共查询到20条相似文献,搜索用时 31 毫秒
1.
Wenxiu Yi Qiang Li Jian Shen Lijie Ren Xiaohui Liu Qi Wang Sudan He Qingyu Wu Hu Hu Xinliang Mao Li Zhu 《PloS one》2014,9(8)
The phosphatidylinositol 3–kinase (PI3K) signaling pathway is critical in modulating platelet functions. In the present study, we evaluated the effect of , a recently identified pan-class I PI3K inhibitor, on platelet activation and thrombus formation. Results showed that S14161 inhibited human platelet aggregation induced by collagen, thrombin, U46619, and ADP in a dose-dependent manner. Flow cytometric studies showed that S14161 inhibited convulxin- or thrombin-induced P-selectin expression and fibrinogen binding of single platelet. S14161 also inhibited platelet spreading on fibrinogen and clot retraction, processes mediated by outside-in signaling. Using a microfluidic chamber we demonstrated that S14161 decreased platelet adhesion on collagen-coated surface by about 80%. Western blot showed that S14161 inhibited phosphorylation of Akt at both Ser473 and Thr308 sites, and GSK3β at Ser9 in response to collagen, thrombin, or U46619. Comparable studies showed that S14161 has a higher potential bioavailability than S14161, a prototypical inhibitor of pan-class I PI3K. Finally, the effects of LY294002 on thrombus formation in vivo were measured using a ferric chloride-induced carotid artery injury model in mice. The intraperitoneal injection of S14161 (2 mg/kg) to male C57BL/6 mice significantly extended the first occlusion time (5.05±0.99 min, n = 9) compared to the vehicle controls (3.72±0.95 min, n = 8) (P<0.05), but did not prolong the bleeding time (P>0.05). Taken together, our data showed that S14161 inhibits platelet activation and thrombus formation without significant bleeding tendency and toxicity, and considering its potential higher bioavailability, it may be developed as a novel therapeutic agent for the prevention of thrombotic disorders. S14161相似文献
2.
Shuanglin Peng Yujin Gao Sirong Shi Dan Zhao Huayue Cao Ting Fu Xiaoxiao Cai Jingang Xiao 《Cell proliferation》2022,55(1)
ObjectivesBone tissue engineering based on adipose‐derived stem cells (ASCs) is expected to become a new treatment for diabetic osteoporosis (DOP) patients with bone defects. However, compared with control ASCs (CON‐ASCs), osteogenic potential of DOP‐ASCs is decreased, which increased the difficulty of bone reconstruction in DOP patients. Moreover, the cause of the poor osteogenesis of ASCs in a hyperglycemic microenvironment has not been elucidated. Therefore, this study explored the molecular mechanism of the decline in the osteogenic potential of DOP‐ASCs from the perspective of epigenetics to provide a possible therapeutic target for bone repair in DOP patients with bone defects.Materials and methodsAn animal model of DOP was established in mice. CON‐ASCs and DOP‐ASCs were isolated from CON and DOP mice, respectively. small interfering RNA (SiRNA) and an AK137033 overexpression plasmid were used to regulate the expression of AK137033 in CON‐ASCs and DOP‐ASCs in vitro. Lentiviruses that carried shRNA‐ AK137033 or AK137033 cDNA were used to knockdown or overexpress AK137033, respectively, in CON‐ASCs and DOP‐ASCs in vivo. Hematoxylin and eosin (H&E), Masson''s, alizarin red, and alkaline phosphatase (ALP) staining, micro‐computed tomography (Micro‐CT), flow cytometry, qPCR, western blotting, immunofluorescence, and bisulfite‐specific PCR (BSP) were used to analyze the functional changes of ASCs.ResultsThe DOP mouse model was established successfully. Compared with CON‐ASCs, AK137033 expression, the DNA methylation level of the sFrp2 promoter region, Wnt signaling pathway markers, and the osteogenic differentiation potential were decreased in DOP‐ASCs. In vitro experiments showed that AK137033 silencing inhibited the Wnt signaling pathway and osteogenic ability of CON‐ASCs by reducing the DNA methylation level in the sFrp2 promoter region. Additionally, overexpression of AK137033 in DOP‐ASCs rescued these changes caused by DOP. Moreover, the same results were obtained in vivo.ConclusionsLncRNA‐ AK137033 inhibits the osteogenic potential of DOP‐ASCs by regulating the Wnt signaling pathway via modulating the DNA methylation level in the sFrp2 promoter region. This study provides an important reference to find new targets for the treatment of bone defects in DOP patients. AK137033相似文献
3.
Céline J Rocca Daniele G Soares Hana Bouzid Jo?o A P Henriques Annette K Larsen Alexandre E Escargueil 《Cell cycle (Georgetown, Tex.)》2015,14(13):2080-2090
Repair of DNA-targeted anticancer agents is an active area of investigation of both fundamental and clinical interest. However, most studies have focused on a small number of compounds limiting our understanding of both DNA repair and the DNA damage response. is an acronycine derivative that shows strong activity toward solid tumors in experimental models. S23906 forms bulky monofunctional DNA adducts in the minor groove which leads to destabilization of the double-stranded helix. We now report that S23906 induces formation of DNA double strand breaks that are processed through homologous recombination (HR) but not Non-Homologous End-Joining (NHEJ) repair. Interestingly, S23906 exposure was accompanied by a higher sensitivity of BRCA2-deficient cells compared to other HR deficient cell lines and by an S-phase accumulation in wild-type (wt), but not in BRCA2-deficient cells. Recently, we have shown that S23906-induced S phase arrest was mediated by the checkpoint kinase Chk1. However, its activated phosphorylated form is equally induced by S23906 in wt and BRCA2-deficient cells, likely indicating a role for BRCA2 downstream of Chk1. Accordingly, override of the S phase arrest by either 7-hydroxystaurosporine (UCN-01) or AZD7762 potentiates the cytotoxic activity of S23906 in wt, but not in BRCA2-deficient cells. Together, our findings suggest that the pronounced sensitivity of BRCA2-deficient cells to S23906 is due to both a defective S-phase arrest and the absence of HR repair. Tumors with deficiencies for proteins involved in HR, and BRCA2 in particular, may thus show increased sensitivity to S23906, thereby providing a rationale for patient selection in clinical trials. S23906相似文献
4.
Xue-Qin Chen Jing Zhang John L. Neumeyer Guo-Zhang Jin Guo-Yuan Hu Ao Zhang Xuechu Zhen 《PloS one》2009,4(6)
(±) , like many other arylbenzazepines, elicits powerful neuroprotection in vitro and in vivo. The neuroprotective action of the compound was found to partially depend on its D1-like dopamine receptor agonistic activity. The precise mechanism for the (±) SKF83959-mediated neuroprotection remains elusive. We report here that (±) SKF83959 is a potent blocker for delayed rectifier K+ channel. (±) SKF83959 inhibited the delayed rectifier K+ current (I
K) dose-dependently in rat hippocampal neurons. The IC
50 value for inhibition of I
K was 41.9±2.3 µM (Hill coefficient = 1.81±0.13, n = 6), whereas that for inhibition of I
A was 307.9±38.5 µM (Hill coefficient = 1.37±0.08, n = 6). Thus, (±) SKF83959 is 7.3-fold more potent in suppressing I
K than I
A. Moreover, the inhibition of I
K by (±) SKF83959 was voltage-dependent and not related to dopamine receptors. The rapidly onset of inhibition and recovery suggests that the inhibition resulted from a direct interaction of (±) SKF83959 with the K+ channel. The intracellular application of (±) SKF83959 had no effects of on I
K, indicating that the compound most likely acts at the outer mouth of the pore of K+ channel. We also tested the enantiomers of (±) SKF83959, R-(+) SKF83959 (MCL-201), and S-(−) SKF83959 (MCL-202), as well as SKF83959; all these compounds inhibited I
K. However, (±) SKF38393, at either 0.1 or 1 mM, exhibited the strongest inhibition on the currents among all tested drug. The present findings not only revealed a new potent blocker of I
K , but also provided a novel mechanism for the neuroprotective action of arylbenzazepines such as (±) SKF83959. SKF83959相似文献
5.
Y-H Fan J Cheng S A Vasudevan J Dou H Zhang R H Patel I T Ma Y Rojas Y Zhao Y Yu H Zhang J M Shohet J G Nuchtern E S Kim J Yang 《Cell death & disease》2013,4(10):e867
Neuroblastoma (NB) is a common pediatric cancer and contributes to more than 15% of all pediatric cancer-related deaths. Unlike adult tumors, recurrent somatic mutations in NB, such as tumor protein 53 (p53) mutations, occur with relative paucity. In addition, p53 downstream function is intact in NB cells with wild-type p53, suggesting that reactivation of p53 may be a viable therapeutic strategy for NB treatment. Herein, we report that the ubiquitin-specific protease 7 (USP7) inhibitor, , potently induces apoptosis in NB cells with an intact USP7-HDM2-p53 axis but not in NB cells with mutant p53 or without human homolog of MDM2 (HDM2) expression. In this study, we found that P22077 stabilized p53 by inducing HDM2 protein degradation in NB cells. P22077 also significantly augmented the cytotoxic effects of doxorubicin (Dox) and etoposide (VP-16) in NB cells with an intact USP7-HDM2-p53 axis. Moreover, P22077 was found to be able to sensitize chemoresistant LA-N-6 NB cells to chemotherapy. In an in vivo orthotopic NB mouse model, P22077 significantly inhibited the xenograft growth of three NB cell lines. Database analysis of NB patients shows that high expression of USP7 significantly predicts poor outcomes. Together, our data strongly suggest that targeting USP7 is a novel concept in the treatment of NB. USP7-specific inhibitors like P22077 may serve not only as a stand-alone therapy but also as an effective adjunct to current chemotherapeutic regimens for treating NB with an intact USP7-HDM2-p53 axis. P22077相似文献
6.
Eun-A Kim Kyouk Hwang Ji-Eun Kim Jee-Yin Ahn Soo Young Choi Seung-Ju Yang Sung-Woo Cho 《BMB reports》2021,54(11):557
Microglial activation is closely associated with neuroinflammatory pathologies. The nucleotide-binding and oligomerization domain-like receptor containing a pyrin domain 3 (NLRP3) inflammasomes are highly organized intracellular sensors of neuronal alarm signaling. NLRP3 inflammasomes activate nuclear factor kappa-B (NF-κB) and reactive oxygen species (ROS), which induce inflammatory responses. Moreover, NLRP3 dysfunction is a common feature of chronic inflammatory diseases. The present study investigated the effect of a novel thiazol derivative, N-cyclooctyl-5-methylthiazol-2-amine hydrobromide (), on inflammatory responses in lipopolysaccharide (LPS)-treated BV-2 microglial cells. KHG26700 significantly attenuated the expression of several pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, and interleukin-6, in these cells, as well as the LPS-induced increases in NLRP3, NF-κB, and phospho-IkBα levels. KHG26700 also suppressed the LPS-induced increases in protein levels of autophagy protein 5 (ATG5), microtubule-associated protein 1 light chain 3 (LC3), and beclin-1, as well as downregulating the LPS-enhanced levels of ROS, lipid peroxidation, and nitric oxide. These results suggest that the anti-inflammatory effects of KHG26700 may be due, at least in part, to the regulation of the NLRP3-mediated signaling pathway during microglial activation. KHG26700相似文献
7.
Sang-Hyun Lee YoungSoo Kim Hye Yun Kim Young Hoon Kim Maeng Sup Kim Jae Yang Kong Mun-Han Lee Dong Jin Kim Young Gil Ahn 《PloS one》2014,9(4)
Alzheimer''s disease is an irreversible neurodegenerative disorder that is characterized by the abnormal aggregation of amyloid-β into neurotoxic oligomers and plaques. Although many disease-modifying molecules are currently in Alzheimer clinical trials, a small molecule that inhibits amyloid-β aggregation and ameliorates the disorder has not been approved to date. Herein, we report the effects of a potent small molecule, 6-methoxy-2-(4-dimethylaminostyryl) benzofuran (), that directly disrupts amyloid-β oligomerization, preserving cognitive behavior when used prophylactically and reversing declines in cognitive behavior when used therapeutically. KMS88009 exhibited excellent pharmacokinetic profiles with extensive brain uptake and a high level of safety. When orally administered before and after the onset of Alzheimer''s disease symptoms, KMS88009 significantly reduced assembly of amyloid-β oligomers and improved cognitive behaviors in the APP/PS1 double transgenic mouse model. The unique dual mode of action indicates that KMS88009 may be a powerful therapeutic candidate for the treatment of Alzheimer''s disease. KMS88009相似文献
8.
Nathan Vinod Kumar Mary Esther Rani Rathinasamy Gunaseeli Narayanan Dhiraviam Kannan Jayavel Sridhar 《Bioinformation》2012,8(22):1105-1110
Cellulase is one of the most widely distributed enzymes with wide application. They are involved in conversion of biomass into
simpler sugars. Cellulase of Trichoderma longibrachiatum, a known cellulolytic fungus was compared with Clostridium thermocellum
[] cellulase. Blastp was performed with AAA23226.1 as query sequence to obtain nine similar sequences from NCBI
protein data bank. The physicochemical properties of cellulase were analyzed using ExPASy’s ProtParam tool namely ProtParam,
SOPMA and GOR IV. Homology modeling was done using SWISS MODEL and checked quality by RMSD values using VMD1.9.1.
Active sites of each model were predicted using automated active site prediction server of SCFBio. Study revealed instability of
cellulase of two eukaryotic strains namely Trichoderma longibrachiatum [ AAA23226.1] and Melanocarpus albomyces [ CAA43059.1]. The
negative GRAVY score value of cellulases ensured better interaction and activity in aqueous phase. It was found that molecular
weight (M. Wt) ranges between 25-127.56 kDa. Iso-electric point (pI) of cellulases was found to be acidic in nature. GOR IV and
SOPMA were used to predict secondary structure of cellulase, which showed that random coil, was dominated. Neighbor joining
tree with C. thermocellum [ CAD56665.1] cellulase as root showed that cellulases of Thermoaerobacter subterraneus [ AAA23226.1] and
C. thermocellum [CAA4305.1] were more similar to eukaryotic cellulases supported by least boot strap values. Pseudoalteromonas
haloplanktis cellulase was found to be the ideal model supported by least RMSD score among the predicted structures. Trichoderma
longibrachiatum cellulase was found to be the best compared to other cellulases, which possess high number of active sites with
ASN and THR rich active sites. CYS residues were also present ensuring stable interaction and better bonding. Hydrophilic
residues were found high in active sites of all analyzed models and template. ZP_07835928相似文献
9.
Although the potent anti-parkinsonian action of the atypical D1-like receptor agonist has been attributed to the selective activation of phosphoinositol(PI)-linked D1 receptor, whereas the mechanism underlying its potent neuroprotective effect is not fully understood. In the present study, the actions of SKF83959 on neuronal membrane potential and neuronal excitability were investigated in CA1 pyramidal neurons of rat hippocampal slices. SKF83959 (10–100 µM) caused a concentration-dependent depolarization, associated with a reduction of input resistance in CA1 pyramidal neurons. The depolarization was blocked neither by antagonists for D1, D2, 5-HT2A/2C receptors and α1-adrenoceptor, nor by intracellular dialysis of GDP-β-S. However, the specific HCN channel blocker ZD7288 (10 µM) antagonized both the depolarization and reduction of input resistance caused by SKF83959. In voltage-clamp experiments, SKF83959 (10–100 µM) caused a concentration-dependent increase of Ih current in CA1 pyramidal neurons, which was independent of D1 receptor activation. Moreover, SKF83959 (50 µM) caused a 6 mV positive shift in the activation curve of Ih and significantly accelerated the activation of Ih current. In addition, SKF83959 also reduced the neuronal excitability of CA1 pyramidal neurons, which was manifested by the decrease in the number and amplitude of action potentials evoked by depolarizing currents, and by the increase of firing threshold and rhoebase current. The above results suggest that SKF83959 increased Ih current through a D1 receptor-independent mechanism, which led to the depolarization of hippocampal CA1 pyramidal neurons. These findings provide a novel mechanism for the drug''s neuroprotective effects, which may contributes to its therapeutic benefits in Parkinson''s disease. SKF83959相似文献
10.
Derek M. Shore Gemma L. Baillie Dow H. Hurst Frank Navas III Herbert H. Seltzman Jahan P. Marcu Mary E. Abood Ruth A. Ross Patricia H. Reggio 《The Journal of biological chemistry》2014,289(9):5828-5845
The cannabinoid 1 (CB1) allosteric modulator, 5-chloro-3-ethyl-1H-indole-2-carboxylic acid [2-(4-piperidin-1-yl-phenyl)-ethyl]-amide) (), has the paradoxical effect of increasing the equilibrium binding of [3H](−)-3-[2-hydroxyl-4-(1,1-dimethylheptyl)phenyl]-4-[3-hydroxylpropyl]cyclohexan-1-ol (CP55,940, an orthosteric agonist) while at the same time decreasing its efficacy (in G protein-mediated signaling). ORG27569 also decreases basal signaling, acting as an inverse agonist for the G protein-mediated signaling pathway. In ligand displacement assays, ORG27569 can displace the CB1 antagonist/inverse agonist, N-(piperidiny-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide(SR141716A). The goal of this work was to identify the binding site of ORG27569 at CB1. To this end, we used computation, synthesis, mutation, and functional studies to identify the ORG27569-binding site in the CB1 TMH3-6-7 region. This site is consistent with the results of K3.28192A, F3.36200A, W5.43279A, W6.48356A, and F3.25189A mutation studies, which revealed the ORG27569-binding site overlaps with our previously determined binding site of SR141716A but extends extracellularly. Additionally, we identified a key electrostatic interaction between the ORG27569 piperidine ring nitrogen and K3.28192 that is important for ORG27569 to act as an inverse agonist. At this allosteric site, ORG27569 promotes an intermediate conformation of the CB1 receptor, explaining ORG27569''s ability to increase equilibrium binding of CP55,940. This site also explains ORG27569''s ability to antagonize the efficacy of CP55,940 in three complementary ways. 1) ORG27569 sterically blocks movements of the second extracellular loop that have been linked to receptor activation. 2) ORG27569 sterically blocks a key electrostatic interaction between the third extracellular loop residue Lys-373 and D2.63176. 3) ORG27569 packs against TMH6, sterically hindering movements of this helix that have been shown to be important for receptor activation. ORG27569相似文献
11.
In previous studies, we have shown that the inactivation of the adenosine A2A receptor exacerbates chronic cerebral hypoperfusion-induced white matter lesions (WMLs) by enhancing neuroinflammatory responses. However, the molecular mechanism underlying the effect of the adenosine A2A receptor remains unknown. Recent studies have demonstrated that cystatin F, a potent endogenous cysteine protease inhibitor, is selectively expressed in immune cells in association with inflammatory demyelination in central nervous system diseases. To understand the expression of cystatin F and its potential role in the effect of A2A receptor on WMLs induced through chronic cerebral hypoperfusion, we investigated cystatin F expression in the WMLs of A2A receptor gene knockout mice, the littermate wild-type mice and wild-type mice treated daily with the A2A receptor agonist or both CGS21680 and A2A receptor antagonist CGS21680 after chronic cerebral hypoperfusion. The results of quantitative-PCR and western blot analysis revealed that cystatin F mRNA and protein expression were significantly up-regulated in the WMLs after chronic cerebral hypoperfusion. In addition, cystatin F expression in the corpus callosum was significantly increased in A2A receptor gene knockout mice and markedly decreased in mice treated with SCH58261 on both the mRNA and protein levels. Additionally, CGS21680 counteracted the attenuation of cystatin F expression produced by SCH58261 after chronic cerebral hypoperfusion. Moreover, double immunofluorescence staining revealed that cystatin F was co-localized with the activated microglia marker CD11b. In conclusion, the cystatin F expression in the activated microglia is closely associated with the effect of the A2A receptors, which may be related to the neuroinflammatory responses occurring during the pathological process. CGS21680相似文献
12.
13.
The purpose of this table is to provide the community with a citable record of publications of ongoing genome sequencing projects that have led to a publication in the scientific literature. While our goal is to make the list complete, there is no guarantee that we may have omitted one or more publications appearing in this time frame. Readers and authors who wish to have publications added to subsequent versions of this list are invited to provide the bibliographic data for such references to the SIGS editorial office.
Phylum Crenarchaeota
- Pyrobaculum strain 1860, sequence accession [ CP0030981]
Phylum Deinococcus-Thermus
- “Thermus sp.” Strain CCB_US3_UF1, sequence accession (chromosome), CP003126 (plasmid) [ CP0031272]
Phylum Proteobacteria
- “Achromobacter arsenitoxydans” SY8, sequence accession [ AGUF000000003]
- Acidovorax sp. Strain NO1, sequence accession [ AGTS000000004]
- Acinetobacter baumannii AB4857, sequence accession [ AHAG000000005]
- Acinetobacter baumannii AB5075, sequence accession [ AHAH000000005]
- Acinetobacter baumannii AB5256, sequence accession [ AHAI000000005]
- Acinetobacter baumannii AB5711, sequence accession [ AHAJ000000005]
- Aeromonas salmonicida, sequence accession [ AGVO000000006]
- Aggregatibacter actinomycetemcomitans RHAA1, sequence accession [ AHGR000000007]
- Agrobacterium tumefaciens 5A, sequence accession [ AGVZ000000008]
- Azoarcus sp. Strain KH32C, sequence accession , AP012304 [ AP0123059]
- Burkholderia sp. Strain YI23, sequence accession (Chromosome 1), CP003087 (Chromosome 2), CP003088 (Chromosome 3), CP003089 (plasmid BYI23_D), CP003090 (plasmid BYI23_E) CP003091 (plasmid BYI23_F) [ CP00309210]
- Brucella suis VBI22, sequence accession , CP003128 [ CP00312911]
- Comamonas testosteroni ATCC 11996, sequence accession [ AHIL0000000012]
- “Commensalibacter intestini” A911T, sequence accession [ AGFR0000000013]
- Edwardsiella ictaluri, sequence accession [ CP001600.114]
- Enterobacter cloacae subsp. dissolvens SDM, sequence accession [ AGSY0000000015]
- “Gluconobacter morbifer” G707T, sequence accession [ AGQV0000000016]
- Legionella dumoffii TEX-KL, sequence accession [ AGVT0000000017]
- Legionella dumoffii NY-23, sequence accession [ AGVU0000000017]
- Legionella pneumophila serogroup 12 Strain 570-CO-H, sequence accession [ CP00319218]
- Marinobacterium stanieri S30, sequence accession [ AFPL0000000019]
- “Marinobacter manganoxydans” MnI7-9, sequence accession [ CP001978 to CP00198020]
- Mesorhizobium alhagi CCNWXJ12-2T, sequence accession [ AHAM0000000021]
- Mesorhizobium amorphae, sequence accession [ AGSN0000000022]
- Methylomicrobium alcaliphilum 20Z, sequence accession and FO082060 [ FO08206123]
- Mitsuaria sp. Strain H24L5A, sequence accession [ CAFG01000001 to CAFG0100060724]
- Novosphingobium pentaromativorans US6-1, sequence accession [ AGFM0000000025]
- Pantoea ananatis B1-9, sequence accession [ CAEI01000001 to CAEI0100016926]
- Pantoea ananatis LMG 5342, sequence accession (chromosome), HE617160 (pPANA10) [ HE61716127]
- Pantoea ananatis Strain PA13, sequence accession and CP003085 [ CP00308628]
- Pseudomonas aeruginosa, sequence accession [ AFXI0000000029]
- Pseudomonas aeruginosa, sequence accession [ AFXJ0000000029]
- Pseudomonas aeruginosa, sequence accession [ AFXK0000000029]
- Pseudomonas chlororaphis GP72, sequence accession [ AHAY0100000030]
- Pseudomonas fluorescens F113, sequence accession [ CP00315031]
- Pseudomonas fluorescens Wayne 1R, sequence accession [ CADX01000001 to CADX0100009032]
- Pseudomonas fluorescens Wood1R, sequence accession to CAFF01000001 [ CAFF0100143732]
- Pseudomonas psychrotolerans L19, sequence accession [ AHBD0000000033]
- Pseudoalteromonas rubra ATCC 29570T, sequence accession [ AHCD0000000034]
- Pseudomonas stutzeri SDM-LAC, sequence accession [ AGSX0000000035]
- Pseudoxanthomonas spadix BD-a59, sequence accession [ CP00309336]
- Rickettsia slovaca, sequence accession [ CP00242837]
- Salmonella enterica serovar Pullorum RKS5078, sequence accession [ CP00304738]
- Sinorhizobium meliloti CCNWSX0020, sequence accession [ AGVV0000000039]
- Sphingobium sp. Strain SYK-6, sequence accession and AP012222 [ AP01222340]
- Sphingomonas sp. Strain PAMC 26605, sequence accession [ AHIS0000000041]
- Stenotrophomonas maltophilia RR-10, sequence accession [ AGRB0000000042]
- Strain HIMB30, sequence accession [ AGIG0000000043]
- Taylorella equigenitalis, sequence accession [ CP00305944]
- Vibrio campbellii DS40M4, sequence accession [ AGIE0000000045]
- Vibrio fischeri SR5, sequence accession [ AHIH0000000046]
- Yersinia enterocolitica, sequence accession [ AGQO0000000047]
Phylum Tenericutes
- Candidatus Mycoplasma haemominutum, sequence accession [ HE61325448]
- Mycoplasma haemocanis strain Illinois, sequence accession [ CP00319949]
- Mycoplasma iowae, sequence accession [ AGFP0000000050]
- Mycoplasma pneumoniae Type 2a Strain 309, sequence accession [ AP01230351]
Phylum Firmicutes
- Bacillus cereus F837/76, sequence accession (chromosome) CP003187 (pF837_55kb), CP003188 (pF837_10kb) [ CP00318952]
- Brevibacillus laterosporus Strain GI-9, sequence accession [ CAGD01000001 to CAGD0100006153]
- Clostridium sporogenes PA 3679, sequence accession [ AGAH0000000054]
- Enterococcus mundtii CRL1656, sequence accession [ AFWZ00000000.155]
- Geobacillus thermoleovorans CCB_US3_UF5, sequence accession [ CP00312556]
- Lactobacillus curvatus Strain CRL705, sequence accession [ AGBU0100000057]
- Lactobacillus rhamnosus ATCC 8530, sequence accession [ CP00309458]
- Lactobacillus rhamnosus R0011, sequence accession [ AGKC0000000059]
- Lactococcus garvieae TB25, sequence accession [ AGQX0100000060]
- Lactococcus garvieae LG9, sequence accession [ AGQY0100000060]
- Lactococcus lactis subsp. cremoris A76, sequence accession (chromosome), CP003132 (pQA505), CP003136 (PQA518), CP003135 (pQA549), CP003134 (pQA554) [ CP00313361]
- Leuconostoc citreum LBAE C10, sequence accession [ CAGE0000000062]
- Leuconostoc citreum LBAE C11, sequence accession [ CAGF0000000062]
- Leuconostoc citreum LBAE E16, sequence accession [ CAGG0000000062]
- Leuconostoc mesenteroides subsp. mesenteroides Strain J18, sequence accession [ CP00310163]
- Paenibacillus peoriae Strain KCTC 3763T, sequence accession [ AGFX0000000064]
- Pediococcus acidilactici MA18/5M, sequence accession [ AGKB0000000065]
- Pediococcus claussenii ATCC BAA-344T, sequence accession (chromosome), CP003137 (pPECL-1), CP003138 (pPECL-2), CP003139 (pPECL-3), CP003140 (pPECL-4), CP003141 (pPECL-5), CP003142 (pPECL-6), CP003143 (pPECL-7), CP003144 (pPECL-8) [ CP00314566]
- Staphylococcus aureus M013, sequence accession [ CP00316667]
- Staphylococcus aureus subsp. aureus TW20, sequence accession [ FN43359668]
- Weissella confusa LBAE C39-2, sequence accession [ CAGH0000000069]
Phylum Actinobacteria
- Corynebacterium casei, sequence accession [ CAFW01000001 to CAFW0100010670]
- Corynebacterium glutamicum, sequence accession [ AGQQ0000000071]
- Leucobacter chromiiresistens, sequence accession [ AGCW0000000072]
- Mycobacterium abscessus, sequence accession [ AGQU0000000073]
- Propionibacterium acnes ST9, sequence accession [ CP00319574]
- Propionibacterium acnes ST22, sequence accession [ CP00319674]
- Propionibacterium acnes ST27, sequence accession [ CP00319774]
- Saccharomonospora azurea SZMC 14600, sequence accession [ AHBX0000000075]
- Streptomyces sp. Strain TOR3209, sequence accession [ AGNH0000000076]
- Streptomyces sp. Strain W007, sequence accession [ AGSW0000000077]
Phylum Spirochaetes
- Borrelia valaisiana VS116, sequence accession (chromosome), ABCY02000001 (plasmid Ip17), CP001439 (Ip25), CP001437 (plasmid Ip 28-3), CP001440 (plasmid Ip28-8), CP001442 (Ip 36), CP001436 (plasmid Ip 54), CP001433 (plasmid cp9), CP001438 (plasmid cp26), CP001432 (plasmid cp32-5), CP001441 (plasmid cp32-7), CP001434 (plasmid cp32-10) [ CP00143578]
- “Borrelia bissettii” DN127, sequence accession (chromosome), CP002746 (plasmid Ip12), CP002756 (plasmid Ip25), CP002757 (plasmid 28-3), CP002758 (plasmid Ip 28-4), CP002759 (Ip28-7), CP002760 (plasmid Ip54), CP002761 (plasmid Ip56), CP002762 (plasmid cp9), CP002755 (plasmid cp26), CP002747 (plasmid cp32-3), CP002749 (plasmid cp32-4), CP002750 (plasmid 32-5), CP002751 (plasmid cp32-6), CP002752 (plasmid cp32-7), CP0027554 (plasmid cp32-9), CP002753 (plasmid cp32-11) [ CP00274878]
- Borrelia spielmanii A14S, sequence accession (chromosome), ABKB02000001 (plasmid Ip17), CP001468 (Ip28-3), CP001471 (plasmid Ip28-4), CP001470 (plasmid Ip28-2), CP001465 (plasmid Ip36), CP001466 (plasmid Ip38), CP001464 (plasmid Ip54), CP001469, ABKB02000016 (plasmid cp9), ABKB02000020 (plasmid cp26), CP001467 (plasmid cp32-3), ABKB02000026 (plasmid 32-5), ABKB02000031 (plasmid cp32-12), ABKB02000021 (unidentified) [ ABKB0200001478]
Non-Bacterial genomes
- Aspergillus flavus, sequence accession [ GSE3217779]
- Bacteriophage SPN3UB, sequence accession [ JQ28802180]
- Bamboo mitochondria, sequence accession [ JQ235166 to JQ23517981]
- Boea hygrometrica chloroplast, sequence accession [ JN10781182]
- Boea hygrometrica mitochondrial, sequence accession [ JN10781282]
- Canine Picornavirus, sequence accession [ JN83135683]
- Chandipura virus (CHPV) CIN0327, sequence accession [ GU212856.184]
- Chandipura virus (CHPV) CIN0451, sequence accession [ GU212857.184]
- Chandipura virus (CHPV) CIN0751, sequence accession [ GU212858.184]
- Chandipura virus (CHPV) CIN0755, sequence accession [ GU190711.184]
- Chinese Porcine Parvovirus Strain PPV2010, sequence accession [ JN87244885]
- Common midwife toad megavirus, sequence accession [ JQ23122286]
- Dengue Virus Serotype 4, sequence accession [ JN98381387]
- Duck Tembusu Virus, sequence accession [ JF27048088]
- Duck Tembusu Virus, sequence accession [ JQ31446488]
- Duck Tembusu Virus, sequence accession [ JQ31446588]
- Emiliania huxleyi Virus 202, sequence accession [ HQ63414589]
- Emiliania huxleyi Virus EhV-88, sequence accession [ JF97431089]
- Emiliania huxleyi EhV-201, sequence accession [ JF97431189]
- Emiliania huxleyi EhV-207, sequence accession [ JF97431789]
- Emiliania huxleyi EhV-208, sequence accession [ JF97431889]
- Glarea lozoyensis, sequence accession GUE00000000 [90]
- Nannochloropis gaditana, sequence accession [ AGNI0000000091]
- Oryza sativa cv., sequence accession DRA000499 [92]
- Partetravirus, sequence accession [ JN99026993]
- Porcine Bocavirus PBoV5, sequence accession [ JN83165194]
- Porcine epidemic diarrhea virus, sequence accession [ JQ28290995]
- Pseudomonas aeruginosa lytic bacteriophage PA1Ø, sequence accession [ HM62408096]
- Pseudomonas fluorescens phage OBP, sequence accesssion [ JN62716097]
- RNA Virus from Avocado, sequence accession [ JN88041498]
- Salmonella enterica Serovar Typhimurium Bacteriophage SPN1S, sequence accession [ JN39118099]
- Schistosoma haematobium, sequence accession PRJNA78265 [100]
- Schistosoma mansoni, sequence accession [ ERP00038101]
- Stenopirates sp., sequence accession [ JN100019102]
- T7-Like Virus, sequence accession [ JN651747103]
- Vibrio harveyi siphophage VHS1, sequence accession [ JF713456104]
- Tyrolean ice man, sequence accession ERP001144 [105]
14.
Archaea use glycolytic pathways distinct from those found in bacteria and eukaryotes, where unique enzymes catalyze each reaction step. In this study, we isolated three isozymes of glyceraldehyde oxidoreductase (GAOR1, GAOR2 and GAOR3) from the thermoacidophilic archaeon Sulfolobus tokodaii. GAOR1–3 belong to the xanthine oxidoreductase superfamily, and are composed of a molybdo-pyranopterin subunit (L), a flavin subunit (M), and an iron-sulfur subunit (S), forming an LMS hetero-trimer unit. We found that GAOR1 is a tetramer of the / STK17810/ STK17830 hetero-trimer, GAOR2 is a dimer of the STK17820/ STK23390/ STK05620 hetero-trimer, and GAOR3 is the STK05610/ STK24840/ STK05620 hetero-trimer. GAOR1–3 exhibited diverse substrate specificities for their electron donors and acceptors, due to their different L-subunits, and probably participate in the non-phosphorylative Entner-Doudoroff glycolytic pathway. We determined the crystal structure of GAOR2, as the first three-dimensional structure of an archaeal molybdenum-containing hydroxylase, to obtain structural insights into their substrate specificities and subunit assemblies. The gene arrangement and the crystal structure suggested that the M/S-complex serves as a structural scaffold for the binding of the L-subunit, to construct the three enzymes with different specificities. Collectively, our findings illustrate a novel principle of a prokaryotic multicomponent isozyme system. STK05610相似文献
15.
Kwang H. Ahn Mariam M. Mahmoud Joong-Youn Shim Debra A. Kendall 《The Journal of biological chemistry》2013,288(14):9790-9800
The cannabinoid receptor 1 (CB1) is a G protein-coupled receptor primarily expressed in brain tissue that has been implicated in several disease states. CB1 allosteric compounds, such as , offer enormous potential as drugs over orthosteric ligands, but their mechanistic, structural, and downstream effects upon receptor binding have not been established. Previously, we showed that ORG27569 enhances agonist binding affinity to CB1 but inhibits G protein-dependent agonist signaling efficacy in HEK293 cells and rat brain expressing the CB1 receptor (Ahn, K. H., Mahmoud, M. M., and Kendall, D. A. (2012) J. Biol. Chem. 287, 12070–12082). Here, we identify the mediators of CB1 receptor internalization and ORG27569-induced G protein-independent signaling. Using siRNA technology, we elucidate an ORG27569-induced signaling mechanism for CB1 wherein β-arrestin 1 mediates short term signaling to ERK1/2 with a peak at 5 min and other upstream kinase components including MEK1/2 and c-Src. Consistent with these findings, we demonstrate co-localization of CB1-GFP with red fluorescent protein-β-arrestin 1 upon ORG27569 treatment using confocal microscopy. In contrast, we show the critical role of β-arrestin 2 in CB1 receptor internalization upon treatment with CP55940 (agonist) or treatment with ORG27569. These results demonstrate for the first time the involvement of β-arrestin in CB1-biased signaling by a CB1 allosteric modulator and also define the differential role of the two β-arrestin isoforms in CB1 signaling and internalization. ORG27569相似文献
16.
Brian P. Conlon Joan A. Geoghegan Elaine M. Waters Hannah McCarthy Sarah E. Rowe Julia R. Davies Carolyn R. Schaeffer Timothy J. Foster Paul D. Fey James P. O'Gara 《Journal of bacteriology》2014,196(24):4268-4275
The polysaccharide intercellular adhesin or the cell wall-anchored accumulation-associated protein (Aap) mediates cellular accumulation during Staphylococcus epidermidis biofilm maturation. Mutation of sortase, which anchors up to 11 proteins (including Aap) to the cell wall, blocked biofilm development by the cerebrospinal fluid isolate . Aap was implicated in this phenotype when Western blots and two-dimensional (2D) electrophoresis revealed increased levels of the protein in culture supernatants. Unexpectedly, reduced levels of primary attachment were associated with impaired biofilm formation by CSF41498 srtA and aap mutants. In contrast to previous studies, which implicated Aap proteolytic cleavage and, specifically, the Aap B domains in biofilm accumulation, the CSF41498 Aap protein was unprocessed. Furthermore, aap appeared to play a less important role in the biofilm phenotype of S. epidermidis 1457, in which the Aap protein is processed. Anti-Aap A-domain IgG inhibited primary attachment and biofilm formation in strain CSF41498 but not in strain 1457. The nucleotide sequences of the aap gene A-domain region and cleavage site in strains CSF41498 and 1457 were identical, implicating altered protease activity in the differential Aap processing results in the two strains. These data reveal a new role for the A domain of unprocessed Aap in the attachment phase of biofilm formation and suggest that extracellular protease activity can influence whether Aap contributes to the attachment or accumulation phases of the S. epidermidis biofilm phenotype. CSF41498相似文献
17.
Extracellular signal-regulated kinase 1/2 (ERK1/2) is a member of the mitogen-activated protein kinase family. It can mediate cell migration. Classical dopamine receptor-mediated ERK1/2 phosphorylation is widely studied in neurons. Here, we report that ERK1/2 phosphorylation is also modulated by putative phosphatidylinositol-linked D1-like receptors in cultured rat astrocytes. 6-chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine (), an agonist of the putative phosphatidylinositol-linked D1-like receptors, was found to enhance ERK1/2 phosphorylation, which then promoted the migration of cultured astrocytes. The SKF83959-induced ERK1/2 phosphorylation was found to be Ca2+-independent based on the following observations: i. chelating intracellular Ca2+ did not inhibit ERK1/2 phosphorylation and astrocyte migration; ii. blockage of the release of intracellular Ca2+ from the endoplasmic reticulum by an inhibitor of inositol 1,4,5-trisphosphate (IP3) receptor did not attenuate ERK1/2 phosphorylation. However, inhibition of phospholipase C (PLC), the upstream molecule of internal Ca2+ release, disabled SKF83959’s ability to elevate the level of ERK1/2 phosphorylation. Both non-selective protein kinase C (PKC) inhibitor and PKCδ selective inhibitor prevented ERK1/2 phosphorylation increase and astrocyte migration, but PKCα inhibitor did not. This suggests that Ca2+-independent and diacylglycerol-dependent PKCδ acts downstream of putative phosphatidylinositol-linked D1-like receptor activation and mediates SKF83959-induced elevation of ERK1/2 phosphorylation in order to modulate astrocyte migration. In conclusion, our results demonstrate that SKF83959-induced increases in ERK1/2 phosphorylation and astrocyte migration are dependent on PLC-PKCδ signals. This might help us to further understand the functions of the putative phosphatidylinositol-linked D1-like receptors in the nervous system. SKF83959相似文献
18.
Inhibition of the mitochondrial Na+/Ca2+ exchanger (NCLX) by is protective in models of neuronal injury that involve disruption of intracellular Ca2+ homeostasis. However, the Ca2+ signaling pathways and stores underlying neuroprotection by that inhibitor are not well defined. In the present study, we analyzed how intracellular Ca2+ levels are modulated by CGP37157 (10 μM) during NMDA insults in primary cultures of rat cortical neurons. We initially assessed the presence of NCLX in mitochondria of cultured neurons by immunolabeling, and subsequently, we analyzed the effects of CGP37157 on neuronal Ca2+ homeostasis using cameleon-based mitochondrial Ca2+ and cytosolic Ca2+ ([Ca2+]i) live imaging. We observed that NCLX-driven mitochondrial Ca2+ exchange occurs in cortical neurons under basal conditions as CGP37157 induced a decrease in [Ca2]i concomitant with a Ca2+ accumulation inside the mitochondria. In turn, CGP37157 also inhibited mitochondrial Ca2+ efflux after the stimulation of acetylcholine receptors. In contrast, CGP37157 strongly prevented depolarization-induced [Ca2+]i increase by blocking voltage-gated Ca2+ channels (VGCCs), whereas it did not induce depletion of ER Ca2+ stores. Moreover, mitochondrial Ca2+ overload was reduced as a consequence of diminished Ca2+ entry through VGCCs. The decrease in cytosolic and mitochondrial Ca2+ overload by CGP37157 resulted in a reduction of excitotoxic mitochondrial damage, characterized here by a reduction in mitochondrial membrane depolarization, oxidative stress and calpain activation. In summary, our results provide evidence that during excitotoxicity CGP37157 modulates cytosolic and mitochondrial Ca2+ dynamics that leads to attenuation of NMDA-induced mitochondrial dysfunction and neuronal cell death by blocking VGCCs. CGP37157相似文献
19.
Matthew J. Peirce Matthew Brook Nicholas Morrice Robert Snelgrove Shajna Begum Alessandra Lanfrancotti Clare Notley Tracy Hussell Andrew P. Cope Robin Wait 《PloS one》2010,5(7)
Background
Thymocyte expressed molecule involved in selection 1 (Themis1, SwissProt accession number Q8BGW0) is the recently characterised founder member of a novel family of proteins. A second member of this family, Themis2 ( Q91YX0), also known as ICB1 (Induced on contact with basement membrane 1), remains unreported at the protein level despite microarray and EST databases reporting Themis2 mRNA expression in B cells and macrophages.Methodology/Principal Findings
Here we characterise Themis2 protein for the first time and show that it acts as a macrophage signalling scaffold, exerting a receptor-, mediator- and signalling pathway-specific effect on TLR responses in RAW 264.7 macrophages. Themis2 over-expression enhanced the LPS-induced production of TNF but not IL-6 or Cox-2, nor TNF production induced by ligands for TLR2 (PAM3) or TLR3 (poly I∶C). Moreover, LPS-induced activation of the MAP kinases ERK and p38 was enhanced in cells over-expressing Themis2 whereas the activation of JNK, IRF3 or NF-κB p65, was unaffected. Depletion of Themis2 protein by RNA inteference inhibited LPS-induced TNF production in primary human macrophages demonstrating a requirement for Themis2 in this event. Themis2 was inducibly tyrosine phosphorylated upon LPS challenge and interacted with Lyn kinase (), the Rho guanine nucleotide exchange factor, Vav ( P25911), and the adaptor protein Grb2 ( P27870). Mutation of either tyrosine 660 or a proline-rich sequence (PPPRPPK) simultaneously interrupted this complex and reduced by approximately 50% the capacity of Themis2 to promote LPS-induced TNF production. Finally, Themis2 protein expression was induced during macrophage development from murine bone marrow precursors and was regulated by inflammatory stimuli both in vitro and in vivo. Q60631Conclusions/Significance
We hypothesise that Themis2 may constitute a novel, physiological control point in macrophage inflammatory responses. 相似文献20.
The small chaperone protein Hsp27 confers resistance to apoptosis, and therefore is an attractive anticancer drug target. We report here a novel mechanism underlying the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) sensitizing activity of the small molecule , an inactive analog of the phosphoinositide 3-kinase inhibitor inhibitor LY303511, in HeLa cells that are refractory to TRAIL-induced apoptosis. On the basis of the fact that LY294002 is derived from LY303511, itself derived from quercetin, and earlier findings indicating that quercetin and LY294002 affected Hsp27 expression, we investigated whether LY294002 sensitized cancer cells to TRAIL via a conserved inhibitory effect on Hsp27. We provide evidence that upon treatment with LY303511, Hsp27 is progressively sequestered in the nucleus, thus reducing its protective effect in the cytosol during the apoptotic process. LY303511-induced nuclear translocation of Hsp27 is linked to its sustained phosphorylation via activation of p38 kinase and MAPKAP kinase 2 and the inhibition of PP2A. Furthermore, Hsp27 phosphorylation leads to the subsequent dissociation of its large oligomers and a decrease in its chaperone activity, thereby further compromising the death inhibitory activity of Hsp27. Furthermore, genetic manipulation of Hsp27 expression significantly affected the TRAIL sensitizing activity of LY303511, which corroborated the Hsp27 targeting activity of LY303511. Taken together, these data indicate a novel mechanism of small molecule sensitization to TRAIL through targeting of Hsp27 functions, rather than its overall expression, leading to decreased cellular protection, which could have therapeutic implications for overcoming chemotherapy resistance in tumor cells. LY303511相似文献