytes by initiating lipid metabolism disorder, oxidative stress response, and apoptosis. In addition, xenobiotic metabolism genes, including cytochrome P450 3As (CYP3A46 and CYP3A39), carboxylesterase 1Cs (CES1C4 and CES1C5), and epoxide hydrolase (EPHX1), increased in T-2 toxin treatment cells. Using HepG2 cells to over-express the recombinant xenobiotic metabolism genes above and rapid resolution liquid chromatography/tandem mass spectrometry to detect metabolites of T-2 toxin, we determined that porcine CYP3A46 mainly catalyzed T-2 to form 3'-hydroxy-T-2, which was further confirmed by purified CYP3A46 protein. However, recombinant porcine CES1C5 and EPHX1 did not enhance hydrolysis and de-epoxidation of T-2 implying that other esterases and epoxide hydrolases may play dominant roles in those reactions.
ESTHER : Wang_2011_Mol.Cell.Proteomics_10_M111 008748
PubMedSearch : Wang_2011_Mol.Cell.Proteomics_10_M111 008748
PubMedID: 21685020

Title : The Selaginella genome identifies genetic changes associated with the evolution of vascular plants - Banks_2011_Science_332_960
Author(s) : Banks JA , Nishiyama T , Hasebe M , Bowman JL , Gribskov M , dePamphilis C , Albert VA , Aono N , Aoyama T , Ambrose BA , Ashton NW , Axtell MJ , Barker E , Barker MS , Bennetzen JL , Bonawitz ND , Chapple C , Cheng C , Correa LG , Dacre M , DeBarry J , Dreyer I , Elias M , Engstrom EM , Estelle M , Feng L , Finet C , Floyd SK , Frommer WB , Fujita T , Gramzow L , Gutensohn M , Harholt J , Hattori M , Heyl A , Hirai T , Hiwatashi Y , Ishikawa M , Iwata M , Karol KG , Koehler B , Kolukisaoglu U , Kubo M , Kurata T , Lalonde S , Li K , Li Y , Litt A , Lyons E , Manning G , Maruyama T , Michael TP , Mikami K , Miyazaki S , Morinaga S , Murata T , Mueller-Roeber B , Nelson DR , Obara M , Oguri Y , Olmstead RG , Onodera N , Petersen BL , Pils B , Prigge M , Rensing SA , Riano-Pachon DM , Roberts AW , Sato Y , Scheller HV , Schulz B , Schulz C , Shakirov EV , Shibagaki N , Shinohara N , Shippen DE , Sorensen I , Sotooka R , Sugimoto N , Sugita M , Sumikawa N , Tanurdzic M , Theissen G , Ulvskov P , Wakazuki S , Weng JK , Willats WW , Wipf D , Wolf PG , Yang L , Zimmer AD , Zhu Q , Mitros T , Hellsten U , Loque D , Otillar R , Salamov A , Schmutz J , Shapiro H , Lindquist E , Lucas S , Rokhsar D , Grigoriev IV
Ref : Science , 332 :960 , 2011
Abstract : Vascular plants appeared ~410 million years ago, then diverged into several lineages of which only two survive: the euphyllophytes (ferns and seed plants) and the lycophytes. We report here the genome sequence of the lycophyte Selaginella moellendorffii (Selaginella), the first nonseed vascular plant genome reported. By comparing gene content in evolutionarily diverse taxa, we found that the transition from a gametophyte- to a sporophyte-dominated life cycle required far fewer new genes than the transition from a nonseed vascular to a flowering plant, whereas secondary metabolic genes expanded extensively and in parallel in the lycophyte and angiosperm lineages. Selaginella differs in posttranscriptional gene regulation, including small RNA regulation of repetitive elements, an absence of the trans-acting small interfering RNA pathway, and extensive RNA editing of organellar genes.
ESTHER : Banks_2011_Science_332_960
PubMedSearch : Banks_2011_Science_332_960
PubMedID: 21551031
Gene_locus related to this paper: selml-d8qua5 , selml-d8qva1 , selml-d8qyh7 , selml-d8qza0 , selml-d8r5d4 , selml-d8r6d4 , selml-d8r504 , selml-d8r506 , selml-d8rbi1 , selml-d8rbs1 , selml-d8rck8 , selml-d8rf38 , selml-d8rkl6 , selml-d8rpr1 , selml-d8rpy0 , selml-d8ru47 , selml-d8ry54 , selml-d8rzp6 , selml-d8rzy7 , selml-d8s0c9 , selml-d8s0u3 , selml-d8s2t1 , selml-d8s3z8 , selml-d8s401 , selml-d8sba6 , selml-d8sch9 , selml-d8spq2 , selml-d8sq37 , selml-d8ssx7 , selml-d8swp2 , selml-d8t7a3 , selml-d8t8v4 , selml-d8taz4 , selml-d8tdq6 , selml-d8rai8 , selml-d8qt54 , selml-d8r2d8 , selml-d8rmd3 , selml-d8rra9 , selml-d8slg4 , selml-d8swp0 , selml-d8s7i0 , selml-d8qz37 , selml-d8sz00 , selml-d8s776 , selml-d8qw15 , selml-d8ska7 , selml-d8t0c4 , selml-d8r194 , selml-d8s5m8 , selml-d8s7r2 , selml-d8ta80 , selml-d8ru55

Title : Biocatalytic synthesis and in vitro release of biodegradable linear polyesters with pendant ketoprofen - Wang_2010_Biomacromolecules_11_3290
Author(s) : Wang HY , Zhang WW , Wang N , Li C , Li K , Yu XQ
Ref : Biomacromolecules , 11 :3290 , 2010
Abstract : Enzyme-catalyzed polycondensation for the synthesis of polyester prodrugs of ketoprofen was reported. Lipase acrylic resin from Candida antarctica (CAL-B) was used to synthesize the linear polyesters with pendent ketoprofen groups based on ketoprofen glycerol ester, poly(ethylene glycol), and divinyl sebacate. The products were characterized by GPC and (1)H NMR. The results indicated that the molecular weight and yields of the polyesters depend on experimental conditions such as temperature and feed ratio. The in vitro study showed that the drug release from the polyester was slow under physiological conditions, which indicated that the polyester could be a promising prodrug with extended pharmacological effects by delayed release of ketoprofen.
ESTHER : Wang_2010_Biomacromolecules_11_3290
PubMedSearch : Wang_2010_Biomacromolecules_11_3290
PubMedID: 21053944

Title : A comparison of whole-genome shotgun-derived mouse chromosome 16 and the human genome - Mural_2002_Science_296_1661
Author(s) : Mural RJ , Adams MD , Myers EW , Smith HO , Miklos GL , Wides R , Halpern A , Li PW , Sutton GG , Nadeau J , Salzberg SL , Holt RA , Kodira CD , Lu F , Chen L , Deng Z , Evangelista CC , Gan W , Heiman TJ , Li J , Li Z , Merkulov GV , Milshina NV , Naik AK , Qi R , Shue BC , Wang A , Wang J , Wang X , Yan X , Ye J , Yooseph S , Zhao Q , Zheng L , Zhu SC , Biddick K , Bolanos R , Delcher AL , Dew IM , Fasulo D , Flanigan MJ , Huson DH , Kravitz SA , Miller JR , Mobarry CM , Reinert K , Remington KA , Zhang Q , Zheng XH , Nusskern DR , Lai Z , Lei Y , Zhong W , Yao A , Guan P , Ji RR , Gu Z , Wang ZY , Zhong F , Xiao C , Chiang CC , Yandell M , Wortman JR , Amanatides PG , Hladun SL , Pratts EC , Johnson JE , Dodson KL , Woodford KJ , Evans CA , Gropman B , Rusch DB , Venter E , Wang M , Smith TJ , Houck JT , Tompkins DE , Haynes C , Jacob D , Chin SH , Allen DR , Dahlke CE , Sanders R , Li K , Liu X , Levitsky AA , Majoros WH , Chen Q , Xia AC , Lopez JR , Donnelly MT , Newman MH , Glodek A , Kraft CL , Nodell M , Ali F , An HJ , Baldwin-Pitts D , Beeson KY , Cai S , Carnes M , Carver A , Caulk PM , Center A , Chen YH , Cheng ML , Coyne MD , Crowder M , Danaher S , Davenport LB , Desilets R , Dietz SM , Doup L , Dullaghan P , Ferriera S , Fosler CR , Gire HC , Gluecksmann A , Gocayne JD , Gray J , Hart B , Haynes J , Hoover J , Howland T , Ibegwam C , Jalali M , Johns D , Kline L , Ma DS , MacCawley S , Magoon A , Mann F , May D , McIntosh TC , Mehta S , Moy L , Moy MC , Murphy BJ , Murphy SD , Nelson KA , Nuri Z , Parker KA , Prudhomme AC , Puri VN , Qureshi H , Raley JC , Reardon MS , Regier MA , Rogers YH , Romblad DL , Schutz J , Scott JL , Scott R , Sitter CD , Smallwood M , Sprague AC , Stewart E , Strong RV , Suh E , Sylvester K , Thomas R , Tint NN , Tsonis C , Wang G , Williams MS , Williams SM , Windsor SM , Wolfe K , Wu MM , Zaveri J , Chaturvedi K , Gabrielian AE , Ke Z , Sun J , Subramanian G , Venter JC , Pfannkoch CM , Barnstead M , Stephenson LD
Ref : Science , 296 :1661 , 2002
Abstract : The high degree of similarity between the mouse and human genomes is demonstrated through analysis of the sequence of mouse chromosome 16 (Mmu 16), which was obtained as part of a whole-genome shotgun assembly of the mouse genome. The mouse genome is about 10% smaller than the human genome, owing to a lower repetitive DNA content. Comparison of the structure and protein-coding potential of Mmu 16 with that of the homologous segments of the human genome identifies regions of conserved synteny with human chromosomes (Hsa) 3, 8, 12, 16, 21, and 22. Gene content and order are highly conserved between Mmu 16 and the syntenic blocks of the human genome. Of the 731 predicted genes on Mmu 16, 509 align with orthologs on the corresponding portions of the human genome, 44 are likely paralogous to these genes, and 164 genes have homologs elsewhere in the human genome; there are 14 genes for which we could find no human counterpart.
ESTHER : Mural_2002_Science_296_1661
PubMedSearch : Mural_2002_Science_296_1661
PubMedID: 12040188
Gene_locus related to this paper: mouse-ABH15 , mouse-Ces3b , mouse-Ces4a , mouse-dpp4 , mouse-FAP , mouse-Lipg , mouse-Q8C1A9 , mouse-rbbp9 , mouse-SERHL , mouse-SPG21 , mouse-w4vsp6