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1.
Fernando Echeverri Fernando Torres Wiston Qui?ones Gustavo Escobar Rosendo Archbold 《Phytochemistry Reviews》2012,11(1):1-12
Phenylphenalenones represent a kind of phytoalexins produced in leaves and rhyzomes of banana and plantains (Musaceae), as
well as in species of other families. These compounds are synthesized in plants by induction with aminoglycosides, or in the
first stages of attack by the pathogenic fungus Mycosphaerella fijensis, a causal agent of the disease known as Black Sigatoka, which reduces banana production. In this paper we report the biosynthesis,
synthesis and antifungal activities of these kinds of compounds and discus the possibility to use phytoalexins inductors as
plant protectants. 相似文献
2.
Wang Q Montmain G Ruano E Upadhyaya M Dudley S Liskay RM Thibodeau SN Puisieux A 《Human genetics》2003,112(2):117-123
DNA mismatch repair (MMR) is the process by which incorrectly paired DNA nucleotides are recognized and repaired. A germline mutation in one of the genes involved in the process may be responsible for a dominantly inherited cancer syndrome, hereditary nonpolyposis colon cancer. Cancer progression in predisposed individuals results from the somatic inactivation of the normal copy of the MMR gene, leading to a mutator phenotype affecting preferentially repeat sequences (microsatellite instability, MSI). Recently, we identified children with a constitutional deficiency of MMR activity attributable to a mutation in the h MLH1 gene. These children exhibited a constitutional genetic instability associated with clinical features of de novo neurofibromatosis type 1 (NF1) and early onset of extracolonic cancer. Based on these observations, we hypothesized that somatic NF1 gene mutation was a frequent and possibly early event in MMR-deficient cells. To test this hypothesis, we screened for NF1 mutations in cancer cells. Genetic alterations were identified in five out of ten tumor cell lines with MSI, whereas five MMR-proficient tumor cell lines expressed a wild-type NF1 gene. Somatic NF1 mutations were also detected in two primary tumors exhibiting an MSI phenotype. Finally, a 35-bp deletion in the murine Nf1 coding region was identified in mlh1-/- mouse embryonic fibroblasts. These observations demonstrate that the NF1 gene is a mutational target of MMR deficiency and suggest that its inactivation is an important step of the malignant progression of MMR-deficient cells. 相似文献
3.
A new type II restriction endonuclease which we designated as Bsu121I has been isolated from gram-positive bacterium Bacillus subtilis strain 121 and partially purified. The restriction endonuclease was isolated from cell extracts using step-wise purification through ammonium sulfate precipitation, followed by phosphocellulose column chromatography. SDS-PAGE profile showed denatured molecular weights (23 and 67 kDa) of the endonuclease. The partially purified enzyme restricted pBR322 DNA into two fragments of 3200 and 1700 bp. The endonuclease activity required Mg+2 as cofactor like other type II endonucleases. 相似文献
4.
Králíková S Budesínský M Rosenberg I 《Nucleosides, nucleotides & nucleic acids》2003,22(5-8):1061-1064
The synthesis of monomers (S)-1, (R)-1 and 2 derived from (5'S)-, (5'R)-2'-deoxythymidine-5'-C-phosphonic acids and 2',5'-dideoxythymidine-5'-C-phosphonic acids was elaborated. The protection of the 5'-hydroxyl by the methoxycarbonyl group was a key step of the synthesis. Prepared monomers were used for the solid-phase assembly of several types oligothymidylate 15-mers (S)-3, (S)-4, (S)-5, (R)-4 and (R)-5 containing the chiral 3'-O-P-CH(OH)-5' internucleotide linkage. Their hybridization properties with dA15 and rA15 were studied as well as their resistance against nuclease cleavage. 相似文献
5.
L Henry IK Leung TD Claridge CJ Schofield 《Bioorganic & medicinal chemistry letters》2012,22(15):4975-4978
γ-Butyrobetaine hydroxylase (BBOX) is a 2-oxoglutarate and Fe(II)-dependent oxygenase that catalyses the final step of L-carnitine biosynthesis in animals. BBOX catalyses the oxidation of 3-(2,2,2-trimethylhydrazinium)propionate (THP), a clinically used BBOX inhibitor, to form multiple products including 3-amino-4-(methyamino)butanoic acid (AMBA), which is proposed to be formed via a Stevens type rearrangement mechanism. We report the synthesis of AMBA and confirm that it is a product of the BBOX catalysed oxidation of THP. AMBA reacts with formaldehyde, which is produced enzymatically by BBOX, to give a cyclic adduct. 相似文献
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The NF-κB signaling pathway is central to the innate and adaptive immune responses. Upon their detection of pathogen-associated molecular patterns, Toll-like receptors on the cell surface initiate signal transduction and activate the NF-κB pathway, leading to the production of a wide array of inflammatory cytokines, in attempt to eradicate the invaders. As a countermeasure, pathogens have evolved ways to subvert and manipulate this system to their advantage. Enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC) are closely related bacteria responsible for major food-borne diseases worldwide. Via a needle-like protein complex called the type three secretion system (T3SS), these pathogens deliver virulence factors directly to host cells and modify cellular functions, including by suppressing the inflammatory response. Using gain- and loss-of-function screenings, we identified two bacterial effectors, NleC and NleE, that down-regulate the NF-κB signal upon being injected into a host cell via the T3SS. A recent report showed that NleE inhibits NF-κB activation, although an NleE-deficient pathogen was still immune-suppressive, indicating that other anti-inflammatory effectors are involved. In agreement, our present results showed that NleC was also required to inhibit inflammation. We found that NleC is a zinc protease that disrupts NF-κB activation by the direct cleavage of NF-κB's p65 subunit in the cytoplasm, thereby decreasing the available p65 and reducing the total nuclear entry of active p65. More importantly, we showed that a mutant EPEC/EHEC lacking both NleC and NleE (ΔnleC ΔnleE) caused greater inflammatory response than bacteria carrying ΔnleC or ΔnleE alone. This effect was similar to that of a T3SS-defective mutant. In conclusion, we found that NleC is an anti-inflammatory bacterial zinc protease, and that the cooperative function of NleE and NleC disrupts the NF-κB pathway and accounts for most of the immune suppression caused by EHEC/EPEC. 相似文献
10.
Agnes Bénardeau Jörg Benz Alfred Binggeli Denise Blum Markus Boehringer Uwe Grether Hans Hilpert Bernd Kuhn Hans Peter Märki Markus Meyer Kurt Püntener Susanne Raab Armin Ruf Daniel Schlatter Peter Mohr 《Bioorganic & medicinal chemistry letters》2009,19(9):2468-2473
Design, synthesis, and SAR of novel α-alkoxy-β-arylpropionic acids as potent and balanced PPARαγ coagonists are described. One representative thereof, Aleglitazar ((S)-2Aa), was chosen for clinical development. Its X-ray structure in complex with both receptors as well as its high efficacy in animal models of T2D and dyslipidemia are also presented. 相似文献
11.
《Journal of Fermentation and Bioengineering》1993,75(1):48-52
The applicability of a new aeration-agitation type fermentor with a grid-paddle type impeller and a spiral-sparger, Maxblend Fermentor® (MBF) for high density cultivation of plant cells, was investigated. The MBF showed a high capacity for oxygen supply and extremely low hydrodynamic stress in aeration and mixing compared with a conventional fermentor (CF). When Oryza sativa cells were cultivated at a kLa of 20 h−1, a high cell density cultivation of about 30 g dry cell weight per liter was accomplished in both fermentors and there were few differences in culture performance between the two. On the contrary, considerable differences were observed when Catharanthus roseus cells, which seemed to be sensitive to physical stress, were cultivated at a kLa of 20 h−1 in both fermentors. The MBF exhibited excellent cell growth characteristics, achieving about 19 g dry cell weight per liter, because of its superior oxygen supply and low hydrodynamic stress in aeration and mixing in highly viscous cultures containing high density cells. In CF only about 9.5 g dry cell weight per liter was achieved because of its high hydrodynamic stress. 相似文献
12.
Bo GAO Lin HE Institute for Nutritional Sciences Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai China. Neuropsychiatric Human Genetics Group Bio-X Life Science Research Center Shanghai Jiaotong University Shanghai China. Department of Biochemistry Faculty of Medicine The University of Hong Kong Hong Kong China. 《Cell research》2004,(3)
In 1903, Farabee analyzed the heredity of the human digital malformation, brachydactyly, the first recorded disorder of the autosomal dominant Mendelian trait. In 1951, Bell classified this type of brachydactyly as type A1 (BDA1). Over 100 cases from different ethnic groups have so far been reported. However, the real breakthrough in identifying the cause of BDA1 has only taken place in the last few years with the progress of the mapping and identification of one of the genes responsible for this disorder, thus providing an answer for a century old riddle. In this article, we attempt to review the current state of knowledge on the genetic features of BDA1 with its century-old history and signalling pathway of IHH, and also discuss genotype-phenotype correlation not only of BDA1, but also of all types of brachydactyly. 相似文献
13.
《Bioorganic & medicinal chemistry letters》2014,24(8):1912-1917
Tuberculosis remains a global public health problem in recent years. To develop novel type of potential antitubercular agents, twelve novel dihydroartemisinin–fluoroquinolone (DHA–FQ) conjugates (three types of molecules) were gradually designed and conveniently synthesized. All the newly synthesized conjugates were well characterized and evaluated against different Mycobacterium tuberculosis strains in vitro. The screening results showed that five DHA–FQ conjugates were active toward M. tuberculosis H37Rv, and compound 3a exhibited the strongest inhibitory activity (MIC = 0.0625 μg/mL), which was comparable to the positive control Moxifloxacin and even stronger than Ofloxacin. Conjugates 2a and 3a also displayed comparable activities against various clinically isolated sensitive and resistant M. tuberculosis strains (MIC = 0.125–16 μg/mL) to Moxifloxacin. All target compounds possessed selective anti-M. tuberculosis ability. Preliminary structure–activity relationship demonstrated that short linker between DHA and FQ was favorable for strong antitubercular activity. This study provides a new clue for the development of novel antitubercular lead molecules. 相似文献
14.
Sachi Kashihara Takafumi Nishimura Yoshiteru Noutoshi Mikihiro Yamamoto Kazuhiro Toyoda Yuki Ichinose Hidenori Matsui 《Molecular Plant Pathology》2022,23(6):885-894
Pseudomonas amygdali pv. tabaci (formerly Pseudomonas syringae pv. tabaci; Pta) is a gram-negative bacterium that causes bacterial wildfire disease in Nicotiana tabacum. The pathogen establishes infections by using a type III secretion system to inject type III effector proteins (T3Es) into cells, thereby interfering with the host__s immune system. To counteract the effectors, plants have evolved disease-resistance genes and mechanisms to induce strong resistance on effector recognition. By screening a series of Pta T3E-deficient mutants, we have identified HopAZ1 as the T3E that induces disease resistance in N. tabacum ‘N509’. Inoculation with the Pta ∆hopAZ1 mutant did not induce resistance to Pta in N509. We also found that the Pta ∆hopAZ1 mutant did not induce a hypersensitive response and promoted severe disease symptoms in N509. Furthermore, a C-terminal truncated HopAZ1 abolished HopAZ1-dependent cell death in N509. These results indicate that HopAZ1 is the avirulence factor that induces resistance to Pta by N509. 相似文献
15.
Sen-Miao Ding Tian Lan Gao-Jie Ye Jia-Jun Huang You Hu Yi-Ran Zhu Bo Wang 《Bioorganic & medicinal chemistry》2018,26(12):3370-3378
Xanthone derivatives have shown good α-glucosidase inhibitory activity and have drawn increased attention as potential anti-diabetic compounds. In this study, a series of novel oxazolxanthones were designed, synthesized, and investigated as α-glucosidase inhibitors. Inhibition assays indicated that compounds 4–21 bearing oxazole rings exhibited up to 30-fold greater inhibitory activity compared to their corresponding parent compound 1b. Among them, compounds 5–21 (IC50?=?6.3?±?0.4–38.5?±?4.6?μM) were more active than 1-deoxynojirimycin (IC50?=?60.2?±?6.2?μM), a well-known α-glucosidase inhibitor. In addition, the kinetics of enzyme inhibition measured by using Lineweaver–Burk analysis shows that compound 4 is a competitive inhibitor, while compounds 15, 16 and 20 are non-competitive inhibitors. Molecular docking studies showed that compound 4 bound to the active site pocket of the enzyme while compounds 15, 16, and 20 did not. More interestingly, docking simulations reveal that some of the oxazolxanthone derivatives bind to different sites in the enzyme. This prediction was further confirmed by the synergetic inhibition experiment, and the combination of representative compounds 16 and 20 at the optimal ratio of 4:6 led to an IC50 value of 1.9?±?0.7?μM, better than the IC50 value of 7.1?±?0.9?μM for compound 16 and 8.6?±?0.9?μM for compound 20. 相似文献
16.
We establish the existence of a pulse traveling wave for an infinite system of ODEs modeling a one dimensional string of
nerve cells of identical Morris–Lecar type dynamics:
Here v
j
and w
j
represent, respectively, the electrical potential and the conductance of electrically active membrane of the jth nerve cell. We assume that D is a small positive constant, and F and G are certain nonlinear functions such that the ode system v′=F, w′=G has three equilibria: one is stable, another is a saddle, and the third is unstable.
Received: 15 October 1996 / Revised version: 1 January 1998 相似文献
17.
Answering a century old riddle: brachydactyly type A1 总被引:1,自引:0,他引:1
In 1903, Farabee analyzed the heredity of the human digital malformation, brachydactyly, the first recorded disorder of the autosomal dominant Mendelian trait. In 1951, Bell classified this type of brachydactyly as type A 1 (BDA 1). Over 100 cases from different ethnic groups have so far been reported. However, the real breakthrough in identifying the cause of BDA 1 has only taken place in the last few years with the progress of the mapping and identification of one of the genes responsible for this disorder, thus providing an answer for a century old riddle. In this article, we attempt to review the current state of knowledge on the genetic features of BDA 1 with its century-old history and signalling pathway of IHH, and also discuss genotype-phenotype correlation not only of BDA 1, but also of all types of brachydactyly. 相似文献
18.
Background
The impressive correlation between cardiovascular disease and glucose metabolism alterations has raised the likelihood that atherosclerosis and type 2 diabetes may share common antecedents. Inflammation is emerging as a conceivable etiologic mechanism for both. Interleukins are regulatory proteins with ability to accelerate or inhibit inflammatory processes.Presentation of the hypothesis
A novel interleukins classification is described, based on their role in diabetes and atherosclerosis, hypothesizing that each interleukin (IL) acts on both diseases in the same direction – regardless if harmful, favorable or neutral.Testing the hypothesis
The 29 known interleukins were clustered into three groups: noxious (the "bad", 8 members), comprising IL-1, IL-2, IL-6, IL-7, IL-8, IL-15, IL-17 and IL-18; protective (the "good", 5 members), comprising IL-4, IL-10, IL-11, IL-12 and IL-13; and "aloof", comprising IL-5, IL-9, IL-14, IL-16 and IL-19 through IL-29 (15 members). Each group presented converging effects on both diseases. IL-3 was reluctant to clustering.Implications
These observations imply that 1) favorable effects of a given IL on either diabetes or atherosclerosis predicts similar effects on the other; 2) equally, harmful IL effects on one disease can be extrapolated to the other; and 3) absence of influence of a given IL on one of these diseases forecasts lack of effects on the other. These facts further support the unifying etiologic theory of both ailments, emphasizing the importance of a cardiovascular diabetologic approach to interleukins for future research. Pharmacologic targeting of these cytokines might provide an effective means to simultaneously control both atherosclerosis and diabetes. 相似文献19.
L Wang J Liu A Zhang P Cheng X Zhang S Lv L Wu J Yu W Di J Zha X Kong H Qi Y Zhong G Ding 《PloS one》2012,7(7):e40056
Background
Inhibition of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is being pursued as a new therapeutic approach for the treatment of obesity and metabolic syndrome. Therefore, there is an urgent need to determine the effect of 11β-HSD1 inhibitor, which suppresses glucocorticoid action, on adipose tissue inflammation. The purpose of the present study was to examine the effect of BVT.2733, a selective 11β-HSD1 inhibitor, on expression of pro-inflammatory mediators and macrophage infiltration in adipose tissue in C57BL/6J mice.Methodology/Principal Findings
C57BL/6J mice were fed with a normal chow diet (NC) or high fat diet (HFD). HFD treated mice were then administrated with BVT.2733 (HFD+BVT) or vehicle (HFD) for four weeks. Mice receiving BVT.2733 treatment exhibited decreased body weight and enhanced glucose tolerance and insulin sensitivity compared to control mice. BVT.2733 also down-regulated the expression of inflammation-related genes including monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor alpha (TNF-α) and the number of infiltrated macrophages within the adipose tissue in vivo. Pharmacological inhibition of 11β-HSD1 and RNA interference against 11β-HSD1 reduced the mRNA levels of MCP-1 and interleukin-6 (IL-6) in cultured J774A.1 macrophages and 3T3-L1 preadipocyte in vitro.Conclusions/Significance
These results suggest that BVT.2733 treatment could not only decrease body weight and improve metabolic homeostasis, but also suppress the inflammation of adipose tissue in diet-induced obese mice. 11β-HSD1 may be a very promising therapeutic target for obesity and associated disease. 相似文献20.
《Palaeoworld》2021,30(3):515-537
For more than a century, a number of ammonite taxa of supposed Tethyan origin or affinity have been reported from the Berriasian condensed deposits of Russia (referred to as ‘Ryazanian’). These occurrences have been used to constrain long-distance correlation and palaeobiogeographic interpretation of the Russian Platform during the earliest Cretaceous. We revise these taxa herein. To accommodate the systematic issues, we introduce a new ammonite genus: Mittaites n. gen. (type species: Mazenoticeras ceccai). We also provide re-assessment for the genera Tauricoceras (= Subriasanites), Riasanella, Riasanites, Prorjasanites, and Karasyazites. Considering the strong affinities between these genera (except for Karasyazites), resctricted palaeobiogeographic distribution and a problematic phyletic origin, we erect a new family Riasanitidae n. fam. Our re-examination suggests that the occurrence of western Tethyan migrants in the type ‘Ryazanian’ should be ruled out. Pending new investigation, correlation of the ammonites of the type ‘Ryazanian’ beds with the Berriasian part of the Standard Mediterranean Ammonite Scale (SMAS) should be treated with caution. 相似文献