Ding L

References (27)

Title : Glucose controls lipolysis through Golgi PtdIns4P-mediated regulation of ATGL - Ding_2024_Nat.Cell.Biol__
Author(s) : Ding L , Huwyler F , Long F , Yang W , Binz J , Wernle K , Pfister M , Klug M , Balaz M , Ukropcova B , Ukropec J , Wu C , Wang T , Gao M , Clavien PA , Dutkowski P , Tibbitt MW , Wolfrum C
Ref : Nat Cell Biol , : , 2024
Abstract : Metabolic crosstalk of the major nutrients glucose, amino acids and fatty acids (FAs) ensures systemic metabolic homeostasis. The coordination between the supply of glucose and FAs to meet various physiological demands is especially important as improper nutrient levels lead to metabolic disorders, such as diabetes and metabolic dysfunction-associated steatohepatitis (MASH). In response to the oscillations in blood glucose levels, lipolysis is thought to be mainly regulated hormonally to control FA liberation from lipid droplets by insulin, catecholamine and glucagon. However, whether general cell-intrinsic mechanisms exist to directly modulate lipolysis via glucose sensing remains largely unknown. Here we report the identification of such an intrinsic mechanism, which involves Golgi PtdIns4P-mediated regulation of adipose triglyceride lipase (ATGL)-driven lipolysis via intracellular glucose sensing. Mechanistically, depletion of intracellular glucose results in lower Golgi PtdIns4P levels, and thus reduced assembly of the E3 ligase complex CUL7(FBXW8) in the Golgi apparatus. Decreased levels of the E3 ligase complex lead to reduced polyubiquitylation of ATGL in the Golgi and enhancement of ATGL-driven lipolysis. This cell-intrinsic mechanism regulates both the pool of intracellular FAs and their extracellular release to meet physiological demands during fasting and glucose deprivation. Moreover, genetic and pharmacological manipulation of the Golgi PtdIns4P-CUL7(FBXW8)-ATGL axis in mouse models of simple hepatic steatosis and MASH, as well as during ex vivo perfusion of a human steatotic liver graft leads to the amelioration of steatosis, suggesting that this pathway might be a promising target for metabolic dysfunction-associated steatotic liver disease and possibly MASH.
ESTHER : Ding_2024_Nat.Cell.Biol__
PubMedSearch : Ding_2024_Nat.Cell.Biol__
PubMedID: 38561547

Title : Enhancing the Hydrolysis and Acyl Transfer Activity of Carboxylesterase DLFae4 by a Combinational Mutagenesis and In-Silico Method - Li_2023_Foods_12_1169
Author(s) : Li L , Ding L , Shao Y , Sun S , Wang M , Xiang J , Zhou J , Wu G , Song Z , Xin Z
Ref : Foods , 12 :1169 , 2023
Abstract : In the present study, a feruloyl esterase DLFae4 identified in our previous research was modified by error-prone PCR and site-directed saturation mutation to enhance the catalytic efficiency and acyltransferase activity further. Five mutants with 6.9-118.9% enhanced catalytic activity toward methyl ferulate (MFA) were characterized under the optimum conditions. Double variant DLFae4-m5 exhibited the highest hydrolytic activity (270.97 U/mg), the Km value decreased by 83.91%, and the Kcat/Km value increased by 6.08-fold toward MFA. Molecular docking indicated that a complex hydrogen bond network in DLFae4-m5 was formed, with four of five bond lengths being shortened compared with DLFae4, which might account for the increase in catalytic activity. Acyl transfer activity assay revealed that the activity of DLFae4 was as high as 1550.796 U/mg and enhanced by 375.49% (5823.172 U/mg) toward 4-nitrophenyl acetate when residue Ala-341 was mutated to glycine (A341G), and the corresponding acyl transfer efficiency was increased by 7.7 times, representing the highest acyltransferase activity to date, and demonstrating that the WGG motif was pivotal for the acyltransferase activity in family VIII carboxylesterases. Further experiments indicated that DLFae4 and variant DLFae4 (A341G) could acylate cyanidin-3-O-glucoside effectively in aqueous solution. Taken together, our study suggested the effectiveness of error-prone PCR and site-directed saturation mutation to increase the specific activity of enzymes and may facilitate the practical application of this critical feruloyl esterase.
ESTHER : Li_2023_Foods_12_1169
PubMedSearch : Li_2023_Foods_12_1169
PubMedID: 36981096

Title : Cellular plasticity of the bone marrow niche promotes hematopoietic stem cell regeneration - Hirakawa_2023_Nat.Genet__
Author(s) : Hirakawa H , Gao L , Tavakol DN , Vunjak-Novakovic G , Ding L
Ref : Nat Genet , : , 2023
Abstract : Hematopoietic stem cells (HSCs) regenerate after myeloablation, a procedure that adversely disrupts the bone marrow and drives leptin receptor-expressing cells, a key niche component, to differentiate extensively into adipocytes. Regeneration of the bone marrow niche is associated with the resolution of adipocytes, but the mechanisms remain poorly understood. Using Plin1-creER knock-in mice, we followed the fate of adipocytes in the regenerating niche in vivo. We found that bone marrow adipocytes were highly dynamic and dedifferentiated to leptin receptor-expressing cells during regeneration after myeloablation. Bone marrow adipocytes could give rise to osteolineage cells after skeletal injury. The cellular fate of steady-state bone marrow adipocytes was also plastic. Deletion of adipose triglyceride lipase (Atgl) from bone marrow stromal cells, including adipocytes, obstructed adipocyte dedifferentiation and led to severely compromised regeneration of HSCs as well as impaired B lymphopoiesis after myeloablation, but not in the steady state. Thus, the regeneration of HSCs and their niche depends on the cellular plasticity of bone marrow adipocytes.
ESTHER : Hirakawa_2023_Nat.Genet__
PubMedSearch : Hirakawa_2023_Nat.Genet__
PubMedID: 37857934

Title : Genetic association of lipids and lipid-lowering drug target genes with non-alcoholic fatty liver disease - Li_2023_EBioMedicine_90_104543
Author(s) : Li Z , Zhang B , Liu Q , Tao Z , Ding L , Guo B , Zhang E , Zhang H , Meng Z , Guo S , Chen Y , Peng J , Li J , Wang C , Huang Y , Xu H , Wu Y
Ref : EBioMedicine , 90 :104543 , 2023
Abstract : BACKGROUND: Some observational studies found that dyslipidaemia is a risk factor for non-alcoholic fatty liver disease (NAFLD), and lipid-lowering drugs may lower NAFLD risk. However, it remains unclear whether dyslipidaemia is causative for NAFLD. This Mendelian randomisation (MR) study aimed to explore the causal role of lipid traits in NAFLD and evaluate the potential effect of lipid-lowering drug targets on NAFLD. METHODS: Genetic variants associated with lipid traits and variants of genes encoding lipid-lowering drug targets were extracted from the Global Lipids Genetics Consortium genome-wide association study (GWAS). Summary statistics for NAFLD were obtained from two independent GWAS datasets. Lipid-lowering drug targets that reached significance were further tested using expression quantitative trait loci data in relevant tissues. Colocalisation and mediation analyses were performed to validate the robustness of the results and explore potential mediators. FINDINGS: No significant effect of lipid traits and eight lipid-lowering drug targets on NAFLD risk was found. Genetic mimicry of lipoprotein lipase (LPL) enhancement was associated with lower NAFLD risks in two independent datasets (OR(1) = 0.60 [95% CI 0.50-0.72], p(1) = 2.07 x 10(-8); OR(2) = 0.57 [95% CI 0.39-0.82], p(2) = 3.00 x 10(-3)). A significant MR association (OR = 0.71 [95% CI, 0.58-0.87], p = 1.20 x 10(-3)) and strong colocalisation association (PP.H(4) = 0.85) with NAFLD were observed for LPL expression in subcutaneous adipose tissue. Fasting insulin and type 2 diabetes mediated 7.40% and 9.15%, respectively, of the total effect of LPL on NAFLD risk. INTERPRETATION: Our findings do not support dyslipidaemia as a causal factor for NAFLD. Among nine lipid-lowering drug targets, LPL is a promising candidate drug target in NAFLD. The mechanism of action of LPL in NAFLD may be independent of its lipid-lowering effects. FUNDING: Capital's Funds for Health Improvement and Research (2022-4-4037). CAMS Innovation Fund for Medical Sciences (CIFMS, grant number: 2021-I2M-C&T-A-010).
ESTHER : Li_2023_EBioMedicine_90_104543
PubMedSearch : Li_2023_EBioMedicine_90_104543
PubMedID: 37002989

Title : Association Lp-PLA2 Gene Polymorphisms with Coronary Heart Disease - Ma_2022_Dis.Markers_2022_9775699
Author(s) : Ma S , Ding L , Cai M , Chen L , Yan B , Yang J
Ref : Dis Markers , 2022 :9775699 , 2022
Abstract : OBJECTIVES: The study evaluated the association between lipoprotein-associated phospholipase A2 (Lp-PLA2) gene polymorphisms and coronary heart disease (CHD), in order to explore the molecular genetics of CHD. METHODS: Groups of CHD patients (n = 283) and healthy controls (n = 261) were involved in this study. R92H, V279F, and A379V polymorphisms of LP-PLA2 gene were confirmed using polymerase chain reaction (PCR) and direct DNA sequencing. These polymorphisms and their interaction were also analyzed as potential risk factors of CHD. RESULTS: In this study population, the genotypes of R92H (GG, GA, and AA), V279F (CC, AC, and AA) and A379V (GG, GA, and AA) were studied. There was a significantly difference in frequencies of R92H between CHD patients and controls (P < 0.05). In contrast, no significant difference in frequencies of V279F and A379V existed between CHD patients and controls. Furthermore, R92H and A379V were in strong linkage disequilibrium. CONCLUSIONS: These results suggested that R92H polymorphism might contribute to increased risk of CHD.
ESTHER : Ma_2022_Dis.Markers_2022_9775699
PubMedSearch : Ma_2022_Dis.Markers_2022_9775699
PubMedID: 35818585
Gene_locus related to this paper: human-PLA2G7

Title : Echinacoside Alleviates Cognitive Impairment in Cerebral Ischemia Rats through alpha 7nAChR-Induced Autophagy - Ding_2022_Chin.J.Integr.Med__
Author(s) : Ding L , Ye H , Gu LD , Du AQ , Yuan XL
Ref : Chin J Integr Med , : , 2022
Abstract : OBJECTIVES: To evaluate the effect of echinacoside (ECH) on cognitive dysfunction in post cerebral stroke model rats. METHODS: The post stroke cognitive impairment rat model was created by occlusion of the transient middle cerebral artery (MCAO). The rats were randomly divided into 3 groups by a random number table: the sham group (sham operation), the MCAO group (received operation for focal cerebral ischemia), and the ECH group (received operation for focal cerebral ischemia and ECH 50 mg/kg per day), with 6 rats in each group. The infarct volume and spatial learning were evaluated by triphenyl tetrazolium chloride staining and Morris water maze. The expression of alpha7nAChR in the hippocampus was detected by immunohistochemistry. The contents of acetylcholine (ACh), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), activities of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and catalase (CAT) were evaluated by enzyme linked immunosorbent assay. The neural apoptosis and autophagy were determined by TUNEL staining and LC3 staining, respectively. RESULTS: ECH significantly lessened the brain infarct volume and ameliorated neurological deficit in infarct volume and water content (both P<0.01). Compared with MCAO rats, administration of ECH revealed shorter escape latency and long retention time at 7, 14 and 28 days (all P<0.01), increased the alpha7nAChR protein expression, ACh content, and ChAT activity, and decreased AChE activity in MCAO rats (all P<0.01). ECH significantly decreased MDA content and increased the GSH content, SOD, and CAT activities compared with MCAO rats (all P<0.05). ECH suppressed neuronal apoptosis by reducing TUNEL-positive cells and also enhanced autophagy in MCAO rats (all P<0.01). CONCLUSION: ECH treatment helped improve cognitive impairment by attenuating neurological damage and enhancing autophagy in MCAO rats.
ESTHER : Ding_2022_Chin.J.Integr.Med__
PubMedSearch : Ding_2022_Chin.J.Integr.Med__
PubMedID: 35799084

Title : Accelerated Solvent Extraction of Antioxidant Compounds from Gardeniae Fructus and Its Acetylcholinesterase Inhibitory and PC12 Cell Protective Activities - Fan_2021_Foods_10_
Author(s) : Fan Y , Li X , Ding L , Zhou W , Xu G , Wang Y , Zhang Y , Ni Q
Ref : Foods , 10 : , 2021
Abstract : Gardeniae fructus is a common neuroprotective medicinal food in China, however the extraction efficiency and mixture activities are rarely mentioned. In this study, accelerated solvent extraction (ASE) parameters were optimized by a response surface methodology to extract antioxidants from Gardeniae fructus. Neuroprotective activity was evaluated using H(2)O(2) and amyloid-beta(25-35) peptide-treated PC12 cells. By comparing with three other extract methods (i.e., heated refluxing extraction (HRE), ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE)), it was found that the yield (35.10%), total iridoids (27.69%), total flavonoid (6.12%) content, antioxidant activities (IC(50) on DPPH, 164.46 microg/mL; FRAP value 4703.54 micromol/L), and acetylcholinesterase inhibitory ability (IC(50) 92.58 microg/mL) of ASE extract under the optimal condition (150 degreesC temperature, 10 min static time, 60% ethanol, 2 extract cycles) were significantly higher than other extract methods. The strongest ability to protect PC12 cells from damage was also present in ASE extract, as evidenced by decreasing lactate dehydrogenase and malondialdehyde levels, elevating superoxide dismutase and glutathioneperoxidase activities. Compositional analysis indicated that the extremely high crocetin level in ASE extract (1.30 microg/mg) may offer great potential. Our results indicated that ASE is a proper extraction method that could offer great potential for finding the neuroprotective ability of Gardeniae fructus for the treatment of AD.
ESTHER : Fan_2021_Foods_10_
PubMedSearch : Fan_2021_Foods_10_
PubMedID: 34829086

Title : Peroxisomal beta-oxidation acts as a sensor for intracellular fatty acids and regulates lipolysis - Ding_2021_Nat.Metab__
Author(s) : Ding L , Sun W , Balaz M , He A , Klug M , Wieland S , Caiazzo R , Raverdy V , Pattou F , Lefebvre P , Lodhi IJ , Staels B , Heim M , Wolfrum C
Ref : Nat Metab , : , 2021
Abstract : To liberate fatty acids (FAs) from intracellular stores, lipolysis is regulated by the activity of the lipases adipose triglyceride lipase (ATGL), hormone-sensitive lipase and monoacylglycerol lipase. Excessive FA release as a result of uncontrolled lipolysis results in lipotoxicity, which can in turn promote the progression of metabolic disorders. However, whether cells can directly sense FAs to maintain cellular lipid homeostasis is unknown. Here we report a sensing mechanism for cellular FAs based on peroxisomal degradation of FAs and coupled with reactive oxygen species (ROS) production, which in turn regulates FA release by modulating lipolysis. Changes in ROS levels are sensed by PEX2, which modulates ATGL levels through post-translational ubiquitination. We demonstrate the importance of this pathway for non-alcoholic fatty liver disease progression using genetic and pharmacological approaches to alter ROS levels in vivo, which can be utilized to increase hepatic ATGL levels and ameliorate hepatic steatosis. The discovery of this peroxisomal beta-oxidation-mediated feedback mechanism, which is conserved in multiple organs, couples the functions of peroxisomes and lipid droplets and might serve as a new way to manipulate lipolysis to treat metabolic disorders.
ESTHER : Ding_2021_Nat.Metab__
PubMedSearch : Ding_2021_Nat.Metab__
PubMedID: 34903883

Title : Identification and characterization of a novel carboxylesterase EstQ7 from a soil metagenomic library - Yan_2021_Arch.Microbiol__
Author(s) : Yan Z , Ding L , Zou D , Wang L , Tan Y , Guo S , Zhang Y , Xin Z
Ref : Arch Microbiol , : , 2021
Abstract : A novel lipolytic gene, estq7, was identified from a fosmid metagenomic library. The recombinant enzyme EstQ7 consists of 370 amino acids with an anticipated molecular mass of 42 kDa. Multiple sequence alignments showed that EstQ7 contained a pentapeptide motif GHSMG, and a putative catalytic triad Ser174-Asp306-His344. Interestingly, EstQ7 was found to have very little similarity to the characterized lipolytic enzymes. Phylogenetic analysis revealed that EstQ7 may be a member of a novel family of lipolytic enzymes. Biochemical characterization of the recombinant enzyme revealed that it constitutes a slightly alkalophilic, moderate thermophilic and highly active carboxylesterase against short-chain fatty acid esters with optimum temperature 50 degC and pH 8.2. The Km and kcat values toward p-nitrophenyl acetate were determined to be 0.17 mM and 1910s(-1), respectively. Moreover, EstQ7 was demonstrated to have acyltransferase activity by GC-MS analysis. Structural modeling of the three-dimensional structure of this new enzyme showed that it exhibits a typical alpha/beta hydrolase fold, and the catalytic triad residues are spatially close. Molecular docking revealed the interactions between the enzyme and the ligand. The high levels of lipolytic activity of EstQ7, combined with its moderate thermophilic property and acyltransferase activity, render this novel enzyme a promising candidate biocatalyst for food, pharmaceutical and biotechnological applications.
ESTHER : Yan_2021_Arch.Microbiol__
PubMedSearch : Yan_2021_Arch.Microbiol__
PubMedID: 34057548
Gene_locus related to this paper: 9bact-MW804671

Title : Characterization of a novel carboxylesterase with catalytic activity toward di(2-ethylhexyl) phthalate from a soil metagenomic library - Yan_2021_Sci.Total.Environ_785_147260
Author(s) : Yan Z , Ding L , Zou D , Qiu J , Shao Y , Sun S , Li L , Xin Z
Ref : Sci Total Environ , 785 :147260 , 2021
Abstract : A novel carboxylesterase gene estyz5 was isolated from a soil metagenomic library. The recombinant enzyme EstYZ5 is 298 amino acids in length with a predicted molecular weight of 32 kDa. Sequence alignment and phylogenetic analysis revealed that EstYZ5 belongs to the hormone-sensitive lipase (HSL) family with a deduced catalytic triad of Ser144-Glu238-His268. EstYZ5 contains two conserved motifs, a pentapeptide motif GDSAG and a HGGG motif, which are typically found in members of the HSL family. Esterolytic activity of the recombinant enzyme was optimal at 30 degreesC and pH 8.0, and the kcat/Km value of the enzyme for the optimum substrate p-nitrophenyl butyrate was as high as 1272 mM(-)(1).s(-1). Importantly, EstYZ5 showed activity toward di(2-ethylhexyl) phthalate with complex side chains, which is rare for HSLs. Molecular docking simulations revealed that the catalytic triad and an oxyanion hole likely play vital roles in enzymatic activity and specificity. The phthalate-degrading activity of EstYZ5, combined with its high levels of esterolytic activity, render this new enzyme a candidate for biotechnological applications.
ESTHER : Yan_2021_Sci.Total.Environ_785_147260
PubMedSearch : Yan_2021_Sci.Total.Environ_785_147260
PubMedID: 33957585

Title : Identification and Characterization of a Novel Carboxylesterase Belonging to Family VIII with Promiscuous Acyltransferase Activity Toward Cyanidin-3-O-Glucoside from a Soil Metagenomic Library - Zhang_2021_Appl.Biochem.Biotechnol__
Author(s) : Zhang Y , Ding L , Yan Z , Zhou D , Jiang J , Qiu J , Xin Z
Ref : Appl Biochem Biotechnol , : , 2021
Abstract : An alkaline esterase, designated as EstXT1, was identified through functional screening from a metagenomic library. Sequence analysis revealed that EstXT1 belonged to the family VIII carboxylesterases and contained a characteristic conserved S-x-x-K motif and a deduced catalytic triad Ser56-Lys59-Tyr165. EstXT1 exhibited the strongest activity toward methyl ferulate at pH 8.0 and temperature 55 degreesC and retained over 80% of its original activity after incubation in the pH range of 7.0-10.6 buffers. Biochemical characterization of the recombinant enzyme showed that it was activated by Zn(2+) and Co(2+) metal ion, while inhibited by Cu(2+) and CTAB. EstXT1 exhibited significant promiscuous acyltransferase activity preferred to the acylation of benzyl alcohol acceptor using short-chain pNP-esters (C2-C8) as acyl-donors. A structure-function analysis indicated that a WAG motif is essential to acyltransferase activity. This is the first report example that WAG motif plays a pivotal role in acyltransferase activity in family VIII carboxylesterases beside WGG motif. Further experiment indicated that EstXT1 successfully acylated cyanidin-3-O-glucoside in aqueous solution. The results from the current investigation provided new insights for the family VIII carboxylesterase and lay a foundation for the potential applications of EstXT1 in food and biotechnology fields.
ESTHER : Zhang_2021_Appl.Biochem.Biotechnol__
PubMedSearch : Zhang_2021_Appl.Biochem.Biotechnol__
PubMedID: 34255285

Title : Inhibition of acetylcholinesterase activity and beta-amyloid oligomer formation by 6-bromotryptamine A, a multi-target anti-Alzheimer's molecule - Jin_2020_Oncol.Lett_19_1593
Author(s) : Jin X , Wang M , Shentu J , Huang C , Bai Y , Pan H , Zhang D , Yuan Z , Zhang H , Xiao X , Wu X , Ding L , Wang Q , He S , Cui W
Ref : Oncol Lett , 19 :1593 , 2020
Abstract : Alzheimer's disease (AD) is a neurodegenerative disorder characterized by learning and memory impairments. Recent studies have suggested that AD can be induced by multiple factors, such as cholinergic system dysfunction and beta-amyloid (Abeta) neurotoxicity. It was reported that 6-bromo-N-propionyltryptamine could treat neurological diseases, including AD. In the present study, 6-bromotryptamine A, a derivative of 6-bromo-N-propionyltryptamine, was synthesized by the condensation of 2-(6-bromo-1H-indol-3-yl)ethan-1-amine and 2-(4-bromophenyl)acetic acid, and was used as a potential anti-AD molecule. Furthermore, scopolamine can induce impairments of learning and memory, and was widely used to establish AD animal models. The results demonstrated that 6-bromotryptamine A significantly prevented scopolamine-induced short-term cognitive impairments, as revealed by various behavioral tests in mice. Furthermore, an acetylcholinesterase (AChE) activity assay revealed that 6-bromotryptamine A directly inhibited AChE activity. Notably, it was observed that 6-bromotryptamine A blocked the formation of Abeta oligomer, as evaluated by the dot blot assay. All these results suggested that 6-bromotryptamine A may be used to prevent impairments in short-term learning and memory ability possibly via the inhibition of AChE and the blockade of Abeta oligomer formation.
ESTHER : Jin_2020_Oncol.Lett_19_1593
PubMedSearch : Jin_2020_Oncol.Lett_19_1593
PubMedID: 31966085

Title : Characterization of XtjR8: A novel esterase with phthalate-hydrolyzing activity from a metagenomic library of lotus pond sludge - Qiu_2020_Int.J.Biol.Macromol_164_1510
Author(s) : Qiu J , Yang H , Yan Z , Shi Y , Zou D , Ding L , Shao Y , Li L , Khan U , Sun S , Xin Z
Ref : Int J Biol Macromol , 164 :1510 , 2020
Abstract : A fosmid metagenomic library containing 9.7 x 10(4) clones was constructed. A novel esterase, XtjR8, was isolated through functional screening. XtjR8 shared the maximum amino acid identity (44%) with acetyl-hydrolase from Streptomyces hygroscopicus, and was classified into family IV esterase. XtjR8 exhibited the highest hydrolytic activity for p-nitrophenyl acetate at 40 degreesC and pH 8.0, and presented more than 40% activity from 20 degreesC to 80 degreesC. More importantly, XtjR8 displayed the ability to hydrolyze both phthalate monoesters and diesters, this feature is extremely rare among previously reported esterases. Site-directed mutagenesis experiments revealed that the catalytic triad residues were Ser152, Glu246, and His276. Among them, Ser152 formed a hydrogen bond with dibutyl phthalate (DBP) by molecular docking, Gly84, Gly85, and Leu248 of conserved motifs formed hydrophobic interactions with DBP, respectively, which were important for the catalytic activity. Considering its wide range of temperature and hydrolytic potential toward phthalate esters, XtjR8 will be served as an interesting candidate for biodegradation and industrial applications.
ESTHER : Qiu_2020_Int.J.Biol.Macromol_164_1510
PubMedSearch : Qiu_2020_Int.J.Biol.Macromol_164_1510
PubMedID: 32755708
Gene_locus related to this paper: 9zzzz-XtjR8

Title : Effects of ammonia exposure on antioxidant function, immune response and NF-kappaB pathway in Chinese Strip-necked Turtle (Mauremys sinensis) - Liang_2020_Aquat.Toxicol__105621
Author(s) : Liang L , Huang Z , Li N , Wang D , Ding L , Shi H , Hong M
Ref : Aquat Toxicol , :105621 , 2020
Abstract : As one of the main toxic substances in aquaculture water, ammonia causes seriously physiological harm to aquatic animals. In order to investigate the effects of ammonia exposure on the antioxidant defense, immune response, and NF-kappaB signaling pathway in Chinese Strip-necked Turtle (Mauremys sinensis), we designed two experimental groups (control and 6.45 mM ammonia), and sampled at 6 h, 24 h, 48 h, re 24 h (recover 24 h), and re 48 h. The results showed that the blood ammonia (BA) content was significantly increased when the turtles were subjected to ammonia, and the activities of cholinesterase (CHE) and aspartate aminotransferase (AST) in the serum also showed a significant upward trend. The malondialdehyde (MDA) content continuously increased during ammonia exposure, and more than doubled at 48 h compared with the control group. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (CAT) and their corresponding relative mRNA expression levels in the liver during ammonia exposure were obviously increased when compared to the control group, but most decreased to the normal levels at re 48 h. In addition, the relative mRNA and protein expression levels of NF-E2 related factor 2 (Nrf2) showed similar up-regulation patterns to antioxidase during ammonia exposed periods; whereas kelch-like ECH-binding protein 1 (Keap1), as Nrf2 negative regulator, showed opposite patterns. Moreover, the relative mRNA expression levels of heat shock proteins (HSP70, HSP90) significantly elevated upon the exposure of ammonia. Furthermore, ammonia increased the relative mRNA and protein expression levels of p50 and p65 at different exposed times. The reative mRNA expression levels of immune cytokines (BAFF and IL-6) were upregulated during ammonia exposured time, while there was a decline but did not return to normal levels, in the recovery periods. Taken together, these results indicated that antioxidation, immunity, and NF-kappaB signaling played a certain protective role for Mauremys sinensis under ammonia exposure. Our results will be helpful to understand the mechanism of aquatic toxicology induced by ammonia in turtles.
ESTHER : Liang_2020_Aquat.Toxicol__105621
PubMedSearch : Liang_2020_Aquat.Toxicol__105621
PubMedID: 33129562

Title : Identification and molecular docking study of fish roe-derived peptides as potent BACE 1, AChE, and BChE inhibitors - Yu_2020_Food.Funct_11_6643
Author(s) : Yu Z , Ji H , Shen J , Kan R , Zhao W , Li J , Ding L , Liu J
Ref : Food Funct , 11 :6643 , 2020
Abstract : Acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and beta-secretase 1 (BACE 1) play vital roles in the development and progression of Alzheimer's disease (AD). The objective of the present study was to identify fish roe-derived anti-AD peptides with activities against AChE, BChE, and BACE 1. Fish roe proteins were cleaved in silico by gastrointestinal proteases, and the released peptides were collected. Subsequently, the toxicity, solubility, and biological properties of these novel di- and tri-peptides were predicted and validated. Finally, potential anti-AD peptides were docked to targets, i.e., AChE, BChE, and BACE 1. A novel anti-AD tripeptide WIR with potent inhibition of AChE and BACE 1 was identified, with IC(50) values of 43.32 +/- 1.22 microM and 2.27 +/- 0.35 mM, respectively. In addition, the inhibition rate of WIR (at a concentration of 1.06 +/- 0.87 microM) against BChE was 33.5%, and the peptide WIR was able to simultaneously interact with AChE, BChE, and BACE 1. Residues Ser286 of AChE, Asp70 of BChE, and Thr231, Arg235 of BACE 1 played key roles in the interaction with peptide WIR. In summary, peptide WIR exhibits the potential to be an effective treatment for AD.
ESTHER : Yu_2020_Food.Funct_11_6643
PubMedSearch : Yu_2020_Food.Funct_11_6643
PubMedID: 32656560

Title : Identification of ovalbumin-derived peptides as multi-target inhibitors of AChE, BChE and BACE1 - Yu_2020_J.Sci.Food.Agric__
Author(s) : Yu Z , Dong W , Wu S , Shen J , Zhao W , Ding L , Liu J , Zheng F
Ref : J Sci Food Agric , : , 2020
Abstract : BACKGROUND: Alzheimer's disease (AD) is a kind of progressive neurodegenerative disease that occurs to the elderly. But there is no ideal treatment for AD. Thus, the purpose of this study is to identify anti-AD peptides from ovalbumin. RESULTS: The potential tripeptides IEK, LYR and CIK were selected for molecular docking. The '-CDOCKER_Energy' value of the best docking position of the tripeptide IEK, LYR and CIK interacting with acetylcholinesterase (AChE) were - 93.8119, -86.9556 and - 73.6370 kcal/mol, respectively. The '-CDOCKER_Energy' values for interaction with butyrylcholinesterase (BChE) were - 96.6386, -80.8392 and - 87.4341 kcal/mol, respectively. Most importantly, the '-CDOCKER_Energy' values for interaction with beta-site amyloid precursor protein cleavage enzyme1 (BACE1) were - 85.5903, -71.3342 and - 68.4290 kcal/mol, respectively. Overall, in vitro assays results demonstrated that peptide CIK exhibited impressive inhibitory activities against AChE, BChE, and BACE1, with the IC50 value of 6.76, 7.72, and 34.48 muM, respectively. Especially, CIK can be contacted with some peripheral anion sites (PAS) and catalytic sites on AChE, BChE and BACE1. CONCLUSION: Tripeptide CIK can effectively inhibit the activities of AChE, BChE and BACE1. Therefore, tripeptide CIK has the potential to effectively treat AD. This article is protected by copyright. All rights reserved.
ESTHER : Yu_2020_J.Sci.Food.Agric__
PubMedSearch : Yu_2020_J.Sci.Food.Agric__
PubMedID: 31997357

Title : Ultrasensitive and visible light-responsive photoelectrochemical aptasensor for edifenphos based on Zinc phthalocyanine sensitized MoS2 nanosheets - Ding_2019_Biosens.Bioelectron__111867
Author(s) : Ding L , Jiang D , Wen Z , Xu Y , Guo Y , Ding C , Wang K
Ref : Biosensors & Bioelectronics , :111867 , 2019
Abstract : Developing a simple, rapid detection method for the analysis of edifenphos (EDI) is crucial due to its residue is harmful to acetylcholinesterase on the human cellular system, and cause a lot of complications. Herein, we synthesized visible light-responsive MoS2 nanosheets decorated with Zinc phthalocyanine (ZnPc) nanoparticles (ZnPc/n-MoS2). Due to the sensitization of ZnPc nanoparticles, the resulting ZnPc/n-MoS2 exhibited narrower energy bandgap and efficient charge transfer. Especially, the carrier lifetime of ZnPc/n-MoS2 is 2 more times longer than n-MoS2, and the photocurrent intensity of ZnPc/n-MoS2 is 24 times of n-MoS2 and 22 times of ZnPc nanoparticles under visible light irradiation. Further, a visible light-responsive ultrasensitive photoelectrochemical (PEC) aptasensor for selectivity recognition of EDI was triumphantly established by using EDI aptamer as a biorecognition element, which exhibited a wide linear ranking from 5ngL(-1) to 10mugL(-1) (R(2)=0.996) and a low detection limit of 1.667ngL(-1) (S/N=3). The splendid performance of the ZnPc/n-MoS2 nanosheet ultrasensitive sensing platform can be applied to detect the concentration of EDI in food, biomedical and environmental analysis.
ESTHER : Ding_2019_Biosens.Bioelectron__111867
PubMedSearch : Ding_2019_Biosens.Bioelectron__111867
PubMedID: 31748191

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 : New Dihydroisocoumarin Root Growth Inhibitors From the Sponge-Derived Fungus Aspergillus sp. NBUF87 - Huang_2019_Front.Microbiol_10_2846
Author(s) : Huang L , Ding L , Li X , Wang N , Cui W , Wang X , Naman CB , Lazaro JEH , Yan X , He S
Ref : Front Microbiol , 10 :2846 , 2019
Abstract : Six new dihydroisocoumarins, aspergimarins A-F (1-6), were discovered together with five known analogs (7-11) from a monoculture of the sponge-derived fungus Aspergillus sp. NBUF87. The structures of these compounds were elucidated through comprehensive spectroscopic methods, and absolute configurations were assigned after X-ray crystallography, use of the modified Mosher's method, and comparison of electronic circular dichroism (ECD) data with literature values for previously reported analogs. Compounds 1-11 were evaluated in a variety of bioassays, and at 100 muM, both 1 and 5 showed significant inhibitory effects on the lateral root growth of Arabidopsis thaliana Columbia-0 (Col-0). Moreover, at 100 muM, 5 also possessed notable inhibition against the primary root growth of Col-0. Meanwhile, 1-11 were all found to be inactive in vitro against acetylcholinesterase (AChE) (IC50 > 100 muM), four different types of human-derived cancer cell lines (IC50 > 50 muM), as well as methicillin-resistant Staphylococcus aureus and Escherichia coli (MIC > 50 mug/mL), and Plasmodium falciparum W2 (EC50 > 100 mug/mL), in phenotypic tests.
ESTHER : Huang_2019_Front.Microbiol_10_2846
PubMedSearch : Huang_2019_Front.Microbiol_10_2846
PubMedID: 31921029

Title : (-)Epigallocatechin-3-gallate attenuates anesthesiainduced memory deficit in young mice via modulation of nitric oxide expression - Ding_2018_Mol.Med.Rep_18_4813
Author(s) : Ding L , Gao X , Hu J , Yu S
Ref : Mol Med Rep , 18 :4813 , 2018
Abstract : (-)Epigallocatechin-3gallate- (EGCG) is a type of polyphenol monomer and is the predominant component of catechin compounds extractable from green tea. Previous studies have demonstrated that EGCG exhibits numerous bioactivities both in vitro and in vivo, including antitumor, antioxidant and antiinflammatory activities, as well as lowering blood lipid levels and protecting against radiation. The present study aimed to investigate whether administration of EGCG may attenuate anesthesiainduced memory deficit in young mice and to reveal the associated underlying mechanisms. The present study revealed that EGCG administration significantly attenuated memory deficit, oxidative stress and cell apoptosis exhibited by anesthesiainduced mice, as determined by Morris water maze testing and ELISA analysis. Furthermore, the results of ELISA and western blot analysis demonstrated that EGCG administration restored acetylcholinesterase activity and modulated the expression levels of neuronal nitric oxide synthase (nNOS), betaamyloid and amyloid precursor protein in anesthesiainduced mice. The present study also employed Larginine as an nNOS substrate and 7nitroindazole as an nNOS inhibitor, which were demonstrated to inhibit or potentiate the effects of EGCG, respectively, on anesthesiainduced memory deficit in mice. Therefore, the present study demonstrated that the administration of EGCG attenuated anesthesiainduced memory deficit in young mice, potentially via the modulation of nitric oxide expression and oxidative stress.
ESTHER : Ding_2018_Mol.Med.Rep_18_4813
PubMedSearch : Ding_2018_Mol.Med.Rep_18_4813
PubMedID: 30320383

Title : Anti-Alzheimers activity and molecular mechanism of albumin-derived peptides against AChE and BChE - Yu_2018_Food.Funct_9_1173
Author(s) : Yu Z , Wu S , Zhao W , Ding L , Fan Y , Shiuan D , Liu J , Chen F
Ref : Food Funct , 9 :1173 , 2018
Abstract : Alzheimer's disease (AD) is a global health issue affecting millions of elderly people worldwide. The aim of the present study was to identify novel anti-AD peptides isolated from albumin. Anti-AD activities of the peptides were evaluated via inhibitory activities on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Furthermore, the potential molecular mechanisms of the KLPGF/AChE were investigated by CDOCKER of Discovery studio 2017. The results revealed that peptide KLPGF could effectively inhibit AChE with an inhibition rate of 61.23% at a concentration of 50 mug mL(-1). In addition, the peptide KLPGF came in contact with acylation sites and peripheral anion sites of AChE. The present study demonstrates that the peptide KLPGF could become a potential functional food intervention in AD.
ESTHER : Yu_2018_Food.Funct_9_1173
PubMedSearch : Yu_2018_Food.Funct_9_1173
PubMedID: 29363710

Title : Metabolic profiles of corydaline in rats by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry - Chai_2017_Xenobiotica__1
Author(s) : Chai L , Donkor PO , Wang K , Sun Y , Oppong MB , Ding L , Qiu F
Ref : Xenobiotica , :1 , 2017
Abstract : Corydaline, an isoquinoline alkaloid obtained from the rhizomes of Corydalis yanhusuo, exhibits anti-acetylcholinesterase, anti-angiogenic, anti-allergic and gastric emptying activities. In this study, a rapid and reliable ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) method was developed and employed for the comprehensive study of the metabolites of corydaline in rats. Altogether, 43 metabolites were identified in the plasma (11), bile (9), urine (34) and feces (21) of rats after oral administration of corydaline at a dose of 4.5mg/kg. It was demonstrated that demethylation, hydroxylation, sulfation and glucuronidation were the major metabolic transformation pathways. Among these, two metabolites were identified as tetrahydropalmatine and isocorybulbine, and thirty-three (33) phase I and phase II products were inferred to be new metabolites arising from the in vivo metabolism of corydaline. Importantly, this research provides scientific and reliable support for full understanding of the metabolic profiles of corydaline and the results could help to elucidate its safety and efficacy.
ESTHER : Chai_2017_Xenobiotica__1
PubMedSearch : Chai_2017_Xenobiotica__1
PubMedID: 29235899

Title : Synthesis and characterization of biodegradable poly(ether-ester) urethane acrylates for controlled drug release - Feng_2017_Mater.Sci.Eng.C.Mater.Biol.Appl_74_270
Author(s) : Feng X , Wang G , Neumann K , Yao W , Ding L , Li S , Sheng Y , Jiang Y , Bradley M , Zhang R
Ref : Mater Sci Eng C Mater Biol Appl , 74 :270 , 2017
Abstract : Three polyether-ester triblock diols, with various molecular weights, were synthesized from sigma-caprolactone and polyethylene glycol and used, with diisocyanates, as soft segments for the preparation of polyurethane acrylate oligomers. The polyurethane acrylates were used to generate cross-linked polyurethane films via UV initiated polymerization with and without cargo incorporation. Degradation experiment indicated that in PBS/H(2)O(2)/CoCl(2) the films degraded rapidly compared to PBS alone or with lipase. The polyurethane membrane loaded with the antibiotic tetracycline, demonstrated prolonged release over 200h, suggesting that the polymers could be used as an implant coating for controlled drug release.
ESTHER : Feng_2017_Mater.Sci.Eng.C.Mater.Biol.Appl_74_270
PubMedSearch : Feng_2017_Mater.Sci.Eng.C.Mater.Biol.Appl_74_270
PubMedID: 28254295

Title : Enantioconvergent hydrolysis of racemic styrene oxide at high concentration by a pair of novel epoxide hydrolases into (R)-phenyl-1,2-ethanediol - Wang_2017_Biotechnol.Lett_39_1917
Author(s) : Wang R , Hu D , Zong X , Li J , Ding L , Wu M
Ref : Biotechnol Lett , 39 :1917 , 2017
Abstract : OBJECTIVES: To prepare (R)-phenyl-1,2-ethanediol ((R)-PED) with high enantiomeric excess (ee p) and yield from racemic styrene oxide (rac-SO) at high concentration by bi-enzymatic catalysis.
RESULTS: The bi-enzymatic catalysis was designed for enantioconvergent hydrolysis of rac-SO by a pair of novel epoxide hydrolases (EHs), a Vigna radiata EH3 (VrEH3) and a variant (AuEH2A250I) of Aspergillus usamii EH2. The simultaneous addition mode of VrEH3 and AuEH2A250I, exhibiting the highest average turnover frequency (aTOF) of 0.12 g h-1 g-1, was selected, by which rac-SO (10 mM) was converted into (R)-PED with 92.6% ee p and 96.3% yield. Under the optimized reaction conditions: dry weight ratio 14:1 of VrEH3-expressing E. coli/vreh3 to AuEH2A250I-expressing E. coli/Aueh2 A250I and reaction at 20 degrees C, rac-SO (10 mM) was completely hydrolyzed in 2.3 h, affording (R)-PED with 98% ee p. At the weight ratio 0.8:1 of rac-SO to two mixed dry cells, (R)-PED with 97.4% ee p and 98.7% yield was produced from 200 mM (24 mg/ml) rac-SO in 10.5 h.
CONCLUSIONS: Enantioconvergent hydrolysis of rac-SO at high concentration catalyzed by both VrEH3 and AuEH2A250I is an effective method for preparing (R)-PED with high ee p and yield.
ESTHER : Wang_2017_Biotechnol.Lett_39_1917
PubMedSearch : Wang_2017_Biotechnol.Lett_39_1917
PubMedID: 28875350
Gene_locus related to this paper: vigra-Vreh3 , aspng-q1ktb5

Title : The Dynamic Genome and Transcriptome of the Human Fungal Pathogen Blastomyces and Close Relative Emmonsia - Munoz_2015_PLoS.Genet_11_e1005493
Author(s) : Munoz JF , Gauthier GM , Desjardins CA , Gallo JE , Holder J , Sullivan TD , Marty AJ , Carmen JC , Chen Z , Ding L , Gujja S , Magrini V , Misas E , Mitreva M , Priest M , Saif S , Whiston EA , Young S , Zeng Q , Goldman WE , Mardis ER , Taylor JW , McEwen JG , Clay OK , Klein BS , Cuomo CA
Ref : PLoS Genet , 11 :e1005493 , 2015
Abstract : Three closely related thermally dimorphic pathogens are causal agents of major fungal diseases affecting humans in the Americas: blastomycosis, histoplasmosis and paracoccidioidomycosis. Here we report the genome sequence and analysis of four strains of the etiological agent of blastomycosis, Blastomyces, and two species of the related genus Emmonsia, typically pathogens of small mammals. Compared to related species, Blastomyces genomes are highly expanded, with long, often sharply demarcated tracts of low GC-content sequence. These GC-poor isochore-like regions are enriched for gypsy elements, are variable in total size between isolates, and are least expanded in the avirulent B. dermatitidis strain ER-3 as compared with the virulent B. gilchristii strain SLH14081. The lack of similar regions in related species suggests these isochore-like regions originated recently in the ancestor of the Blastomyces lineage. While gene content is highly conserved between Blastomyces and related fungi, we identified changes in copy number of genes potentially involved in host interaction, including proteases and characterized antigens. In addition, we studied gene expression changes of B. dermatitidis during the interaction of the infectious yeast form with macrophages and in a mouse model. Both experiments highlight a strong antioxidant defense response in Blastomyces, and upregulation of dioxygenases in vivo suggests that dioxide produced by antioxidants may be further utilized for amino acid metabolism. We identify a number of functional categories upregulated exclusively in vivo, such as secreted proteins, zinc acquisition proteins, and cysteine and tryptophan metabolism, which may include critical virulence factors missed before in in vitro studies. Across the dimorphic fungi, loss of certain zinc acquisition genes and differences in amino acid metabolism suggest unique adaptations of Blastomyces to its host environment. These results reveal the dynamics of genome evolution and of factors contributing to virulence in Blastomyces.
ESTHER : Munoz_2015_PLoS.Genet_11_e1005493
PubMedSearch : Munoz_2015_PLoS.Genet_11_e1005493
PubMedID: 26439490
Gene_locus related to this paper: ajedr-c5gqv9 , 9euro-a0a2b7ztc4 , 9euro-a0a2b7wr51 , blags-a0a179v0z0 , 9euro-a0a0h1bel0 , blags-a0a179udh1 , ajedr-kex1 , ajedr-cbpya

Title : The evolution and pathogenic mechanisms of the rice sheath blight pathogen - Zheng_2013_Nat.Commun_4_1424
Author(s) : Zheng A , Lin R , Zhang D , Qin P , Xu L , Ai P , Ding L , Wang Y , Chen Y , Liu Y , Sun Z , Feng H , Liang X , Fu R , Tang C , Li Q , Zhang J , Xie Z , Deng Q , Li S , Wang S , Zhu J , Wang L , Liu H , Li P
Ref : Nat Commun , 4 :1424 , 2013
Abstract : Rhizoctonia solani is a major fungal pathogen of rice (Oryza sativa L.) that causes great yield losses in all rice-growing regions of the world. Here we report the draft genome sequence of the rice sheath blight disease pathogen, R. solani AG1 IA, assembled using next-generation Illumina Genome Analyser sequencing technologies. The genome encodes a large and diverse set of secreted proteins, enzymes of primary and secondary metabolism, carbohydrate-active enzymes, and transporters, which probably reflect an exclusive necrotrophic lifestyle. We find few repetitive elements, a closer relationship to Agaricomycotina among Basidiomycetes, and expand protein domains and families. Among the 25 candidate pathogen effectors identified according to their functionality and evolution, we validate 3 that trigger crop defence responses; hence we reveal the exclusive expression patterns of the pathogenic determinants during host infection.
ESTHER : Zheng_2013_Nat.Commun_4_1424
PubMedSearch : Zheng_2013_Nat.Commun_4_1424
PubMedID: 23361014
Gene_locus related to this paper: thaca-l8wvp3 , thaca-l8wv47 , thaca-l8wp17 , thaca-l8x532

Title : Generation and annotation of the DNA sequences of human chromosomes 2 and 4 - Hillier_2005_Nature_434_724
Author(s) : Hillier LW , Graves TA , Fulton RS , Fulton LA , Pepin KH , Minx P , Wagner-McPherson C , Layman D , Wylie K , Sekhon M , Becker MC , Fewell GA , Delehaunty KD , Miner TL , Nash WE , Kremitzki C , Oddy L , Du H , Sun H , Bradshaw-Cordum H , Ali J , Carter J , Cordes M , Harris A , Isak A , Van Brunt A , Nguyen C , Du F , Courtney L , Kalicki J , Ozersky P , Abbott S , Armstrong J , Belter EA , Caruso L , Cedroni M , Cotton M , Davidson T , Desai A , Elliott G , Erb T , Fronick C , Gaige T , Haakenson W , Haglund K , Holmes A , Harkins R , Kim K , Kruchowski SS , Strong CM , Grewal N , Goyea E , Hou S , Levy A , Martinka S , Mead K , McLellan MD , Meyer R , Randall-Maher J , Tomlinson C , Dauphin-Kohlberg S , Kozlowicz-Reilly A , Shah N , Swearengen-Shahid S , Snider J , Strong JT , Thompson J , Yoakum M , Leonard S , Pearman C , Trani L , Radionenko M , Waligorski JE , Wang C , Rock SM , Tin-Wollam AM , Maupin R , Latreille P , Wendl MC , Yang SP , Pohl C , Wallis JW , Spieth J , Bieri TA , Berkowicz N , Nelson JO , Osborne J , Ding L , Sabo A , Shotland Y , Sinha P , Wohldmann PE , Cook LL , Hickenbotham MT , Eldred J , Williams D , Jones TA , She X , Ciccarelli FD , Izaurralde E , Taylor J , Schmutz J , Myers RM , Cox DR , Huang X , McPherson JD , Mardis ER , Clifton SW , Warren WC , Chinwalla AT , Eddy SR , Marra MA , Ovcharenko I , Furey TS , Miller W , Eichler EE , Bork P , Suyama M , Torrents D , Waterston RH , Wilson RK
Ref : Nature , 434 :724 , 2005
Abstract : Human chromosome 2 is unique to the human lineage in being the product of a head-to-head fusion of two intermediate-sized ancestral chromosomes. Chromosome 4 has received attention primarily related to the search for the Huntington's disease gene, but also for genes associated with Wolf-Hirschhorn syndrome, polycystic kidney disease and a form of muscular dystrophy. Here we present approximately 237 million base pairs of sequence for chromosome 2, and 186 million base pairs for chromosome 4, representing more than 99.6% of their euchromatic sequences. Our initial analyses have identified 1,346 protein-coding genes and 1,239 pseudogenes on chromosome 2, and 796 protein-coding genes and 778 pseudogenes on chromosome 4. Extensive analyses confirm the underlying construction of the sequence, and expand our understanding of the structure and evolution of mammalian chromosomes, including gene deserts, segmental duplications and highly variant regions.
ESTHER : Hillier_2005_Nature_434_724
PubMedSearch : Hillier_2005_Nature_434_724
PubMedID: 15815621
Gene_locus related to this paper: human-ABHD1 , human-LDAH , human-ABHD18 , human-KANSL3 , human-PGAP1 , human-PREPL