Wu K

References (27)

Title : Astaxanthin activates the Nrf2\/Keap1\/HO-1 pathway to inhibit oxidative stress and ferroptosis, reducing triphenyl phosphate (TPhP)-induced neurodevelopmental toxicity - Zhang_2024_Ecotoxicol.Environ.Saf_271_115960
Author(s) : Zhang Q , Luo C , Li Z , Huang W , Zheng S , Liu C , Shi X , Ma Y , Ni Q , Tan W , Peng J , Chen Y , Wu W , Li J , Wu K
Ref : Ecotoxicology & Environmental Safety , 271 :115960 , 2024
Abstract : Triphenyl phosphate (TPhP) serves as a major organophosphorus flame retardant, and its induced neurodevelopmental toxicity has attracted widespread attention, but the mechanism remains unclear. In this study, we involved zebrafish to explore the new mechanism of TPhP inducing oxidative stress and ferroptosis to promote neurodevelopmental toxicity. The results suggested that TPhP affected the embryonic development, reduced the number of new neurons, and led to abnormal neural behavior in zebrafish larvae. TPhP also induced ROS accumulation, activated the antioxidant defense signal Nrf2 and Keap1, and significantly changed the activities of Acetylcholinesterase (AChE), Adenosine triphosphatase (ATPase) and glutathione S-transferase (GST). In addition, TPhP induced ferroptosis in zebrafish, which was reflected in the increase of Fe(2+) content, the abnormal expression of GPX4 protein and genes related to iron metabolism (gpx4a, slc7a11, acsl4b, tfa, slc40a1, fth1b, tfr2, tfr1a, tfr1b and ncoa4). Astaxanthin intervention specifically inhibited ROS levels, and reversed SLC7A11 and GPX4 expression levels and Fe(2+) metabolism thus alleviating ferroptosis induced by TPhP. Astaxanthin also partially reversed the activity of AChE, GST and the expression of neurodevelopmental-related genes (gap43, gfap, neurog1 and syn2a), so as to partially rescue the embryonic developmental abnormalities and motor behavior disorders induced by TPhP. More interestingly, the expression of mitochondrial apoptosis-related protein BAX, anti-apoptotic protein BCL-2, Caspase3 and Caspase9 was significantly altered in the TPhP exposed group, which could be also reversed by Astaxanthin intervention. In summary, our results suggested that TPhP exposure can induce oxidative stress and ferroptosis, thereby causing neurodevelopment toxicity to zebrafish, while Astaxanthin can partially reverse oxidative stress and reduce the neurodevelopmental toxicity of zebrafish larvae by activating Nrf2/Keap1/HO-1 signaling pathway.
ESTHER : Zhang_2024_Ecotoxicol.Environ.Saf_271_115960
PubMedSearch : Zhang_2024_Ecotoxicol.Environ.Saf_271_115960
PubMedID: 38219622

Title : Identification and Functions of JHE 6 Specifically Expressed in Bombyx mori Silk Gland - Zhang_2023_Insects_14_
Author(s) : Zhang X , Zhang J , Wu K , Yang H , Cheng T , Liu C
Ref : Insects , 14 : , 2023
Abstract : Juvenile hormone esterase (JHE) is the specific enzyme that degrades juvenile hormone (JH) and regulates the JH titer in insects. JH also regulates the development of the silk gland and the synthesis and secretion of silk proteins in Bombyx mori. Here, we identified nine possible JHE family members, Bmjhe1-9. Notably, Bmjhe6 is specifically expressed in the silk gland. Using semi-quantitative, quantitative real-time RT-PCR and Western blot, it was confirmed that Bmjhe6 was specifically expressed in the middle silk gland (MSG) with high levels in the anterior region of the MSG (A-MSG). The immunofluorescence localization analysis revealed that Bmjhe6 is produced within cells, secreted into the gland lumen, and co-transported with silk proteins into the anterior silk gland (ASG). In vitro hormone induction experiments demonstrated that Bmjhe6 responds to a JH analog, increasing its expression after 12-24 h, whereas 20-hydroxyecdysone inhibited it. In addition, Bmjhe6 knockdown using dsBmjhe6 injections accelerated larval development, resulting in increased larval body and silk gland weight. This induced disordered sericin genes (Ser2, Ser3) expression, and key genes in the JH synthesis pathway (BmKr-h1 and BmMet1) were significantly upregulated along with the transcription factors (SGF-1 and Sage). These results indicate that Bmjhe6 plays an important role in silk gland growth and silk protein synthesis by modulating JH signal.
ESTHER : Zhang_2023_Insects_14_
PubMedSearch : Zhang_2023_Insects_14_
PubMedID: 38132582

Title : Roles and Mechanisms of Dipeptidyl Peptidase 4 Inhibitors in Vascular Aging - Cao_2021_Front.Endocrinol.(Lausanne)_12_731273
Author(s) : Cao F , Wu K , Zhu YZ , Bao ZW
Ref : Front Endocrinol (Lausanne) , 12 :731273 , 2021
Abstract : Vascular aging is characterized by alterations in the constitutive properties and biological functions of the blood vessel wall. Endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are indispensability elements in the inner layer and the medial layer of the blood vessel wall, respectively. Dipeptidyl peptidase-4 (DPP4) inhibitors, as a hypoglycemic agent, play a protective role in reversing vascular aging regardless of their effects in meliorating glycemic control in humans and animal models of type 2 diabetes mellitus (T2DM) through complex cellular mechanisms, including improving EC dysfunction, promoting EC proliferation and migration, alleviating EC senescence, obstructing EC apoptosis, suppressing the proliferation and migration of VSMCs, increasing circulating endothelial progenitor cell (EPC) levels, and preventing the infiltration of mononuclear macrophages. All of these showed that DPP4 inhibitors may exert a positive effect against vascular aging, thereby preventing vascular aging-related diseases. In the current review, we will summarize the cellular mechanism of DPP4 inhibitors regulating vascular aging; moreover, we also intend to compile the roles and the promising therapeutic application of DPP4 inhibitors in vascular aging-related diseases.
ESTHER : Cao_2021_Front.Endocrinol.(Lausanne)_12_731273
PubMedSearch : Cao_2021_Front.Endocrinol.(Lausanne)_12_731273
PubMedID: 34489872

Title : Influence of seasonal migration on evolution of insecticide resistance in Plutella xylostella - Wang_2021_Insect.Sci__
Author(s) : Wang M , Zhu B , Zhang L , Xiao Y , Liang P , Wu K
Ref : Insect Sci , : , 2021
Abstract : The diamondback moth, Plutella xylostella (L.), is one of the most destructive migratory pest species of cruciferous vegetables worldwide and has developed resistance to most of the insecticides used for its control. The migration regularity, migratory behavior, and relationship between flight and reproduction of P. xylostella have been widely reported. However, the effect of migration on insecticide resistance in this pest is still unclear. In this study, the effect of migration on P. xylostella resistance to seven insecticides was investigated using populations across the Bohai Sea that were collected in the early and late seasons during 2017-2019. The bioassay results showed that the early season populations of P. xylostella from South China possessed much higher resistance to insecticides because of intensive insecticide application; alternatively, the late season populations migrated from Northeast China, where the insecticides were only used occasionally, showed much lower insecticide resistance. The genome re-sequencing results revealed that, among the eight mutations involved in insecticide resistance, the frequencies of two acetylcholinesterase mutations (A298S and G324A) responsible for organophosphorus insecticide resistance were significantly decreased in the late season populations. The results indicated that P. xylostella migration between tropical and temperate regions significantly delayed the development of insecticide resistance. These findings illustrated the effect of regional migration on the evolution of insecticide resistance in P. xylostella, and provided foundational information for further research on the relationship between migration and insecticide resistance development in other insects. This article is protected by copyright. All rights reserved.
ESTHER : Wang_2021_Insect.Sci__
PubMedSearch : Wang_2021_Insect.Sci__
PubMedID: 34873833

Title : Isolation, sequencing of the HvnHID gene and its role in the purple-grain colour development in Tibetan hulless barley - Yao_2021_Czech.J.Genet.Plant.Breed__
Author(s) : Yao X , Su L , Yao Y , An L , Bai Y , Li X , Wu K
Ref : _Czech J Genet Plant Breed , : , 2021
Abstract : 2-hydroxyisoflavanone dehydratase (HID) plays an important role in isoflavone biosynthesis. In this study, HID was isolated from the seeds of the purple-grained Tibetan hulless barley variety Nerumuzha and the white-grained variety Kunlun 10. The HvnHID gene includes the 981 bp open reading frame and encodes a protein of 327 amino acids. It has a typical Abhydrolase_3 domain (78-306) and belongs to the carboxylesterase (CXE) family of the Abhydrolase_3 (alpha/beta hydrolase) superfamily. There are eight nucleotide differences in the HvnHID coding sequence and two amino acid differences (one in the Abhydrolase_3 domain) between Nerumuzha and Kunlun 10. The HvnHID of hulless barley has the closest relationship with the HID in Hordeum vulgare, and the most distant relationship in Panicum hallii. At the early-mid stage of the seed colour development, the HvnHID expression levels in the purple and black seeds were significantly higher than in the white and blue ones (P < 0.01). During the seed colour development of purple-grained hulless barley, the expression of the key genes (HvnF3'H, HvnDRF, HvnANT1, and HvnGT) in the anthocyanidin biosynthetic pathway increased significantly, while the HvnHID expression decreased significantly (P < 0.01). Thus, it is likely that HvnHID negatively regulates the anthocyanidin biosynthesis. This result provides an important basis for further study of the biological functions of HvnHID in the anthocyanidin biosynthetic pathway.
ESTHER : Yao_2021_Czech.J.Genet.Plant.Breed__
PubMedSearch : Yao_2021_Czech.J.Genet.Plant.Breed__
PubMedID:
Gene_locus related to this paper: horvv-f2da29

Title : A Cluster of Autism-Associated Variants on X-Linked NLGN4X Functionally Resemble NLGN4Y - Nguyen_2020_Neuron_106_759
Author(s) : Nguyen TA , Wu K , Pandey S , Lehr AW , Li Y , Bemben MA , Badger JD, 2nd , Lauzon JL , Wang T , Zaghloul KA , Thurm A , Jain M , Lu W , Roche KW
Ref : Neuron , 106 :759 , 2020
Abstract : Autism spectrum disorder (ASD) is more prevalent in males; however, the etiology for this sex bias is not well understood. Many mutations on X-linked cell adhesion molecule NLGN4X result in ASD or intellectual disability. NLGN4X is part of an X-Y pair, with NLGN4Y sharing approximately 97% sequence homology. Using biochemistry, electrophysiology, and imaging, we show that NLGN4Y displays severe deficits in maturation, surface expression, and synaptogenesis regulated by one amino acid difference with NLGN4X. Furthermore, we identify a cluster of ASD-associated mutations surrounding the critical amino acid in NLGN4X, and these mutations phenocopy NLGN4Y. We show that NLGN4Y cannot compensate for the functional deficits observed in ASD-associated NLGN4X mutations. Altogether, our data reveal a potential pathogenic mechanism for male bias in NLGN4X-associated ASD.
ESTHER : Nguyen_2020_Neuron_106_759
PubMedSearch : Nguyen_2020_Neuron_106_759
PubMedID: 32243781
Gene_locus related to this paper: human-NLGN4X

Title : Prophylactic inhibition of soluble epoxide hydrolase delays onset of nephritis and ameliorates kidney damage in NZB\/W F1 mice - Klocke_2019_Sci.Rep_9_8993
Author(s) : Klocke J , Ulu A , Wu K , Rudolph B , Dragun D , Gollasch M , Schunck WH , Hammock BD , Riemekasten G , Enghard P
Ref : Sci Rep , 9 :8993 , 2019
Abstract : Epoxy-fatty-acids (EpFAs), cytochrome P450 dependent arachidonic acid derivatives, have been suggested to have anti-inflammatory properties, though their effects on autoimmune diseases like systemic lupus erythematosus (SLE) have yet to be investigated. We assessed the influence of EpFAs and their metabolites in lupus prone NZB/W F1 mice by pharmacological inhibition of soluble epoxide hydrolase (sEH, EPHX2). The sEH inhibitor 1770 was administered to lupus prone NZB/W F1 mice in a prophylactic and a therapeutic setting. Prophylactic inhibition of sEH significantly improved survival and reduced proteinuria. By contrast, sEH inhibitor-treated nephritic mice had no survival benefit; however, histological changes were reduced when compared to controls. In humans, urinary EpFA levels were significantly different in 47 SLE patients when compared to 10 healthy controls. Gene expression of EPHX2 was significantly reduced in the kidneys of both NZB/W F1 mice and lupus nephritis (LN) patients. Correlation of EpFAs with SLE disease activity and reduced renal EPHX gene expression in LN suggest roles for these components in human disease.
ESTHER : Klocke_2019_Sci.Rep_9_8993
PubMedSearch : Klocke_2019_Sci.Rep_9_8993
PubMedID: 31222024

Title : Fast emerging insecticide resistance in Aedes albopictus in Guangzhou, China: Alarm to the dengue epidemic - Su_2019_PLoS.Negl.Trop.Dis_13_e0007665
Author(s) : Su X , Guo Y , Deng J , Xu J , Zhou G , Zhou T , Li Y , Zhong D , Kong L , Wang X , Liu M , Wu K , Yan G , Chen XG
Ref : PLoS Negl Trop Dis , 13 :e0007665 , 2019
Abstract : Dengue is one of the most serious mosquito-borne infectious diseases in the world. Aedes albopictus is the most invasive mosquito and one of the primary vectors of dengue. Vector control using insecticides is the only viable strategy to prevent dengue virus transmission. In Guangzhou, after the 2014 pandemic, massive insecticides have been implemented. Massive insecticide use may lead to the development of resistance, but few reports are available on the status of insecticide resistance in Guangzhou after 2014. In this study, Ae. albopictus were collected from four districts with varied dengue virus transmission intensity in Guangzhou from 2015 to 2017. Adult Ae. albopictus insecticide susceptibility to deltamethrin (0.03%), permethrin(0.25%), DDT(4%), malathion (0.8%) and bendiocarb (0.1%) was determined by the standard WHO tube test, and larval resistance bioassays were conducted using temephos, Bacillus thuringiensis israelensis (Bti), pyriproxyfen (PPF) and hexaflumuron. Mutations at the voltage-gated sodium channel (VGSC) gene and acetylcholinesterase (AChE) gene were analyzed. The effect of cytochrome P450s on the resistance of Ae. albopictus to deltamethrin was tested using the synergistic agent piperonyl butoxide (PBO). The results showed that Ae. albopictus populations have rapidly developed very high resistances to multiple commonly used insecticides at all study areas except malathion, Bti and hexaflumuron. We found 1534 codon mutations in the VGSC gene that were significantly correlated with the resistance to pyrethroids and DDT, and 11 synonymous mutations were also found in the gene. The resistance to deltamethrin can be significantly reduced by PBO but may generated cross-resistance to PPF. Fast emerging resistance in Ae. albopictus may affect mosquito management and threaten the prevention and control of dengue, similar to the resistance in Anopheles mosquitoes has prevented the elimination of malaria and call for timely and guided insecticide management.
ESTHER : Su_2019_PLoS.Negl.Trop.Dis_13_e0007665
PubMedSearch : Su_2019_PLoS.Negl.Trop.Dis_13_e0007665
PubMedID: 31525199

Title : Acetylcholinesterase modified AuNPs-MoS2-rGO\/PI flexible film biosensor: Towards efficient fabrication and application in paraoxon detection - Jia_2019_Bioelectrochemistry_131_107392
Author(s) : Jia L , Zhou Y , Wu K , Feng Q , Wang C , He P
Ref : Bioelectrochemistry , 131 :107392 , 2019
Abstract : A flexible acetylcholinesterase (AChE) film biosensor, based on a AuNPs-MoS2-reduced graphene oxide/polyimide flexible film (rGO/PI) electrode, has been synthesized for paraoxon detection. In this study, the rGO/PI film acts as the flexible substrate and AuNPs are reduced by monolayer MoS2 under illumination. Transmission electron microscopy revealed that AuNPs are uniformly dispersed on the MoS2-rGO/PI electrode surface with a diameter ~10nm. X-ray photoelectron spectroscopy indicated that a strong binding force exists between reduced AuNPs and monolayer MoS2. The AChE modified AuNPs-MoS2-rGO/PI flexible film biosensor is used to hydrolyze acetylcholine chloride and obtain a large current response at 0.49V by differential pulse voltammetry, demonstrating successful immobilization of AChE. In view of the inhibition of paraoxon on the AChE, under optimal conditions, the AChE/AuNPs-MoS2-rGO/PI film biosensor shows a linear response over a concentration range 0.005-0.150mug/mL, a sensitivity of 4.44 uA/mugmL(-1), a detection limit of 0.0014mug/mL, acceptable reproducibility and stability to paraoxon. The flexible film biosensor has also proved used for detection of paraoxon in real samples.
ESTHER : Jia_2019_Bioelectrochemistry_131_107392
PubMedSearch : Jia_2019_Bioelectrochemistry_131_107392
PubMedID: 31707277

Title : A Conserved Tyrosine Residue in Slitrk3 Carboxyl-Terminus Is Critical for GABAergic Synapse Development - Li_2019_Front.Mol.Neurosci_12_213
Author(s) : Li J , Han W , Wu K , Li YD , Liu Q , Lu W
Ref : Front Mol Neurosci , 12 :213 , 2019
Abstract : Single-passing transmembrane protein, Slitrk3 (Slit and Trk-like family member 3, ST3), is a synaptic cell adhesion molecule highly expressed at inhibitory synapses. Recent studies have shown that ST3, through its extracellular domain, selectively regulates inhibitory synapse development via the trans-synaptic interaction with presynaptic cell adhesion molecule, receptor protein tyrosine phosphatase delta (PTPdelta) and the cis-interaction with postsynaptic cell adhesion molecule, Neuroligin 2 (NL2). However, little is known about the physiological function of ST3 intracellular, carboxyl (C)-terminal region. Here we report that in heterologous cells, ST3 C-terminus is not required for ST3 homo-dimerization and trafficking to the cell surface. In contrast, in hippocampal neurons, ST3 C-terminus, more specifically, the conserved tyrosine Y969 (in mice), is critical for GABAergic synapse development. Indeed, overexpression of ST3 Y969A mutant markedly reduced the gephyrin puncta density and GABAergic transmission in hippocampal neurons. In addition, single-cell genetic deletion of ST3 strongly impaired GABAergic transmission. Importantly, wild-type (WT) ST3, but not the ST3 Y969A mutant, could fully rescue GABAergic transmission deficits in neurons lacking endogenous ST3, confirming a critical role of Y969 in the regulation of inhibitory synapses. Taken together, our data identify a single critical residue in ST3 C-terminus that is important for GABAergic synapse development and function.
ESTHER : Li_2019_Front.Mol.Neurosci_12_213
PubMedSearch : Li_2019_Front.Mol.Neurosci_12_213
PubMedID: 31551708

Title : Effects of feed intake restriction during late pregnancy on the function, anti-oxidation capability and acute phase protein synthesis of ovine liver - Yang_2019_Asian-Australas.J.Anim.Sci_32_217
Author(s) : Yang H , Wang Y , Ma C , Sun C , Liu Y , Wu K , Li M , Borjigin G , Gao F
Ref : Asian-Australas J Anim Sci , 32 :217 , 2019
Abstract : OBJECTIVE: An experiment was conducted to investigate the effects of feed intake restriction during late pregnancy on the function, anti-oxidation capability and acute phase protein synthesis of ovine liver. METHODS: Eighteen time-mated ewes with singleton fetuses were allocated to three groups: restricted group 1 (RG1, 0.18 MJ ME/kg W0.75 d, n = 6), restricted group 2 (RG2, 0.33 MJ ME/kg W0.75 d), n = 6) and a control group (CG, ad libitum, 0.67 MJ ME/kg W0.75 d, n = 6). The feed restriction period was from 90 days to 140 days of pregnancy. RESULTS: The ewe's body weight, liver weights, water, and protein content of liver in the restricted groups were reduced compared with the CG group (p<0.05), but the liver fat contents in the RG1 group were higher than those of the CG group (p<0.05). The increased hepatic collagen fibers and reticular fibers were observed in the restricted groups with the reduction of energy intake. The concentrations of nonesterified free fatty acids in the RG1 and RG2 groups were higher than those of the CG group with the reduction of energy intake (p<0.05), but there were decreased concentrations of lipoprotein lipase and hepatic lipase in both restricted groups compared with the CG group (p<0.05). In addition, the increased concentrations of beta-hydroxybutyric acid, triglycerides, malondialdehyde, total antioxidant capacity and activities of superoxide dismutase activity and catalase were found in the RG1 group, and the concentrations of cholinesterase in the RG1 group were reduced compared with the CG group (p<0.05). For the concentrations of acute phase proteins, the C-reactive protein (CRP) in the RG1 group were reduced compared with the CG group, but there were no differences in haptoglobin relative to the controls (p>0.05). CONCLUSION: The fat accumulation, increased hepatic fibrosis, antioxidant imbalance and modified synthesis of acute phase proteins were induced in ewe's liver by maternal malnutrition during late pregnancy, which were detrimental for liver function to accommodate pregnancy.
ESTHER : Yang_2019_Asian-Australas.J.Anim.Sci_32_217
PubMedSearch : Yang_2019_Asian-Australas.J.Anim.Sci_32_217
PubMedID: 30056659

Title : Evidence for multiple-insecticide resistance in urban Aedes albopictus populations in southern China - Li_2018_Parasit.Vectors_11_4
Author(s) : Li Y , Xu J , Zhong D , Zhang H , Yang W , Zhou G , Su X , Wu Y , Wu K , Cai S , Yan G , Chen XG
Ref : Parasit Vectors , 11 :4 , 2018
Abstract : BACKGROUND: Aedes albopictus (Skuse) is an invasive mosquito that has become an important vector of chikungunya, dengue and Zika viruses. In the absence of specific antiviral therapy or a vaccine, vector management is the sole method available for reducing Aedes-induced disease morbidity. Determining the resistance status of Ae. albopictus to insecticides and exploring the resistance mechanisms is essential for future vector control planning. METHODS: Aedes albopictus larvae and pupae were sampled from six sites (two sites each from urban, suburban and rural) in Guangzhou. The resistance bioassays were conducted against Bacillus thuringiensis israelensis (Bti): deltamethrin, propoxur and malathion for larvae; and deltamethrin, DDT, propoxur and malathion for adults. P450 monooxygenase (P450s), glutathione S-transferase (GSTs) and carboxylesterase (COEs) activities of adult mosquitoes were measured. Mutations at the knockdown resistance (kdr) gene were analyzed, and the association between kdr mutations and phenotypic resistance was tested. RESULTS: Adult bioassays revealed varied susceptibility against DDT, deltamethrin and propoxur in the six Ae. albopictus populations. Significantly lower mortality rates were found in urban populations than suburban and rural populations. Urban mosquito populations showed resistance against DDT, deltamethrin and propoxur, while one rural population was resistant to DDT. All populations tested were susceptible to malathion. Larval bioassays results indicated that all populations of Ae. albopictus were sensitive to the larvicide Bti and malathion. Resistance to deltamethrin and propoxur was common in larval populations. The F1534S and F1534 L mutations were found to be significantly associated with deltamethrin resistance. Biochemical assays indicated elevated detoxification enzyme activities in the field mosquito populations. CONCLUSIONS: Aedes albopictus populations in Guangzhou, especially in urban areas, have developed resistance to the commonly used insecticides, primarily DDT and deltamethrin. This finding calls for resistance management and developing counter measures to mitigate the spread of resistance.
ESTHER : Li_2018_Parasit.Vectors_11_4
PubMedSearch : Li_2018_Parasit.Vectors_11_4
PubMedID: 29298700

Title : Targeting dipeptidyl peptidase 8 genes inhibits proliferation, migration and invasion by inhibition of cyclin D1 and MMP2MMP9 signal pathway in cervical cancer - Chen_2018_J.Gene.Med_20_e3056
Author(s) : Chen Y , Liu F , Wu K , Wu W , Wu H , Zhang W
Ref : J Gene Med , 20 :e3056 , 2018
Abstract : BACKGROUND: DPP8 is a member of the dipeptidyl peptidase IV family, which belongs to the S9b protease subfamily. It regulates cell proliferation, apoptosis, migration and invasion during cancer progression. METHODS: To investigate the role of DPP8 in cervical cancer, we examined DPP8 levels in cervical cancer tissues and cells. The localization of DPP8 was determined by immunofluorescence staining. Subsequently, SiHa and HeLa cells were treated with small interfering RNA (siRNA)-DPP8. We used cell cycle analysis, an 5-ethyl-2'-deoxyuridine assay proliferation assay and a cellular apoptosis assay to determine the effect of DPP8 on the proliferation and apoptosis of cervical cancer cells. We used a Transwell assay to assess the number of transfection cancer cells migrating through the matrix. A real-time polymerase chain reaction and western blot analysis were used to analyze the expression of related proteins and to determine the phenotype caused by the depletion or overexpression of DPP8 in cervical cancer cells. RESULTS: We observed that DPP8 was highly expressed in cervical cancer tissues and cells. DPP8 expression was observed in the cytosol and in the perinuclear area, as well as in the nuclei of cervical cancer cells. Notably, when cells were treated with siRNA-DPP8, the expression of BAX increased, and the expression of cyclin D1, Bcl-2, MMP2 and MMP9 was downregulated. In cervical cancer cell lines, silencing the expression of DPP8 not only suppressed the proliferation, migration and invasion of the cervical cancer cells, but also promoted cervical cancer cell apoptosis. CONCLUSIONS: The data obtained in the present study reveal that DPP8 promotes the progression of cervical cancer.
ESTHER : Chen_2018_J.Gene.Med_20_e3056
PubMedSearch : Chen_2018_J.Gene.Med_20_e3056
PubMedID: 30225951

Title : A novel esterase from a marine mud metagenomic library for biocatalytic synthesis of short-chain flavor esters - Gao_2016_Microb.Cell.Fact_15_41
Author(s) : Gao W , Wu K , Chen L , Fan H , Zhao Z , Gao B , Wang H , Wei D
Ref : Microb Cell Fact , 15 :41 , 2016
Abstract : BACKGROUND: Marine mud is an abundant and largely unexplored source of enzymes with unique properties that may be useful for industrial and biotechnological purposes. However, since most microbes cannot be cultured in the laboratory, a cultivation-independent metagenomic approach would be advantageous for the identification of novel enzymes. Therefore, with the objective of screening novel lipolytic enzymes, a metagenomic library was constructed using the total genomic DNA extracted from marine mud.
RESULTS: Based on functional heterologous expression, 34 clones that showed lipolytic activity were isolated. The five clones with the largest halos were identified, and the corresponding genes were successfully overexpressed in Escherichia coli. Molecular analysis revealed that these encoded proteins showed 48-79 % similarity with other proteins in the GenBank database. Multiple sequence alignment and phylogenetic tree analysis classified these five protein sequences as new members of known families of bacterial lipolytic enzymes. Among them, EST4, which has 316 amino acids with a predicted molecular weight of 33.8 kDa, was further studied in detail due to its strong hydrolytic activity. Characterization of EST4 indicated that it is an alkaline esterase that exhibits highest hydrolytic activity towards p-nitrophenyl butyrate (specific activity: 1389 U mg(-1)) at 45 degrees C and pH 8.0. The half-life of EST4 is 55 and 46 h at 40 and 45 degrees C, respectively, indicating a relatively high thermostability. EST4 also showed remarkable stability in organic solvents, retaining 90 % of its initial activity when incubated for 12 h in the presence of hydrophobic alkanes. Furthermore, EST4 was used as an efficient whole-cell biocatalyst for the synthesis of short-chain flavor esters, showing high conversion rate and good tolerance for high substrate concentrations (up to 3.0 M). These results demonstrate a promising potential for industrial scaling-up to produce short-chain flavor esters at high substrate concentrations in non-aqueous media.
CONCLUSIONS: This manuscript reports unprecedented alcohol tolerance and conversion of an esterase biocatalyst identified from a marine mud metagenomic library. The high organic solvent tolerance and thermostability of EST4 suggest that it has great potential as a biocatalyst.
ESTHER : Gao_2016_Microb.Cell.Fact_15_41
PubMedSearch : Gao_2016_Microb.Cell.Fact_15_41
PubMedID: 26892801

Title : Butyrylcholinesterase nanocapsule as a long circulating bioscavenger with reduced immune response - Zhang_2016_J.Control.Release_230_73
Author(s) : Zhang P , Jain P , Tsao C , Sinclair A , Sun F , Hung HC , Bai T , Wu K , Jiang S
Ref : J Control Release , 230 :73 , 2016
Abstract : Butyrylcholinesterase (BChE) is the most promising bioscavenger candidate to treat or prevent organophosphate (OP) poisoning. However, the clinical application of BChE is limited by two obstacles: an inadequate circulation half-life and limited sources for production. Although several modification technologies including glycosylation and PEGylation have been developed to improve its pharmacokinetics, none of them have been able to outperform blood-derived native BChE. In this work, we designed a long-circulating bioscavenger nanogel by coating equine serum-derived BChE with a zwitterionic polymer gel layer. This zwitterionic gel coating protected BChE from denaturation and degradation under harsh conditions. Notably, the nanocapsule exhibited a long circulation half-life of ~45h, a three-fold increase from the unmodified native version, enabling both therapeutic and prophylactic applications. In addition, the gel coating reduced the immunogenicity of equine BChE, unlocking the possibility to use non-human derived BChE as an OP bioscavenger in humans.
ESTHER : Zhang_2016_J.Control.Release_230_73
PubMedSearch : Zhang_2016_J.Control.Release_230_73
PubMedID: 27063423

Title : The Glutathione-S-Transferase, Cytochrome P450 and Carboxyl\/Cholinesterase Gene Superfamilies in Predatory Mite Metaseiulus occidentalis - Wu_2016_PLoS.One_11_e0160009
Author(s) : Wu K , Hoy MA
Ref : PLoS ONE , 11 :e0160009 , 2016
Abstract : Pesticide-resistant populations of the predatory mite Metaseiulus (= Typhlodromus or Galendromus) occidentalis (Arthropoda: Chelicerata: Acari: Phytoseiidae) have been used in the biological control of pest mites such as phytophagous Tetranychus urticae. However, the pesticide resistance mechanisms in M. occidentalis remain largely unknown. In other arthropods, members of the glutathione-S-transferase (GST), cytochrome P450 (CYP) and carboxyl/cholinesterase (CCE) gene superfamilies are involved in the diverse biological pathways such as the metabolism of xenobiotics (e.g. pesticides) in addition to hormonal and chemosensory processes. In the current study, we report the identification and initial characterization of 123 genes in the GST, CYP and CCE superfamilies in the recently sequenced M. occidentalis genome. The gene count represents a reduction of 35% compared to T. urticae. The distribution of genes in the GST and CCE superfamilies in M. occidentalis differs significantly from those of insects and resembles that of T. urticae. Specifically, we report the presence of the Mu class GSTs, and the J' and J" clade CCEs that, within the Arthropoda, appear unique to Acari. Interestingly, the majority of CCEs in the J' and J" clades contain a catalytic triad, suggesting that they are catalytically active. They likely represent two Acari-specific CCE clades that may participate in detoxification of xenobiotics. The current study of genes in these superfamilies provides preliminary insights into the potential molecular components that may be involved in pesticide metabolism as well as hormonal/chemosensory processes in the agriculturally important M. occidentalis.
ESTHER : Wu_2016_PLoS.One_11_e0160009
PubMedSearch : Wu_2016_PLoS.One_11_e0160009
PubMedID: 27467523

Title : Efficient kinetic resolution of phenyl glycidyl ether by a novel epoxide hydrolase from Tsukamurella paurometabola - Wu_2015_Appl.Microbiol.Biotechnol_99_9511
Author(s) : Wu K , Wang H , Sun H , Wei D
Ref : Applied Microbiology & Biotechnology , 99 :9511 , 2015
Abstract : Enantioselective hydrolysis of racemic epoxides mediated by epoxide hydrolases (EHs) is one of the most promising approaches to obtain enantiopure epoxides. In this study, we identified and characterized a novel EH (TpEH1) from Tsukamurella paurometabola by analyzing the conserved catalytic residues of EH. TpEH1 was overexpressed and purified, and its catalytic properties were studied using racemic phenyl glycidyl ether (PGE) and its derivatives as substrates. TpEH1 showed excellent enantioselectivity to the substrates PGE, 3-methylPGE, and 3-nitroPGE. The highest enantioselectivity (E > 100) was achieved when 3-nitroPGE was used as the substrate. The recombinant Escherichia coli TpEH1 demonstrated high substrate tolerance toward PGE and could hydrolyze PGE at concentrations of up to 400 mM (60 g/L) with high enantioselectivity (E = 65), giving (R)-PGE with enantiomeric excess of more than 99 % ee and 45 % yield within 1 h. This concentration of PGE is the highest reported concentration catalyzed by native EHs to date. Thus, the easily available and highly active E. coli TpEH1 showed great potential for the practical preparation of optically pure (R)-PGE.
ESTHER : Wu_2015_Appl.Microbiol.Biotechnol_99_9511
PubMedSearch : Wu_2015_Appl.Microbiol.Biotechnol_99_9511
PubMedID: 26088175
Gene_locus related to this paper: tsupd-d5us69

Title : Genome sequence of the Asian Tiger mosquito, Aedes albopictus, reveals insights into its biology, genetics, and evolution - Chen_2015_Proc.Natl.Acad.Sci.U.S.A_112_E5907
Author(s) : Chen XG , Jiang X , Gu J , Xu M , Wu Y , Deng Y , Zhang C , Bonizzoni M , Dermauw W , Vontas J , Armbruster P , Huang X , Yang Y , Zhang H , He W , Peng H , Liu Y , Wu K , Chen J , Lirakis M , Topalis P , Van Leeuwen T , Hall AB , Thorpe C , Mueller RL , Sun C , Waterhouse RM , Yan G , Tu ZJ , Fang X , James AA
Ref : Proc Natl Acad Sci U S A , 112 :E5907 , 2015
Abstract : The Asian tiger mosquito, Aedes albopictus, is a highly successful invasive species that transmits a number of human viral diseases, including dengue and Chikungunya fevers. This species has a large genome with significant population-based size variation. The complete genome sequence was determined for the Foshan strain, an established laboratory colony derived from wild mosquitoes from southeastern China, a region within the historical range of the origin of the species. The genome comprises 1,967 Mb, the largest mosquito genome sequenced to date, and its size results principally from an abundance of repetitive DNA classes. In addition, expansions of the numbers of members in gene families involved in insecticide-resistance mechanisms, diapause, sex determination, immunity, and olfaction also contribute to the larger size. Portions of integrated flavivirus-like genomes support a shared evolutionary history of association of these viruses with their vector. The large genome repertory may contribute to the adaptability and success of Ae. albopictus as an invasive species.
ESTHER : Chen_2015_Proc.Natl.Acad.Sci.U.S.A_112_E5907
PubMedSearch : Chen_2015_Proc.Natl.Acad.Sci.U.S.A_112_E5907
PubMedID: 26483478
Gene_locus related to this paper: aedae-q177c7 , aedal-a0a182gwe3 , aedal-a0a182gwt8 , aedal-a0a023eq67

Title : Whole-genome sequence of a flatfish provides insights into ZW sex chromosome evolution and adaptation to a benthic lifestyle - Chen_2014_Nat.Genet_46_253
Author(s) : Chen S , Zhang G , Shao C , Huang Q , Liu G , Zhang P , Song W , An N , Chalopin D , Volff JN , Hong Y , Li Q , Sha Z , Zhou H , Xie M , Yu Q , Liu Y , Xiang H , Wang N , Wu K , Yang C , Zhou Q , Liao X , Yang L , Hu Q , Zhang J , Meng L , Jin L , Tian Y , Lian J , Yang J , Miao G , Liu S , Liang Z , Yan F , Li Y , Sun B , Zhang H , Zhu Y , Du M , Zhao Y , Schartl M , Tang Q , Wang J
Ref : Nat Genet , 46 :253 , 2014
Abstract : Genetic sex determination by W and Z chromosomes has developed independently in different groups of organisms. To better understand the evolution of sex chromosomes and the plasticity of sex-determination mechanisms, we sequenced the whole genomes of a male (ZZ) and a female (ZW) half-smooth tongue sole (Cynoglossus semilaevis). In addition to insights into adaptation to a benthic lifestyle, we find that the sex chromosomes of these fish are derived from the same ancestral vertebrate protochromosome as the avian W and Z chromosomes. Notably, the same gene on the Z chromosome, dmrt1, which is the male-determining gene in birds, showed convergent evolution of features that are compatible with a similar function in tongue sole. Comparison of the relatively young tongue sole sex chromosomes with those of mammals and birds identified events that occurred during the early phase of sex-chromosome evolution. Pertinent to the current debate about heterogametic sex-chromosome decay, we find that massive gene loss occurred in the wake of sex-chromosome 'birth'.
ESTHER : Chen_2014_Nat.Genet_46_253
PubMedSearch : Chen_2014_Nat.Genet_46_253
PubMedID: 24487278
Gene_locus related to this paper: cynse-a0a3p8wch2 , cynse-a0a3p8vd14 , cynse-a0a3p8w747 , cynse-a0a3p8wq40 , cynse-a0a3p8wul3 , cynse-a0a3p8vqr4 , cynse-a0a3p8vmz4

Title : Hormone-sensitive lipase in yellow catfish Pelteobagrus fulvidraco: Molecular characterization, mRNA tissue expression and transcriptional regulation by leptin in vivo and in vitro - Chen_2014_Gen.Comp.Endocrinol_206_130
Author(s) : Chen QL , Luo Z , Song YF , Wu K , Huang C , Pan YX , Zhu QL
Ref : General & Comparative Endocrinology , 206 :130 , 2014
Abstract : Hormone-sensitive lipase (hsl) plays a pivotal role in regulation of lipolysis in mammals, but information is very scarce about its gene structure and function in fish. In this study, two distinct hsl cDNAs, designated hsl1 and hsl2, were firstly isolated and characterized from yellow catfish Pelteobagrus fulvidraco. The validated cDNAs encoding for hsl1 and hsl2 were 2739 and 2629bp in length, encoding peptides of 679 and 813 amino acid residues, respectively, and shared 57.7% amino acid identity. The phylogenetic analysis revealed that hsl1 and hsl2 derived from paralogous genes that might have arisen during a teleost-specific genome duplication event. Both hsl mRNAs were expressed in a wide range of tissues, but the abundance of each hsl mRNA showed the tissue- and developmental stage-dependent expression patterns. Intraperitoneal injection in vivo and incubation in vitro of recombinant human leptin (rb-hLEP) stimulated the mRNA expression of hsl2, but not hsl1, in the liver and hepatocytes of P. fulvidraco, respectively, suggesting that two hsl isoforms might serve different roles in lipid metabolism. To our knowledge, for the first time, the present study provides evidence that two hsl mRNAs are differentially expressed with and among tissues during different developmental stages and also differentially regulated by leptin both in vivo and in vitro, which serves to increase our understanding on hsl physiological function in fish.
ESTHER : Chen_2014_Gen.Comp.Endocrinol_206_130
PubMedSearch : Chen_2014_Gen.Comp.Endocrinol_206_130
PubMedID: 25016050

Title : Enhanced brain distribution and pharmacodynamics of rivastigmine by liposomes following intranasal administration - Yang_2013_Int.J.Pharm_452_344
Author(s) : Yang ZZ , Zhang YQ , Wang ZZ , Wu K , Lou JN , Qi XR
Ref : Int J Pharm , 452 :344 , 2013
Abstract : Alzheimer's disease (AD) is a common progressive neurodegenerative disorder associated with cholinergic neurons degeneration. The blood-brain barrier (BBB) not only provides protection for the brain but also hinders the treatment and diagnosis of this neurological disease, because the drugs must cross BBB to reach the lesions. The present work was aimed at formulating rivastigmine liposomes (Lp) and cell-penetrating peptide (CPP) modified liposomes (CPP-Lp) to improve rivastigmine distribution in brain and proceed to enhance pharmacodynamics by intranasal (IN) administration and minimize side effects. The results revealed that Lp especially the CPP-Lp can enhance the permeability across the BBB by murine brain microvascular endothelial cells model in vitro. IN administration of rivastigmine solution and rivastigmine liposomes demonstrated the capacity to improve rivastigmine distribution and adequate retention in CNS regions especially in hippocampus and cortex, which were the regions most affected by AD, than that of IV administration. Importantly, the lagging but intense inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BCHE) activities were relative to the extended release, absorption and retention. In addition, there was very mild nasal toxicity of liposomal formulations. The data suggest that rivastigmine liposomes especially CPP-Lp improve the brain delivery and enhance pharmacodynamics which respect to BBB penetration and nasal olfactory pathway into brain after IN administration, and simultaneously decrease the hepatic first pass metabolism and gastrointestinal adverse effects.
ESTHER : Yang_2013_Int.J.Pharm_452_344
PubMedSearch : Yang_2013_Int.J.Pharm_452_344
PubMedID: 23680731

Title : Donepezil attenuates hippocampal neuronal damage and cognitive deficits after global cerebral ischemia in gerbils - Min_2012_Neurosci.Lett_510_29
Author(s) : Min D , Mao X , Wu K , Cao Y , Guo F , Zhu S , Xie N , Wang L , Chen T , Shaw C , Cai J
Ref : Neuroscience Letters , 510 :29 , 2012
Abstract : Decreased cerebral blood flow causes cognitive impairments and neuronal injury in vascular dementia. In the present study, we reported that donepezil, a cholinesterase inhibitor, improved transient global cerebral ischemia-induced spatial memory impairment in gerbils. Treatment with 5mg/kg of donepezil for 21 consecutive days following a 10-min period of ischemia significantly inhibited delayed neuronal death in the hippocampal CA1 region. In Morris water maze test, memory impairment was significantly improved by donepezil treatment. Western blot analysis showed that donepezil treatment prevented reductions in p-CaMKII and p-CREB protein levels in the hippocampus. These results suggest that donepezil attenuates the memory deficit induced by transient global cerebral ischemia and this neuroprotection may be associated with the phosphorylation of CaMKII and CERB in the hippocampus.
ESTHER : Min_2012_Neurosci.Lett_510_29
PubMedSearch : Min_2012_Neurosci.Lett_510_29
PubMedID: 22240104

Title : Tissue distribution and pharmacodynamics of rivastigmine after intranasal and intravenous administration in rats - Yang_2012_Curr.Alzheimer.Res_9_315
Author(s) : Yang ZZ , Zhang YQ , Wu K , Wang ZZ , Qi XR
Ref : Curr Alzheimer Res , 9 :315 , 2012
Abstract : The aim of the study was mainly to investigate the relationship between concentration of rivastigmine and its inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) following intranasal (IN) and intravenous (IV) administration in rats, and to provide a novel nasal delivery route for the brain disease therapy. Rivastigmine was administered to male rats at 2 mg/kg by IN and IV route. Drug concentration, AChE and BuChE activity were measured in the plasma, central nervous system (CNS) regions i.e. olfactory region, hippocampus, cerebrum and cerebellum, and peripheral tissues. It was determined that rivastigmine was characterized by extremely rapid and complete absorption into the systemic circulation followed by a rapid decline in the plasma concentrations, and can also quickly distribute into CNS and peripheral tissues by the two routes. IN administration showed higher concentration in CNS regions and longer action on inhibiting the activity of AChE and BuChE than IV administration. More significant decrease of the two enzymes was observed in CNS regions than in peripheral tissues for both administrations. A close relationship was found between the concentration of rivastigmine and enzyme inhibition in plasma and CNS tissues in rats. Based on these findings, it was concluded that rivastigmine could cause relatively strong inhibition of AChE and BuChE in plasma and brain tissues, especially in hippocampus, cortex and cerebrum. The pharmacodynamics was closely related to its concentration in vivo. The intranasal route can be strategy for delivering the drug into brain.
ESTHER : Yang_2012_Curr.Alzheimer.Res_9_315
PubMedSearch : Yang_2012_Curr.Alzheimer.Res_9_315
PubMedID: 22044027

Title : The genome of the mesopolyploid crop species Brassica rapa - Wang_2011_Nat.Genet_43_1035
Author(s) : Wang X , Wang H , Wang J , Sun R , Wu J , Liu S , Bai Y , Mun JH , Bancroft I , Cheng F , Huang S , Li X , Hua W , Freeling M , Pires JC , Paterson AH , Chalhoub B , Wang B , Hayward A , Sharpe AG , Park BS , Weisshaar B , Liu B , Li B , Tong C , Song C , Duran C , Peng C , Geng C , Koh C , Lin C , Edwards D , Mu D , Shen D , Soumpourou E , Li F , Fraser F , Conant G , Lassalle G , King GJ , Bonnema G , Tang H , Belcram H , Zhou H , Hirakawa H , Abe H , Guo H , Jin H , Parkin IA , Batley J , Kim JS , Just J , Li J , Xu J , Deng J , Kim JA , Yu J , Meng J , Min J , Poulain J , Hatakeyama K , Wu K , Wang L , Fang L , Trick M , Links MG , Zhao M , Jin M , Ramchiary N , Drou N , Berkman PJ , Cai Q , Huang Q , Li R , Tabata S , Cheng S , Zhang S , Sato S , Sun S , Kwon SJ , Choi SR , Lee TH , Fan W , Zhao X , Tan X , Xu X , Wang Y , Qiu Y , Yin Y , Li Y , Du Y , Liao Y , Lim Y , Narusaka Y , Wang Z , Li Z , Xiong Z , Zhang Z
Ref : Nat Genet , 43 :1035 , 2011
Abstract : We report the annotation and analysis of the draft genome sequence of Brassica rapa accession Chiifu-401-42, a Chinese cabbage. We modeled 41,174 protein coding genes in the B. rapa genome, which has undergone genome triplication. We used Arabidopsis thaliana as an outgroup for investigating the consequences of genome triplication, such as structural and functional evolution. The extent of gene loss (fractionation) among triplicated genome segments varies, with one of the three copies consistently retaining a disproportionately large fraction of the genes expected to have been present in its ancestor. Variation in the number of members of gene families present in the genome may contribute to the remarkable morphological plasticity of Brassica species. The B. rapa genome sequence provides an important resource for studying the evolution of polyploid genomes and underpins the genetic improvement of Brassica oil and vegetable crops.
ESTHER : Wang_2011_Nat.Genet_43_1035
PubMedSearch : Wang_2011_Nat.Genet_43_1035
PubMedID: 21873998
Gene_locus related to this paper: braol-Q8GTM3 , braol-Q8GTM4 , brarp-m4ei94 , brarp-m4c988 , brana-a0a078j4a9 , brana-a0a078e1m0 , brana-a0a078cd75 , brarp-m4dwa6 , brana-a0a078j4f0 , brana-a0a078cus4 , brana-a0a078f8c2 , brana-a0a078jql1 , brana-a0a078dgj3 , brana-a0a078hw50 , brana-a0a078cuu0 , brana-a0a078dfa9 , brana-a0a078ic91 , brarp-m4ctw3 , brana-a0a078ca65 , brana-a0a078ctc8 , brana-a0a078h021 , brana-a0a078jx23 , brarp-m4da84 , brarp-m4dwr7 , brana-a0a078dh94 , brana-a0a078h612 , brana-a0a078j2t3 , braol-a0a0d3dpb2 , braol-a0a0d3dx76 , brana-a0a078jxa8 , brana-a0a078i2k3 , brarp-m4cwq4 , brarp-m4dcj8 , brarp-m4eh17 , brarp-m4eey4 , brarp-m4dnj8 , brarp-m4ey83 , brarp-m4ey84

Title : The DNA sequence and biology of human chromosome 19 - Grimwood_2004_Nature_428_529
Author(s) : Grimwood J , Gordon LA , Olsen A , Terry A , Schmutz J , Lamerdin J , Hellsten U , Goodstein D , Couronne O , Tran-Gyamfi M , Aerts A , Altherr M , Ashworth L , Bajorek E , Black S , Branscomb E , Caenepeel S , Carrano A , Caoile C , Chan YM , Christensen M , Cleland CA , Copeland A , Dalin E , Dehal P , Denys M , Detter JC , Escobar J , Flowers D , Fotopulos D , Garcia C , Georgescu AM , Glavina T , Gomez M , Gonzales E , Groza M , Hammon N , Hawkins T , Haydu L , Ho I , Huang W , Israni S , Jett J , Kadner K , Kimball H , Kobayashi A , Larionov V , Leem SH , Lopez F , Lou Y , Lowry S , Malfatti S , Martinez D , McCready P , Medina C , Morgan J , Nelson K , Nolan M , Ovcharenko I , Pitluck S , Pollard M , Popkie AP , Predki P , Quan G , Ramirez L , Rash S , Retterer J , Rodriguez A , Rogers S , Salamov A , Salazar A , She X , Smith D , Slezak T , Solovyev V , Thayer N , Tice H , Tsai M , Ustaszewska A , Vo N , Wagner M , Wheeler J , Wu K , Xie G , Yang J , Dubchak I , Furey TS , DeJong P , Dickson M , Gordon D , Eichler EE , Pennacchio LA , Richardson P , Stubbs L , Rokhsar DS , Myers RM , Rubin EM , Lucas SM
Ref : Nature , 428 :529 , 2004
Abstract : Chromosome 19 has the highest gene density of all human chromosomes, more than double the genome-wide average. The large clustered gene families, corresponding high G + C content, CpG islands and density of repetitive DNA indicate a chromosome rich in biological and evolutionary significance. Here we describe 55.8 million base pairs of highly accurate finished sequence representing 99.9% of the euchromatin portion of the chromosome. Manual curation of gene loci reveals 1,461 protein-coding genes and 321 pseudogenes. Among these are genes directly implicated in mendelian disorders, including familial hypercholesterolaemia and insulin-resistant diabetes. Nearly one-quarter of these genes belong to tandemly arranged families, encompassing more than 25% of the chromosome. Comparative analyses show a fascinating picture of conservation and divergence, revealing large blocks of gene orthology with rodents, scattered regions with more recent gene family expansions and deletions, and segments of coding and non-coding conservation with the distant fish species Takifugu.
ESTHER : Grimwood_2004_Nature_428_529
PubMedSearch : Grimwood_2004_Nature_428_529
PubMedID: 15057824

Title : The sequence and analysis of duplication-rich human chromosome 16 - Martin_2004_Nature_432_988
Author(s) : Martin J , Han C , Gordon LA , Terry A , Prabhakar S , She X , Xie G , Hellsten U , Chan YM , Altherr M , Couronne O , Aerts A , Bajorek E , Black S , Blumer H , Branscomb E , Brown NC , Bruno WJ , Buckingham JM , Callen DF , Campbell CS , Campbell ML , Campbell EW , Caoile C , Challacombe JF , Chasteen LA , Chertkov O , Chi HC , Christensen M , Clark LM , Cohn JD , Denys M , Detter JC , Dickson M , Dimitrijevic-Bussod M , Escobar J , Fawcett JJ , Flowers D , Fotopulos D , Glavina T , Gomez M , Gonzales E , Goodstein D , Goodwin LA , Grady DL , Grigoriev I , Groza M , Hammon N , Hawkins T , Haydu L , Hildebrand CE , Huang W , Israni S , Jett J , Jewett PB , Kadner K , Kimball H , Kobayashi A , Krawczyk MC , Leyba T , Longmire JL , Lopez F , Lou Y , Lowry S , Ludeman T , Manohar CF , Mark GA , McMurray KL , Meincke LJ , Morgan J , Moyzis RK , Mundt MO , Munk AC , Nandkeshwar RD , Pitluck S , Pollard M , Predki P , Parson-Quintana B , Ramirez L , Rash S , Retterer J , Ricke DO , Robinson DL , Rodriguez A , Salamov A , Saunders EH , Scott D , Shough T , Stallings RL , Stalvey M , Sutherland RD , Tapia R , Tesmer JG , Thayer N , Thompson LS , Tice H , Torney DC , Tran-Gyamfi M , Tsai M , Ulanovsky LE , Ustaszewska A , Vo N , White PS , Williams AL , Wills PL , Wu JR , Wu K , Yang J , DeJong P , Bruce D , Doggett NA , Deaven L , Schmutz J , Grimwood J , Richardson P , Rokhsar DS , Eichler EE , Gilna P , Lucas SM , Myers RM , Rubin EM , Pennacchio LA
Ref : Nature , 432 :988 , 2004
Abstract : Human chromosome 16 features one of the highest levels of segmentally duplicated sequence among the human autosomes. We report here the 78,884,754 base pairs of finished chromosome 16 sequence, representing over 99.9% of its euchromatin. Manual annotation revealed 880 protein-coding genes confirmed by 1,670 aligned transcripts, 19 transfer RNA genes, 341 pseudogenes and three RNA pseudogenes. These genes include metallothionein, cadherin and iroquois gene families, as well as the disease genes for polycystic kidney disease and acute myelomonocytic leukaemia. Several large-scale structural polymorphisms spanning hundreds of kilobase pairs were identified and result in gene content differences among humans. Whereas the segmental duplications of chromosome 16 are enriched in the relatively gene-poor pericentromere of the p arm, some are involved in recent gene duplication and conversion events that are likely to have had an impact on the evolution of primates and human disease susceptibility.
ESTHER : Martin_2004_Nature_432_988
PubMedSearch : Martin_2004_Nature_432_988
PubMedID: 15616553
Gene_locus related to this paper: human-CES1 , human-CES2 , human-CES3 , human-CES4A , human-CES5A

Title : The FK520 gene cluster of Streptomyces hygroscopicus var. ascomyceticus (ATCC 14891) contains genes for biosynthesis of unusual polyketide extender units - Wu_2000_Gene_251_81
Author(s) : Wu K , Chung L , Revill WP , Katz L , Reeves CD
Ref : Gene , 251 :81 , 2000
Abstract : FK520 (ascomycin) is a macrolide produced by Streptomyces hygroscopicus var. ascomyceticus (ATCC 14891) that has immunosuppressive, neurotrophic and antifungal activities. To further elucidate the biosynthesis of this and related macrolides, we cloned and sequenced an 80kb region encompassing the FK520 gene cluster. Genes encoding the three polyketide synthase (PKS) subunits (fkbB, fkbC and fkbA), the peptide synthetase (fkbP), the 31-O-methyltransferase (fkbM), the C-9 hydroxylase (fkbD) and the 9-hydroxyl oxidase (fkbO) had the same organization as the genes reported in the FK506 gene cluster of Streptomyces sp. MA6548 (Motamedi, H., Shafiee, A., 1998. The biosynthetic gene cluster for the macrolactone ring of the immunosuppressant FK506. Eur. J. Biochem. 256, 528-534). Disruption of a PKS gene in the cluster using the φC31 phage vector, KC515, led to antibiotic non-producing strains, proving the identity of the cluster. Previous labeling data have indicated that FK520 biosynthesis uses novel polyketide extender units (Byrne, K.M., Shafiee, A., Nielson, J., Arison, B., Monaghan, R.L., Kaplan, L., 1993. The biosynthesis and enzymology of an immunosuppressant, immunomycin, produced by Streptomyces hygroscopicus var, ascomyceticus. Dev. Ind. Microbiol. 32, 29-45). Genes in the flanking regions of the FK520 cluster were identified that appear to be involved in synthesis of these extender units. All but two of these genes were homologous to genes with known function. In addition to a crotonyl-CoA reductase gene (fkbS), at least two other genes are proposed to be involved in biosynthesis of the atypical PKS extender unit ethylmalonyl-CoA, which accounts for the ethyl side chain on C-21 of FK520. A set of five contiguous genes (fkbGHIJK) is proposed to be involved in biosynthesis of an unusual PKS extender unit bearing an oxygen on the alpha-carbon, and leading to the 13- and 15-methoxy side chains. These putative precursor synthesis genes in the flanking regions of the FK520 cluster are not found in the flanking regions of the rapamycin cluster (Molnar, I., Aparicio, J.F., Haydock, S.F., Khaw, L.E., Schwecke, T., Konig, A., Staunton, J., Leadlay, P.F., 1996. Organisation of the biosynthetic gene cluster for rapamycin in Streptomyces hygroscopicus: analysis of genes flanking the polyketide synthase. Gene 169, 1-7), consistent with labeling data showing that rapamycin biosynthesis uses only malonyl and methylmalonyl extender units.
ESTHER : Wu_2000_Gene_251_81
PubMedSearch : Wu_2000_Gene_251_81
PubMedID: 10863099
Gene_locus related to this paper: strhy-FKBQ , strhy-FKBU , strhy-FKBW